Acne

People whose gender identity differs from the sex assigned at birth are referred to as transgender. For some, gender identity may not fit into the binary constructs of male and female but rather falls between, within, or outside this construct. These people often consider themselves nonbinary or gender diverse. As the terminology continues to evolve, current recommendations include referring to this patient population as transgender and gender diverse (TGD) to ensure the broadest inclusivity.¹ In this article, the following terms are used as defined below:

• The terms transgender woman and trans feminine describe persons who were assigned male gender at birth but their affirmed gender is female or nonmasculine.
• The terms transgender man and trans masculine describe persons who were assigned female gender at birth but their affirmed gender is male or nonfeminine.

The US Military’s policies on the service of TGD persons have evolved considerably over the past decade. Initial military policies barred TGD service members (TSMs) from service all together, leading to challenges in accessing necessary health care. The first official memorandum explicitly allowing military service by TGD persons was released on June 30, 2016.² The intention of this memorandum was 2-fold: (1) to allow TGD persons to serve in the military so long as they meet “the rigorous standards for military service and readiness” by fulfilling the same standards and procedures as other military service members, including medical fitness for duty, physical fitness, uniform and grooming, deployability, and retention, and (2) to direct the establishment of new or updated policies to specific departments and prescribe procedures for retention standards, separation from service, in-service transition, and medical coverage.² Several other official policies were released following this initial memorandum that provided more specific guidance on how to implement these policies at the level of the force, unit, and individual service member.

Modifications to the original 2016 policies had varying impacts on transgender health care provision and access.³ At the time of publication of this article, the current policy—the Department of Defense Instruction 1300.28⁴—among others, establishes standards and procedures for the process by which active and reserve TSMs may medically, socially, and legally transition genders within the military. The current policy applies to all military branches and serves as the framework by which each branch currently organizes their gender-affirmation processes (GAP).⁴

There currently are several different GAP models among the military branches.⁵ Each branch has a different model or approach to implementing the current policy, with varying service-specific processes in place for TSMs to access gender-affirming care; however, this may be changing. The Defense Health Agency is in the process of consolidating and streamlining the GAP across the Department of Defense branches in an effort to optimize costs and ensure uniformity of care. Per the Defense Health Agency Procedural Instruction Number 6025.21 published in May 2023, the proposed consolidated model likely will entail a single central transgender health center that provides oversight and guidance for several regional joint-service gender-affirming medical hubs. Patients would either be managed at the level of the hub or be referred to the central site.⁵

Herein, we discuss the importance of gender-affirming care and how military and civilian dermatologists can contribute. We also review disparities in health care and identify areas of improvement.

Benefits of Gender-Affirming Care

Gender-affirming procedures are critical for aligning physical appearance with gender identity. Physical appearance is essential for psychological well-being, operational readiness, and the safety of TSMs.⁶ It is well documented that TGD persons experience suicidal ideation, depression, stigma, discrimination and violence at higher rates than their cisgender peers.^7,8 It is important to recognize that transgender identity is not a mental illness, and these elevated rates have been linked to complex trauma, societal stigma, violence, and discrimination.¹ Other studies have suggested that increased access to gender-affirming interventions may ameliorate these mental health concerns.^1,7-9

The major components of gender-affirming care include hormone therapy, gender confirmation surgery, and mental health care, if needed. These are covered by TRICARE, the health care program for military service members; however, at the time of publication, many of the dermatologic gender-affirming procedures are not covered by TRICARE because they are considered “cosmetic procedures,” which is a term used by insurance companies but does not accurately indicate whether a procedure is medically necessary or not. Newer literature has demonstrated that gender-affirming care positively affects the lives of TGD patients, strengthening the argument that gender-affirming care is a medical necessity and not just cosmetic.¹

Aesthetic Procedures in Gender-Affirming Care

Surgeons, including those within the specialties of oto-laryngology, oral and maxillofacial surgery, urology, gynecology, and plastic surgery, provide major gender-affirming interventions; however, dermatologists may offer less invasive solutions that can serve as a temporary experience prior to undergoing more permanent procedures.Hormonally driven disorders including acne, hair loss, and melasma also are managed by dermatologists, along with scar treatment following surgeries.

Because human variation is expansive and subjective, what is considered feminine or masculine may vary by person, group, culture, and country; therefore, it is imperative to ask patients about their individual aesthetic goals and tailor their treatment accordingly. Feminine and masculine are terms that will be used to describe prototypical appearances and are not meant to define a patient’s current state or ultimate goals. The following procedures and medical interventions are where dermatologists can play an important role in TGD persons’ GAPs.

Botulinum Toxin Injections—Botulinum toxin injection is the most common nonsurgical aesthetic procedure performed around the world.¹⁰ The selective paralysis afforded by botulinum toxin has several uses for people undergoing transition. Aesthetically, the feminine eyebrow tends to be positioned above the orbital rim and is arched with its apex between the lateral limbus and lateral canthus,¹¹ while the masculine eyebrow tends to be flatter and fuller and runs over the orbital rim without a peak. For people seeking a more feminine appearance, an eyebrow lift with botulinum toxin can help reshape the typical flatter masculine eyebrow to give it lateral lift that often is considered more feminine. The targeted muscle is the superolateral orbicularis oculi, which serves as a depressor on the eyebrow. This can be combined with purposefully avoiding total lateral frontalis paralysis, which leads to a “Spock” brow for extra lift. Conversely, a naturally arched and higher eyebrow can be flattened and lowered by selectively targeting areas of the frontalis muscle.

Broad square jawlines typically are considered a masculine feature and are another area where botulinum toxin can be used to feminize a patient’s facial features. Targeting the masseter muscle induces muscle weakness, which ultimately may result in atrophy after one or more treatment sessions. This atrophy may lead to narrowing of the lower face and thus may lead to a fuller-appearing midface or overall more heart-shaped face. Every individual’s aesthetic goals are unique and therefore should be discussed prior to any treatment.

Dermal Fillers—Dermal fillers are gel-like substances injected under the skin for subtle contouring of the face. Fillers also can be used to help promote a more masculine or feminine appearance. Filler can be placed in the lips to create a fuller, more projected, feminine-appearing lip. Malar cheek and central lower chin filler can be used to help define a heart-shaped face by accentuating the upper portion of the face and creating a more pointed chin, respectively. Alternatively, filler can be used to masculinize the chin by placing it where it can increase jawline squareness and increase anterior jaw projection. Additionally, filler at the angle of the jaw can help accentuate a square facial shape and a more defined jawline. Although not as widely practiced, lateral brow filler can create a heavier-appearing and broader forehead for a more masculine appearance. These procedures can be combined with the previously mentioned botulinum toxin procedures for a synergistic effect.

Deoxycholic Acid—Deoxycholic acid is an injectable product used to selectively remove unwanted fat. It currently is approved by the US Food and Drug Administration for submental fat, but some providers are experimenting with off-label uses. Buccal fat pad removal—or in this case reduction by dissolution—tends to give a thinner, more feminine facial appearance.¹² Reducing fat around the axillae also can help promote a more masculine upper torso.¹³ The safety of deoxycholic acid in these areas has not been adequately tested; thus, caution should be used when discussing these off-label uses with patients.

Hair and Tattoo Removal—Hair removal may be desired by TGD persons for a variety of reasons. Because cisgender females tend to have less body hair overall, transgender people in pursuit of a more feminine appearance often desire removal of facial, neck, and body hair. Although shaving and other modalities such as waxing and chemical depilatories are readily available at-home options, they are not permanent and may lead to folliculitis or pseudofolliculitis barbae. Laser hair removal (LHR) and electrolysis are modalities provided by dermatologists that tend to be more permanent and lead to better outcomes, including less irritation and better aesthetic appearance. It is important to keep in mind that not every person and not every body site can be safely treated with LHR. Patients with lighter skin types and darker hair tend to have the most effective response with a higher margin of safety, as these features allow the laser energy to be selectively absorbed by the melanin in the hair bulb and not by the background skin pigmentation.^14,15 Inappropriate patient selection or improper settings for wavelength, pulse width, or fluences can lead to burns and permanent scarring.^14,15 Electrolysis is an alternative to hair removal within tattoos and is more effective for those individuals with blonde, red, or white hair.¹⁶

Another novel treatment for unwanted hair is eflor­nithine hydrochloride cream, which works by blocking ornithine decarboxylase, the enzyme that stimulates hair growth. It currently is approved to reduce unwanted hair on the face and adjacent areas under the chin; however the effects of this medication are modest and the medication can be expensive.¹⁷

Cosmetic hair and tattoo removal are not currently covered by TRICARE, except in cases of surgical and donor-site preparation for some GAPs. Individuals may desire removal of tattoos at surgery sites to obtain more natural-appearing skin. Currently, GAPs such as vaginoplasty, phalloplasty, and metoidioplasty—often referred to by patients as “bottom surgeries”—include insurance coverage for tattoo removal, LHR, and/or electrolysis.

Management of Hormonal Adverse Effects

Acne—Individuals on testosterone supplementation tend to develop acne for the first several years of treatment, but it may improve with time.¹⁸ Acne is treated in individuals receiving testosterone the same way as it is treated in cisgender men, with numerous options for topical and oral medications. In trans masculine persons, spironolactone therapy typically is avoided because it may interfere with the actions of exogenous testosterone administered as part of gender-affirming medical treatment and may lead to other undesired adverse effects such as impotence and gynecomastia.¹

Although acne typically improves after starting estrogen therapy, patients receiving estrogens may still develop acne. Most trans feminine patients will already be on an estrogen and an antiandrogen, often spironolactone.¹ Spironolactone often is used as monotherapy for acne control in cisgender women. Additionally, an important factor to consider with spironolactone is the possible adverse effect of increased micturition. Currently, the military rarely has gender-inclusive restroom options, which can create a challenge for TSMs who find themselves needing to use the restroom more frequently in the workplace.

If planning therapy with isotretinoin, dermatologists should discuss several important factors with all patients, including TGD patients. One consideration is the patient’s planned future surgeries. Although new literature shows that isotretinoin does not adversely affect wound healing,¹⁹ some surgeons still adhere to an isotretinoin washout period of 6 to 12 months prior to performing any elective procedures due to concerns about wound healing.^20,21 Second, be sure to properly assess and document pregnancy potential in TGD persons. Providers should not assume that a patient is not pregnant or is not trying to become pregnant just because they are trans masculine. It also is important to note that testosterone is not a reliable birth control method.¹ If a patient still has ovaries, fallopian tubes, and a uterus, they are considered medically capable of pregnancy, and providers should keep this in mind regarding all procedures in the TGD population.

Another newer acne treatment modality is the 1762-nm laser, which targets sebaceous glands.²² This device allows for targeted treatment of acne-prone areas without systemic therapy such as retinoids or antiandrogens. The 1762-nm laser is not widely available but may become a regular treatment option once its benefits are proven over time.

Alopecia and Hyperpigmentation—Androgens, whether endogenously or exogenously derived, can lead to androgenetic alopecia (AGA) in genetically susceptible individuals. Trans masculine persons and others receiving androgen therapy are at higher risk for AGA, which often is undesirable and may be considered gender affirming by some TGD persons. Standard AGA treatments for cisgender men also can be used in trans masculine persons. Some of the most common anti-AGA medications are topical minoxidil, oral finasteride, and oral minoxidil. Although Coleman et al¹ recently reported that finasteride may be an appropriate treatment option in trans masculine persons experiencing alopecia, treatment with 5α-reductase inhibitors may impair clitoral growth and the development of facial and body hair. Further studies are needed to assess the efficacy and safety of 5α-reductase inhibitors in transgender populations.¹ Dutasteride may be used off-label and comes with a similar potential adverse-event profile as finasteride, which includes depression, decreased libido, erectile dysfunction, ejaculation disorders, and gynecomastia.

Conversely, AGA tends to improve in trans feminine persons and others receiving estrogen and antiandrogen therapy. Natural testosterone production is suppressed by estrogens and spironolactone as well as in patients who undergo orchiectomy.¹ Although spironolactone is not approved for acne, AGA, or hirsutism, it is a standard treatment of AGA in cisgender women because it functions to block the effects of androgens, including at the hair follicle. Finasteride may be used for AGA in cisgender women but it is not recommended for trans feminine persons.¹

There are many other modalities available for the treatment of AGA that are less commonly used—some may be cost prohibitive or do not have robust supporting evidence, or both. One example is hair transplantation. Although this procedure gives dramatic results, it typically is performed by a specialized dermatologist, is not covered by insurance, and can cost up to tens of thousands of dollars out-of-pocket. Patients typically require continuous medical management of AGA even after the procedure. Examples of treatment modalities with uncertain supporting evidence are platelet-rich plasma injections, laser combs or hats, and microneedling. Additionally, clascoterone is a topical antiandrogen currently approved for acne, but it is under investigation for the treatment of AGA and may become an additional nonsystemic medication available for AGA in the future.²³

Melasma is a hyperpigmentation disorder related to estrogens, UV light exposure, and sometimes medication use (eg, hormonal birth control, spironolactone).²⁴ The mainstay of treatment is prevention, including sun avoidance as well as use of sun-protective clothing and broad-spectrum sunscreens. Dermatologists tend to recommend physical sunscreens containing zinc oxide, titanium dioxide, and/or iron oxide, as they cover a wider UV spectrum and also provide some protection from visible light. Once melasma is present, dermatologists still have several treatment options. Topical hydroquinone is a proven treatment; however, it must be used with caution to avoid ochronosis. With careful patient selection, chemical peels also are effective treatment options for dyspigmentation and hyperpigmentation. Energy devices such as intense pulsed light and tattoo removal lasers—Q-switched lasers and picosecond pulse widths—also can be used to treat hyperpigmentation. Oral, intralesional, and topical tranexamic acid are newer treatment options for melasma that still are being studied and have shown promising results. Further studies are needed to determine long-term safety and optimal treatment regimens.^24,25

Many insurance carriers, including TRICARE, do not routinely cover medical management of AGA or melasma. Patients should be advised that they likely will have to pay for any medications prescribed and procedures undertaken for these purposes; however, some medication costs can be offset by ordering larger prescription quantities, such as a 90-day supply vs a 30-day supply, as well as utilizing pharmacy discount programs.

Scar Management Following Surgery

In TSMs who undergo gender-affirming surgeries, dermatologists play an important role when scar symptoms develop, including pruritus, tenderness, and/or paresthesia. In the military, some common treatment modalities for symptomatic scars include intralesional steroids with or without 5-fluouroruacil and the fractionated CO₂ laser. There also are numerous experimental treatment options for scars, including intralesional or perilesional botulinum toxin, the pulsed dye laser, or nonablative fractionated lasers. These modalities also may be used on hypertrophic scars or keloids. Another option for keloids is scar excision followed by superficial radiation therapy.²⁶

Mental Health Considerations

Providers must take psychological adverse effects into consideration when considering medical therapies for dermatologic conditions in TGD patients. In particular, it is important to consider the risks for increased rates of depression and suicidal ideation formerly associated with the use of isotretinoin and finasteride, though much of the evidence regarding these risks has been called into question in recent years.^27,28 Nonetheless, it remains prominent in lay media and may be a more important consideration in patients at higher baseline risk.²⁷ Although there are no known studies that have expressly assessed rates of depression or suicidal ideation in TGD patients taking isotretinoin or finasteride, it is well established that TGD persons are at higher baseline risk for depression and suicidality.^1,7,8 All patients should be carefully assessed for depression and suicidal ideation as well as counseled regarding these risks prior to initiating these therapies. If concerns for untreated mental health issues arise during screening and counseling, patients should be referred for assessment by a behavioral health specialist prior to starting therapy.

Future Directions

The future of TGD health care in the military could see an expansion of covered benefits and the development of new dermatologic procedures or medications. Research and policy evolution are necessary to bridge the current gaps in care; however, it is unlikely that all procedures currently considered to be cosmetic will become covered benefits.

Facial LHR is a promising candidate for future coverage for trans feminine persons. When cisgender men develop adverse effects from mandatory daily shaving, LHR is already a covered benefit. Two arguments in support of adding LHR for TGD patients revolve around achieving and maintaining an appearance congruent with their gender along with avoiding unwanted adverse effects related to daily shaving. Visual conformity with one’s affirmed gender has been associated with improvements in well-being, quality of life, and some mental health conditions.²⁹

Scar prevention, treatment, and reduction are additional areas under active research in which dermatologists likely will play a crucial role.^30,31 As more dermatologic procedures are performed on TGD persons, the published data and collective knowledge regarding best practices in this population will continue to grow, which will lead to improved cosmetic and safety outcomes.

Final Thoughts

Although dermatologists do not directly perform gender-affirming surgeries or hormone management, they do play an important role in enhancing a TGD person’s desired appearance and managing possible adverse effects resulting from gender-affirming interventions. There have been considerable advancements in TGD health care over the past decade, but there likely are more changes on the way. As policies and understanding of TGD health care needs evolve, it is crucial that the military health care system adapts to provide comprehensive, accessible, and equitable care, which includes expanding the range of covered dermatologic treatments to fully support the health and readiness of TSMs.

Acknowledgment—We would like to extend our sincere appreciation to the invaluable contributions and editorial support provided by Allison Higgins, JD (San Antonio, Texas), throughout the writing of this article.

People whose gender identity differs from the sex assigned at birth are referred to as transgender. For some, gender identity may not fit into the binary constructs of male and female but rather falls between, within, or outside this construct. These people often consider themselves nonbinary or gender diverse. As the terminology continues to evolve, current recommendations include referring to this patient population as transgender and gender diverse (TGD) to ensure the broadest inclusivity.¹ In this article, the following terms are used as defined below:

• The terms transgender woman and trans feminine describe persons who were assigned male gender at birth but their affirmed gender is female or nonmasculine.
• The terms transgender man and trans masculine describe persons who were assigned female gender at birth but their affirmed gender is male or nonfeminine.

The US Military’s policies on the service of TGD persons have evolved considerably over the past decade. Initial military policies barred TGD service members (TSMs) from service all together, leading to challenges in accessing necessary health care. The first official memorandum explicitly allowing military service by TGD persons was released on June 30, 2016.² The intention of this memorandum was 2-fold: (1) to allow TGD persons to serve in the military so long as they meet “the rigorous standards for military service and readiness” by fulfilling the same standards and procedures as other military service members, including medical fitness for duty, physical fitness, uniform and grooming, deployability, and retention, and (2) to direct the establishment of new or updated policies to specific departments and prescribe procedures for retention standards, separation from service, in-service transition, and medical coverage.² Several other official policies were released following this initial memorandum that provided more specific guidance on how to implement these policies at the level of the force, unit, and individual service member.

Modifications to the original 2016 policies had varying impacts on transgender health care provision and access.³ At the time of publication of this article, the current policy—the Department of Defense Instruction 1300.28⁴—among others, establishes standards and procedures for the process by which active and reserve TSMs may medically, socially, and legally transition genders within the military. The current policy applies to all military branches and serves as the framework by which each branch currently organizes their gender-affirmation processes (GAP).⁴

There currently are several different GAP models among the military branches.⁵ Each branch has a different model or approach to implementing the current policy, with varying service-specific processes in place for TSMs to access gender-affirming care; however, this may be changing. The Defense Health Agency is in the process of consolidating and streamlining the GAP across the Department of Defense branches in an effort to optimize costs and ensure uniformity of care. Per the Defense Health Agency Procedural Instruction Number 6025.21 published in May 2023, the proposed consolidated model likely will entail a single central transgender health center that provides oversight and guidance for several regional joint-service gender-affirming medical hubs. Patients would either be managed at the level of the hub or be referred to the central site.⁵

Herein, we discuss the importance of gender-affirming care and how military and civilian dermatologists can contribute. We also review disparities in health care and identify areas of improvement.

