OBG Management

With the increasing prevalence of pelvic floor disorders among our aging population, women’s health clinicians should be prepared to counsel patients on treatment options and posttreatment expectations. In this Update, we will review recent literature on surgical treatments for pelvic organ prolapse (POP) and stress urinary incontinence (SUI). We also include our review of an award-winning and practice-changing study on office-based pessary care. Lastly, we will finish with a summary of a recent Society of Gynecologic Surgeons collaborative systematic review on sexual function after surgery.

5-year RCT data on hysteropexy vs hysterectomy for POP

Nager CW, Visco AG, Richter HE, et al; National Institute of Child Health and Human Development Pelvic Floor Disorders Network. Effect of sacrospinous hysteropexy with graft vs vaginal hysterectomy with uterosacral ligament suspension on treatment failure in women with uterovaginal prolapse: 5-year results of a randomized clinical trial. Am J Obstet Gynecol. 2021;225:153. e1-153.e31. doi: 10.1016/j.ajog.2021.03.012.

The Pelvic Floor Disorders Network conducted a multisite randomized superiority trial comparing sacrospinous hysteropexy with mesh graft to vaginal hysterectomy with uterosacral ligament suspension for POP.

Study details

Postmenopausal women who desired surgery for symptomatic uterovaginal prolapse were randomly assigned to sacrospinous hysteropexy with polypropylene mesh graft using the Uphold-LITE device (Boston Scientific) versus vaginal hysterectomy with uterosacral ligament suspension. Participants were masked to treatment allocation and completed study visits at 6-month intervals through 60 months. Quantitative prolapse POP-Q exams were performed and patients completed multiple validated questionnaires regarding the presence; severity; and impact of prolapse, urinary, bowel, and pelvic pain symptoms.

Results

A total of 183 postmenopausal women were randomized, and 156 (81 hysteropexy and 75 hysterectomy) patients completed 5-year follow up with no demographic differences between the 2 intervention groups. Operative time was statistically less in the hysteropexy group (111.5 min vs 156.7 min). There were fewer treatment failures (a composite including retreatment for prolapse, prolapse beyond the hymen, and/or bothersome bulge symptoms) in the hysteropexy than in the hysterectomy group (37% vs 54%, respectively) at 5 years of follow up. However, most patients with treatment failure were classified as an intermittent failure, with only 16% of hysteropexy patients and 22% of hysterectomy patients classified as persistent failures. There were no meaningful  differences between patient-reported outcomes. Hysteropexy had an 8% mesh exposure risk, with none requiring surgical management.

Continue to: Preliminary 12-month data for a single-incision sling for surgical management of SUI...

Preliminary 12-month data for a single-incision sling for surgical management of SUI

Erickson T, Roovers JP, Gheiler E, et al. A multicenter prospective study evaluating efficacy and safety of a single-incision sling procedure for stress urinary incontinence. J Minim Invasive Gynecol. 2021;28:93-99. doi: 10.1016/j.jmig.2020.04.014.

In this industry-sponsored study, researchers compared a novel single-incision sling to currently available midurethral slings for SUI with 12-month outcomes and adverse event details. However, results are primarily descriptive with no statistical testing.

Study details

Patients were eligible for inclusion in this prospective, nonrandomized cohort study if SUI was their primary incontinence symptom, with confirmatory office testing. Exclusion criteria included POP greater than stage 2, prior SUI surgery, plans for future pregnancy, elevated postvoid residuals, or concomitant surgical procedures. The single-incision Altis (Coloplast) sling was compared to all commercially available transobturator and retropubic midurethral slings. The primary outcome of this study was reduction in 24-hour pad weights, and secondary outcomes included negative cough-stress test and subjective patient-reported outcomes via validated questionnaires.

Results

A total of 184 women were enrolled in the Altis group and 171 in the comparator other sling group. Symptom severity was similar between groups, but more patients in the comparator group had mixed urinary incontinence, and more patients in the Altis group had intrinsic sphincter deficiency. The Altis group had a higher proportion of “dry patients,” but otherwise the outcomes were similar between the 2 groups, including negative cough-stress test and patientreported outcomes. Two patients in the Altis group and 7 patients in the comparator group underwent device revisions. Again, statistical analysis was not performed.

Office-based pessary care can be safely spaced out to 24 weeks without an increase in erosions

Propst K, Mellen C, O’Sullivan DM, et al. Timing of office-based pessary care: a randomized controlled trial. Obstet Gynecol. 2020;135:100-105. doi: 10.1097 /AOG.0000000000003580.

For women already using a pessary without issues, extending office visits to every 6 months does not increase rates of vaginal epithelial abnormalities, according to results of this randomized controlled trial.

Study details

Women already using a Gelhorn, ring, or incontinence dish pessary for POP, SUI, or both were randomized to continue routine care with office evaluation every 12 weeks versus the extended-care cohort (with office evaluation every 24 weeks). Women were excluded if they removed and replaced the pessary themselves or if there was a presence of vaginal epithelial abnormalities, such as erosion or granulation tissue.

Results

The rate of vaginal epithelium erosion was 7.4% in the routine arm and 1.7% in the extended-care arm, meeting criteria for noninferiority of extended care. The majority of patients with office visits every 24 weeks preferred the less frequent examinations, and there was no difference in degree of bother due to vaginal discharge. There was also no difference in the percentage of patients with unscheduled visits. The only factors associated with vaginal epithelium abnormalities were prior abnormalities and lifetime duration of pessary use.

Continue to: How can we counsel patients regarding changes in sexual activity and function after surgery for POP?... 

How can we counsel patients regarding changes in sexual activity and function after surgery for POP?

Antosh DD, Dieter AA, Balk EM, et al. Sexual function after pelvic organ prolapse surgery: a systematic review comparing different approaches to pelvic floor repair. Am J Obstet Gynecol. 2021;2:S0002-9378(21)00610-4. doi: 10.1016/j.ajog.2021.05.042.

A secondary analysis of a recent systematic review found overall moderate- to high-quality evidence that were no differences in total dyspareunia, de novo dyspareunia, and scores on a validated sexual function questionnaire (PISQ12) when comparing postoperative sexual function outcomes of native tissue repair to sacrocolpopexy, transvaginal mesh, or biologic graft. Rates of postoperative dyspareunia were higher for transvaginal mesh than for sacrocolpopexy.

Study details

The Society of Gynecologic Surgeons Systematic Review Group identified 43 original prospective, comparative studies of reconstructive prolapse surgery that reported sexual function outcomes when comparing 2 different types of POP procedures. Thirty-seven of those studies were randomized controlled trials. Specifically, they looked at data comparing outcomes for native tissue versus sacrocolpopexy, native tissue versus transvaginal mesh, native tissue versus biologic graft, and transvaginal mesh versus sacrocolpopexy.

Results

Overall, the prevalence of postoperative dyspareunia was lower than preoperatively after all surgery types. The only statistical difference in this review demonstrated higher postoperative prevalence of dyspareunia after transvaginal mesh than sacrocolpopexy, based on 2 studies. When comparing native tissue prolapse repair to transvaginal mesh, sacrocolpopexy, or biologic grafts, there were no significant differences in sexual activity, baseline, or postoperative total dyspareunia, de-novo dyspareunia, or sexual function changes as measured by the PISQ12 validated questionnaire. ●

With the increasing prevalence of pelvic floor disorders among our aging population, women’s health clinicians should be prepared to counsel patients on treatment options and posttreatment expectations. In this Update, we will review recent literature on surgical treatments for pelvic organ prolapse (POP) and stress urinary incontinence (SUI). We also include our review of an award-winning and practice-changing study on office-based pessary care. Lastly, we will finish with a summary of a recent Society of Gynecologic Surgeons collaborative systematic review on sexual function after surgery.