Benefits of Gender-Affirming Care

Gender-affirming procedures are critical for aligning physical appearance with gender identity. Physical appearance is essential for psychological well-being, operational readiness, and the safety of TSMs.⁶ It is well documented that TGD persons experience suicidal ideation, depression, stigma, discrimination and violence at higher rates than their cisgender peers.^7,8 It is important to recognize that transgender identity is not a mental illness, and these elevated rates have been linked to complex trauma, societal stigma, violence, and discrimination.¹ Other studies have suggested that increased access to gender-affirming interventions may ameliorate these mental health concerns.^1,7-9

The major components of gender-affirming care include hormone therapy, gender confirmation surgery, and mental health care, if needed. These are covered by TRICARE, the health care program for military service members; however, at the time of publication, many of the dermatologic gender-affirming procedures are not covered by TRICARE because they are considered “cosmetic procedures,” which is a term used by insurance companies but does not accurately indicate whether a procedure is medically necessary or not. Newer literature has demonstrated that gender-affirming care positively affects the lives of TGD patients, strengthening the argument that gender-affirming care is a medical necessity and not just cosmetic.¹

Aesthetic Procedures in Gender-Affirming Care

Surgeons, including those within the specialties of oto-laryngology, oral and maxillofacial surgery, urology, gynecology, and plastic surgery, provide major gender-affirming interventions; however, dermatologists may offer less invasive solutions that can serve as a temporary experience prior to undergoing more permanent procedures.Hormonally driven disorders including acne, hair loss, and melasma also are managed by dermatologists, along with scar treatment following surgeries.

Because human variation is expansive and subjective, what is considered feminine or masculine may vary by person, group, culture, and country; therefore, it is imperative to ask patients about their individual aesthetic goals and tailor their treatment accordingly. Feminine and masculine are terms that will be used to describe prototypical appearances and are not meant to define a patient’s current state or ultimate goals. The following procedures and medical interventions are where dermatologists can play an important role in TGD persons’ GAPs.

Botulinum Toxin Injections—Botulinum toxin injection is the most common nonsurgical aesthetic procedure performed around the world.¹⁰ The selective paralysis afforded by botulinum toxin has several uses for people undergoing transition. Aesthetically, the feminine eyebrow tends to be positioned above the orbital rim and is arched with its apex between the lateral limbus and lateral canthus,¹¹ while the masculine eyebrow tends to be flatter and fuller and runs over the orbital rim without a peak. For people seeking a more feminine appearance, an eyebrow lift with botulinum toxin can help reshape the typical flatter masculine eyebrow to give it lateral lift that often is considered more feminine. The targeted muscle is the superolateral orbicularis oculi, which serves as a depressor on the eyebrow. This can be combined with purposefully avoiding total lateral frontalis paralysis, which leads to a “Spock” brow for extra lift. Conversely, a naturally arched and higher eyebrow can be flattened and lowered by selectively targeting areas of the frontalis muscle.

Broad square jawlines typically are considered a masculine feature and are another area where botulinum toxin can be used to feminize a patient’s facial features. Targeting the masseter muscle induces muscle weakness, which ultimately may result in atrophy after one or more treatment sessions. This atrophy may lead to narrowing of the lower face and thus may lead to a fuller-appearing midface or overall more heart-shaped face. Every individual’s aesthetic goals are unique and therefore should be discussed prior to any treatment.

Dermal Fillers—Dermal fillers are gel-like substances injected under the skin for subtle contouring of the face. Fillers also can be used to help promote a more masculine or feminine appearance. Filler can be placed in the lips to create a fuller, more projected, feminine-appearing lip. Malar cheek and central lower chin filler can be used to help define a heart-shaped face by accentuating the upper portion of the face and creating a more pointed chin, respectively. Alternatively, filler can be used to masculinize the chin by placing it where it can increase jawline squareness and increase anterior jaw projection. Additionally, filler at the angle of the jaw can help accentuate a square facial shape and a more defined jawline. Although not as widely practiced, lateral brow filler can create a heavier-appearing and broader forehead for a more masculine appearance. These procedures can be combined with the previously mentioned botulinum toxin procedures for a synergistic effect.

Deoxycholic Acid—Deoxycholic acid is an injectable product used to selectively remove unwanted fat. It currently is approved by the US Food and Drug Administration for submental fat, but some providers are experimenting with off-label uses. Buccal fat pad removal—or in this case reduction by dissolution—tends to give a thinner, more feminine facial appearance.¹² Reducing fat around the axillae also can help promote a more masculine upper torso.¹³ The safety of deoxycholic acid in these areas has not been adequately tested; thus, caution should be used when discussing these off-label uses with patients.

Hair and Tattoo Removal—Hair removal may be desired by TGD persons for a variety of reasons. Because cisgender females tend to have less body hair overall, transgender people in pursuit of a more feminine appearance often desire removal of facial, neck, and body hair. Although shaving and other modalities such as waxing and chemical depilatories are readily available at-home options, they are not permanent and may lead to folliculitis or pseudofolliculitis barbae. Laser hair removal (LHR) and electrolysis are modalities provided by dermatologists that tend to be more permanent and lead to better outcomes, including less irritation and better aesthetic appearance. It is important to keep in mind that not every person and not every body site can be safely treated with LHR. Patients with lighter skin types and darker hair tend to have the most effective response with a higher margin of safety, as these features allow the laser energy to be selectively absorbed by the melanin in the hair bulb and not by the background skin pigmentation.^14,15 Inappropriate patient selection or improper settings for wavelength, pulse width, or fluences can lead to burns and permanent scarring.^14,15 Electrolysis is an alternative to hair removal within tattoos and is more effective for those individuals with blonde, red, or white hair.¹⁶

Another novel treatment for unwanted hair is eflor­nithine hydrochloride cream, which works by blocking ornithine decarboxylase, the enzyme that stimulates hair growth. It currently is approved to reduce unwanted hair on the face and adjacent areas under the chin; however the effects of this medication are modest and the medication can be expensive.¹⁷

Cosmetic hair and tattoo removal are not currently covered by TRICARE, except in cases of surgical and donor-site preparation for some GAPs. Individuals may desire removal of tattoos at surgery sites to obtain more natural-appearing skin. Currently, GAPs such as vaginoplasty, phalloplasty, and metoidioplasty—often referred to by patients as “bottom surgeries”—include insurance coverage for tattoo removal, LHR, and/or electrolysis.

Management of Hormonal Adverse Effects

Acne—Individuals on testosterone supplementation tend to develop acne for the first several years of treatment, but it may improve with time.¹⁸ Acne is treated in individuals receiving testosterone the same way as it is treated in cisgender men, with numerous options for topical and oral medications. In trans masculine persons, spironolactone therapy typically is avoided because it may interfere with the actions of exogenous testosterone administered as part of gender-affirming medical treatment and may lead to other undesired adverse effects such as impotence and gynecomastia.¹

Although acne typically improves after starting estrogen therapy, patients receiving estrogens may still develop acne. Most trans feminine patients will already be on an estrogen and an antiandrogen, often spironolactone.¹ Spironolactone often is used as monotherapy for acne control in cisgender women. Additionally, an important factor to consider with spironolactone is the possible adverse effect of increased micturition. Currently, the military rarely has gender-inclusive restroom options, which can create a challenge for TSMs who find themselves needing to use the restroom more frequently in the workplace.

If planning therapy with isotretinoin, dermatologists should discuss several important factors with all patients, including TGD patients. One consideration is the patient’s planned future surgeries. Although new literature shows that isotretinoin does not adversely affect wound healing,¹⁹ some surgeons still adhere to an isotretinoin washout period of 6 to 12 months prior to performing any elective procedures due to concerns about wound healing.^20,21 Second, be sure to properly assess and document pregnancy potential in TGD persons. Providers should not assume that a patient is not pregnant or is not trying to become pregnant just because they are trans masculine. It also is important to note that testosterone is not a reliable birth control method.¹ If a patient still has ovaries, fallopian tubes, and a uterus, they are considered medically capable of pregnancy, and providers should keep this in mind regarding all procedures in the TGD population.

Another newer acne treatment modality is the 1762-nm laser, which targets sebaceous glands.²² This device allows for targeted treatment of acne-prone areas without systemic therapy such as retinoids or antiandrogens. The 1762-nm laser is not widely available but may become a regular treatment option once its benefits are proven over time.

Alopecia and Hyperpigmentation—Androgens, whether endogenously or exogenously derived, can lead to androgenetic alopecia (AGA) in genetically susceptible individuals. Trans masculine persons and others receiving androgen therapy are at higher risk for AGA, which often is undesirable and may be considered gender affirming by some TGD persons. Standard AGA treatments for cisgender men also can be used in trans masculine persons. Some of the most common anti-AGA medications are topical minoxidil, oral finasteride, and oral minoxidil. Although Coleman et al¹ recently reported that finasteride may be an appropriate treatment option in trans masculine persons experiencing alopecia, treatment with 5α-reductase inhibitors may impair clitoral growth and the development of facial and body hair. Further studies are needed to assess the efficacy and safety of 5α-reductase inhibitors in transgender populations.¹ Dutasteride may be used off-label and comes with a similar potential adverse-event profile as finasteride, which includes depression, decreased libido, erectile dysfunction, ejaculation disorders, and gynecomastia.

Conversely, AGA tends to improve in trans feminine persons and others receiving estrogen and antiandrogen therapy. Natural testosterone production is suppressed by estrogens and spironolactone as well as in patients who undergo orchiectomy.¹ Although spironolactone is not approved for acne, AGA, or hirsutism, it is a standard treatment of AGA in cisgender women because it functions to block the effects of androgens, including at the hair follicle. Finasteride may be used for AGA in cisgender women but it is not recommended for trans feminine persons.¹

There are many other modalities available for the treatment of AGA that are less commonly used—some may be cost prohibitive or do not have robust supporting evidence, or both. One example is hair transplantation. Although this procedure gives dramatic results, it typically is performed by a specialized dermatologist, is not covered by insurance, and can cost up to tens of thousands of dollars out-of-pocket. Patients typically require continuous medical management of AGA even after the procedure. Examples of treatment modalities with uncertain supporting evidence are platelet-rich plasma injections, laser combs or hats, and microneedling. Additionally, clascoterone is a topical antiandrogen currently approved for acne, but it is under investigation for the treatment of AGA and may become an additional nonsystemic medication available for AGA in the future.²³

Melasma is a hyperpigmentation disorder related to estrogens, UV light exposure, and sometimes medication use (eg, hormonal birth control, spironolactone).²⁴ The mainstay of treatment is prevention, including sun avoidance as well as use of sun-protective clothing and broad-spectrum sunscreens. Dermatologists tend to recommend physical sunscreens containing zinc oxide, titanium dioxide, and/or iron oxide, as they cover a wider UV spectrum and also provide some protection from visible light. Once melasma is present, dermatologists still have several treatment options. Topical hydroquinone is a proven treatment; however, it must be used with caution to avoid ochronosis. With careful patient selection, chemical peels also are effective treatment options for dyspigmentation and hyperpigmentation. Energy devices such as intense pulsed light and tattoo removal lasers—Q-switched lasers and picosecond pulse widths—also can be used to treat hyperpigmentation. Oral, intralesional, and topical tranexamic acid are newer treatment options for melasma that still are being studied and have shown promising results. Further studies are needed to determine long-term safety and optimal treatment regimens.^24,25

Many insurance carriers, including TRICARE, do not routinely cover medical management of AGA or melasma. Patients should be advised that they likely will have to pay for any medications prescribed and procedures undertaken for these purposes; however, some medication costs can be offset by ordering larger prescription quantities, such as a 90-day supply vs a 30-day supply, as well as utilizing pharmacy discount programs.

Scar Management Following Surgery

In TSMs who undergo gender-affirming surgeries, dermatologists play an important role when scar symptoms develop, including pruritus, tenderness, and/or paresthesia. In the military, some common treatment modalities for symptomatic scars include intralesional steroids with or without 5-fluouroruacil and the fractionated CO₂ laser. There also are numerous experimental treatment options for scars, including intralesional or perilesional botulinum toxin, the pulsed dye laser, or nonablative fractionated lasers. These modalities also may be used on hypertrophic scars or keloids. Another option for keloids is scar excision followed by superficial radiation therapy.²⁶

Mental Health Considerations

Providers must take psychological adverse effects into consideration when considering medical therapies for dermatologic conditions in TGD patients. In particular, it is important to consider the risks for increased rates of depression and suicidal ideation formerly associated with the use of isotretinoin and finasteride, though much of the evidence regarding these risks has been called into question in recent years.^27,28 Nonetheless, it remains prominent in lay media and may be a more important consideration in patients at higher baseline risk.²⁷ Although there are no known studies that have expressly assessed rates of depression or suicidal ideation in TGD patients taking isotretinoin or finasteride, it is well established that TGD persons are at higher baseline risk for depression and suicidality.^1,7,8 All patients should be carefully assessed for depression and suicidal ideation as well as counseled regarding these risks prior to initiating these therapies. If concerns for untreated mental health issues arise during screening and counseling, patients should be referred for assessment by a behavioral health specialist prior to starting therapy.

Future Directions

The future of TGD health care in the military could see an expansion of covered benefits and the development of new dermatologic procedures or medications. Research and policy evolution are necessary to bridge the current gaps in care; however, it is unlikely that all procedures currently considered to be cosmetic will become covered benefits.

Facial LHR is a promising candidate for future coverage for trans feminine persons. When cisgender men develop adverse effects from mandatory daily shaving, LHR is already a covered benefit. Two arguments in support of adding LHR for TGD patients revolve around achieving and maintaining an appearance congruent with their gender along with avoiding unwanted adverse effects related to daily shaving. Visual conformity with one’s affirmed gender has been associated with improvements in well-being, quality of life, and some mental health conditions.²⁹

Scar prevention, treatment, and reduction are additional areas under active research in which dermatologists likely will play a crucial role.^30,31 As more dermatologic procedures are performed on TGD persons, the published data and collective knowledge regarding best practices in this population will continue to grow, which will lead to improved cosmetic and safety outcomes.

Final Thoughts

Although dermatologists do not directly perform gender-affirming surgeries or hormone management, they do play an important role in enhancing a TGD person’s desired appearance and managing possible adverse effects resulting from gender-affirming interventions. There have been considerable advancements in TGD health care over the past decade, but there likely are more changes on the way. As policies and understanding of TGD health care needs evolve, it is crucial that the military health care system adapts to provide comprehensive, accessible, and equitable care, which includes expanding the range of covered dermatologic treatments to fully support the health and readiness of TSMs.

Acknowledgment—We would like to extend our sincere appreciation to the invaluable contributions and editorial support provided by Allison Higgins, JD (San Antonio, Texas), throughout the writing of this article.

People whose gender identity differs from the sex assigned at birth are referred to as transgender. For some, gender identity may not fit into the binary constructs of male and female but rather falls between, within, or outside this construct. These people often consider themselves nonbinary or gender diverse. As the terminology continues to evolve, current recommendations include referring to this patient population as transgender and gender diverse (TGD) to ensure the broadest inclusivity.¹ In this article, the following terms are used as defined below:

• The terms transgender woman and trans feminine describe persons who were assigned male gender at birth but their affirmed gender is female or nonmasculine.
• The terms transgender man and trans masculine describe persons who were assigned female gender at birth but their affirmed gender is male or nonfeminine.

The US Military’s policies on the service of TGD persons have evolved considerably over the past decade. Initial military policies barred TGD service members (TSMs) from service all together, leading to challenges in accessing necessary health care. The first official memorandum explicitly allowing military service by TGD persons was released on June 30, 2016.² The intention of this memorandum was 2-fold: (1) to allow TGD persons to serve in the military so long as they meet “the rigorous standards for military service and readiness” by fulfilling the same standards and procedures as other military service members, including medical fitness for duty, physical fitness, uniform and grooming, deployability, and retention, and (2) to direct the establishment of new or updated policies to specific departments and prescribe procedures for retention standards, separation from service, in-service transition, and medical coverage.² Several other official policies were released following this initial memorandum that provided more specific guidance on how to implement these policies at the level of the force, unit, and individual service member.

Modifications to the original 2016 policies had varying impacts on transgender health care provision and access.³ At the time of publication of this article, the current policy—the Department of Defense Instruction 1300.28⁴—among others, establishes standards and procedures for the process by which active and reserve TSMs may medically, socially, and legally transition genders within the military. The current policy applies to all military branches and serves as the framework by which each branch currently organizes their gender-affirmation processes (GAP).⁴

There currently are several different GAP models among the military branches.⁵ Each branch has a different model or approach to implementing the current policy, with varying service-specific processes in place for TSMs to access gender-affirming care; however, this may be changing. The Defense Health Agency is in the process of consolidating and streamlining the GAP across the Department of Defense branches in an effort to optimize costs and ensure uniformity of care. Per the Defense Health Agency Procedural Instruction Number 6025.21 published in May 2023, the proposed consolidated model likely will entail a single central transgender health center that provides oversight and guidance for several regional joint-service gender-affirming medical hubs. Patients would either be managed at the level of the hub or be referred to the central site.⁵

Herein, we discuss the importance of gender-affirming care and how military and civilian dermatologists can contribute. We also review disparities in health care and identify areas of improvement.

Benefits of Gender-Affirming Care

Gender-affirming procedures are critical for aligning physical appearance with gender identity. Physical appearance is essential for psychological well-being, operational readiness, and the safety of TSMs.⁶ It is well documented that TGD persons experience suicidal ideation, depression, stigma, discrimination and violence at higher rates than their cisgender peers.^7,8 It is important to recognize that transgender identity is not a mental illness, and these elevated rates have been linked to complex trauma, societal stigma, violence, and discrimination.¹ Other studies have suggested that increased access to gender-affirming interventions may ameliorate these mental health concerns.^1,7-9

The major components of gender-affirming care include hormone therapy, gender confirmation surgery, and mental health care, if needed. These are covered by TRICARE, the health care program for military service members; however, at the time of publication, many of the dermatologic gender-affirming procedures are not covered by TRICARE because they are considered “cosmetic procedures,” which is a term used by insurance companies but does not accurately indicate whether a procedure is medically necessary or not. Newer literature has demonstrated that gender-affirming care positively affects the lives of TGD patients, strengthening the argument that gender-affirming care is a medical necessity and not just cosmetic.¹

Aesthetic Procedures in Gender-Affirming Care

Surgeons, including those within the specialties of oto-laryngology, oral and maxillofacial surgery, urology, gynecology, and plastic surgery, provide major gender-affirming interventions; however, dermatologists may offer less invasive solutions that can serve as a temporary experience prior to undergoing more permanent procedures.Hormonally driven disorders including acne, hair loss, and melasma also are managed by dermatologists, along with scar treatment following surgeries.

Because human variation is expansive and subjective, what is considered feminine or masculine may vary by person, group, culture, and country; therefore, it is imperative to ask patients about their individual aesthetic goals and tailor their treatment accordingly. Feminine and masculine are terms that will be used to describe prototypical appearances and are not meant to define a patient’s current state or ultimate goals. The following procedures and medical interventions are where dermatologists can play an important role in TGD persons’ GAPs.

Botulinum Toxin Injections—Botulinum toxin injection is the most common nonsurgical aesthetic procedure performed around the world.¹⁰ The selective paralysis afforded by botulinum toxin has several uses for people undergoing transition. Aesthetically, the feminine eyebrow tends to be positioned above the orbital rim and is arched with its apex between the lateral limbus and lateral canthus,¹¹ while the masculine eyebrow tends to be flatter and fuller and runs over the orbital rim without a peak. For people seeking a more feminine appearance, an eyebrow lift with botulinum toxin can help reshape the typical flatter masculine eyebrow to give it lateral lift that often is considered more feminine. The targeted muscle is the superolateral orbicularis oculi, which serves as a depressor on the eyebrow. This can be combined with purposefully avoiding total lateral frontalis paralysis, which leads to a “Spock” brow for extra lift. Conversely, a naturally arched and higher eyebrow can be flattened and lowered by selectively targeting areas of the frontalis muscle.

Broad square jawlines typically are considered a masculine feature and are another area where botulinum toxin can be used to feminize a patient’s facial features. Targeting the masseter muscle induces muscle weakness, which ultimately may result in atrophy after one or more treatment sessions. This atrophy may lead to narrowing of the lower face and thus may lead to a fuller-appearing midface or overall more heart-shaped face. Every individual’s aesthetic goals are unique and therefore should be discussed prior to any treatment.

Dermal Fillers—Dermal fillers are gel-like substances injected under the skin for subtle contouring of the face. Fillers also can be used to help promote a more masculine or feminine appearance. Filler can be placed in the lips to create a fuller, more projected, feminine-appearing lip. Malar cheek and central lower chin filler can be used to help define a heart-shaped face by accentuating the upper portion of the face and creating a more pointed chin, respectively. Alternatively, filler can be used to masculinize the chin by placing it where it can increase jawline squareness and increase anterior jaw projection. Additionally, filler at the angle of the jaw can help accentuate a square facial shape and a more defined jawline. Although not as widely practiced, lateral brow filler can create a heavier-appearing and broader forehead for a more masculine appearance. These procedures can be combined with the previously mentioned botulinum toxin procedures for a synergistic effect.

Deoxycholic Acid—Deoxycholic acid is an injectable product used to selectively remove unwanted fat. It currently is approved by the US Food and Drug Administration for submental fat, but some providers are experimenting with off-label uses. Buccal fat pad removal—or in this case reduction by dissolution—tends to give a thinner, more feminine facial appearance.¹² Reducing fat around the axillae also can help promote a more masculine upper torso.¹³ The safety of deoxycholic acid in these areas has not been adequately tested; thus, caution should be used when discussing these off-label uses with patients.

Hair and Tattoo Removal—Hair removal may be desired by TGD persons for a variety of reasons. Because cisgender females tend to have less body hair overall, transgender people in pursuit of a more feminine appearance often desire removal of facial, neck, and body hair. Although shaving and other modalities such as waxing and chemical depilatories are readily available at-home options, they are not permanent and may lead to folliculitis or pseudofolliculitis barbae. Laser hair removal (LHR) and electrolysis are modalities provided by dermatologists that tend to be more permanent and lead to better outcomes, including less irritation and better aesthetic appearance. It is important to keep in mind that not every person and not every body site can be safely treated with LHR. Patients with lighter skin types and darker hair tend to have the most effective response with a higher margin of safety, as these features allow the laser energy to be selectively absorbed by the melanin in the hair bulb and not by the background skin pigmentation.^14,15 Inappropriate patient selection or improper settings for wavelength, pulse width, or fluences can lead to burns and permanent scarring.^14,15 Electrolysis is an alternative to hair removal within tattoos and is more effective for those individuals with blonde, red, or white hair.¹⁶

Another novel treatment for unwanted hair is eflor­nithine hydrochloride cream, which works by blocking ornithine decarboxylase, the enzyme that stimulates hair growth. It currently is approved to reduce unwanted hair on the face and adjacent areas under the chin; however the effects of this medication are modest and the medication can be expensive.¹⁷

Cosmetic hair and tattoo removal are not currently covered by TRICARE, except in cases of surgical and donor-site preparation for some GAPs. Individuals may desire removal of tattoos at surgery sites to obtain more natural-appearing skin. Currently, GAPs such as vaginoplasty, phalloplasty, and metoidioplasty—often referred to by patients as “bottom surgeries”—include insurance coverage for tattoo removal, LHR, and/or electrolysis.

Management of Hormonal Adverse Effects

Acne—Individuals on testosterone supplementation tend to develop acne for the first several years of treatment, but it may improve with time.¹⁸ Acne is treated in individuals receiving testosterone the same way as it is treated in cisgender men, with numerous options for topical and oral medications. In trans masculine persons, spironolactone therapy typically is avoided because it may interfere with the actions of exogenous testosterone administered as part of gender-affirming medical treatment and may lead to other undesired adverse effects such as impotence and gynecomastia.¹

Although acne typically improves after starting estrogen therapy, patients receiving estrogens may still develop acne. Most trans feminine patients will already be on an estrogen and an antiandrogen, often spironolactone.¹ Spironolactone often is used as monotherapy for acne control in cisgender women. Additionally, an important factor to consider with spironolactone is the possible adverse effect of increased micturition. Currently, the military rarely has gender-inclusive restroom options, which can create a challenge for TSMs who find themselves needing to use the restroom more frequently in the workplace.

If planning therapy with isotretinoin, dermatologists should discuss several important factors with all patients, including TGD patients. One consideration is the patient’s planned future surgeries. Although new literature shows that isotretinoin does not adversely affect wound healing,¹⁹ some surgeons still adhere to an isotretinoin washout period of 6 to 12 months prior to performing any elective procedures due to concerns about wound healing.^20,21 Second, be sure to properly assess and document pregnancy potential in TGD persons. Providers should not assume that a patient is not pregnant or is not trying to become pregnant just because they are trans masculine. It also is important to note that testosterone is not a reliable birth control method.¹ If a patient still has ovaries, fallopian tubes, and a uterus, they are considered medically capable of pregnancy, and providers should keep this in mind regarding all procedures in the TGD population.

Another newer acne treatment modality is the 1762-nm laser, which targets sebaceous glands.²² This device allows for targeted treatment of acne-prone areas without systemic therapy such as retinoids or antiandrogens. The 1762-nm laser is not widely available but may become a regular treatment option once its benefits are proven over time.

Alopecia and Hyperpigmentation—Androgens, whether endogenously or exogenously derived, can lead to androgenetic alopecia (AGA) in genetically susceptible individuals. Trans masculine persons and others receiving androgen therapy are at higher risk for AGA, which often is undesirable and may be considered gender affirming by some TGD persons. Standard AGA treatments for cisgender men also can be used in trans masculine persons. Some of the most common anti-AGA medications are topical minoxidil, oral finasteride, and oral minoxidil. Although Coleman et al¹ recently reported that finasteride may be an appropriate treatment option in trans masculine persons experiencing alopecia, treatment with 5α-reductase inhibitors may impair clitoral growth and the development of facial and body hair. Further studies are needed to assess the efficacy and safety of 5α-reductase inhibitors in transgender populations.¹ Dutasteride may be used off-label and comes with a similar potential adverse-event profile as finasteride, which includes depression, decreased libido, erectile dysfunction, ejaculation disorders, and gynecomastia.

Conversely, AGA tends to improve in trans feminine persons and others receiving estrogen and antiandrogen therapy. Natural testosterone production is suppressed by estrogens and spironolactone as well as in patients who undergo orchiectomy.¹ Although spironolactone is not approved for acne, AGA, or hirsutism, it is a standard treatment of AGA in cisgender women because it functions to block the effects of androgens, including at the hair follicle. Finasteride may be used for AGA in cisgender women but it is not recommended for trans feminine persons.¹

There are many other modalities available for the treatment of AGA that are less commonly used—some may be cost prohibitive or do not have robust supporting evidence, or both. One example is hair transplantation. Although this procedure gives dramatic results, it typically is performed by a specialized dermatologist, is not covered by insurance, and can cost up to tens of thousands of dollars out-of-pocket. Patients typically require continuous medical management of AGA even after the procedure. Examples of treatment modalities with uncertain supporting evidence are platelet-rich plasma injections, laser combs or hats, and microneedling. Additionally, clascoterone is a topical antiandrogen currently approved for acne, but it is under investigation for the treatment of AGA and may become an additional nonsystemic medication available for AGA in the future.²³

Melasma is a hyperpigmentation disorder related to estrogens, UV light exposure, and sometimes medication use (eg, hormonal birth control, spironolactone).²⁴ The mainstay of treatment is prevention, including sun avoidance as well as use of sun-protective clothing and broad-spectrum sunscreens. Dermatologists tend to recommend physical sunscreens containing zinc oxide, titanium dioxide, and/or iron oxide, as they cover a wider UV spectrum and also provide some protection from visible light. Once melasma is present, dermatologists still have several treatment options. Topical hydroquinone is a proven treatment; however, it must be used with caution to avoid ochronosis. With careful patient selection, chemical peels also are effective treatment options for dyspigmentation and hyperpigmentation. Energy devices such as intense pulsed light and tattoo removal lasers—Q-switched lasers and picosecond pulse widths—also can be used to treat hyperpigmentation. Oral, intralesional, and topical tranexamic acid are newer treatment options for melasma that still are being studied and have shown promising results. Further studies are needed to determine long-term safety and optimal treatment regimens.^24,25

Many insurance carriers, including TRICARE, do not routinely cover medical management of AGA or melasma. Patients should be advised that they likely will have to pay for any medications prescribed and procedures undertaken for these purposes; however, some medication costs can be offset by ordering larger prescription quantities, such as a 90-day supply vs a 30-day supply, as well as utilizing pharmacy discount programs.

Scar Management Following Surgery

In TSMs who undergo gender-affirming surgeries, dermatologists play an important role when scar symptoms develop, including pruritus, tenderness, and/or paresthesia. In the military, some common treatment modalities for symptomatic scars include intralesional steroids with or without 5-fluouroruacil and the fractionated CO₂ laser. There also are numerous experimental treatment options for scars, including intralesional or perilesional botulinum toxin, the pulsed dye laser, or nonablative fractionated lasers. These modalities also may be used on hypertrophic scars or keloids. Another option for keloids is scar excision followed by superficial radiation therapy.²⁶

Mental Health Considerations

Providers must take psychological adverse effects into consideration when considering medical therapies for dermatologic conditions in TGD patients. In particular, it is important to consider the risks for increased rates of depression and suicidal ideation formerly associated with the use of isotretinoin and finasteride, though much of the evidence regarding these risks has been called into question in recent years.^27,28 Nonetheless, it remains prominent in lay media and may be a more important consideration in patients at higher baseline risk.²⁷ Although there are no known studies that have expressly assessed rates of depression or suicidal ideation in TGD patients taking isotretinoin or finasteride, it is well established that TGD persons are at higher baseline risk for depression and suicidality.^1,7,8 All patients should be carefully assessed for depression and suicidal ideation as well as counseled regarding these risks prior to initiating these therapies. If concerns for untreated mental health issues arise during screening and counseling, patients should be referred for assessment by a behavioral health specialist prior to starting therapy.

Future Directions

The future of TGD health care in the military could see an expansion of covered benefits and the development of new dermatologic procedures or medications. Research and policy evolution are necessary to bridge the current gaps in care; however, it is unlikely that all procedures currently considered to be cosmetic will become covered benefits.

Facial LHR is a promising candidate for future coverage for trans feminine persons. When cisgender men develop adverse effects from mandatory daily shaving, LHR is already a covered benefit. Two arguments in support of adding LHR for TGD patients revolve around achieving and maintaining an appearance congruent with their gender along with avoiding unwanted adverse effects related to daily shaving. Visual conformity with one’s affirmed gender has been associated with improvements in well-being, quality of life, and some mental health conditions.²⁹

Scar prevention, treatment, and reduction are additional areas under active research in which dermatologists likely will play a crucial role.^30,31 As more dermatologic procedures are performed on TGD persons, the published data and collective knowledge regarding best practices in this population will continue to grow, which will lead to improved cosmetic and safety outcomes.

Final Thoughts

Although dermatologists do not directly perform gender-affirming surgeries or hormone management, they do play an important role in enhancing a TGD person’s desired appearance and managing possible adverse effects resulting from gender-affirming interventions. There have been considerable advancements in TGD health care over the past decade, but there likely are more changes on the way. As policies and understanding of TGD health care needs evolve, it is crucial that the military health care system adapts to provide comprehensive, accessible, and equitable care, which includes expanding the range of covered dermatologic treatments to fully support the health and readiness of TSMs.

Acknowledgment—We would like to extend our sincere appreciation to the invaluable contributions and editorial support provided by Allison Higgins, JD (San Antonio, Texas), throughout the writing of this article.

March 2024 proved to be a busy month for benzoyl peroxide in the media! We are now at almost 4 months since Valisure, an independent analytical laboratory located in Connecticut, filed a Citizen Petition on benzene in benzoyl peroxide drug products with the US Food and Drug Administration (FDA) on March 5, 2024.¹ This petition was filed shortly before the annual meeting of the American Academy of Dermatology was held in San Diego, California, creating quite a stir of concern in the dermatology world. Further information on the degradation of benzoyl peroxide with production of benzene was published in the medical literature in March 2024.² As benzene is recognized as a human carcinogen, manufacturing regulations exist to assure that it does not appear in topical products either through contamination or degradation over the course of a product’s shelf-life.³

As anticipated, several opinions and commentaries appeared quickly, both on video and in various articles. The American Acne & Rosacea Society (AARS) released a statement on this issue on March 20, 2024.⁴ The safety of the public is the overarching primary concern. This AARS statement does include some general suggestions related to benzoyl peroxide use based on the best assessment to date while awaiting further guidance from the FDA on this issue. Benzoyl peroxide is approved for use by the FDA as an over-the-counter (OTC) topical product for acne and also is in several FDA-approved prescription topical products.^5,6

The following reflects my personal viewpoint as both a dermatologist and a grandfather who has grandchildren who use acne products. My views are not necessarily those of AARS. Since early March 2024, I have read several documents and spoken to several dermatologists, scientists, and formulators with knowledge in this area, including contacts at Valisure. I was hoping to get to some reasonable definitive answer but have not been able to achieve this to my full satisfaction. There are many opinions and concerns, and each one makes sense based on the vantage point of the presenter. However, several unanswered questions remain related to what testing and data are currently required of companies to gain FDA approval of a benzoyl peroxide product, including:

• assessment of stability and degradation products (including benzene),
• validation of testing methods,
• the issue of benzoyl peroxide stability in commercial products, and
• the relevant magnitude of resultant benzene exposures, especially as we are all exposed to benzene from several sources each day.

I am certain that companies with benzoyl peroxide products will evaluate their already-approved products and also do further testing. However, in this situation, which impacts millions of people on so many levels, I feel there needs to be an organized approach to evaluate and resolve the issue, otherwise the likelihood of continued confusion and uncertainty is high. As the FDA is the approval body, I am hoping it will provide definitive guidance within a reasonable timeline so that clinicians, patients, and manufacturers of benzoyl peroxide can proceed with full confidence. Right now, we all remain in a state of limbo. It is time for less talk and more definitive action to sort out this issue.

March 2024 proved to be a busy month for benzoyl peroxide in the media! We are now at almost 4 months since Valisure, an independent analytical laboratory located in Connecticut, filed a Citizen Petition on benzene in benzoyl peroxide drug products with the US Food and Drug Administration (FDA) on March 5, 2024.¹ This petition was filed shortly before the annual meeting of the American Academy of Dermatology was held in San Diego, California, creating quite a stir of concern in the dermatology world. Further information on the degradation of benzoyl peroxide with production of benzene was published in the medical literature in March 2024.² As benzene is recognized as a human carcinogen, manufacturing regulations exist to assure that it does not appear in topical products either through contamination or degradation over the course of a product’s shelf-life.³

As anticipated, several opinions and commentaries appeared quickly, both on video and in various articles. The American Acne & Rosacea Society (AARS) released a statement on this issue on March 20, 2024.⁴ The safety of the public is the overarching primary concern. This AARS statement does include some general suggestions related to benzoyl peroxide use based on the best assessment to date while awaiting further guidance from the FDA on this issue. Benzoyl peroxide is approved for use by the FDA as an over-the-counter (OTC) topical product for acne and also is in several FDA-approved prescription topical products.^5,6

The following reflects my personal viewpoint as both a dermatologist and a grandfather who has grandchildren who use acne products. My views are not necessarily those of AARS. Since early March 2024, I have read several documents and spoken to several dermatologists, scientists, and formulators with knowledge in this area, including contacts at Valisure. I was hoping to get to some reasonable definitive answer but have not been able to achieve this to my full satisfaction. There are many opinions and concerns, and each one makes sense based on the vantage point of the presenter. However, several unanswered questions remain related to what testing and data are currently required of companies to gain FDA approval of a benzoyl peroxide product, including:

• assessment of stability and degradation products (including benzene),
• validation of testing methods,
• the issue of benzoyl peroxide stability in commercial products, and
• the relevant magnitude of resultant benzene exposures, especially as we are all exposed to benzene from several sources each day.

I am certain that companies with benzoyl peroxide products will evaluate their already-approved products and also do further testing. However, in this situation, which impacts millions of people on so many levels, I feel there needs to be an organized approach to evaluate and resolve the issue, otherwise the likelihood of continued confusion and uncertainty is high. As the FDA is the approval body, I am hoping it will provide definitive guidance within a reasonable timeline so that clinicians, patients, and manufacturers of benzoyl peroxide can proceed with full confidence. Right now, we all remain in a state of limbo. It is time for less talk and more definitive action to sort out this issue.

March 2024 proved to be a busy month for benzoyl peroxide in the media! We are now at almost 4 months since Valisure, an independent analytical laboratory located in Connecticut, filed a Citizen Petition on benzene in benzoyl peroxide drug products with the US Food and Drug Administration (FDA) on March 5, 2024.¹ This petition was filed shortly before the annual meeting of the American Academy of Dermatology was held in San Diego, California, creating quite a stir of concern in the dermatology world. Further information on the degradation of benzoyl peroxide with production of benzene was published in the medical literature in March 2024.² As benzene is recognized as a human carcinogen, manufacturing regulations exist to assure that it does not appear in topical products either through contamination or degradation over the course of a product’s shelf-life.³

As anticipated, several opinions and commentaries appeared quickly, both on video and in various articles. The American Acne & Rosacea Society (AARS) released a statement on this issue on March 20, 2024.⁴ The safety of the public is the overarching primary concern. This AARS statement does include some general suggestions related to benzoyl peroxide use based on the best assessment to date while awaiting further guidance from the FDA on this issue. Benzoyl peroxide is approved for use by the FDA as an over-the-counter (OTC) topical product for acne and also is in several FDA-approved prescription topical products.^5,6

The following reflects my personal viewpoint as both a dermatologist and a grandfather who has grandchildren who use acne products. My views are not necessarily those of AARS. Since early March 2024, I have read several documents and spoken to several dermatologists, scientists, and formulators with knowledge in this area, including contacts at Valisure. I was hoping to get to some reasonable definitive answer but have not been able to achieve this to my full satisfaction. There are many opinions and concerns, and each one makes sense based on the vantage point of the presenter. However, several unanswered questions remain related to what testing and data are currently required of companies to gain FDA approval of a benzoyl peroxide product, including:

• assessment of stability and degradation products (including benzene),
• validation of testing methods,
• the issue of benzoyl peroxide stability in commercial products, and
• the relevant magnitude of resultant benzene exposures, especially as we are all exposed to benzene from several sources each day.