5-year RCT data on hysteropexy vs hysterectomy for POP

Nager CW, Visco AG, Richter HE, et al; National Institute of Child Health and Human Development Pelvic Floor Disorders Network. Effect of sacrospinous hysteropexy with graft vs vaginal hysterectomy with uterosacral ligament suspension on treatment failure in women with uterovaginal prolapse: 5-year results of a randomized clinical trial. Am J Obstet Gynecol. 2021;225:153. e1-153.e31. doi: 10.1016/j.ajog.2021.03.012.

The Pelvic Floor Disorders Network conducted a multisite randomized superiority trial comparing sacrospinous hysteropexy with mesh graft to vaginal hysterectomy with uterosacral ligament suspension for POP.

Study details

Postmenopausal women who desired surgery for symptomatic uterovaginal prolapse were randomly assigned to sacrospinous hysteropexy with polypropylene mesh graft using the Uphold-LITE device (Boston Scientific) versus vaginal hysterectomy with uterosacral ligament suspension. Participants were masked to treatment allocation and completed study visits at 6-month intervals through 60 months. Quantitative prolapse POP-Q exams were performed and patients completed multiple validated questionnaires regarding the presence; severity; and impact of prolapse, urinary, bowel, and pelvic pain symptoms.

Results

A total of 183 postmenopausal women were randomized, and 156 (81 hysteropexy and 75 hysterectomy) patients completed 5-year follow up with no demographic differences between the 2 intervention groups. Operative time was statistically less in the hysteropexy group (111.5 min vs 156.7 min). There were fewer treatment failures (a composite including retreatment for prolapse, prolapse beyond the hymen, and/or bothersome bulge symptoms) in the hysteropexy than in the hysterectomy group (37% vs 54%, respectively) at 5 years of follow up. However, most patients with treatment failure were classified as an intermittent failure, with only 16% of hysteropexy patients and 22% of hysterectomy patients classified as persistent failures. There were no meaningful  differences between patient-reported outcomes. Hysteropexy had an 8% mesh exposure risk, with none requiring surgical management.

Continue to: Preliminary 12-month data for a single-incision sling for surgical management of SUI...

Preliminary 12-month data for a single-incision sling for surgical management of SUI

Erickson T, Roovers JP, Gheiler E, et al. A multicenter prospective study evaluating efficacy and safety of a single-incision sling procedure for stress urinary incontinence. J Minim Invasive Gynecol. 2021;28:93-99. doi: 10.1016/j.jmig.2020.04.014.

In this industry-sponsored study, researchers compared a novel single-incision sling to currently available midurethral slings for SUI with 12-month outcomes and adverse event details. However, results are primarily descriptive with no statistical testing.

Study details

Patients were eligible for inclusion in this prospective, nonrandomized cohort study if SUI was their primary incontinence symptom, with confirmatory office testing. Exclusion criteria included POP greater than stage 2, prior SUI surgery, plans for future pregnancy, elevated postvoid residuals, or concomitant surgical procedures. The single-incision Altis (Coloplast) sling was compared to all commercially available transobturator and retropubic midurethral slings. The primary outcome of this study was reduction in 24-hour pad weights, and secondary outcomes included negative cough-stress test and subjective patient-reported outcomes via validated questionnaires.

Results

A total of 184 women were enrolled in the Altis group and 171 in the comparator other sling group. Symptom severity was similar between groups, but more patients in the comparator group had mixed urinary incontinence, and more patients in the Altis group had intrinsic sphincter deficiency. The Altis group had a higher proportion of “dry patients,” but otherwise the outcomes were similar between the 2 groups, including negative cough-stress test and patientreported outcomes. Two patients in the Altis group and 7 patients in the comparator group underwent device revisions. Again, statistical analysis was not performed.

Office-based pessary care can be safely spaced out to 24 weeks without an increase in erosions

Propst K, Mellen C, O’Sullivan DM, et al. Timing of office-based pessary care: a randomized controlled trial. Obstet Gynecol. 2020;135:100-105. doi: 10.1097 /AOG.0000000000003580.

For women already using a pessary without issues, extending office visits to every 6 months does not increase rates of vaginal epithelial abnormalities, according to results of this randomized controlled trial.

Study details

Women already using a Gelhorn, ring, or incontinence dish pessary for POP, SUI, or both were randomized to continue routine care with office evaluation every 12 weeks versus the extended-care cohort (with office evaluation every 24 weeks). Women were excluded if they removed and replaced the pessary themselves or if there was a presence of vaginal epithelial abnormalities, such as erosion or granulation tissue.

Results

The rate of vaginal epithelium erosion was 7.4% in the routine arm and 1.7% in the extended-care arm, meeting criteria for noninferiority of extended care. The majority of patients with office visits every 24 weeks preferred the less frequent examinations, and there was no difference in degree of bother due to vaginal discharge. There was also no difference in the percentage of patients with unscheduled visits. The only factors associated with vaginal epithelium abnormalities were prior abnormalities and lifetime duration of pessary use.

Continue to: How can we counsel patients regarding changes in sexual activity and function after surgery for POP?... 

How can we counsel patients regarding changes in sexual activity and function after surgery for POP?

Antosh DD, Dieter AA, Balk EM, et al. Sexual function after pelvic organ prolapse surgery: a systematic review comparing different approaches to pelvic floor repair. Am J Obstet Gynecol. 2021;2:S0002-9378(21)00610-4. doi: 10.1016/j.ajog.2021.05.042.

A secondary analysis of a recent systematic review found overall moderate- to high-quality evidence that were no differences in total dyspareunia, de novo dyspareunia, and scores on a validated sexual function questionnaire (PISQ12) when comparing postoperative sexual function outcomes of native tissue repair to sacrocolpopexy, transvaginal mesh, or biologic graft. Rates of postoperative dyspareunia were higher for transvaginal mesh than for sacrocolpopexy.

Study details

The Society of Gynecologic Surgeons Systematic Review Group identified 43 original prospective, comparative studies of reconstructive prolapse surgery that reported sexual function outcomes when comparing 2 different types of POP procedures. Thirty-seven of those studies were randomized controlled trials. Specifically, they looked at data comparing outcomes for native tissue versus sacrocolpopexy, native tissue versus transvaginal mesh, native tissue versus biologic graft, and transvaginal mesh versus sacrocolpopexy.

Results

Overall, the prevalence of postoperative dyspareunia was lower than preoperatively after all surgery types. The only statistical difference in this review demonstrated higher postoperative prevalence of dyspareunia after transvaginal mesh than sacrocolpopexy, based on 2 studies. When comparing native tissue prolapse repair to transvaginal mesh, sacrocolpopexy, or biologic grafts, there were no significant differences in sexual activity, baseline, or postoperative total dyspareunia, de-novo dyspareunia, or sexual function changes as measured by the PISQ12 validated questionnaire. ●

With the increasing prevalence of pelvic floor disorders among our aging population, women’s health clinicians should be prepared to counsel patients on treatment options and posttreatment expectations. In this Update, we will review recent literature on surgical treatments for pelvic organ prolapse (POP) and stress urinary incontinence (SUI). We also include our review of an award-winning and practice-changing study on office-based pessary care. Lastly, we will finish with a summary of a recent Society of Gynecologic Surgeons collaborative systematic review on sexual function after surgery.

5-year RCT data on hysteropexy vs hysterectomy for POP

Nager CW, Visco AG, Richter HE, et al; National Institute of Child Health and Human Development Pelvic Floor Disorders Network. Effect of sacrospinous hysteropexy with graft vs vaginal hysterectomy with uterosacral ligament suspension on treatment failure in women with uterovaginal prolapse: 5-year results of a randomized clinical trial. Am J Obstet Gynecol. 2021;225:153. e1-153.e31. doi: 10.1016/j.ajog.2021.03.012.

The Pelvic Floor Disorders Network conducted a multisite randomized superiority trial comparing sacrospinous hysteropexy with mesh graft to vaginal hysterectomy with uterosacral ligament suspension for POP.