I am certain that companies with benzoyl peroxide products will evaluate their already-approved products and also do further testing. However, in this situation, which impacts millions of people on so many levels, I feel there needs to be an organized approach to evaluate and resolve the issue, otherwise the likelihood of continued confusion and uncertainty is high. As the FDA is the approval body, I am hoping it will provide definitive guidance within a reasonable timeline so that clinicians, patients, and manufacturers of benzoyl peroxide can proceed with full confidence. Right now, we all remain in a state of limbo. It is time for less talk and more definitive action to sort out this issue.

Isotretinoin was introduced more than 3 decades ago and marked a major advancement in the treatment of severe refractory cystic acne. The most common adverse effects linked to isotretinoin usage are mucocutaneous in nature, manifesting as xerosis and cheilitis.¹ Skin fragility and poor wound healing also have been reported.^2-6 Current recommendations for avoiding these adverse effects include refraining from waxing, laser procedures, and other elective cutaneous procedures for at least 6 months.⁷ We present a case of isotretinoin-induced cutaneous fragility resulting in blistering and erosions on the palms of a competitive aerial trapeze artist.

Case Report

A 25-year-old woman presented for follow-up during week 12 of isotretinoin therapy (40 mg twice daily) prescribed for acne. She reported peeling of the skin on the palms following intense aerial acrobatic workouts. She had been a performing aerialist for many years and had never sustained a similar injury. The wounds were painful and led to decreased activity. She had no notable medical history. Physical examination of the palms revealed erosions in a distribution that corresponded to horizontal bar contact and friction (Figure). The patient was advised on proper wound care, application of emollients, and minimizing friction. She completed the course of isotretinoin and has continued aerialist activity without recurrence of skin fragility.

Comment

Skin fragility is a well-known adverse effect of isotretinoin therapy.⁸ Pavlis and Lieblich⁹ reported skin fragility in a young wrestler who experienced similar skin erosions due to isotretinoin therapy. The proposed mechanism of isotretinoin-induced skin fragility is multifactorial. It involves an apoptotic effect on sebocytes,⁵ which results in reduced stratum corneum hydration and an associated increase in transepidermal water loss.^6,10,11 Retinoids also are known to cause thinning of the skin, likely due to the disadhesion of both the epidermis and the stratum corneum, which was demonstrated by the easy removal of cornified cells through tape stripping in hairless mice treated with isotretinoin.¹² In further investigations, human patients and hairless mice treated with isotretinoin readily developed friction blisters through pencil eraser abrasion.¹³ Examination of the friction blisters using light and electron microscopy revealed fraying or loss of the stratum corneum and viable epidermis as well as loss of desmosomes and tonofilaments. Additionally, intracellular and intercellular deposits of an unidentified amorphous material were noted.¹³

Overall, the origin of skin fragility induced by isotretinoin is supported by its effect on sebocytes, increased transepidermal water loss, and profound disruption of the integrity of the epidermis, resulting in an elevated risk for inadvertent skin damage. Patients were encouraged to avoid cosmetic procedures in prior case reports,^14-16 and because our case demonstrates the risk for cutaneous injury in athletes due to isotretinoin-induced skin fragility, we propose an extension of these warnings to encompass athletes receiving isotretinoin treatment. Offering early guidance on wound prevention is of paramount importance in maintaining athletic performance and minimizing painful injuries.

Isotretinoin was introduced more than 3 decades ago and marked a major advancement in the treatment of severe refractory cystic acne. The most common adverse effects linked to isotretinoin usage are mucocutaneous in nature, manifesting as xerosis and cheilitis.¹ Skin fragility and poor wound healing also have been reported.^2-6 Current recommendations for avoiding these adverse effects include refraining from waxing, laser procedures, and other elective cutaneous procedures for at least 6 months.⁷ We present a case of isotretinoin-induced cutaneous fragility resulting in blistering and erosions on the palms of a competitive aerial trapeze artist.

Case Report

A 25-year-old woman presented for follow-up during week 12 of isotretinoin therapy (40 mg twice daily) prescribed for acne. She reported peeling of the skin on the palms following intense aerial acrobatic workouts. She had been a performing aerialist for many years and had never sustained a similar injury. The wounds were painful and led to decreased activity. She had no notable medical history. Physical examination of the palms revealed erosions in a distribution that corresponded to horizontal bar contact and friction (Figure). The patient was advised on proper wound care, application of emollients, and minimizing friction. She completed the course of isotretinoin and has continued aerialist activity without recurrence of skin fragility.

Comment

Skin fragility is a well-known adverse effect of isotretinoin therapy.⁸ Pavlis and Lieblich⁹ reported skin fragility in a young wrestler who experienced similar skin erosions due to isotretinoin therapy. The proposed mechanism of isotretinoin-induced skin fragility is multifactorial. It involves an apoptotic effect on sebocytes,⁵ which results in reduced stratum corneum hydration and an associated increase in transepidermal water loss.^6,10,11 Retinoids also are known to cause thinning of the skin, likely due to the disadhesion of both the epidermis and the stratum corneum, which was demonstrated by the easy removal of cornified cells through tape stripping in hairless mice treated with isotretinoin.¹² In further investigations, human patients and hairless mice treated with isotretinoin readily developed friction blisters through pencil eraser abrasion.¹³ Examination of the friction blisters using light and electron microscopy revealed fraying or loss of the stratum corneum and viable epidermis as well as loss of desmosomes and tonofilaments. Additionally, intracellular and intercellular deposits of an unidentified amorphous material were noted.¹³

Overall, the origin of skin fragility induced by isotretinoin is supported by its effect on sebocytes, increased transepidermal water loss, and profound disruption of the integrity of the epidermis, resulting in an elevated risk for inadvertent skin damage. Patients were encouraged to avoid cosmetic procedures in prior case reports,^14-16 and because our case demonstrates the risk for cutaneous injury in athletes due to isotretinoin-induced skin fragility, we propose an extension of these warnings to encompass athletes receiving isotretinoin treatment. Offering early guidance on wound prevention is of paramount importance in maintaining athletic performance and minimizing painful injuries.

Isotretinoin was introduced more than 3 decades ago and marked a major advancement in the treatment of severe refractory cystic acne. The most common adverse effects linked to isotretinoin usage are mucocutaneous in nature, manifesting as xerosis and cheilitis.¹ Skin fragility and poor wound healing also have been reported.^2-6 Current recommendations for avoiding these adverse effects include refraining from waxing, laser procedures, and other elective cutaneous procedures for at least 6 months.⁷ We present a case of isotretinoin-induced cutaneous fragility resulting in blistering and erosions on the palms of a competitive aerial trapeze artist.

Case Report

A 25-year-old woman presented for follow-up during week 12 of isotretinoin therapy (40 mg twice daily) prescribed for acne. She reported peeling of the skin on the palms following intense aerial acrobatic workouts. She had been a performing aerialist for many years and had never sustained a similar injury. The wounds were painful and led to decreased activity. She had no notable medical history. Physical examination of the palms revealed erosions in a distribution that corresponded to horizontal bar contact and friction (Figure). The patient was advised on proper wound care, application of emollients, and minimizing friction. She completed the course of isotretinoin and has continued aerialist activity without recurrence of skin fragility.

Comment

Skin fragility is a well-known adverse effect of isotretinoin therapy.⁸ Pavlis and Lieblich⁹ reported skin fragility in a young wrestler who experienced similar skin erosions due to isotretinoin therapy. The proposed mechanism of isotretinoin-induced skin fragility is multifactorial. It involves an apoptotic effect on sebocytes,⁵ which results in reduced stratum corneum hydration and an associated increase in transepidermal water loss.^6,10,11 Retinoids also are known to cause thinning of the skin, likely due to the disadhesion of both the epidermis and the stratum corneum, which was demonstrated by the easy removal of cornified cells through tape stripping in hairless mice treated with isotretinoin.¹² In further investigations, human patients and hairless mice treated with isotretinoin readily developed friction blisters through pencil eraser abrasion.¹³ Examination of the friction blisters using light and electron microscopy revealed fraying or loss of the stratum corneum and viable epidermis as well as loss of desmosomes and tonofilaments. Additionally, intracellular and intercellular deposits of an unidentified amorphous material were noted.¹³

Overall, the origin of skin fragility induced by isotretinoin is supported by its effect on sebocytes, increased transepidermal water loss, and profound disruption of the integrity of the epidermis, resulting in an elevated risk for inadvertent skin damage. Patients were encouraged to avoid cosmetic procedures in prior case reports,^14-16 and because our case demonstrates the risk for cutaneous injury in athletes due to isotretinoin-induced skin fragility, we propose an extension of these warnings to encompass athletes receiving isotretinoin treatment. Offering early guidance on wound prevention is of paramount importance in maintaining athletic performance and minimizing painful injuries.

TOPLINE:

Isotretinoin was effective in treating acne in individuals undergoing masculinizing gender-affirming hormone therapy in a case series, but more information is needed on dosing and barriers to treatment.

METHODOLOGY:

• Acne can be a side effect of masculinizing hormone therapy for transmasculine individuals. While isotretinoin is an effective treatment option for acne, its effectiveness and safety in transgender and gender-diverse individuals are not well understood.
• This retrospective case series included 55 patients (mean age, 25.4 years) undergoing masculinizing hormone therapy at four medical centers, who were prescribed isotretinoin for acne associated with treatment.
• Isotretinoin treatment was started a median of 22.1 months after hormone therapy was initiated and continued for a median of 6 months with a median cumulative dose of 132.7 mg/kg.
• Researchers assessed acne improvement, clearance, recurrence, adverse effects, and reasons for treatment discontinuation.

TAKEAWAY:

• Overall, 48 patients (87.3%) experienced improvement, and 26 (47.3%) achieved clearance during treatment. A higher proportion of patients experienced improvement (97% vs 72.7%) and achieved clearance (63.6% vs 22.7%) with cumulative doses of ≥ 120 mg/kg than those who received cumulative doses < 120 mg/kg.
• The risk for recurrence was 20% (in four patients) among 20 patients who achieved clearance and had any subsequent health care encounters, with a mean follow-up time of 734.3 days.
• Common adverse effects included dryness (80%), joint pain (14.5%), and headaches (10.9%). Other adverse effects included nose bleeds (9.1%) and depression (5.5%).
• Of the 22 patients with a cumulative dose < 120 mg/kg, 14 (63.6%) were lost to follow-up; among those not lost to follow-up, 2 patients discontinued treatment because of transfer of care, 1 because of adverse effects, and 1 because of gender-affirming surgery, with concerns about wound healing.

IN PRACTICE:

“Although isotretinoin appears to be an effective treatment option for acne among individuals undergoing masculinizing hormone therapy, further efforts are needed to understand optimal dosing and treatment barriers to improve outcomes in transgender and gender-diverse individuals receiving testosterone,” the authors concluded.

SOURCE:

The study, led by James Choe, BS, Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, was published online in JAMA Dermatology.

LIMITATIONS:

The study population was limited to four centers, and variability in clinician- and patient-reported acne outcomes and missing information could affect the reliability of data. Because of the small sample size, the association of masculinizing hormone therapy regimens with outcomes could not be evaluated.

DISCLOSURES:

One author is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Three authors reported receiving grants or personal fees from various sources. The other authors declared no conflicts of interest.

A version of this article first appeared on Medscape.com.

TOPLINE:

Isotretinoin was effective in treating acne in individuals undergoing masculinizing gender-affirming hormone therapy in a case series, but more information is needed on dosing and barriers to treatment.

METHODOLOGY:

• Acne can be a side effect of masculinizing hormone therapy for transmasculine individuals. While isotretinoin is an effective treatment option for acne, its effectiveness and safety in transgender and gender-diverse individuals are not well understood.
• This retrospective case series included 55 patients (mean age, 25.4 years) undergoing masculinizing hormone therapy at four medical centers, who were prescribed isotretinoin for acne associated with treatment.
• Isotretinoin treatment was started a median of 22.1 months after hormone therapy was initiated and continued for a median of 6 months with a median cumulative dose of 132.7 mg/kg.
• Researchers assessed acne improvement, clearance, recurrence, adverse effects, and reasons for treatment discontinuation.

TAKEAWAY:

• Overall, 48 patients (87.3%) experienced improvement, and 26 (47.3%) achieved clearance during treatment. A higher proportion of patients experienced improvement (97% vs 72.7%) and achieved clearance (63.6% vs 22.7%) with cumulative doses of ≥ 120 mg/kg than those who received cumulative doses < 120 mg/kg.
• The risk for recurrence was 20% (in four patients) among 20 patients who achieved clearance and had any subsequent health care encounters, with a mean follow-up time of 734.3 days.
• Common adverse effects included dryness (80%), joint pain (14.5%), and headaches (10.9%). Other adverse effects included nose bleeds (9.1%) and depression (5.5%).
• Of the 22 patients with a cumulative dose < 120 mg/kg, 14 (63.6%) were lost to follow-up; among those not lost to follow-up, 2 patients discontinued treatment because of transfer of care, 1 because of adverse effects, and 1 because of gender-affirming surgery, with concerns about wound healing.

IN PRACTICE:

“Although isotretinoin appears to be an effective treatment option for acne among individuals undergoing masculinizing hormone therapy, further efforts are needed to understand optimal dosing and treatment barriers to improve outcomes in transgender and gender-diverse individuals receiving testosterone,” the authors concluded.

SOURCE:

The study, led by James Choe, BS, Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, was published online in JAMA Dermatology.

LIMITATIONS:

The study population was limited to four centers, and variability in clinician- and patient-reported acne outcomes and missing information could affect the reliability of data. Because of the small sample size, the association of masculinizing hormone therapy regimens with outcomes could not be evaluated.

DISCLOSURES:

One author is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Three authors reported receiving grants or personal fees from various sources. The other authors declared no conflicts of interest.

A version of this article first appeared on Medscape.com.

TOPLINE:

Isotretinoin was effective in treating acne in individuals undergoing masculinizing gender-affirming hormone therapy in a case series, but more information is needed on dosing and barriers to treatment.

METHODOLOGY:

• Acne can be a side effect of masculinizing hormone therapy for transmasculine individuals. While isotretinoin is an effective treatment option for acne, its effectiveness and safety in transgender and gender-diverse individuals are not well understood.
• This retrospective case series included 55 patients (mean age, 25.4 years) undergoing masculinizing hormone therapy at four medical centers, who were prescribed isotretinoin for acne associated with treatment.
• Isotretinoin treatment was started a median of 22.1 months after hormone therapy was initiated and continued for a median of 6 months with a median cumulative dose of 132.7 mg/kg.
• Researchers assessed acne improvement, clearance, recurrence, adverse effects, and reasons for treatment discontinuation.

TAKEAWAY:

• Overall, 48 patients (87.3%) experienced improvement, and 26 (47.3%) achieved clearance during treatment. A higher proportion of patients experienced improvement (97% vs 72.7%) and achieved clearance (63.6% vs 22.7%) with cumulative doses of ≥ 120 mg/kg than those who received cumulative doses < 120 mg/kg.
• The risk for recurrence was 20% (in four patients) among 20 patients who achieved clearance and had any subsequent health care encounters, with a mean follow-up time of 734.3 days.
• Common adverse effects included dryness (80%), joint pain (14.5%), and headaches (10.9%). Other adverse effects included nose bleeds (9.1%) and depression (5.5%).
• Of the 22 patients with a cumulative dose < 120 mg/kg, 14 (63.6%) were lost to follow-up; among those not lost to follow-up, 2 patients discontinued treatment because of transfer of care, 1 because of adverse effects, and 1 because of gender-affirming surgery, with concerns about wound healing.

IN PRACTICE:

“Although isotretinoin appears to be an effective treatment option for acne among individuals undergoing masculinizing hormone therapy, further efforts are needed to understand optimal dosing and treatment barriers to improve outcomes in transgender and gender-diverse individuals receiving testosterone,” the authors concluded.

SOURCE:

The study, led by James Choe, BS, Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, was published online in JAMA Dermatology.

LIMITATIONS:

The study population was limited to four centers, and variability in clinician- and patient-reported acne outcomes and missing information could affect the reliability of data. Because of the small sample size, the association of masculinizing hormone therapy regimens with outcomes could not be evaluated.

DISCLOSURES:

One author is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Three authors reported receiving grants or personal fees from various sources. The other authors declared no conflicts of interest.

A version of this article first appeared on Medscape.com.

Dermatologists are well aware of guidelines limiting long-term antibiotic use for acne to 3-4 months, but a perceived lack of supporting data, along with in-office realities unaddressed by guidelines, hinder clinicians’ ability and willingness to follow them, according to the authors of a recently published study.

“This study explored why dermatologists still prescribe a good number of long-term antibiotics for people with acne,” the study’s senior author Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, said in an interview. “And we found a lot of reasons.” The study was published online in JAMA Dermatology.

Dr. Yeung

Using online surveys and semi-structured video interviews of 30 dermatologists, infectious disease physicians with expertise in antimicrobial stewardship, dermatology residents, and nonphysician clinicians, the investigators assessed respondents’ knowledge and attitudes regarding long-term antibiotics in acne. Salient themes impacting long-term antibiotic prescriptions included the following:

• A perceived dearth of evidence to justify changes in practice.
• Difficulties with iPLEDGE, the Risk Evaluation and Mitigation Strategy (REMS) for managing the teratogenic risks associated with isotretinoin, and with discussing oral contraceptives.
• “Navigating” discussions with about tapering-off of antibiotics.
• Challenging patient demands.
• A lack of effective tools for monitoring progress in antibiotic stewardship.

“It’s surprising there are so many barriers that make it difficult for dermatologists to stick with the guidelines even if they want to,” said Dr. Yeung, a coauthor of the recently released updated American Academy of Dermatology (AAD) acne management guidelines.

A dermatologist who wants to stop systemic antibiotics within 3 months may not know how to do so, he explained, or high demand for appointments may prevent timely follow-ups.

A major reason why dermatologists struggle to limit long-term antibiotic use is that there are very few substitutes that are perceived to work as well, said David J. Margolis, MD, PhD, who was not involved with the study and was asked to comment on the results. He is professor of epidemiology and dermatology at the University of Pennsylvania, Philadelphia.

Dr. Margolis

“Part of the reason antibiotics are being used to treat acne is that they’re effective, and effective for severe disease,” he said. The alternatives, which are mostly topicals, said Dr. Margolis, do not work as well for moderate to severe disease or, with isotretinoin, involve time-consuming hurdles. Dr. Margolis said that he often hears such concerns from individual dermatologists. “But it’s helpful to see these in a well-organized, well-reported qualitative study.”

Infectious disease specialists surveyed considered limiting long-term antibiotic use as extremely important, while several dermatologists “argued that other specialties ‘underestimate the impact acne has on people’s lives,’ ” the authors wrote. Other respondents prioritized making the right choice for the patient at hand.

Although guidelines were never meant to be black and white, Dr. Yeung said, it is crucial to target the goal of tapering off after about 3-4 months — a cutoff with which guidelines from groups including the AAD, the Japanese Dermatological Association in guidelines from 2016, and 2017, respectively, and others concur.

He added, “Some folks believe that if the oral antibiotic is working, why stop? We need to develop evidence to show that reducing oral antibiotic use is important to our patients, not just to a theoretical problem of antibiotic resistance in society.” For example, in a study published in The Lancet in 2004, patients who used strictly topical regimens achieved efficacy similar to that of those who used only oral antibiotics.