Study details

Postmenopausal women who desired surgery for symptomatic uterovaginal prolapse were randomly assigned to sacrospinous hysteropexy with polypropylene mesh graft using the Uphold-LITE device (Boston Scientific) versus vaginal hysterectomy with uterosacral ligament suspension. Participants were masked to treatment allocation and completed study visits at 6-month intervals through 60 months. Quantitative prolapse POP-Q exams were performed and patients completed multiple validated questionnaires regarding the presence; severity; and impact of prolapse, urinary, bowel, and pelvic pain symptoms.

Results

A total of 183 postmenopausal women were randomized, and 156 (81 hysteropexy and 75 hysterectomy) patients completed 5-year follow up with no demographic differences between the 2 intervention groups. Operative time was statistically less in the hysteropexy group (111.5 min vs 156.7 min). There were fewer treatment failures (a composite including retreatment for prolapse, prolapse beyond the hymen, and/or bothersome bulge symptoms) in the hysteropexy than in the hysterectomy group (37% vs 54%, respectively) at 5 years of follow up. However, most patients with treatment failure were classified as an intermittent failure, with only 16% of hysteropexy patients and 22% of hysterectomy patients classified as persistent failures. There were no meaningful  differences between patient-reported outcomes. Hysteropexy had an 8% mesh exposure risk, with none requiring surgical management.

Continue to: Preliminary 12-month data for a single-incision sling for surgical management of SUI...

Preliminary 12-month data for a single-incision sling for surgical management of SUI

Erickson T, Roovers JP, Gheiler E, et al. A multicenter prospective study evaluating efficacy and safety of a single-incision sling procedure for stress urinary incontinence. J Minim Invasive Gynecol. 2021;28:93-99. doi: 10.1016/j.jmig.2020.04.014.

In this industry-sponsored study, researchers compared a novel single-incision sling to currently available midurethral slings for SUI with 12-month outcomes and adverse event details. However, results are primarily descriptive with no statistical testing.

Study details

Patients were eligible for inclusion in this prospective, nonrandomized cohort study if SUI was their primary incontinence symptom, with confirmatory office testing. Exclusion criteria included POP greater than stage 2, prior SUI surgery, plans for future pregnancy, elevated postvoid residuals, or concomitant surgical procedures. The single-incision Altis (Coloplast) sling was compared to all commercially available transobturator and retropubic midurethral slings. The primary outcome of this study was reduction in 24-hour pad weights, and secondary outcomes included negative cough-stress test and subjective patient-reported outcomes via validated questionnaires.

Results

A total of 184 women were enrolled in the Altis group and 171 in the comparator other sling group. Symptom severity was similar between groups, but more patients in the comparator group had mixed urinary incontinence, and more patients in the Altis group had intrinsic sphincter deficiency. The Altis group had a higher proportion of “dry patients,” but otherwise the outcomes were similar between the 2 groups, including negative cough-stress test and patientreported outcomes. Two patients in the Altis group and 7 patients in the comparator group underwent device revisions. Again, statistical analysis was not performed.

Office-based pessary care can be safely spaced out to 24 weeks without an increase in erosions

Propst K, Mellen C, O’Sullivan DM, et al. Timing of office-based pessary care: a randomized controlled trial. Obstet Gynecol. 2020;135:100-105. doi: 10.1097 /AOG.0000000000003580.

For women already using a pessary without issues, extending office visits to every 6 months does not increase rates of vaginal epithelial abnormalities, according to results of this randomized controlled trial.

Study details

Women already using a Gelhorn, ring, or incontinence dish pessary for POP, SUI, or both were randomized to continue routine care with office evaluation every 12 weeks versus the extended-care cohort (with office evaluation every 24 weeks). Women were excluded if they removed and replaced the pessary themselves or if there was a presence of vaginal epithelial abnormalities, such as erosion or granulation tissue.

Results

The rate of vaginal epithelium erosion was 7.4% in the routine arm and 1.7% in the extended-care arm, meeting criteria for noninferiority of extended care. The majority of patients with office visits every 24 weeks preferred the less frequent examinations, and there was no difference in degree of bother due to vaginal discharge. There was also no difference in the percentage of patients with unscheduled visits. The only factors associated with vaginal epithelium abnormalities were prior abnormalities and lifetime duration of pessary use.

Continue to: How can we counsel patients regarding changes in sexual activity and function after surgery for POP?... 

How can we counsel patients regarding changes in sexual activity and function after surgery for POP?

Antosh DD, Dieter AA, Balk EM, et al. Sexual function after pelvic organ prolapse surgery: a systematic review comparing different approaches to pelvic floor repair. Am J Obstet Gynecol. 2021;2:S0002-9378(21)00610-4. doi: 10.1016/j.ajog.2021.05.042.

A secondary analysis of a recent systematic review found overall moderate- to high-quality evidence that were no differences in total dyspareunia, de novo dyspareunia, and scores on a validated sexual function questionnaire (PISQ12) when comparing postoperative sexual function outcomes of native tissue repair to sacrocolpopexy, transvaginal mesh, or biologic graft. Rates of postoperative dyspareunia were higher for transvaginal mesh than for sacrocolpopexy.

Study details

The Society of Gynecologic Surgeons Systematic Review Group identified 43 original prospective, comparative studies of reconstructive prolapse surgery that reported sexual function outcomes when comparing 2 different types of POP procedures. Thirty-seven of those studies were randomized controlled trials. Specifically, they looked at data comparing outcomes for native tissue versus sacrocolpopexy, native tissue versus transvaginal mesh, native tissue versus biologic graft, and transvaginal mesh versus sacrocolpopexy.

Results

Overall, the prevalence of postoperative dyspareunia was lower than preoperatively after all surgery types. The only statistical difference in this review demonstrated higher postoperative prevalence of dyspareunia after transvaginal mesh than sacrocolpopexy, based on 2 studies. When comparing native tissue prolapse repair to transvaginal mesh, sacrocolpopexy, or biologic grafts, there were no significant differences in sexual activity, baseline, or postoperative total dyspareunia, de-novo dyspareunia, or sexual function changes as measured by the PISQ12 validated questionnaire. ●

As more and more gynecologic therapies move to the outpatient setting, keeping up on the latest data regarding emerging options can be challenging. Furthermore, it can be difficult to justify purchasing expensive equipment for the office when a therapy is not covered by medical insurance plans. However, if a therapy is efficacious and patients are willing to pay out of pocket, clinicians may want to have these options available for their patients.

In an effort to work through these complex issues, a panel of experts was convened at the 47th Annual Scientific Meeting of the Society of Gynecologic Surgeons in Palm Springs, California, on June 29, 2021. This article includes the salient points from that panel discussion.

Fractionated CO2 laser therapy

Fractionated CO2 laser therapy is considered second-line therapy for the treatment of genitourinary syndrome of menopause (GSM). In 2018, the US Food and Drug Administration (FDA) issued a safety warning about the use of CO2 laser therapy and warned patients and clinicians that the FDA had not approved the treatment for vaginal rejuvenation or treatment of vaginal symptoms related to menopause, urinary incontinence, or sexual function. Despite this warning, laser treatments are still performed in many practices.

In 2019, the International Continence Society (ICS) and the International Society for the Study of Vulvovaginal Disease (ISSVD) put out a joint practice consensus statement that essentially did not recommend the routine use of laser treatment for GSM, urinary incontinence, or lichen sclerosus.¹ Conversely, the 2020 American Urogynecologic Society (AUGS) published a clinical consensus statement that spoke to the promising results of laser therapy for the treatment of vulvovaginal atrophy, vaginal dryness, and menopausal dyspareunia, with benefits lasting up to 1 year.² This statement also suggested that the short-term safety profile of the CO2 laser device was favorable.

How CO2 lasers work

Fractionated CO2 laser therapy differs from unfractionated treatment (which often is used in the treatment of condyloma) in that it is not ablative. The laser works by using fractionated beams of light to penetrate the affected tissue to create small wounds in the epithelium and underlying lamina propria, which leads to collagen remodeling and regeneration that then results in the restoration of the superficial epithelium, vaginal rugae, and lubrication.³ Most clinicians perform 3 applications of the laser treatment 6 weeks apart, a recommendation that is based on manufacturer-sponsored studies in menopausal women.

Study results of patient outcomes with laser therapy

GSM. Several retrospective^4,5 and prospective studies^6-10 have looked at short- and longer-term outcomes in patients undergoing treatment with the CO2 laser. All of these studies showed improvement in patient symptoms related to GSM.

The VeLVET trial, conducted by Paraiso and colleagues, was a randomized trial that compared CO2 laser treatment with vaginal estrogen in women with GSM.¹¹ While the study was underpowered due to cessation of enrollment once the FDA safety warning was issued, the authors reported that at 6 months, both the fractionated CO2 laser therapy group and the vaginal estrogen group had similar improvements, with 70% to 80% of participants reporting satisfaction with treatment. The authors concluded that laser therapy is likely to be as efficacious as vaginal estrogen and may be a good option for patients who cannot use vaginal estrogen to treat GSM.¹¹

Lichen sclerosus. Some data exist on the efficacy of laser therapy for the treatment of lichen sclerosus. One recently published randomized trial showed that at 6 months, fractionated CO2 laser treatment and prior treatment with high potency topical corticosteroids was associated with higher improvement in subjective symptoms and objective measures compared with clobetasol propionate treatment.¹² Another trial, however, revealed that laser treatment was not an effective monotherapy treatment for lichen sclerosus when compared with placebo.¹³ Fewer studies have examined the effect of laser therapy on urinary incontinence.

More prospective data are emerging, evidenced by trials currently registered in ClinicalTrials.gov. While some studies provide evidence that laser therapy may be efficacious in the treatment of vulvovaginal atrophy, additional data are needed to confirm the favorable outcomes observed with laser therapy for the treatment of lichen sclerosus, and a significant amount of data are needed to evaluate the efficacy of laser treatment for urinary incontinence.

Until such evidence is available, fractionated CO2 vaginal laser therapy will remain a fee-for-service treatment option and will be inaccessible to patients who cannot afford the cost of treatment.

Continue to: Hydrogel urethral bulking...

Urethral bulking agents have been used for 5 decades in the treatment of stress urinary incontinence (SUI) in women. Unlike midurethral slings, in which many medical device companies use the same implant material (microporous, monofilament polypropylene mesh), the material for bulking agents has varied greatly. A 2017 Cochrane review of urethral bulking listed these agents used for this indication: autologous fat, carbon beads, calcium hydroxylapatite, ethylene vinyl alcohol copolymer, glutaraldehyde cross-linked bovine collagen, hyaluronic acid with dextranomer, porcine dermal implant, polytetrafluoroethylene, and silicone particles.¹⁴ These agents can be injected through a transurethral or periurethral technique. The review failed to find superiority of one material or injection technique over another.

New bulking agent available

In January 2020, the FDA approved the premarket application for a new bulking agent. This new agent is a permanently implanted, nonresorbable hydrogel that consists of cross-linked polyacrylamide (2.5%) and water (97.5%). It is intended to be used with a transurethral bulking system that includes a rotatable sheath and two 23-guage needles; a total of 1.5 to 2.0 mL of the hydrogel is injected in 3 locations in the proximal urethra per session. Patients may undergo an additional 2 sessions, if needed, at least 4 weeks after the previous session.

Polyacrylamide hydrogel has been used as a bulking agent in cosmetic and ophthalmic surgery for many years, and it was first approved for medical use in Europe in 2001. The initial European data on its use as a urethral bulking agent was published in 2006.¹⁵ The first North American data came in 2014 from a multicenter, randomized trial that compared polyacrylamide hydrogel with collagen gel.¹⁶ This investigation followed 345 women for 12 months and concluded that the safety and efficacy of polyacrylamide hydrogel was not inferior to collagen, with a little over half of both cohorts demonstrating a 50% or greater decrease in incontinence episodes.

Since these initial studies, 3-year¹⁷ and 7-year safety and efficacy data¹⁸ have been reported, with reassuring findings, but both studies experienced significant attrition of the original group of patients. The most commonly reported adverse events associated with the procedure are pain at the injection site (4%–14%) and urinary tract infection (3%–7%); transient urinary retention rates range in incidence from 1.5% to 15%.¹⁹

Short procedure, long-term results

Given that a urethral bulking procedure can be done in less than 10 minutes in the office under local analgesia, this treatment may lend itself to use in more brittle patient populations. One study of women aged 80 or older showed a greater than 50% decrease in the number of daily pads used for up to 2 years after initial injection.²⁰ Another study found the greatest treatment success in women aged 60 years or older with fewer than 2.5 episodes of SUI per day.²¹

Platelet-rich plasma therapy

Platelet-rich plasma (PRP) therapy has been used in multiple disciplines for more than 2 decades as a treatment to regenerate damaged tissue, particularly in sports medicine for treating tendonitis as well as in plastic surgery, gynecology, urology, and ophthalmology, and good outcomes have been demonstrated with no serious adverse effects. PRP is a natural product in which high levels of platelets are concentrated through centrifugation with bioactive growth factors, including platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), fibroblast growth factor (FGF), and insulin growth factor (IGF).²² The activated platelets are then injected autologously back into the patient’s tissue. This process releases activated growth factors that accelerate tissue healing by stimulating the number of reparative cells to create collagen production, angiogenesis, and neurogenesis while fighting infection and downregulating the autoimmune system.

Continue to: Uses for PRP in gynecology...

In gynecology, dating back to 2007 PRP was shown to facilitate wound healing, when Fanning and colleagues reported PRP applications in gynecologic operative wounds, such as hysterectomies and urogynecologic procedures, to reduce postoperative pain.²³ In the last decade, there has been a dramatic increasing trend in the application of PRP injections as an alternative therapy in gynecology to improve intimate health. PRP has been used to treat lichen sclerosus, atrophic vaginitis, SUI, and female sexual dysfunction; however, there is a dearth of studies that compare PRP with traditional therapies.

Runels and colleagues described the effects of localized injections of autologous PRP for the treatment of sexual dysfunction early in 2014.²⁴ Those authors pioneered PRP use in women with dyspareunia and other symptoms related to sexual dysfunction. Women were offered PRP injections into the periurethral area of the Skene glands and the clitoris. Sexual satisfaction and pain were improved but results did not reach statistical significance. The results of this pilot study of 11 patients suggested that PRP injections could perhaps be an effective method to treat certain types of female sexual dysfunction, including desire, arousal, lubrication, and orgasm.

In another pilot study, Long and colleagues looked at the effectiveness of local injection of PRP for treating women with SUI.²⁵ In that study, younger patients with mild severity of SUI had promising results, with up to 75% cured or improved. Results in the older group, with 50% cured or improved, did not reach statistical significance. Other small, limited studies have been conducted under the hypothesis that PRP as an “O-shot” may be a promising treatment that is a safe, effective, nonsurgical, and nonhormonal option for women with dyspareunia from lack of lubrication and related sexual dysfunction, such as decreased libido or arousal.^26-29 A pilot study by Behnia-Willison and colleagues demonstrated clinical improvement in PRP use as an alternative to topical steroids for lichen sclerosus.³⁰ Several other studies also have shown efficacy for the treatment of lichen sclerosus.^31-34

More evidence of efficacy needed

To date, preliminary studies suggest that PRP holds promise for a host of gynecologic conditions. Since PRP is autologous, there are no significant contraindications, and thus far there have been no known serious adverse effects. However, most health insurers still do not cover this therapy, so for now patients must pay out-of-pocket fees for these treatments.