In addition, some clinicians worried that limiting antibiotics could reduce patient satisfaction, spurring switches to other providers. However, he and the other authors of the JAMA Dermatology study noted that in a survey of patients with acne published in the Journal of Clinical and Aesthetic Dermatology in 2019, 76.9% said they would be “very or extremely likely” to use effective antibiotic-free treatments if offered.

Because most respondents were highly aware of the importance of antibiotic stewardship, Dr. Yeung said, additional passive education is not necessarily the answer. “It will take a concerted effort by our national societies to come up with resources and solutions for individual dermatologists to overcome some of these larger barriers.” Such solutions could range from training in communication and shared decision-making to implementing systems that provide individualized feedback to support antibiotic stewardship.

Many ongoing studies are examining antibiotic stewardship, Dr. Margolis said in the interview. However, he added, dermatologists’ idea of long-term use is 3 months, versus 1 month or less in other specialties. “Moreover, dermatology patients tend to be much healthier individuals and are rarely hospitalized, so there may be some issues comparing the ongoing studies to individuals with acne.” Future research will need to account for such differences, he said.

The study was funded by an American Acne & Rosacea Society Clinical Research Award. Dr. Yeung is associate editor of JAMA Dermatology. Dr. Margolis has received a National Institutes of Health grant to study doxycycline versus spironolactone in acne.

Dermatologists are well aware of guidelines limiting long-term antibiotic use for acne to 3-4 months, but a perceived lack of supporting data, along with in-office realities unaddressed by guidelines, hinder clinicians’ ability and willingness to follow them, according to the authors of a recently published study.

“This study explored why dermatologists still prescribe a good number of long-term antibiotics for people with acne,” the study’s senior author Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, said in an interview. “And we found a lot of reasons.” The study was published online in JAMA Dermatology.

Dr. Yeung

Using online surveys and semi-structured video interviews of 30 dermatologists, infectious disease physicians with expertise in antimicrobial stewardship, dermatology residents, and nonphysician clinicians, the investigators assessed respondents’ knowledge and attitudes regarding long-term antibiotics in acne. Salient themes impacting long-term antibiotic prescriptions included the following:

• A perceived dearth of evidence to justify changes in practice.
• Difficulties with iPLEDGE, the Risk Evaluation and Mitigation Strategy (REMS) for managing the teratogenic risks associated with isotretinoin, and with discussing oral contraceptives.
• “Navigating” discussions with about tapering-off of antibiotics.
• Challenging patient demands.
• A lack of effective tools for monitoring progress in antibiotic stewardship.

“It’s surprising there are so many barriers that make it difficult for dermatologists to stick with the guidelines even if they want to,” said Dr. Yeung, a coauthor of the recently released updated American Academy of Dermatology (AAD) acne management guidelines.

A dermatologist who wants to stop systemic antibiotics within 3 months may not know how to do so, he explained, or high demand for appointments may prevent timely follow-ups.

A major reason why dermatologists struggle to limit long-term antibiotic use is that there are very few substitutes that are perceived to work as well, said David J. Margolis, MD, PhD, who was not involved with the study and was asked to comment on the results. He is professor of epidemiology and dermatology at the University of Pennsylvania, Philadelphia.

Dr. Margolis

“Part of the reason antibiotics are being used to treat acne is that they’re effective, and effective for severe disease,” he said. The alternatives, which are mostly topicals, said Dr. Margolis, do not work as well for moderate to severe disease or, with isotretinoin, involve time-consuming hurdles. Dr. Margolis said that he often hears such concerns from individual dermatologists. “But it’s helpful to see these in a well-organized, well-reported qualitative study.”

Infectious disease specialists surveyed considered limiting long-term antibiotic use as extremely important, while several dermatologists “argued that other specialties ‘underestimate the impact acne has on people’s lives,’ ” the authors wrote. Other respondents prioritized making the right choice for the patient at hand.

Although guidelines were never meant to be black and white, Dr. Yeung said, it is crucial to target the goal of tapering off after about 3-4 months — a cutoff with which guidelines from groups including the AAD, the Japanese Dermatological Association in guidelines from 2016, and 2017, respectively, and others concur.

He added, “Some folks believe that if the oral antibiotic is working, why stop? We need to develop evidence to show that reducing oral antibiotic use is important to our patients, not just to a theoretical problem of antibiotic resistance in society.” For example, in a study published in The Lancet in 2004, patients who used strictly topical regimens achieved efficacy similar to that of those who used only oral antibiotics.

In addition, some clinicians worried that limiting antibiotics could reduce patient satisfaction, spurring switches to other providers. However, he and the other authors of the JAMA Dermatology study noted that in a survey of patients with acne published in the Journal of Clinical and Aesthetic Dermatology in 2019, 76.9% said they would be “very or extremely likely” to use effective antibiotic-free treatments if offered.

Because most respondents were highly aware of the importance of antibiotic stewardship, Dr. Yeung said, additional passive education is not necessarily the answer. “It will take a concerted effort by our national societies to come up with resources and solutions for individual dermatologists to overcome some of these larger barriers.” Such solutions could range from training in communication and shared decision-making to implementing systems that provide individualized feedback to support antibiotic stewardship.

Many ongoing studies are examining antibiotic stewardship, Dr. Margolis said in the interview. However, he added, dermatologists’ idea of long-term use is 3 months, versus 1 month or less in other specialties. “Moreover, dermatology patients tend to be much healthier individuals and are rarely hospitalized, so there may be some issues comparing the ongoing studies to individuals with acne.” Future research will need to account for such differences, he said.

The study was funded by an American Acne & Rosacea Society Clinical Research Award. Dr. Yeung is associate editor of JAMA Dermatology. Dr. Margolis has received a National Institutes of Health grant to study doxycycline versus spironolactone in acne.

Dermatologists are well aware of guidelines limiting long-term antibiotic use for acne to 3-4 months, but a perceived lack of supporting data, along with in-office realities unaddressed by guidelines, hinder clinicians’ ability and willingness to follow them, according to the authors of a recently published study.

“This study explored why dermatologists still prescribe a good number of long-term antibiotics for people with acne,” the study’s senior author Howa Yeung, MD, MSc, assistant professor of dermatology at Emory University, Atlanta, said in an interview. “And we found a lot of reasons.” The study was published online in JAMA Dermatology.

Dr. Yeung

Using online surveys and semi-structured video interviews of 30 dermatologists, infectious disease physicians with expertise in antimicrobial stewardship, dermatology residents, and nonphysician clinicians, the investigators assessed respondents’ knowledge and attitudes regarding long-term antibiotics in acne. Salient themes impacting long-term antibiotic prescriptions included the following:

• A perceived dearth of evidence to justify changes in practice.
• Difficulties with iPLEDGE, the Risk Evaluation and Mitigation Strategy (REMS) for managing the teratogenic risks associated with isotretinoin, and with discussing oral contraceptives.
• “Navigating” discussions with about tapering-off of antibiotics.
• Challenging patient demands.
• A lack of effective tools for monitoring progress in antibiotic stewardship.

“It’s surprising there are so many barriers that make it difficult for dermatologists to stick with the guidelines even if they want to,” said Dr. Yeung, a coauthor of the recently released updated American Academy of Dermatology (AAD) acne management guidelines.

A dermatologist who wants to stop systemic antibiotics within 3 months may not know how to do so, he explained, or high demand for appointments may prevent timely follow-ups.

A major reason why dermatologists struggle to limit long-term antibiotic use is that there are very few substitutes that are perceived to work as well, said David J. Margolis, MD, PhD, who was not involved with the study and was asked to comment on the results. He is professor of epidemiology and dermatology at the University of Pennsylvania, Philadelphia.

Dr. Margolis

“Part of the reason antibiotics are being used to treat acne is that they’re effective, and effective for severe disease,” he said. The alternatives, which are mostly topicals, said Dr. Margolis, do not work as well for moderate to severe disease or, with isotretinoin, involve time-consuming hurdles. Dr. Margolis said that he often hears such concerns from individual dermatologists. “But it’s helpful to see these in a well-organized, well-reported qualitative study.”

Infectious disease specialists surveyed considered limiting long-term antibiotic use as extremely important, while several dermatologists “argued that other specialties ‘underestimate the impact acne has on people’s lives,’ ” the authors wrote. Other respondents prioritized making the right choice for the patient at hand.

Although guidelines were never meant to be black and white, Dr. Yeung said, it is crucial to target the goal of tapering off after about 3-4 months — a cutoff with which guidelines from groups including the AAD, the Japanese Dermatological Association in guidelines from 2016, and 2017, respectively, and others concur.

He added, “Some folks believe that if the oral antibiotic is working, why stop? We need to develop evidence to show that reducing oral antibiotic use is important to our patients, not just to a theoretical problem of antibiotic resistance in society.” For example, in a study published in The Lancet in 2004, patients who used strictly topical regimens achieved efficacy similar to that of those who used only oral antibiotics.

In addition, some clinicians worried that limiting antibiotics could reduce patient satisfaction, spurring switches to other providers. However, he and the other authors of the JAMA Dermatology study noted that in a survey of patients with acne published in the Journal of Clinical and Aesthetic Dermatology in 2019, 76.9% said they would be “very or extremely likely” to use effective antibiotic-free treatments if offered.

Because most respondents were highly aware of the importance of antibiotic stewardship, Dr. Yeung said, additional passive education is not necessarily the answer. “It will take a concerted effort by our national societies to come up with resources and solutions for individual dermatologists to overcome some of these larger barriers.” Such solutions could range from training in communication and shared decision-making to implementing systems that provide individualized feedback to support antibiotic stewardship.

Many ongoing studies are examining antibiotic stewardship, Dr. Margolis said in the interview. However, he added, dermatologists’ idea of long-term use is 3 months, versus 1 month or less in other specialties. “Moreover, dermatology patients tend to be much healthier individuals and are rarely hospitalized, so there may be some issues comparing the ongoing studies to individuals with acne.” Future research will need to account for such differences, he said.

The study was funded by an American Acne & Rosacea Society Clinical Research Award. Dr. Yeung is associate editor of JAMA Dermatology. Dr. Margolis has received a National Institutes of Health grant to study doxycycline versus spironolactone in acne.

Nine days after the independent laboratory Valisure petitioned the Food and Drug Administration (FDA) to recall acne products with benzoyl peroxide (BP) because of the lab’s findings of extremely high levels of the carcinogen benzene, it published another report in Environmental Health Perspectives (EHP), on March 14, also warning about BP acne products.

The bottom line was the same: The laboratory, based in New Haven, Connecticut, said its analyses raise substantial concerns about the safety of BP-containing acne products currently on the market.

The lab’s results showed that the products can form over 800 times the conditionally restricted FDA concentration limit of 2 parts per million (ppm) of benzene, with both prescription and over-the-counter products affected.

“This is a problem of degradation, not contamination,” David Light, CEO and founder of Valisure, said in a telephone interview. BP can decompose into benzene, and exposure to benzene has been linked with a higher risk for leukemia and other blood cancers, according to the American Cancer Society.

In the wake of the findings, however, debate has erupted over the method and approach used by Valisure to test these products, with critics and companies contending that more “real-world” use data are needed. And the US Pharmacopeia (USP) is asking for full transparency about the testing methods.

In a March 8 statement, USP said the petition indicated that modified USP methods were used in the study, noting that “if changes are made to a USP method, complete validation data is necessary to demonstrate that a product meets USP standards.”

However, Valisure contended that drug products need to demonstrate stability over the entire life cycle, from shipment to continued use, emphasizing that constitutes the best “real-world” approach. It also defended the methodology it used.

The reports have led to a state of uncertainty about the use of BP products.

“Right now, we have more unknowns than anything else,” John Barbieri, MD, MBA, assistant professor of dermatology at Harvard Medical School and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, said in a video posted on X and YouTube, summarizing the findings released by Valisure on March 6 and 14. He was not involved in the Valisure research.

Brigham and Women&#039;s Hospital

In a telephone interview, Dr. Barbieri said the report “needs to be taken seriously,” but he also believed the Valisure report is lacking information about testing under “real-world” conditions. He is calling for more information and more transparency about the data. What’s clear, Dr. Barbieri told this news organization, is that the findings about high benzene levels are not a manufacturing error. “It’s something to do with the molecule itself.”
 

Valisure’s Analyses

Valisure performed an initial analysis, using a method called gas chromatography-mass spectrometry, which is the FDA-preferred method for detecting benzene, Mr. Light said. It tested 175 acne products, 99 containing BP and 76 with other ingredients, such as salicylic acid. All the products without BP had no detectable benzene or values below 2 ppm, the FDA concentration limit for benzene.

Of the 99 BP products, 94 contained benzene without any elevated temperature incubation, according to Valisure. Using 50 °C (122 °F, the accepted pharmaceutical stability testing temperature) on 66 products, Valisure detected over 1500 ppm of benzene in two products, over 100 ppm in 17 products, and over 10 ppm in 42 products over an 18-day period.

The analysis confirmed, Valisure said in a press release and the petition, that a substantial amount of benzene can form in a BP product and leak outside the packaging into surrounding air.

The EHP paper, which includes authors from Valisure, reported that researchers took single lots of seven branded BP products, namely, Equate Beauty 2.5% BP cleansers, Neutrogena 10% BP cleanser, CVS Health 10% BP face wash, Walgreens 10% BP cream, Clean & Clear 10% cleanser, Equate Beauty 10% BP acne wash, and Proactiv 2.5% BP cleanser.

Using testing that involved gas chromatography-mass spectrometry, benzene was detected in all the BP products samples tested, and levels increased during incubation at body and shelf-life performance temperatures to more than 2 ppm. The authors concluded that the study “raises substantial concerns” about the safety of BP products currently on the market.
 

Methodology Debates

Two days after Valisure released its analysis on March 6, the USP reviewed the citizen’s petition filed by Valisure and called for more transparency around the testing methods.

“The petition referenced USP and indicated that modified USP methods and procedures were used in the study. The presence of unsafe levels of benzene should be taken seriously,” the statement said. The USP statement also noted that the Valisure analysis used modified USP methods and said that “if changes are made to a USP method, complete validation data is necessary to demonstrate that a product meets USP standards.”

In its statement, USP took issue with a practice known as accelerated thermal degradation, which it said Valisure used. USP said the approach involves raising the storage temperature of a product to higher than the temperature indicated on the label for the purpose of simulating degradation over a longer period. While the approach may be acceptable, USP said, the temperatures chosen may not be what is expected to happen to the products.

In response, Mr. Light of Valisure referenced guidance issued in August, 2020, from the FDA, stating that the method it used in the BP analysis can be used to detect impurities in hand sanitizers, including benzene. (In 2021, Valisure detected high levels of benzene in some hand sanitizers and asked the FDA to take action.)
 

Company Response

Among the companies that took issue with the report was Reckitt, which makes Clearasil, which contains BP. In a statement, the company said, in part: “The products and their ingredients are stable over the storage conditions described on their packaging which represent all reasonable and foreseeable conditions.” It said the findings presented by Valisure reflect “unrealistic scenarios rather than real-world conditions.”

The Personal Care Products Council, a national trade association that represents cosmetic and personal care product manufacturers, also took issue with the findings and the approach used to evaluate the products.
 

FDA and the Citizen’s Petition

The FDA accepted the petition, Mr. Light said, and gave it a docket number. “We’ll hopefully hear more soon” because the FDA is required to respond to a citizen’s petition within 180 days, he said.

“We generally don’t comment on pending citizens’ petitions,” an FDA spokesperson said in an email. “When we respond, we will respond directly to the petitioner and post the response in the designated agency public docket.”
 

Valisure’s Patent Application

Mr. Light and others have applied for a patent on methods of producing shelf-stable formulations to prevent degradation of BP to benzene.

“We saw the problem long before we had any sort of application,” Mr. Light said. The issue has been “known for decades.”
 

Role of BP Products for Acne

In the midst of uncertainty, “the first discussion is, do we want to use it?” Dr. Barbieri said in the interview. Some patients may want to avoid it altogether, until more data are available, including more verification of the findings, while others may be comfortable accepting the potential risk, he said.

“Benzoyl peroxide is one of our foundational acne treatments,” Dr. Barbieri said. In the American Academy of Dermatology updated guidelines on acne, published in January, 2024, strong recommendations were made for BP products, as well as topical retinoids, topical antibiotics, and oral doxycycline.

“When you take away BP, there’s no substitute for it,” Dr. Barbieri said. And if patients don’t get improvement with topicals, oral medications might be needed, and “these all have their own risks.”
 

In the Interim

Until more information is available, Dr. Barbieri is advising patients not to store the products at high temperatures or for a long time. Don’t keep the products past their expiration date, and perhaps keep products for a shorter time, “something like a month,” he said.

Those living in a hot climate might consider storing the products in the refrigerator, he said.

“We need more data from Valisure, from other groups that confirm their findings, and we need to hear from the FDA,” Dr. Barbieri said. “There’s a lot of uncertainty right now. But it’s important not to overreact.”

Dr. Barbieri had no relevant disclosures.


 

A version of this article appeared on Medscape.com.

Nine days after the independent laboratory Valisure petitioned the Food and Drug Administration (FDA) to recall acne products with benzoyl peroxide (BP) because of the lab’s findings of extremely high levels of the carcinogen benzene, it published another report in Environmental Health Perspectives (EHP), on March 14, also warning about BP acne products.

The bottom line was the same: The laboratory, based in New Haven, Connecticut, said its analyses raise substantial concerns about the safety of BP-containing acne products currently on the market.

The lab’s results showed that the products can form over 800 times the conditionally restricted FDA concentration limit of 2 parts per million (ppm) of benzene, with both prescription and over-the-counter products affected.

“This is a problem of degradation, not contamination,” David Light, CEO and founder of Valisure, said in a telephone interview. BP can decompose into benzene, and exposure to benzene has been linked with a higher risk for leukemia and other blood cancers, according to the American Cancer Society.

In the wake of the findings, however, debate has erupted over the method and approach used by Valisure to test these products, with critics and companies contending that more “real-world” use data are needed. And the US Pharmacopeia (USP) is asking for full transparency about the testing methods.

In a March 8 statement, USP said the petition indicated that modified USP methods were used in the study, noting that “if changes are made to a USP method, complete validation data is necessary to demonstrate that a product meets USP standards.”

However, Valisure contended that drug products need to demonstrate stability over the entire life cycle, from shipment to continued use, emphasizing that constitutes the best “real-world” approach. It also defended the methodology it used.

The reports have led to a state of uncertainty about the use of BP products.

“Right now, we have more unknowns than anything else,” John Barbieri, MD, MBA, assistant professor of dermatology at Harvard Medical School and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, said in a video posted on X and YouTube, summarizing the findings released by Valisure on March 6 and 14. He was not involved in the Valisure research.

Brigham and Women&#039;s Hospital

In a telephone interview, Dr. Barbieri said the report “needs to be taken seriously,” but he also believed the Valisure report is lacking information about testing under “real-world” conditions. He is calling for more information and more transparency about the data. What’s clear, Dr. Barbieri told this news organization, is that the findings about high benzene levels are not a manufacturing error. “It’s something to do with the molecule itself.”
 

Valisure’s Analyses

Valisure performed an initial analysis, using a method called gas chromatography-mass spectrometry, which is the FDA-preferred method for detecting benzene, Mr. Light said. It tested 175 acne products, 99 containing BP and 76 with other ingredients, such as salicylic acid. All the products without BP had no detectable benzene or values below 2 ppm, the FDA concentration limit for benzene.