As we continue to investigate therapies in regenerative medicine, the continued efforts of our discipline are required to conduct well-designed prospective, randomized controlled studies. While initial series suggest that PRP is safe, it is unlikely that this therapy will be embraced widely in the paradigm as an alternative treatment option for many genitourinary symptoms of menopause and vulvar disorders until efficacy is better established.

Radiofrequency therapy

For the past 20 years, radiofrequency (RF) energy has been used through the vagina, urethra, and periurethral tissues for the treatment of genitourinary symptoms, with limited success. More recently, because some patients hesitate to receive mesh implants for treatment of urinary incontinence,³⁵ there has been gravitation to office-based procedures.

In contrast to lasers, which transmit energy through light, RF waves (measured in hertz) transform the kinetic energy of the intracellular atoms, which move and collide, generating thermal energy.^36,37 RF therapy has been shown to increase the proportion of smooth muscle and connective tissue; stimulate proliferation of the epithelium, neovascularization, and collagen formation in the lamina propria; and improve natural lubrication.^36,38 In addition, RF is:

• ablative when the heat is capable of generating ablation and/or necrosis of the epidermis and dermis
• microablative when energy fractionation produces microscopic columns of ablative thermal lesions in the epidermis and upper dermis, resulting in microscopic columns of treated tissue interspersed with areas of untreated skin,³⁹ and
• nonablative when trauma occurs only in the dermis by heating without causing ablation of the epidermis.³⁹

The RF devices discussed below are used with settings for microablation in the treatment of SUI and sexual health/vaginal laxity, and with nonablative settings in the treatment of GSM.

RF for the treatment of urinary incontinence

Studies with RF have shown its benefits in urinary symptoms as secondary outcomes, such as improvement of SUI.^38,40 One theory that favors energy devices as a treatment for SUI is that the treatment strengthens suburethral and pubocervical support, thereby decreasing urethral mobility.⁴¹

In 2016, the Viveve system (Viveve) received FDA 510(k) clearance for “use in general surgical procedures for electrocoagulation and hemostasis.” A single-site, randomized, nonblinded pilot study compared 1 treatment (group 1) versus 2 treatments (group 2) with the Viveve system for SUI in 35 participants.⁴² At 12 months, only for group 2 did mean scores on the Incontinence Impact Questionnaire Short Form (IIQ-7) and the International Consultation on Incontinence Modular Questionnaire-Urinary Incontinence-Short Form (ICIQ-UI-SF) decrease by the minimum clinically important difference of 16 and 2.52 points, respectively, compared with baseline.

The ThermiVa device (ThermiGen, LLC) received FDA clearance for “use in dermatological and general surgical procedures for electrocoagulation and hemostasis” in 2017. A single-site, prospective, double-blind, randomized controlled pilot trial evaluated the efficacy of this device for the treatment of SUI in 20 participants randomly assigned in a 1:1 fashion to active and sham groups.⁴³ At 12 weeks, mean scores of the Urogenital Distress Inventory (UDI-6) and the ICIQ-UI-SF decreased by the minimal clinically important difference only in the treatment group arm. Additionally, 70% of treatment group participants had a negative stress test at 12 weeks compared with 0% of control group participants.⁴³ In another study of 48 patients who were followed longitudinally for 5 months, a substantial improvement in genital appearance was observed.⁴⁴ Assessment based on validated instruments demonstrated significant improvements in sexual function and SUI.⁴⁴

A microablative RF device (Wavetronic 6000 Touch Device, Megapulse HF FRAXX system; Loktal Medical Electronics) consists of a vaginal probe with 64 microneedles at the tip, each capable of penetrating to a depth of 1 mm. During activation, delivery of RF energy, which results in vaporization of tissue at 100 °C, occurs in a preset sequence of 8 needles at a time, preventing the overheating of intervening tissue between adjacent needles.

Slongo and colleagues conducted a 3-arm randomized clinical trial that included 117 climacteric women with SUI.⁴⁵ In group 1, treatment consisted of 3 monthly sessions of RF; group 2 received 12 weekly sessions of pelvic floor muscle training (PFMT); and group 3 received RF treatment plus PFMT simultaneously. Assessments were conducted at baseline and 30 days after the end of therapy using validated questionnaires and scales for urinary, vaginal, and sexual functions, and cytology was used to assess vaginal atrophy. The association between RF and PFMT showed significant improvement in the SUI symptoms assessed by questionnaire. The vaginal symptoms and dryness showed more substantial improvement with the RF treatment, and vaginal laxity showed similar improvement in the 3 treatment groups.⁴⁵

Continue to: RF for the treatment of GSM...

RF for the treatment of GSM

For women who are not candidates for localized hormone therapy, as well as others who simply do not wish to use hormones, nonablative RF laser therapy may be an alternative for the management of GSM.

The VIVEVE I trial was one of the largest randomized, sham-controlled trials performed to determine the efficacy of vaginal rejuvenation using surface-cooled RF; 174 women received either RF treatment (90 J/cm²) or sham treatment (1 J/cm²).⁴⁶ Treated participants had a significant improvement in perception of vaginal laxity/looseness and sexual function up to 6 months posttreatment.⁴⁶ Overall, participants were satisfied with the treatment (77.8%–100%) and reported significant improvements in vaginal laxity and symptoms of atrophy. RF was well tolerated with minimal adverse effects, such as procedure-related erythema and edema of treated tissue, and vaginal discharge. One patient discontinued treatment because of procedural pain.^47,48

The ThermiVa system also was evaluated for efficacy in the treatment of GSM in a single-site, double-blind randomized controlled pilot study, the methods of which were previously described above.⁴³ GSM symptoms were evaluated at baseline and 12 weeks using the Vaginal Health Index (VHI) and visual analog scale (VAS). At the 12-week follow-up, compared with baseline scores, VHI scores were unchanged in the control group and improved in the treatment group. Additionally, VAS scores for dyspareunia decreased in the treatment group compared with baseline while VAS for dyspareunia in the sham group did not change from baseline to 12 weeks.

RF treatment for sexual health

The efficacy of the Viveve RF system for female sexual dysfunction was evaluated in an international, randomized, controlled, single-blinded study (n = 154) that compared 6-month outcomes of RF treatment versus sham treatment.⁴⁶ Although there was a statistically significant improvement in patient-reported sexual dysfunction on validated instruments, it is essential to note that the study was powered for the primary outcome of vaginal laxity. In addition, the study was not adequately powered to evaluate safety; however, the adverse events reported were mild, and the most frequently reported adverse event was vaginal discharge.

Microablative monopolar RF treatment for GSM has been evaluated in 2 single-arm clinical trials that included a total of 70 patients.^39,49 Pre- and posttreatment outcomes were analyzed after delivery of 3 treatment sessions 28 to 40 days apart. Although the only significant improvement in quality of life was in the health domain of the World Health Organization Quality of Life Adapted Questionnaire (P = .04), significant improvements in sexual functioning were seen in terms of the desire (P = .002), lubrication (P = .001), satisfaction (P = .003), and pain (P = .007) domains of the Female Sexual Function Index (FSFI) questionnaire except for excitation and orgasm.³⁹ Overall, 100% of participants reported being satisfied or very satisfied with treatments, and 13 of 14 women felt “cured” or “much better.”³⁹ After treatment, significant increases in vaginal Lactobacillus (P<.001), decreases in vaginal pH (P<.001), improvements in maturation of vaginal cellularity (decreased parabasal cells, P<.001; increased superficial cells, P<.001), and increased VHI score (P<.001) alone occurred.⁴⁹ No adverse events beyond self-limited vaginal burning and redness were reported.^39,49 In another study mentioned above, the combination of RF and PFMT in sexual function does not offer benefits superior to those achieved by the therapies alone.⁴⁵

Evidence on RF treatment does not support marketing efforts

Radiofrequency devices have been marketed for a variety of genitourinary problems in women, with limited high-quality, randomized, comparative evidence of efficacy and durability in the literature. It is unfortunate that RF treatment continues to be promoted by practitioners around the world who cite small, short-term studies that lack biostatistical rigor in their reporting of protocols and results. Statements from both AUGS and the International Urogynecological Association have heeded caution on the use of lasers but they could not even evaluate RF devices due to lack of evidence.^2,41

Informed counseling and shared decision making remain the bottom line

By the year 2025, all members of the Baby Boom generation will be aged 60 or older. While in the past there has been a reluctance to discuss women’s sexual health, urinary incontinence, and GSM, the need for open discussion and a variety of treatment options for these conditions has never been more critical.

Many patients prefer office-based therapies over hospital-based procedures, and others are leery of synthetic implants. These concerns are leading toward great interest in the types of treatments covered in this article. However, it is paramount that clinicians are aware of the evidence-based data behind these emerging options so that we can openly and accurately counsel our patients.

As we have shown, the quality of the data behind these officed-based therapies varies significantly. Until a greater body of research data is available, we must carefully balance our desire to meet patient wishes with solid, informed counseling and shared decision making. ●

As more and more gynecologic therapies move to the outpatient setting, keeping up on the latest data regarding emerging options can be challenging. Furthermore, it can be difficult to justify purchasing expensive equipment for the office when a therapy is not covered by medical insurance plans. However, if a therapy is efficacious and patients are willing to pay out of pocket, clinicians may want to have these options available for their patients.

In an effort to work through these complex issues, a panel of experts was convened at the 47th Annual Scientific Meeting of the Society of Gynecologic Surgeons in Palm Springs, California, on June 29, 2021. This article includes the salient points from that panel discussion.

Fractionated CO2 laser therapy

Fractionated CO2 laser therapy is considered second-line therapy for the treatment of genitourinary syndrome of menopause (GSM). In 2018, the US Food and Drug Administration (FDA) issued a safety warning about the use of CO2 laser therapy and warned patients and clinicians that the FDA had not approved the treatment for vaginal rejuvenation or treatment of vaginal symptoms related to menopause, urinary incontinence, or sexual function. Despite this warning, laser treatments are still performed in many practices.

In 2019, the International Continence Society (ICS) and the International Society for the Study of Vulvovaginal Disease (ISSVD) put out a joint practice consensus statement that essentially did not recommend the routine use of laser treatment for GSM, urinary incontinence, or lichen sclerosus.¹ Conversely, the 2020 American Urogynecologic Society (AUGS) published a clinical consensus statement that spoke to the promising results of laser therapy for the treatment of vulvovaginal atrophy, vaginal dryness, and menopausal dyspareunia, with benefits lasting up to 1 year.² This statement also suggested that the short-term safety profile of the CO2 laser device was favorable.

How CO2 lasers work

Fractionated CO2 laser therapy differs from unfractionated treatment (which often is used in the treatment of condyloma) in that it is not ablative. The laser works by using fractionated beams of light to penetrate the affected tissue to create small wounds in the epithelium and underlying lamina propria, which leads to collagen remodeling and regeneration that then results in the restoration of the superficial epithelium, vaginal rugae, and lubrication.³ Most clinicians perform 3 applications of the laser treatment 6 weeks apart, a recommendation that is based on manufacturer-sponsored studies in menopausal women.

Study results of patient outcomes with laser therapy

GSM. Several retrospective^4,5 and prospective studies^6-10 have looked at short- and longer-term outcomes in patients undergoing treatment with the CO2 laser. All of these studies showed improvement in patient symptoms related to GSM.

The VeLVET trial, conducted by Paraiso and colleagues, was a randomized trial that compared CO2 laser treatment with vaginal estrogen in women with GSM.¹¹ While the study was underpowered due to cessation of enrollment once the FDA safety warning was issued, the authors reported that at 6 months, both the fractionated CO2 laser therapy group and the vaginal estrogen group had similar improvements, with 70% to 80% of participants reporting satisfaction with treatment. The authors concluded that laser therapy is likely to be as efficacious as vaginal estrogen and may be a good option for patients who cannot use vaginal estrogen to treat GSM.¹¹

Lichen sclerosus. Some data exist on the efficacy of laser therapy for the treatment of lichen sclerosus. One recently published randomized trial showed that at 6 months, fractionated CO2 laser treatment and prior treatment with high potency topical corticosteroids was associated with higher improvement in subjective symptoms and objective measures compared with clobetasol propionate treatment.¹² Another trial, however, revealed that laser treatment was not an effective monotherapy treatment for lichen sclerosus when compared with placebo.¹³ Fewer studies have examined the effect of laser therapy on urinary incontinence.

More prospective data are emerging, evidenced by trials currently registered in ClinicalTrials.gov. While some studies provide evidence that laser therapy may be efficacious in the treatment of vulvovaginal atrophy, additional data are needed to confirm the favorable outcomes observed with laser therapy for the treatment of lichen sclerosus, and a significant amount of data are needed to evaluate the efficacy of laser treatment for urinary incontinence.

Until such evidence is available, fractionated CO2 vaginal laser therapy will remain a fee-for-service treatment option and will be inaccessible to patients who cannot afford the cost of treatment.

Continue to: Hydrogel urethral bulking...

Urethral bulking agents have been used for 5 decades in the treatment of stress urinary incontinence (SUI) in women. Unlike midurethral slings, in which many medical device companies use the same implant material (microporous, monofilament polypropylene mesh), the material for bulking agents has varied greatly. A 2017 Cochrane review of urethral bulking listed these agents used for this indication: autologous fat, carbon beads, calcium hydroxylapatite, ethylene vinyl alcohol copolymer, glutaraldehyde cross-linked bovine collagen, hyaluronic acid with dextranomer, porcine dermal implant, polytetrafluoroethylene, and silicone particles.¹⁴ These agents can be injected through a transurethral or periurethral technique. The review failed to find superiority of one material or injection technique over another.

New bulking agent available

In January 2020, the FDA approved the premarket application for a new bulking agent. This new agent is a permanently implanted, nonresorbable hydrogel that consists of cross-linked polyacrylamide (2.5%) and water (97.5%). It is intended to be used with a transurethral bulking system that includes a rotatable sheath and two 23-guage needles; a total of 1.5 to 2.0 mL of the hydrogel is injected in 3 locations in the proximal urethra per session. Patients may undergo an additional 2 sessions, if needed, at least 4 weeks after the previous session.

Polyacrylamide hydrogel has been used as a bulking agent in cosmetic and ophthalmic surgery for many years, and it was first approved for medical use in Europe in 2001. The initial European data on its use as a urethral bulking agent was published in 2006.¹⁵ The first North American data came in 2014 from a multicenter, randomized trial that compared polyacrylamide hydrogel with collagen gel.¹⁶ This investigation followed 345 women for 12 months and concluded that the safety and efficacy of polyacrylamide hydrogel was not inferior to collagen, with a little over half of both cohorts demonstrating a 50% or greater decrease in incontinence episodes.