Of the 99 BP products, 94 contained benzene without any elevated temperature incubation, according to Valisure. Using 50 °C (122 °F, the accepted pharmaceutical stability testing temperature) on 66 products, Valisure detected over 1500 ppm of benzene in two products, over 100 ppm in 17 products, and over 10 ppm in 42 products over an 18-day period.

The analysis confirmed, Valisure said in a press release and the petition, that a substantial amount of benzene can form in a BP product and leak outside the packaging into surrounding air.

The EHP paper, which includes authors from Valisure, reported that researchers took single lots of seven branded BP products, namely, Equate Beauty 2.5% BP cleansers, Neutrogena 10% BP cleanser, CVS Health 10% BP face wash, Walgreens 10% BP cream, Clean & Clear 10% cleanser, Equate Beauty 10% BP acne wash, and Proactiv 2.5% BP cleanser.

Using testing that involved gas chromatography-mass spectrometry, benzene was detected in all the BP products samples tested, and levels increased during incubation at body and shelf-life performance temperatures to more than 2 ppm. The authors concluded that the study “raises substantial concerns” about the safety of BP products currently on the market.
 

Methodology Debates

Two days after Valisure released its analysis on March 6, the USP reviewed the citizen’s petition filed by Valisure and called for more transparency around the testing methods.

“The petition referenced USP and indicated that modified USP methods and procedures were used in the study. The presence of unsafe levels of benzene should be taken seriously,” the statement said. The USP statement also noted that the Valisure analysis used modified USP methods and said that “if changes are made to a USP method, complete validation data is necessary to demonstrate that a product meets USP standards.”

In its statement, USP took issue with a practice known as accelerated thermal degradation, which it said Valisure used. USP said the approach involves raising the storage temperature of a product to higher than the temperature indicated on the label for the purpose of simulating degradation over a longer period. While the approach may be acceptable, USP said, the temperatures chosen may not be what is expected to happen to the products.

In response, Mr. Light of Valisure referenced guidance issued in August, 2020, from the FDA, stating that the method it used in the BP analysis can be used to detect impurities in hand sanitizers, including benzene. (In 2021, Valisure detected high levels of benzene in some hand sanitizers and asked the FDA to take action.)
 

Company Response

Among the companies that took issue with the report was Reckitt, which makes Clearasil, which contains BP. In a statement, the company said, in part: “The products and their ingredients are stable over the storage conditions described on their packaging which represent all reasonable and foreseeable conditions.” It said the findings presented by Valisure reflect “unrealistic scenarios rather than real-world conditions.”

The Personal Care Products Council, a national trade association that represents cosmetic and personal care product manufacturers, also took issue with the findings and the approach used to evaluate the products.
 

FDA and the Citizen’s Petition

The FDA accepted the petition, Mr. Light said, and gave it a docket number. “We’ll hopefully hear more soon” because the FDA is required to respond to a citizen’s petition within 180 days, he said.

“We generally don’t comment on pending citizens’ petitions,” an FDA spokesperson said in an email. “When we respond, we will respond directly to the petitioner and post the response in the designated agency public docket.”
 

Valisure’s Patent Application

Mr. Light and others have applied for a patent on methods of producing shelf-stable formulations to prevent degradation of BP to benzene.

“We saw the problem long before we had any sort of application,” Mr. Light said. The issue has been “known for decades.”
 

Role of BP Products for Acne

In the midst of uncertainty, “the first discussion is, do we want to use it?” Dr. Barbieri said in the interview. Some patients may want to avoid it altogether, until more data are available, including more verification of the findings, while others may be comfortable accepting the potential risk, he said.

“Benzoyl peroxide is one of our foundational acne treatments,” Dr. Barbieri said. In the American Academy of Dermatology updated guidelines on acne, published in January, 2024, strong recommendations were made for BP products, as well as topical retinoids, topical antibiotics, and oral doxycycline.

“When you take away BP, there’s no substitute for it,” Dr. Barbieri said. And if patients don’t get improvement with topicals, oral medications might be needed, and “these all have their own risks.”
 

In the Interim

Until more information is available, Dr. Barbieri is advising patients not to store the products at high temperatures or for a long time. Don’t keep the products past their expiration date, and perhaps keep products for a shorter time, “something like a month,” he said.

Those living in a hot climate might consider storing the products in the refrigerator, he said.

“We need more data from Valisure, from other groups that confirm their findings, and we need to hear from the FDA,” Dr. Barbieri said. “There’s a lot of uncertainty right now. But it’s important not to overreact.”

Dr. Barbieri had no relevant disclosures.


 

A version of this article appeared on Medscape.com.

Nine days after the independent laboratory Valisure petitioned the Food and Drug Administration (FDA) to recall acne products with benzoyl peroxide (BP) because of the lab’s findings of extremely high levels of the carcinogen benzene, it published another report in Environmental Health Perspectives (EHP), on March 14, also warning about BP acne products.

The bottom line was the same: The laboratory, based in New Haven, Connecticut, said its analyses raise substantial concerns about the safety of BP-containing acne products currently on the market.

The lab’s results showed that the products can form over 800 times the conditionally restricted FDA concentration limit of 2 parts per million (ppm) of benzene, with both prescription and over-the-counter products affected.

“This is a problem of degradation, not contamination,” David Light, CEO and founder of Valisure, said in a telephone interview. BP can decompose into benzene, and exposure to benzene has been linked with a higher risk for leukemia and other blood cancers, according to the American Cancer Society.

In the wake of the findings, however, debate has erupted over the method and approach used by Valisure to test these products, with critics and companies contending that more “real-world” use data are needed. And the US Pharmacopeia (USP) is asking for full transparency about the testing methods.

In a March 8 statement, USP said the petition indicated that modified USP methods were used in the study, noting that “if changes are made to a USP method, complete validation data is necessary to demonstrate that a product meets USP standards.”

However, Valisure contended that drug products need to demonstrate stability over the entire life cycle, from shipment to continued use, emphasizing that constitutes the best “real-world” approach. It also defended the methodology it used.

The reports have led to a state of uncertainty about the use of BP products.

“Right now, we have more unknowns than anything else,” John Barbieri, MD, MBA, assistant professor of dermatology at Harvard Medical School and director of the Advanced Acne Therapeutics Clinic at Brigham and Women’s Hospital, Boston, said in a video posted on X and YouTube, summarizing the findings released by Valisure on March 6 and 14. He was not involved in the Valisure research.

Brigham and Women&#039;s Hospital

In a telephone interview, Dr. Barbieri said the report “needs to be taken seriously,” but he also believed the Valisure report is lacking information about testing under “real-world” conditions. He is calling for more information and more transparency about the data. What’s clear, Dr. Barbieri told this news organization, is that the findings about high benzene levels are not a manufacturing error. “It’s something to do with the molecule itself.”
 

Valisure’s Analyses

Valisure performed an initial analysis, using a method called gas chromatography-mass spectrometry, which is the FDA-preferred method for detecting benzene, Mr. Light said. It tested 175 acne products, 99 containing BP and 76 with other ingredients, such as salicylic acid. All the products without BP had no detectable benzene or values below 2 ppm, the FDA concentration limit for benzene.

Of the 99 BP products, 94 contained benzene without any elevated temperature incubation, according to Valisure. Using 50 °C (122 °F, the accepted pharmaceutical stability testing temperature) on 66 products, Valisure detected over 1500 ppm of benzene in two products, over 100 ppm in 17 products, and over 10 ppm in 42 products over an 18-day period.

The analysis confirmed, Valisure said in a press release and the petition, that a substantial amount of benzene can form in a BP product and leak outside the packaging into surrounding air.

The EHP paper, which includes authors from Valisure, reported that researchers took single lots of seven branded BP products, namely, Equate Beauty 2.5% BP cleansers, Neutrogena 10% BP cleanser, CVS Health 10% BP face wash, Walgreens 10% BP cream, Clean & Clear 10% cleanser, Equate Beauty 10% BP acne wash, and Proactiv 2.5% BP cleanser.

Using testing that involved gas chromatography-mass spectrometry, benzene was detected in all the BP products samples tested, and levels increased during incubation at body and shelf-life performance temperatures to more than 2 ppm. The authors concluded that the study “raises substantial concerns” about the safety of BP products currently on the market.
 

Methodology Debates

Two days after Valisure released its analysis on March 6, the USP reviewed the citizen’s petition filed by Valisure and called for more transparency around the testing methods.

“The petition referenced USP and indicated that modified USP methods and procedures were used in the study. The presence of unsafe levels of benzene should be taken seriously,” the statement said. The USP statement also noted that the Valisure analysis used modified USP methods and said that “if changes are made to a USP method, complete validation data is necessary to demonstrate that a product meets USP standards.”

In its statement, USP took issue with a practice known as accelerated thermal degradation, which it said Valisure used. USP said the approach involves raising the storage temperature of a product to higher than the temperature indicated on the label for the purpose of simulating degradation over a longer period. While the approach may be acceptable, USP said, the temperatures chosen may not be what is expected to happen to the products.

In response, Mr. Light of Valisure referenced guidance issued in August, 2020, from the FDA, stating that the method it used in the BP analysis can be used to detect impurities in hand sanitizers, including benzene. (In 2021, Valisure detected high levels of benzene in some hand sanitizers and asked the FDA to take action.)
 

Company Response

Among the companies that took issue with the report was Reckitt, which makes Clearasil, which contains BP. In a statement, the company said, in part: “The products and their ingredients are stable over the storage conditions described on their packaging which represent all reasonable and foreseeable conditions.” It said the findings presented by Valisure reflect “unrealistic scenarios rather than real-world conditions.”

The Personal Care Products Council, a national trade association that represents cosmetic and personal care product manufacturers, also took issue with the findings and the approach used to evaluate the products.
 

FDA and the Citizen’s Petition

The FDA accepted the petition, Mr. Light said, and gave it a docket number. “We’ll hopefully hear more soon” because the FDA is required to respond to a citizen’s petition within 180 days, he said.

“We generally don’t comment on pending citizens’ petitions,” an FDA spokesperson said in an email. “When we respond, we will respond directly to the petitioner and post the response in the designated agency public docket.”
 

Valisure’s Patent Application

Mr. Light and others have applied for a patent on methods of producing shelf-stable formulations to prevent degradation of BP to benzene.

“We saw the problem long before we had any sort of application,” Mr. Light said. The issue has been “known for decades.”
 

Role of BP Products for Acne

In the midst of uncertainty, “the first discussion is, do we want to use it?” Dr. Barbieri said in the interview. Some patients may want to avoid it altogether, until more data are available, including more verification of the findings, while others may be comfortable accepting the potential risk, he said.

“Benzoyl peroxide is one of our foundational acne treatments,” Dr. Barbieri said. In the American Academy of Dermatology updated guidelines on acne, published in January, 2024, strong recommendations were made for BP products, as well as topical retinoids, topical antibiotics, and oral doxycycline.

“When you take away BP, there’s no substitute for it,” Dr. Barbieri said. And if patients don’t get improvement with topicals, oral medications might be needed, and “these all have their own risks.”
 

In the Interim

Until more information is available, Dr. Barbieri is advising patients not to store the products at high temperatures or for a long time. Don’t keep the products past their expiration date, and perhaps keep products for a shorter time, “something like a month,” he said.

Those living in a hot climate might consider storing the products in the refrigerator, he said.

“We need more data from Valisure, from other groups that confirm their findings, and we need to hear from the FDA,” Dr. Barbieri said. “There’s a lot of uncertainty right now. But it’s important not to overreact.”

Dr. Barbieri had no relevant disclosures.


 

A version of this article appeared on Medscape.com.

TOPLINE: 

Despite the risk of worsening acne with progestin-only long-acting reversible contraception (LARC) in a study of adolescents and young adults, acne alone was not a common reason for discontinuation.

METHODOLOGY:

• Progestin-only LARC may increase the risk for acne, but this has not been well studied in adolescents and young adults.
• In the study, researchers evaluated the incidence of acne, acne as a reason for removal, and strategies used to manage acne after insertion of a progestin-only intrauterine device (IUD) or contraceptive implant in 1319 adolescents and young adults across four Adolescent Medicine LARC Collaborative study sites from January 2017 to June 2021.The mean age at insertion was 18.6 years.
• Overall, 24% of participants had acne at the time of LARC insertion.
• Worsening acne was defined as new patient reports of concern about acne, observations of acne, or addition of an acne medication after insertion; increased severity noted on an exam during follow-up or at the time of LARC removal; or acne reported as a side effect and/or reason for LARC removal.

TAKEAWAY: 

• During the study period, 376 participants (28.5%) experienced worsening acne after LARC insertion, and 17% reported acne as a new concern, with no differences between those who received an IUD or an implant.
• Only 44 of the 376 participants (11.7%) who reported worsening acne were being treated with an oral agent at follow-up.
• Of the 542 individuals (41% of the total) who had the LARC device removed, 40 (7.4%) cited concerns about acne for removing the device, although just 5 (0.92%) said that acne was the only reason for removal. Of the 40 with concerns about acne when the device was removed, 18 (45%) had documented acne at the time of insertion.

IN PRACTICE:

The authors recommend that clinicians prescribing progestin-only LARC should counsel patients that acne may be a side effect, reassuring them that if they develop acne, “it typically is not problematic enough to warrant discontinuation,” and concluded that “concerns about the development or worsening of acne should not be cause to avoid these forms of contraception.”

SOURCE:

The study, led by Markus D. Boos, MD, PhD, of the division of dermatology in the Department of Pediatrics, University of Washington in Seattle and Seattle Children’s Hospital, was published in Pediatric Dermatology.

LIMITATIONS:

Individuals without documented acne were assumed to be acne-free, creating potential bias. Acne evaluation and treatment were not standardized and were not performed by dermatologists; acne severity was not recorded for many participants, possibly underestimating severity, and excluding LARC insertions without follow-up or with removal within 8 weeks may have underestimated the percentage of participants who developed new or worsening acne.

DISCLOSURES: 

The study was supported by Investigator-Initiated Studies Program of Organon and by the Health Resources and Services Administration of the US Department of Health and Human Services. Many authors received grants for this work. The authors did not disclose any other competing interests.

A version of this article appeared on Medscape.com.

TOPLINE: 

Despite the risk of worsening acne with progestin-only long-acting reversible contraception (LARC) in a study of adolescents and young adults, acne alone was not a common reason for discontinuation.

METHODOLOGY:

• Progestin-only LARC may increase the risk for acne, but this has not been well studied in adolescents and young adults.
• In the study, researchers evaluated the incidence of acne, acne as a reason for removal, and strategies used to manage acne after insertion of a progestin-only intrauterine device (IUD) or contraceptive implant in 1319 adolescents and young adults across four Adolescent Medicine LARC Collaborative study sites from January 2017 to June 2021.The mean age at insertion was 18.6 years.
• Overall, 24% of participants had acne at the time of LARC insertion.
• Worsening acne was defined as new patient reports of concern about acne, observations of acne, or addition of an acne medication after insertion; increased severity noted on an exam during follow-up or at the time of LARC removal; or acne reported as a side effect and/or reason for LARC removal.

TAKEAWAY: 

• During the study period, 376 participants (28.5%) experienced worsening acne after LARC insertion, and 17% reported acne as a new concern, with no differences between those who received an IUD or an implant.
• Only 44 of the 376 participants (11.7%) who reported worsening acne were being treated with an oral agent at follow-up.
• Of the 542 individuals (41% of the total) who had the LARC device removed, 40 (7.4%) cited concerns about acne for removing the device, although just 5 (0.92%) said that acne was the only reason for removal. Of the 40 with concerns about acne when the device was removed, 18 (45%) had documented acne at the time of insertion.

IN PRACTICE:

The authors recommend that clinicians prescribing progestin-only LARC should counsel patients that acne may be a side effect, reassuring them that if they develop acne, “it typically is not problematic enough to warrant discontinuation,” and concluded that “concerns about the development or worsening of acne should not be cause to avoid these forms of contraception.”

SOURCE:

The study, led by Markus D. Boos, MD, PhD, of the division of dermatology in the Department of Pediatrics, University of Washington in Seattle and Seattle Children’s Hospital, was published in Pediatric Dermatology.

LIMITATIONS:

Individuals without documented acne were assumed to be acne-free, creating potential bias. Acne evaluation and treatment were not standardized and were not performed by dermatologists; acne severity was not recorded for many participants, possibly underestimating severity, and excluding LARC insertions without follow-up or with removal within 8 weeks may have underestimated the percentage of participants who developed new or worsening acne.

DISCLOSURES: 

The study was supported by Investigator-Initiated Studies Program of Organon and by the Health Resources and Services Administration of the US Department of Health and Human Services. Many authors received grants for this work. The authors did not disclose any other competing interests.

A version of this article appeared on Medscape.com.

TOPLINE: 

Despite the risk of worsening acne with progestin-only long-acting reversible contraception (LARC) in a study of adolescents and young adults, acne alone was not a common reason for discontinuation.

METHODOLOGY:

• Progestin-only LARC may increase the risk for acne, but this has not been well studied in adolescents and young adults.
• In the study, researchers evaluated the incidence of acne, acne as a reason for removal, and strategies used to manage acne after insertion of a progestin-only intrauterine device (IUD) or contraceptive implant in 1319 adolescents and young adults across four Adolescent Medicine LARC Collaborative study sites from January 2017 to June 2021.The mean age at insertion was 18.6 years.
• Overall, 24% of participants had acne at the time of LARC insertion.
• Worsening acne was defined as new patient reports of concern about acne, observations of acne, or addition of an acne medication after insertion; increased severity noted on an exam during follow-up or at the time of LARC removal; or acne reported as a side effect and/or reason for LARC removal.

TAKEAWAY: 

• During the study period, 376 participants (28.5%) experienced worsening acne after LARC insertion, and 17% reported acne as a new concern, with no differences between those who received an IUD or an implant.
• Only 44 of the 376 participants (11.7%) who reported worsening acne were being treated with an oral agent at follow-up.
• Of the 542 individuals (41% of the total) who had the LARC device removed, 40 (7.4%) cited concerns about acne for removing the device, although just 5 (0.92%) said that acne was the only reason for removal. Of the 40 with concerns about acne when the device was removed, 18 (45%) had documented acne at the time of insertion.

IN PRACTICE:

The authors recommend that clinicians prescribing progestin-only LARC should counsel patients that acne may be a side effect, reassuring them that if they develop acne, “it typically is not problematic enough to warrant discontinuation,” and concluded that “concerns about the development or worsening of acne should not be cause to avoid these forms of contraception.”

SOURCE:

The study, led by Markus D. Boos, MD, PhD, of the division of dermatology in the Department of Pediatrics, University of Washington in Seattle and Seattle Children’s Hospital, was published in Pediatric Dermatology.

LIMITATIONS:

Individuals without documented acne were assumed to be acne-free, creating potential bias. Acne evaluation and treatment were not standardized and were not performed by dermatologists; acne severity was not recorded for many participants, possibly underestimating severity, and excluding LARC insertions without follow-up or with removal within 8 weeks may have underestimated the percentage of participants who developed new or worsening acne.

DISCLOSURES: 

The study was supported by Investigator-Initiated Studies Program of Organon and by the Health Resources and Services Administration of the US Department of Health and Human Services. Many authors received grants for this work. The authors did not disclose any other competing interests.

A version of this article appeared on Medscape.com.

SAN DIEGO — Transmasculine patients with acne require unique care that not only is sensitive but also reflects an understanding about factors that can affect their skin such as hormone therapy, a dermatologist told colleagues in a session at the American Academy of Dermatology annual meeting.