Since these initial studies, 3-year¹⁷ and 7-year safety and efficacy data¹⁸ have been reported, with reassuring findings, but both studies experienced significant attrition of the original group of patients. The most commonly reported adverse events associated with the procedure are pain at the injection site (4%–14%) and urinary tract infection (3%–7%); transient urinary retention rates range in incidence from 1.5% to 15%.¹⁹

Short procedure, long-term results

Given that a urethral bulking procedure can be done in less than 10 minutes in the office under local analgesia, this treatment may lend itself to use in more brittle patient populations. One study of women aged 80 or older showed a greater than 50% decrease in the number of daily pads used for up to 2 years after initial injection.²⁰ Another study found the greatest treatment success in women aged 60 years or older with fewer than 2.5 episodes of SUI per day.²¹

Platelet-rich plasma therapy

Platelet-rich plasma (PRP) therapy has been used in multiple disciplines for more than 2 decades as a treatment to regenerate damaged tissue, particularly in sports medicine for treating tendonitis as well as in plastic surgery, gynecology, urology, and ophthalmology, and good outcomes have been demonstrated with no serious adverse effects. PRP is a natural product in which high levels of platelets are concentrated through centrifugation with bioactive growth factors, including platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), fibroblast growth factor (FGF), and insulin growth factor (IGF).²² The activated platelets are then injected autologously back into the patient’s tissue. This process releases activated growth factors that accelerate tissue healing by stimulating the number of reparative cells to create collagen production, angiogenesis, and neurogenesis while fighting infection and downregulating the autoimmune system.

Continue to: Uses for PRP in gynecology...

In gynecology, dating back to 2007 PRP was shown to facilitate wound healing, when Fanning and colleagues reported PRP applications in gynecologic operative wounds, such as hysterectomies and urogynecologic procedures, to reduce postoperative pain.²³ In the last decade, there has been a dramatic increasing trend in the application of PRP injections as an alternative therapy in gynecology to improve intimate health. PRP has been used to treat lichen sclerosus, atrophic vaginitis, SUI, and female sexual dysfunction; however, there is a dearth of studies that compare PRP with traditional therapies.

Runels and colleagues described the effects of localized injections of autologous PRP for the treatment of sexual dysfunction early in 2014.²⁴ Those authors pioneered PRP use in women with dyspareunia and other symptoms related to sexual dysfunction. Women were offered PRP injections into the periurethral area of the Skene glands and the clitoris. Sexual satisfaction and pain were improved but results did not reach statistical significance. The results of this pilot study of 11 patients suggested that PRP injections could perhaps be an effective method to treat certain types of female sexual dysfunction, including desire, arousal, lubrication, and orgasm.

In another pilot study, Long and colleagues looked at the effectiveness of local injection of PRP for treating women with SUI.²⁵ In that study, younger patients with mild severity of SUI had promising results, with up to 75% cured or improved. Results in the older group, with 50% cured or improved, did not reach statistical significance. Other small, limited studies have been conducted under the hypothesis that PRP as an “O-shot” may be a promising treatment that is a safe, effective, nonsurgical, and nonhormonal option for women with dyspareunia from lack of lubrication and related sexual dysfunction, such as decreased libido or arousal.^26-29 A pilot study by Behnia-Willison and colleagues demonstrated clinical improvement in PRP use as an alternative to topical steroids for lichen sclerosus.³⁰ Several other studies also have shown efficacy for the treatment of lichen sclerosus.^31-34

More evidence of efficacy needed

To date, preliminary studies suggest that PRP holds promise for a host of gynecologic conditions. Since PRP is autologous, there are no significant contraindications, and thus far there have been no known serious adverse effects. However, most health insurers still do not cover this therapy, so for now patients must pay out-of-pocket fees for these treatments.

As we continue to investigate therapies in regenerative medicine, the continued efforts of our discipline are required to conduct well-designed prospective, randomized controlled studies. While initial series suggest that PRP is safe, it is unlikely that this therapy will be embraced widely in the paradigm as an alternative treatment option for many genitourinary symptoms of menopause and vulvar disorders until efficacy is better established.

Radiofrequency therapy

For the past 20 years, radiofrequency (RF) energy has been used through the vagina, urethra, and periurethral tissues for the treatment of genitourinary symptoms, with limited success. More recently, because some patients hesitate to receive mesh implants for treatment of urinary incontinence,³⁵ there has been gravitation to office-based procedures.

In contrast to lasers, which transmit energy through light, RF waves (measured in hertz) transform the kinetic energy of the intracellular atoms, which move and collide, generating thermal energy.^36,37 RF therapy has been shown to increase the proportion of smooth muscle and connective tissue; stimulate proliferation of the epithelium, neovascularization, and collagen formation in the lamina propria; and improve natural lubrication.^36,38 In addition, RF is:

• ablative when the heat is capable of generating ablation and/or necrosis of the epidermis and dermis
• microablative when energy fractionation produces microscopic columns of ablative thermal lesions in the epidermis and upper dermis, resulting in microscopic columns of treated tissue interspersed with areas of untreated skin,³⁹ and
• nonablative when trauma occurs only in the dermis by heating without causing ablation of the epidermis.³⁹

The RF devices discussed below are used with settings for microablation in the treatment of SUI and sexual health/vaginal laxity, and with nonablative settings in the treatment of GSM.

RF for the treatment of urinary incontinence

Studies with RF have shown its benefits in urinary symptoms as secondary outcomes, such as improvement of SUI.^38,40 One theory that favors energy devices as a treatment for SUI is that the treatment strengthens suburethral and pubocervical support, thereby decreasing urethral mobility.⁴¹

In 2016, the Viveve system (Viveve) received FDA 510(k) clearance for “use in general surgical procedures for electrocoagulation and hemostasis.” A single-site, randomized, nonblinded pilot study compared 1 treatment (group 1) versus 2 treatments (group 2) with the Viveve system for SUI in 35 participants.⁴² At 12 months, only for group 2 did mean scores on the Incontinence Impact Questionnaire Short Form (IIQ-7) and the International Consultation on Incontinence Modular Questionnaire-Urinary Incontinence-Short Form (ICIQ-UI-SF) decrease by the minimum clinically important difference of 16 and 2.52 points, respectively, compared with baseline.

The ThermiVa device (ThermiGen, LLC) received FDA clearance for “use in dermatological and general surgical procedures for electrocoagulation and hemostasis” in 2017. A single-site, prospective, double-blind, randomized controlled pilot trial evaluated the efficacy of this device for the treatment of SUI in 20 participants randomly assigned in a 1:1 fashion to active and sham groups.⁴³ At 12 weeks, mean scores of the Urogenital Distress Inventory (UDI-6) and the ICIQ-UI-SF decreased by the minimal clinically important difference only in the treatment group arm. Additionally, 70% of treatment group participants had a negative stress test at 12 weeks compared with 0% of control group participants.⁴³ In another study of 48 patients who were followed longitudinally for 5 months, a substantial improvement in genital appearance was observed.⁴⁴ Assessment based on validated instruments demonstrated significant improvements in sexual function and SUI.⁴⁴

A microablative RF device (Wavetronic 6000 Touch Device, Megapulse HF FRAXX system; Loktal Medical Electronics) consists of a vaginal probe with 64 microneedles at the tip, each capable of penetrating to a depth of 1 mm. During activation, delivery of RF energy, which results in vaporization of tissue at 100 °C, occurs in a preset sequence of 8 needles at a time, preventing the overheating of intervening tissue between adjacent needles.

Slongo and colleagues conducted a 3-arm randomized clinical trial that included 117 climacteric women with SUI.⁴⁵ In group 1, treatment consisted of 3 monthly sessions of RF; group 2 received 12 weekly sessions of pelvic floor muscle training (PFMT); and group 3 received RF treatment plus PFMT simultaneously. Assessments were conducted at baseline and 30 days after the end of therapy using validated questionnaires and scales for urinary, vaginal, and sexual functions, and cytology was used to assess vaginal atrophy. The association between RF and PFMT showed significant improvement in the SUI symptoms assessed by questionnaire. The vaginal symptoms and dryness showed more substantial improvement with the RF treatment, and vaginal laxity showed similar improvement in the 3 treatment groups.⁴⁵

Continue to: RF for the treatment of GSM...

RF for the treatment of GSM

For women who are not candidates for localized hormone therapy, as well as others who simply do not wish to use hormones, nonablative RF laser therapy may be an alternative for the management of GSM.