In these patients, treatment of acne is crucial, said Howa Yeung, MD, MSc, assistant professor of dermatology, Emory University, Atlanta. “These are patients who are suffering and reporting that they’re having mental health impacts” related to acne.

In transmasculine patients — those who were biologically female at birth but identify as masculine — testosterone therapy greatly boosts the risk for acne, even in adults who are long past adolescence, Dr. Yeung said. Data suggest that acne appears within the first 6 months after testosterone therapy begins, he said, “and the maximal and complete effect occurs within 1-2 years.”

A 2021 study tracked 988 transgender patients receiving testosterone at Fenway Health in Boston and found that 31% had a diagnosis of acne, up from 6.3% prior to taking hormones. And 2 years following the start of therapy, 25.1% had acne, with cases especially common among those aged 18-20.75 years (29.6%). Even among those aged 28.25-66.5 years, 17.1% had acne.

Transmasculine patients may develop acne in areas across the body “in places that you normally won’t see by just looking at the patient,” Dr. Yeung said. Excoriation in addition to comedones, papules, pustules, and nodules can be common, he added.

Dr. Yeung highlighted a 2019 study of transgender men that linked higher levels of acne to higher levels of serum testosterone, higher body mass index, and current smoking. And in a 2014 study, 6% of 50 transmasculine patients had moderate to severe acne after an average of 10 years on testosterone therapy.

A 2020 study of 696 transgender adults surveyed in California and Georgia found that 14% of transmasculine patients had moderate to severe acne — two thirds attributed it to hormone therapy — vs 1% of transfeminine patients, said Dr. Yeung, the lead author of the study. However, transmasculine patients were less likely to have seen a dermatologist.

Dr. Yeung also highlighted a 2021 study he coauthored that linked current moderate to severe acne in transmasculine patients taking testosterone to higher levels of depression and anxiety vs counterparts who had never had those forms of acne.

Another factor affecting acne in transmasculine patients is the use of chest binders to reduce breast size. “Wearing a chest binder is really helpful for a lot of our patients and is associated with improved self-esteem, mood, mental health, and safety in public,” Dr. Yeung said. However, the binders can contribute to skin problems.

Dr. Yeung said he and his colleagues emphasize the importance of breathable material in binders and suggest to patients that they not wear them when they’re in “safe spaces.”

Isotretinoin, Contraception Considerations

As for treatment of acne in transgender patients, Dr. Yeung cautioned colleagues to not automatically reject isotretinoin as an option for transgender patients who have a history of depression. Dermatologists may be tempted to avoid the drug in these patients because of its link to suicide, he said. (This apparent association has long been debated.) But, Dr. Yeung said, it’s important to consider that many of these patients suffered from anxiety and depression because of the lack of access to proper gender-reassignment treatment.

When using isotretinoin, he emphasized, it’s crucial to consider whether transmasculine patients could become pregnant while on this therapy. Consider whether the patient has the organs needed to become pregnant and ask questions about the potential that they could be impregnated.

“Remember that sexual behavior is different from gender identity,” Dr. Yeung said. A transmasculine person with a uterus and vagina, for example, may still have vaginal intercourse with males and potentially become pregnant. “So, we need to assess what kind of sexual behavior our patients are taking part in.”

Contraceptives such as intrauterine devices, implants, and injectable options may be helpful for transmasculine patients because they can reduce menstrual symptoms like spotting that can be distressing to them, he said. By helping a patient take a contraceptive, “you may actually be helping with their gender dysphoria and helping them get on isotretinoin.”

Dr. Yeung disclosed fees from JAMA and American Academy of Dermatology; grants/research funding from the American Acne & Rosacea Society, Dermatology Foundation, Department of Veterans Affairs, National Eczema Association, and National Institutes of Health; and speaker/faculty education honoraria from Dermatology Digest.

A version of this article appeared on Medscape.com.

SAN DIEGO — Transmasculine patients with acne require unique care that not only is sensitive but also reflects an understanding about factors that can affect their skin such as hormone therapy, a dermatologist told colleagues in a session at the American Academy of Dermatology annual meeting.

In these patients, treatment of acne is crucial, said Howa Yeung, MD, MSc, assistant professor of dermatology, Emory University, Atlanta. “These are patients who are suffering and reporting that they’re having mental health impacts” related to acne.

In transmasculine patients — those who were biologically female at birth but identify as masculine — testosterone therapy greatly boosts the risk for acne, even in adults who are long past adolescence, Dr. Yeung said. Data suggest that acne appears within the first 6 months after testosterone therapy begins, he said, “and the maximal and complete effect occurs within 1-2 years.”

A 2021 study tracked 988 transgender patients receiving testosterone at Fenway Health in Boston and found that 31% had a diagnosis of acne, up from 6.3% prior to taking hormones. And 2 years following the start of therapy, 25.1% had acne, with cases especially common among those aged 18-20.75 years (29.6%). Even among those aged 28.25-66.5 years, 17.1% had acne.

Transmasculine patients may develop acne in areas across the body “in places that you normally won’t see by just looking at the patient,” Dr. Yeung said. Excoriation in addition to comedones, papules, pustules, and nodules can be common, he added.

Dr. Yeung highlighted a 2019 study of transgender men that linked higher levels of acne to higher levels of serum testosterone, higher body mass index, and current smoking. And in a 2014 study, 6% of 50 transmasculine patients had moderate to severe acne after an average of 10 years on testosterone therapy.

A 2020 study of 696 transgender adults surveyed in California and Georgia found that 14% of transmasculine patients had moderate to severe acne — two thirds attributed it to hormone therapy — vs 1% of transfeminine patients, said Dr. Yeung, the lead author of the study. However, transmasculine patients were less likely to have seen a dermatologist.

Dr. Yeung also highlighted a 2021 study he coauthored that linked current moderate to severe acne in transmasculine patients taking testosterone to higher levels of depression and anxiety vs counterparts who had never had those forms of acne.

Another factor affecting acne in transmasculine patients is the use of chest binders to reduce breast size. “Wearing a chest binder is really helpful for a lot of our patients and is associated with improved self-esteem, mood, mental health, and safety in public,” Dr. Yeung said. However, the binders can contribute to skin problems.

Dr. Yeung said he and his colleagues emphasize the importance of breathable material in binders and suggest to patients that they not wear them when they’re in “safe spaces.”

Isotretinoin, Contraception Considerations

As for treatment of acne in transgender patients, Dr. Yeung cautioned colleagues to not automatically reject isotretinoin as an option for transgender patients who have a history of depression. Dermatologists may be tempted to avoid the drug in these patients because of its link to suicide, he said. (This apparent association has long been debated.) But, Dr. Yeung said, it’s important to consider that many of these patients suffered from anxiety and depression because of the lack of access to proper gender-reassignment treatment.

When using isotretinoin, he emphasized, it’s crucial to consider whether transmasculine patients could become pregnant while on this therapy. Consider whether the patient has the organs needed to become pregnant and ask questions about the potential that they could be impregnated.

“Remember that sexual behavior is different from gender identity,” Dr. Yeung said. A transmasculine person with a uterus and vagina, for example, may still have vaginal intercourse with males and potentially become pregnant. “So, we need to assess what kind of sexual behavior our patients are taking part in.”

Contraceptives such as intrauterine devices, implants, and injectable options may be helpful for transmasculine patients because they can reduce menstrual symptoms like spotting that can be distressing to them, he said. By helping a patient take a contraceptive, “you may actually be helping with their gender dysphoria and helping them get on isotretinoin.”

Dr. Yeung disclosed fees from JAMA and American Academy of Dermatology; grants/research funding from the American Acne & Rosacea Society, Dermatology Foundation, Department of Veterans Affairs, National Eczema Association, and National Institutes of Health; and speaker/faculty education honoraria from Dermatology Digest.

A version of this article appeared on Medscape.com.

SAN DIEGO — Transmasculine patients with acne require unique care that not only is sensitive but also reflects an understanding about factors that can affect their skin such as hormone therapy, a dermatologist told colleagues in a session at the American Academy of Dermatology annual meeting.

In these patients, treatment of acne is crucial, said Howa Yeung, MD, MSc, assistant professor of dermatology, Emory University, Atlanta. “These are patients who are suffering and reporting that they’re having mental health impacts” related to acne.

In transmasculine patients — those who were biologically female at birth but identify as masculine — testosterone therapy greatly boosts the risk for acne, even in adults who are long past adolescence, Dr. Yeung said. Data suggest that acne appears within the first 6 months after testosterone therapy begins, he said, “and the maximal and complete effect occurs within 1-2 years.”

A 2021 study tracked 988 transgender patients receiving testosterone at Fenway Health in Boston and found that 31% had a diagnosis of acne, up from 6.3% prior to taking hormones. And 2 years following the start of therapy, 25.1% had acne, with cases especially common among those aged 18-20.75 years (29.6%). Even among those aged 28.25-66.5 years, 17.1% had acne.

Transmasculine patients may develop acne in areas across the body “in places that you normally won’t see by just looking at the patient,” Dr. Yeung said. Excoriation in addition to comedones, papules, pustules, and nodules can be common, he added.

Dr. Yeung highlighted a 2019 study of transgender men that linked higher levels of acne to higher levels of serum testosterone, higher body mass index, and current smoking. And in a 2014 study, 6% of 50 transmasculine patients had moderate to severe acne after an average of 10 years on testosterone therapy.

A 2020 study of 696 transgender adults surveyed in California and Georgia found that 14% of transmasculine patients had moderate to severe acne — two thirds attributed it to hormone therapy — vs 1% of transfeminine patients, said Dr. Yeung, the lead author of the study. However, transmasculine patients were less likely to have seen a dermatologist.

Dr. Yeung also highlighted a 2021 study he coauthored that linked current moderate to severe acne in transmasculine patients taking testosterone to higher levels of depression and anxiety vs counterparts who had never had those forms of acne.

Another factor affecting acne in transmasculine patients is the use of chest binders to reduce breast size. “Wearing a chest binder is really helpful for a lot of our patients and is associated with improved self-esteem, mood, mental health, and safety in public,” Dr. Yeung said. However, the binders can contribute to skin problems.

Dr. Yeung said he and his colleagues emphasize the importance of breathable material in binders and suggest to patients that they not wear them when they’re in “safe spaces.”

Isotretinoin, Contraception Considerations

As for treatment of acne in transgender patients, Dr. Yeung cautioned colleagues to not automatically reject isotretinoin as an option for transgender patients who have a history of depression. Dermatologists may be tempted to avoid the drug in these patients because of its link to suicide, he said. (This apparent association has long been debated.) But, Dr. Yeung said, it’s important to consider that many of these patients suffered from anxiety and depression because of the lack of access to proper gender-reassignment treatment.

When using isotretinoin, he emphasized, it’s crucial to consider whether transmasculine patients could become pregnant while on this therapy. Consider whether the patient has the organs needed to become pregnant and ask questions about the potential that they could be impregnated.

“Remember that sexual behavior is different from gender identity,” Dr. Yeung said. A transmasculine person with a uterus and vagina, for example, may still have vaginal intercourse with males and potentially become pregnant. “So, we need to assess what kind of sexual behavior our patients are taking part in.”

Contraceptives such as intrauterine devices, implants, and injectable options may be helpful for transmasculine patients because they can reduce menstrual symptoms like spotting that can be distressing to them, he said. By helping a patient take a contraceptive, “you may actually be helping with their gender dysphoria and helping them get on isotretinoin.”

Dr. Yeung disclosed fees from JAMA and American Academy of Dermatology; grants/research funding from the American Acne & Rosacea Society, Dermatology Foundation, Department of Veterans Affairs, National Eczema Association, and National Institutes of Health; and speaker/faculty education honoraria from Dermatology Digest.

A version of this article appeared on Medscape.com.

SAN DIEGO — Just weeks after the American Academy of Dermatology (AAD) published its updated acne management guidelines, a dermatologist who helped write the recommendations provided colleagues with insight into recently approved topical therapies, the importance of multimodal therapy, and a controversial report linking benzoyl peroxide (BP) to the carcinogen benzene.

In regard to topical treatments, the guidelines make a “strong” recommendation for topical retinoids based on “moderate” evidence, Andrea L. Zaenglein, MD, professor of dermatology and pediatrics, Penn State University, Hershey, Pennsylvania, said at the annual meeting of the American Academy of Dermatology. The recommendation was based on a pooled analysis of four randomized controlled trials that found patients with acne who used the medications were more likely to have improvement via the Investigator Global Assessment (IGA) scale at 12 weeks than were those treated with a vehicle (risk ratio [RR], 1.57; 1.21-2.04).

The updated guidelines were published on January 30 in the Journal of the American Academy of Dermatology. The previous guidelines were issued in 2016.

“We have four current retinoids that we use: adapalene, tretinoin, tazarotene, and trifarotene,” Dr. Zaenglein said. “Typically, when we think about retinoids, we think of adapalene as being more tolerable and tazarotene as being more effective. But we also know that they can work to prevent and treat scarring, and they work against comedonal lesions and inflammatory lesions.”

Newer concentrations include tretinoin 0.05% lotion, tazarotene 0.045% lotion, and trifarotene 0.005% cream. She noted that this trifarotene concentration can be helpful for moderate truncal acne and also referred to evidence that whey protein appears to exacerbate that condition. “I always ask teenage kids about that: Are they using those protein powders?”
 

Recommendations for ‘Multimodal Therapy,’ Especially With Antibiotics

Dr. Zaenglein highlighted a “good practice statement” in the new guidelines that says, “when managing acne with topical medications, we recommend multimodal therapy combining multiple mechanisms of action.”

Topical antibiotics are effective treatments on their own and include erythromycin, clindamycin, and minocycline (Minocin), she said. But the guidelines, which refer to evidence supporting them as “moderate,” do not recommend them as monotherapy because of the risk for antibiotic resistance.

The oral retinoid isotretinoin may be appropriate in conjunction with topical medications, she said, “and we also recommend fixed combination products because they’re associated with increased adherence.”

Dermatologists are familiar with several of these products because “we’ve been using them for years and years,” she said. The guidelines note that “compared to vehicle at 12 weeks, a greater proportion of patients treated with combined BP and topical retinoid achieved IGA success in three RCTs (RR, 2.19; 1.77-2.72).”

Dr. Zaenglein noted that the guidelines recommend that patients taking antibiotics also use benzoyl peroxide, which has “moderate” evidence regarding preventing the development of antibiotic resistance. “Lower strengths tend to be less irritating, and over-the-counter formulations are readily available,” she said, adding that colleagues should make sure to warn patients about the risk of bleaching clothes and towels with BP.

Now, there’s a newly approved treatment, the first fixed-dose triple combination therapy for acne, she said. It combines 1.2% clindamycin, 3.1% benzoyl peroxide, and 0.15% adapalene (Cabtreo) and is Food and Drug Administration (FDA)-approved for treating acne in patients ages 12 and up.

The new AAD guidelines note that “potential adverse effect profiles of the fixed-dose combinations generally reflect those of the individual agents in summation. Some fixed-dose combination products may be less expensive than prescribing their individual components separately.” The evidence supporting fixed-dose combinations in conjunction with benzoyl peroxide is considered “moderate.”

Dapsone gel, 7.5% (Aczone) is another option for acne. “It’s a topical so you don’t need to do G6PD [glucose-6-phosphate dehydrogenase] testing,” Dr. Zaenglein said. “It’s well tolerated, and mean total lesions fell by 48.9% vs 43.2% for vehicle,” in a 2018 study, which she said also found that females benefited more than males from this treatment.

Clascoterone 1% cream (Winlevi), approved in 2020, is appropriate for males and females aged 12 and up, Dr. Zaenglein said. She noted that it’s the only topical anti-androgen that can be used in males. However, while it has a “high” level of evidence because of phase 3 clinical trials showing benefits in moderate to severe acne, the AAD guidelines only conditionally recommend this option because the high price of clascoterone “may impact equitable acne treatment access.” The price listed on the website GoodRx (accessed on March 12) lists drugstore prices for a single 60-gram tube as ranging from $590 to $671.

“One of the harder things is trying to figure out where clascoterone fits in our kind of standard combination therapy,” she said. “Much like other hormonal therapies, it works better over the long term.”

Two more topical options per the AAD guidelines are salicylic acid, based on one randomized controlled trial, and azelaic acid (Azelex, Finacea), based on three randomized controlled trials. Both of these recommendations are conditional because of limited evidence: Evidence is considered “low” for salicylic acid and “moderate” for azelaic acid, the guidelines say, and azelaic acid “may be particularly helpful for patients with sensitive skin or darker skin types due to its lightening effect on dyspigmentation.”

As for risk for topical treatments during pregnancy/lactation, the guidelines note that topical therapies other than topical retinoids are “preferred” during pregnancy. Tazarotene is contraindicated during pregnancy, and salicylic acid should be used only in limited areas of exposure. There are no data for dapsone and clascoterone during pregnancy/lactation, and minocycline is “not recommended.”

The guideline authors noted that “available evidence is insufficient to develop a recommendation on the use of topical glycolic acid, sulfur, sodium sulfacetamide, and resorcinol for acne treatment or to make recommendations that compare topical BP, retinoids, antibiotics, and their combinations directly against each other.”
 

Could BP Post a Risk From Benzene?

Dr. Zaenglein highlighted a recently released report by Valisure, an independent laboratory, which reported finding high levels of the cancer-causing chemical benzene in several acne treatments, including brands such as Clearasil. “They didn’t release all of the ones that they evaluated, but there were a lot ... that we commonly recommend for our patients,” she said.

On March 6, CBS News reported that Valisure “ran tests at various temperatures over 18 days and found some products ‘can form over 800 times the conditionally restricted FDA concentration limit of two parts per million (ppm) for benzene’ in 2 weeks at 50° C (122° F),” but that benzene levels “at room temperature were more modest, ranging from about one to 24 parts per million.”

Dr. Zaenglein said she’s not ready to urge patients to discontinue BP, although in light of the findings, “I will tell them to store it at room temperature or lower.”

For now, it’s important to wait for independent verification of the results, she said. “And then it’s up to the manufacturers to reevaluate the stability of their benzoyl peroxide products with heat.”

Dr. Zaenglein disclosed relationships with AbbVie, Arcutis, Biofrontera, Galderma, and Incyte (grants/research funding), Church & Dwight (consulting fees), and UCB (consulting honoraria).

A version of this article appeared on Medscape.com.

SAN DIEGO — Just weeks after the American Academy of Dermatology (AAD) published its updated acne management guidelines, a dermatologist who helped write the recommendations provided colleagues with insight into recently approved topical therapies, the importance of multimodal therapy, and a controversial report linking benzoyl peroxide (BP) to the carcinogen benzene.

In regard to topical treatments, the guidelines make a “strong” recommendation for topical retinoids based on “moderate” evidence, Andrea L. Zaenglein, MD, professor of dermatology and pediatrics, Penn State University, Hershey, Pennsylvania, said at the annual meeting of the American Academy of Dermatology. The recommendation was based on a pooled analysis of four randomized controlled trials that found patients with acne who used the medications were more likely to have improvement via the Investigator Global Assessment (IGA) scale at 12 weeks than were those treated with a vehicle (risk ratio [RR], 1.57; 1.21-2.04).

The updated guidelines were published on January 30 in the Journal of the American Academy of Dermatology. The previous guidelines were issued in 2016.

“We have four current retinoids that we use: adapalene, tretinoin, tazarotene, and trifarotene,” Dr. Zaenglein said. “Typically, when we think about retinoids, we think of adapalene as being more tolerable and tazarotene as being more effective. But we also know that they can work to prevent and treat scarring, and they work against comedonal lesions and inflammatory lesions.”

Newer concentrations include tretinoin 0.05% lotion, tazarotene 0.045% lotion, and trifarotene 0.005% cream. She noted that this trifarotene concentration can be helpful for moderate truncal acne and also referred to evidence that whey protein appears to exacerbate that condition. “I always ask teenage kids about that: Are they using those protein powders?”
 

Recommendations for ‘Multimodal Therapy,’ Especially With Antibiotics

Dr. Zaenglein highlighted a “good practice statement” in the new guidelines that says, “when managing acne with topical medications, we recommend multimodal therapy combining multiple mechanisms of action.”

Topical antibiotics are effective treatments on their own and include erythromycin, clindamycin, and minocycline (Minocin), she said. But the guidelines, which refer to evidence supporting them as “moderate,” do not recommend them as monotherapy because of the risk for antibiotic resistance.

The oral retinoid isotretinoin may be appropriate in conjunction with topical medications, she said, “and we also recommend fixed combination products because they’re associated with increased adherence.”

Dermatologists are familiar with several of these products because “we’ve been using them for years and years,” she said. The guidelines note that “compared to vehicle at 12 weeks, a greater proportion of patients treated with combined BP and topical retinoid achieved IGA success in three RCTs (RR, 2.19; 1.77-2.72).”

Dr. Zaenglein noted that the guidelines recommend that patients taking antibiotics also use benzoyl peroxide, which has “moderate” evidence regarding preventing the development of antibiotic resistance. “Lower strengths tend to be less irritating, and over-the-counter formulations are readily available,” she said, adding that colleagues should make sure to warn patients about the risk of bleaching clothes and towels with BP.

Now, there’s a newly approved treatment, the first fixed-dose triple combination therapy for acne, she said. It combines 1.2% clindamycin, 3.1% benzoyl peroxide, and 0.15% adapalene (Cabtreo) and is Food and Drug Administration (FDA)-approved for treating acne in patients ages 12 and up.

The new AAD guidelines note that “potential adverse effect profiles of the fixed-dose combinations generally reflect those of the individual agents in summation. Some fixed-dose combination products may be less expensive than prescribing their individual components separately.” The evidence supporting fixed-dose combinations in conjunction with benzoyl peroxide is considered “moderate.”

Dapsone gel, 7.5% (Aczone) is another option for acne. “It’s a topical so you don’t need to do G6PD [glucose-6-phosphate dehydrogenase] testing,” Dr. Zaenglein said. “It’s well tolerated, and mean total lesions fell by 48.9% vs 43.2% for vehicle,” in a 2018 study, which she said also found that females benefited more than males from this treatment.

Clascoterone 1% cream (Winlevi), approved in 2020, is appropriate for males and females aged 12 and up, Dr. Zaenglein said. She noted that it’s the only topical anti-androgen that can be used in males. However, while it has a “high” level of evidence because of phase 3 clinical trials showing benefits in moderate to severe acne, the AAD guidelines only conditionally recommend this option because the high price of clascoterone “may impact equitable acne treatment access.” The price listed on the website GoodRx (accessed on March 12) lists drugstore prices for a single 60-gram tube as ranging from $590 to $671.

“One of the harder things is trying to figure out where clascoterone fits in our kind of standard combination therapy,” she said. “Much like other hormonal therapies, it works better over the long term.”

Two more topical options per the AAD guidelines are salicylic acid, based on one randomized controlled trial, and azelaic acid (Azelex, Finacea), based on three randomized controlled trials. Both of these recommendations are conditional because of limited evidence: Evidence is considered “low” for salicylic acid and “moderate” for azelaic acid, the guidelines say, and azelaic acid “may be particularly helpful for patients with sensitive skin or darker skin types due to its lightening effect on dyspigmentation.”

As for risk for topical treatments during pregnancy/lactation, the guidelines note that topical therapies other than topical retinoids are “preferred” during pregnancy. Tazarotene is contraindicated during pregnancy, and salicylic acid should be used only in limited areas of exposure. There are no data for dapsone and clascoterone during pregnancy/lactation, and minocycline is “not recommended.”

The guideline authors noted that “available evidence is insufficient to develop a recommendation on the use of topical glycolic acid, sulfur, sodium sulfacetamide, and resorcinol for acne treatment or to make recommendations that compare topical BP, retinoids, antibiotics, and their combinations directly against each other.”
 

Could BP Post a Risk From Benzene?

Dr. Zaenglein highlighted a recently released report by Valisure, an independent laboratory, which reported finding high levels of the cancer-causing chemical benzene in several acne treatments, including brands such as Clearasil. “They didn’t release all of the ones that they evaluated, but there were a lot ... that we commonly recommend for our patients,” she said.

On March 6, CBS News reported that Valisure “ran tests at various temperatures over 18 days and found some products ‘can form over 800 times the conditionally restricted FDA concentration limit of two parts per million (ppm) for benzene’ in 2 weeks at 50° C (122° F),” but that benzene levels “at room temperature were more modest, ranging from about one to 24 parts per million.”

Dr. Zaenglein said she’s not ready to urge patients to discontinue BP, although in light of the findings, “I will tell them to store it at room temperature or lower.”

For now, it’s important to wait for independent verification of the results, she said. “And then it’s up to the manufacturers to reevaluate the stability of their benzoyl peroxide products with heat.”

Dr. Zaenglein disclosed relationships with AbbVie, Arcutis, Biofrontera, Galderma, and Incyte (grants/research funding), Church & Dwight (consulting fees), and UCB (consulting honoraria).

A version of this article appeared on Medscape.com.

SAN DIEGO — Just weeks after the American Academy of Dermatology (AAD) published its updated acne management guidelines, a dermatologist who helped write the recommendations provided colleagues with insight into recently approved topical therapies, the importance of multimodal therapy, and a controversial report linking benzoyl peroxide (BP) to the carcinogen benzene.

In regard to topical treatments, the guidelines make a “strong” recommendation for topical retinoids based on “moderate” evidence, Andrea L. Zaenglein, MD, professor of dermatology and pediatrics, Penn State University, Hershey, Pennsylvania, said at the annual meeting of the American Academy of Dermatology. The recommendation was based on a pooled analysis of four randomized controlled trials that found patients with acne who used the medications were more likely to have improvement via the Investigator Global Assessment (IGA) scale at 12 weeks than were those treated with a vehicle (risk ratio [RR], 1.57; 1.21-2.04).

The updated guidelines were published on January 30 in the Journal of the American Academy of Dermatology. The previous guidelines were issued in 2016.

“We have four current retinoids that we use: adapalene, tretinoin, tazarotene, and trifarotene,” Dr. Zaenglein said. “Typically, when we think about retinoids, we think of adapalene as being more tolerable and tazarotene as being more effective. But we also know that they can work to prevent and treat scarring, and they work against comedonal lesions and inflammatory lesions.”

Newer concentrations include tretinoin 0.05% lotion, tazarotene 0.045% lotion, and trifarotene 0.005% cream. She noted that this trifarotene concentration can be helpful for moderate truncal acne and also referred to evidence that whey protein appears to exacerbate that condition. “I always ask teenage kids about that: Are they using those protein powders?”
 

Recommendations for ‘Multimodal Therapy,’ Especially With Antibiotics

Dr. Zaenglein highlighted a “good practice statement” in the new guidelines that says, “when managing acne with topical medications, we recommend multimodal therapy combining multiple mechanisms of action.”

Topical antibiotics are effective treatments on their own and include erythromycin, clindamycin, and minocycline (Minocin), she said. But the guidelines, which refer to evidence supporting them as “moderate,” do not recommend them as monotherapy because of the risk for antibiotic resistance.

The oral retinoid isotretinoin may be appropriate in conjunction with topical medications, she said, “and we also recommend fixed combination products because they’re associated with increased adherence.”

Dermatologists are familiar with several of these products because “we’ve been using them for years and years,” she said. The guidelines note that “compared to vehicle at 12 weeks, a greater proportion of patients treated with combined BP and topical retinoid achieved IGA success in three RCTs (RR, 2.19; 1.77-2.72).”

Dr. Zaenglein noted that the guidelines recommend that patients taking antibiotics also use benzoyl peroxide, which has “moderate” evidence regarding preventing the development of antibiotic resistance. “Lower strengths tend to be less irritating, and over-the-counter formulations are readily available,” she said, adding that colleagues should make sure to warn patients about the risk of bleaching clothes and towels with BP.

Now, there’s a newly approved treatment, the first fixed-dose triple combination therapy for acne, she said. It combines 1.2% clindamycin, 3.1% benzoyl peroxide, and 0.15% adapalene (Cabtreo) and is Food and Drug Administration (FDA)-approved for treating acne in patients ages 12 and up.

The new AAD guidelines note that “potential adverse effect profiles of the fixed-dose combinations generally reflect those of the individual agents in summation. Some fixed-dose combination products may be less expensive than prescribing their individual components separately.” The evidence supporting fixed-dose combinations in conjunction with benzoyl peroxide is considered “moderate.”

Dapsone gel, 7.5% (Aczone) is another option for acne. “It’s a topical so you don’t need to do G6PD [glucose-6-phosphate dehydrogenase] testing,” Dr. Zaenglein said. “It’s well tolerated, and mean total lesions fell by 48.9% vs 43.2% for vehicle,” in a 2018 study, which she said also found that females benefited more than males from this treatment.

Clascoterone 1% cream (Winlevi), approved in 2020, is appropriate for males and females aged 12 and up, Dr. Zaenglein said. She noted that it’s the only topical anti-androgen that can be used in males. However, while it has a “high” level of evidence because of phase 3 clinical trials showing benefits in moderate to severe acne, the AAD guidelines only conditionally recommend this option because the high price of clascoterone “may impact equitable acne treatment access.” The price listed on the website GoodRx (accessed on March 12) lists drugstore prices for a single 60-gram tube as ranging from $590 to $671.

“One of the harder things is trying to figure out where clascoterone fits in our kind of standard combination therapy,” she said. “Much like other hormonal therapies, it works better over the long term.”

Two more topical options per the AAD guidelines are salicylic acid, based on one randomized controlled trial, and azelaic acid (Azelex, Finacea), based on three randomized controlled trials. Both of these recommendations are conditional because of limited evidence: Evidence is considered “low” for salicylic acid and “moderate” for azelaic acid, the guidelines say, and azelaic acid “may be particularly helpful for patients with sensitive skin or darker skin types due to its lightening effect on dyspigmentation.”

As for risk for topical treatments during pregnancy/lactation, the guidelines note that topical therapies other than topical retinoids are “preferred” during pregnancy. Tazarotene is contraindicated during pregnancy, and salicylic acid should be used only in limited areas of exposure. There are no data for dapsone and clascoterone during pregnancy/lactation, and minocycline is “not recommended.”

The guideline authors noted that “available evidence is insufficient to develop a recommendation on the use of topical glycolic acid, sulfur, sodium sulfacetamide, and resorcinol for acne treatment or to make recommendations that compare topical BP, retinoids, antibiotics, and their combinations directly against each other.”
 

Could BP Post a Risk From Benzene?

Dr. Zaenglein highlighted a recently released report by Valisure, an independent laboratory, which reported finding high levels of the cancer-causing chemical benzene in several acne treatments, including brands such as Clearasil. “They didn’t release all of the ones that they evaluated, but there were a lot ... that we commonly recommend for our patients,” she said.

On March 6, CBS News reported that Valisure “ran tests at various temperatures over 18 days and found some products ‘can form over 800 times the conditionally restricted FDA concentration limit of two parts per million (ppm) for benzene’ in 2 weeks at 50° C (122° F),” but that benzene levels “at room temperature were more modest, ranging from about one to 24 parts per million.”

Dr. Zaenglein said she’s not ready to urge patients to discontinue BP, although in light of the findings, “I will tell them to store it at room temperature or lower.”

For now, it’s important to wait for independent verification of the results, she said. “And then it’s up to the manufacturers to reevaluate the stability of their benzoyl peroxide products with heat.”

Dr. Zaenglein disclosed relationships with AbbVie, Arcutis, Biofrontera, Galderma, and Incyte (grants/research funding), Church & Dwight (consulting fees), and UCB (consulting honoraria).

A version of this article appeared on Medscape.com.

TOPLINE:

Women with daily exposure to spironolactone for dermatologic conditions showed no higher risk of developing breast or gynecologic cancer than that of unexposed women.

METHODOLOGY:

• Spironolactone, used off-label for several skin conditions in women, carries a warning about an increased tumor risk associated with high doses in rat models, and its antiandrogen properties have prompted hypotheses about a possible increased risk for breast or gynecologic cancers.
• The researchers reviewed data on 420 women with a history of spironolactone use for acne, hair loss, and hirsutism and 3272 women with no spironolactone use at the authors› institution. Their mean age ranged from 42 to 63 years; the majority were White, and 38% were non-White.
• Median spironolactone doses ranged from 25 mg to 225 mg; chart reviews included 5-year follow-up data from the first spironolactone exposure to allow time for tumor development.

TAKEAWAY:

• A total of 37 of the 420 women exposed to spironolactone developed any tumors, as did 546 of the 3272 with no spironolactone exposure.
• After the researchers controlled for age and race, women exposed to spironolactone were no more likely to develop a malignant tumor than a benign tumor, compared with unexposed women (odds ratio [OR], 0.48, P = .2).
• The risk for breast or uterine cancer was not significantly different in the spironolactone and non-spironolactone groups (OR, 0.95, P > .9).

IN PRACTICE:

“Women taking spironolactone for acne, hair loss, and hirsutism and who are at low risk of breast or gynecologic cancers may be counseled to have regular gynecology follow-up, but no more frequently than the general population,” but more studies are needed to evaluate risk over longer periods of time, the researchers wrote.

SOURCE:

The lead author of the study was Rachel C. Hill, BS, a student at Weill Cornell Medical College, New York City, and Shari R. Lipner, MD, PhD, of the department of dermatology at Weill Cornell Medical College, was the corresponding author. The study was published online in The Journal of the American Academy of Dermatology.

LIMITATIONS:

The findings were limited by the retrospective design, as well as the small number of spironolactone patients analyzed, the short follow-up period, the lack of information about spironolactone courses, and the inability to control for family history of malignancy.

DISCLOSURES:

The study was supported by the National Center for Advancing Translational Sciences and a grant from the Clinical and Translational Science Center at Weill Cornell Medical College awarded to Ms. Hill. None of the authors had relevant disclosures; Dr. Lipner disclosed serving as a consultant for Ortho-Dermatologics, Eli Lilly, Moberg Pharmaceuticals, and BelleTorus Corporation.

A version of this article appeared on Medscape.com.

TOPLINE:

Women with daily exposure to spironolactone for dermatologic conditions showed no higher risk of developing breast or gynecologic cancer than that of unexposed women.

METHODOLOGY:

• Spironolactone, used off-label for several skin conditions in women, carries a warning about an increased tumor risk associated with high doses in rat models, and its antiandrogen properties have prompted hypotheses about a possible increased risk for breast or gynecologic cancers.
• The researchers reviewed data on 420 women with a history of spironolactone use for acne, hair loss, and hirsutism and 3272 women with no spironolactone use at the authors› institution. Their mean age ranged from 42 to 63 years; the majority were White, and 38% were non-White.
• Median spironolactone doses ranged from 25 mg to 225 mg; chart reviews included 5-year follow-up data from the first spironolactone exposure to allow time for tumor development.

TAKEAWAY:

• A total of 37 of the 420 women exposed to spironolactone developed any tumors, as did 546 of the 3272 with no spironolactone exposure.
• After the researchers controlled for age and race, women exposed to spironolactone were no more likely to develop a malignant tumor than a benign tumor, compared with unexposed women (odds ratio [OR], 0.48, P = .2).
• The risk for breast or uterine cancer was not significantly different in the spironolactone and non-spironolactone groups (OR, 0.95, P > .9).

IN PRACTICE:

“Women taking spironolactone for acne, hair loss, and hirsutism and who are at low risk of breast or gynecologic cancers may be counseled to have regular gynecology follow-up, but no more frequently than the general population,” but more studies are needed to evaluate risk over longer periods of time, the researchers wrote.

SOURCE:

The lead author of the study was Rachel C. Hill, BS, a student at Weill Cornell Medical College, New York City, and Shari R. Lipner, MD, PhD, of the department of dermatology at Weill Cornell Medical College, was the corresponding author. The study was published online in The Journal of the American Academy of Dermatology.

LIMITATIONS:

The findings were limited by the retrospective design, as well as the small number of spironolactone patients analyzed, the short follow-up period, the lack of information about spironolactone courses, and the inability to control for family history of malignancy.

DISCLOSURES:

The study was supported by the National Center for Advancing Translational Sciences and a grant from the Clinical and Translational Science Center at Weill Cornell Medical College awarded to Ms. Hill. None of the authors had relevant disclosures; Dr. Lipner disclosed serving as a consultant for Ortho-Dermatologics, Eli Lilly, Moberg Pharmaceuticals, and BelleTorus Corporation.

A version of this article appeared on Medscape.com.

TOPLINE:

Women with daily exposure to spironolactone for dermatologic conditions showed no higher risk of developing breast or gynecologic cancer than that of unexposed women.

METHODOLOGY:

• Spironolactone, used off-label for several skin conditions in women, carries a warning about an increased tumor risk associated with high doses in rat models, and its antiandrogen properties have prompted hypotheses about a possible increased risk for breast or gynecologic cancers.
• The researchers reviewed data on 420 women with a history of spironolactone use for acne, hair loss, and hirsutism and 3272 women with no spironolactone use at the authors› institution. Their mean age ranged from 42 to 63 years; the majority were White, and 38% were non-White.
• Median spironolactone doses ranged from 25 mg to 225 mg; chart reviews included 5-year follow-up data from the first spironolactone exposure to allow time for tumor development.

TAKEAWAY:

• A total of 37 of the 420 women exposed to spironolactone developed any tumors, as did 546 of the 3272 with no spironolactone exposure.
• After the researchers controlled for age and race, women exposed to spironolactone were no more likely to develop a malignant tumor than a benign tumor, compared with unexposed women (odds ratio [OR], 0.48, P = .2).
• The risk for breast or uterine cancer was not significantly different in the spironolactone and non-spironolactone groups (OR, 0.95, P > .9).

IN PRACTICE:

“Women taking spironolactone for acne, hair loss, and hirsutism and who are at low risk of breast or gynecologic cancers may be counseled to have regular gynecology follow-up, but no more frequently than the general population,” but more studies are needed to evaluate risk over longer periods of time, the researchers wrote.

SOURCE:

The lead author of the study was Rachel C. Hill, BS, a student at Weill Cornell Medical College, New York City, and Shari R. Lipner, MD, PhD, of the department of dermatology at Weill Cornell Medical College, was the corresponding author. The study was published online in The Journal of the American Academy of Dermatology.

LIMITATIONS:

The findings were limited by the retrospective design, as well as the small number of spironolactone patients analyzed, the short follow-up period, the lack of information about spironolactone courses, and the inability to control for family history of malignancy.

DISCLOSURES:

The study was supported by the National Center for Advancing Translational Sciences and a grant from the Clinical and Translational Science Center at Weill Cornell Medical College awarded to Ms. Hill. None of the authors had relevant disclosures; Dr. Lipner disclosed serving as a consultant for Ortho-Dermatologics, Eli Lilly, Moberg Pharmaceuticals, and BelleTorus Corporation.

A version of this article appeared on Medscape.com.