The VIVEVE I trial was one of the largest randomized, sham-controlled trials performed to determine the efficacy of vaginal rejuvenation using surface-cooled RF; 174 women received either RF treatment (90 J/cm²) or sham treatment (1 J/cm²).⁴⁶ Treated participants had a significant improvement in perception of vaginal laxity/looseness and sexual function up to 6 months posttreatment.⁴⁶ Overall, participants were satisfied with the treatment (77.8%–100%) and reported significant improvements in vaginal laxity and symptoms of atrophy. RF was well tolerated with minimal adverse effects, such as procedure-related erythema and edema of treated tissue, and vaginal discharge. One patient discontinued treatment because of procedural pain.^47,48

The ThermiVa system also was evaluated for efficacy in the treatment of GSM in a single-site, double-blind randomized controlled pilot study, the methods of which were previously described above.⁴³ GSM symptoms were evaluated at baseline and 12 weeks using the Vaginal Health Index (VHI) and visual analog scale (VAS). At the 12-week follow-up, compared with baseline scores, VHI scores were unchanged in the control group and improved in the treatment group. Additionally, VAS scores for dyspareunia decreased in the treatment group compared with baseline while VAS for dyspareunia in the sham group did not change from baseline to 12 weeks.

RF treatment for sexual health

The efficacy of the Viveve RF system for female sexual dysfunction was evaluated in an international, randomized, controlled, single-blinded study (n = 154) that compared 6-month outcomes of RF treatment versus sham treatment.⁴⁶ Although there was a statistically significant improvement in patient-reported sexual dysfunction on validated instruments, it is essential to note that the study was powered for the primary outcome of vaginal laxity. In addition, the study was not adequately powered to evaluate safety; however, the adverse events reported were mild, and the most frequently reported adverse event was vaginal discharge.

Microablative monopolar RF treatment for GSM has been evaluated in 2 single-arm clinical trials that included a total of 70 patients.^39,49 Pre- and posttreatment outcomes were analyzed after delivery of 3 treatment sessions 28 to 40 days apart. Although the only significant improvement in quality of life was in the health domain of the World Health Organization Quality of Life Adapted Questionnaire (P = .04), significant improvements in sexual functioning were seen in terms of the desire (P = .002), lubrication (P = .001), satisfaction (P = .003), and pain (P = .007) domains of the Female Sexual Function Index (FSFI) questionnaire except for excitation and orgasm.³⁹ Overall, 100% of participants reported being satisfied or very satisfied with treatments, and 13 of 14 women felt “cured” or “much better.”³⁹ After treatment, significant increases in vaginal Lactobacillus (P<.001), decreases in vaginal pH (P<.001), improvements in maturation of vaginal cellularity (decreased parabasal cells, P<.001; increased superficial cells, P<.001), and increased VHI score (P<.001) alone occurred.⁴⁹ No adverse events beyond self-limited vaginal burning and redness were reported.^39,49 In another study mentioned above, the combination of RF and PFMT in sexual function does not offer benefits superior to those achieved by the therapies alone.⁴⁵

Evidence on RF treatment does not support marketing efforts

Radiofrequency devices have been marketed for a variety of genitourinary problems in women, with limited high-quality, randomized, comparative evidence of efficacy and durability in the literature. It is unfortunate that RF treatment continues to be promoted by practitioners around the world who cite small, short-term studies that lack biostatistical rigor in their reporting of protocols and results. Statements from both AUGS and the International Urogynecological Association have heeded caution on the use of lasers but they could not even evaluate RF devices due to lack of evidence.^2,41

Informed counseling and shared decision making remain the bottom line

By the year 2025, all members of the Baby Boom generation will be aged 60 or older. While in the past there has been a reluctance to discuss women’s sexual health, urinary incontinence, and GSM, the need for open discussion and a variety of treatment options for these conditions has never been more critical.

Many patients prefer office-based therapies over hospital-based procedures, and others are leery of synthetic implants. These concerns are leading toward great interest in the types of treatments covered in this article. However, it is paramount that clinicians are aware of the evidence-based data behind these emerging options so that we can openly and accurately counsel our patients.

As we have shown, the quality of the data behind these officed-based therapies varies significantly. Until a greater body of research data is available, we must carefully balance our desire to meet patient wishes with solid, informed counseling and shared decision making. ●

As more and more gynecologic therapies move to the outpatient setting, keeping up on the latest data regarding emerging options can be challenging. Furthermore, it can be difficult to justify purchasing expensive equipment for the office when a therapy is not covered by medical insurance plans. However, if a therapy is efficacious and patients are willing to pay out of pocket, clinicians may want to have these options available for their patients.

In an effort to work through these complex issues, a panel of experts was convened at the 47th Annual Scientific Meeting of the Society of Gynecologic Surgeons in Palm Springs, California, on June 29, 2021. This article includes the salient points from that panel discussion.

Fractionated CO2 laser therapy

Fractionated CO2 laser therapy is considered second-line therapy for the treatment of genitourinary syndrome of menopause (GSM). In 2018, the US Food and Drug Administration (FDA) issued a safety warning about the use of CO2 laser therapy and warned patients and clinicians that the FDA had not approved the treatment for vaginal rejuvenation or treatment of vaginal symptoms related to menopause, urinary incontinence, or sexual function. Despite this warning, laser treatments are still performed in many practices.

In 2019, the International Continence Society (ICS) and the International Society for the Study of Vulvovaginal Disease (ISSVD) put out a joint practice consensus statement that essentially did not recommend the routine use of laser treatment for GSM, urinary incontinence, or lichen sclerosus.¹ Conversely, the 2020 American Urogynecologic Society (AUGS) published a clinical consensus statement that spoke to the promising results of laser therapy for the treatment of vulvovaginal atrophy, vaginal dryness, and menopausal dyspareunia, with benefits lasting up to 1 year.² This statement also suggested that the short-term safety profile of the CO2 laser device was favorable.

How CO2 lasers work

Fractionated CO2 laser therapy differs from unfractionated treatment (which often is used in the treatment of condyloma) in that it is not ablative. The laser works by using fractionated beams of light to penetrate the affected tissue to create small wounds in the epithelium and underlying lamina propria, which leads to collagen remodeling and regeneration that then results in the restoration of the superficial epithelium, vaginal rugae, and lubrication.³ Most clinicians perform 3 applications of the laser treatment 6 weeks apart, a recommendation that is based on manufacturer-sponsored studies in menopausal women.

Study results of patient outcomes with laser therapy

GSM. Several retrospective^4,5 and prospective studies^6-10 have looked at short- and longer-term outcomes in patients undergoing treatment with the CO2 laser. All of these studies showed improvement in patient symptoms related to GSM.

The VeLVET trial, conducted by Paraiso and colleagues, was a randomized trial that compared CO2 laser treatment with vaginal estrogen in women with GSM.¹¹ While the study was underpowered due to cessation of enrollment once the FDA safety warning was issued, the authors reported that at 6 months, both the fractionated CO2 laser therapy group and the vaginal estrogen group had similar improvements, with 70% to 80% of participants reporting satisfaction with treatment. The authors concluded that laser therapy is likely to be as efficacious as vaginal estrogen and may be a good option for patients who cannot use vaginal estrogen to treat GSM.¹¹

Lichen sclerosus. Some data exist on the efficacy of laser therapy for the treatment of lichen sclerosus. One recently published randomized trial showed that at 6 months, fractionated CO2 laser treatment and prior treatment with high potency topical corticosteroids was associated with higher improvement in subjective symptoms and objective measures compared with clobetasol propionate treatment.¹² Another trial, however, revealed that laser treatment was not an effective monotherapy treatment for lichen sclerosus when compared with placebo.¹³ Fewer studies have examined the effect of laser therapy on urinary incontinence.

More prospective data are emerging, evidenced by trials currently registered in ClinicalTrials.gov. While some studies provide evidence that laser therapy may be efficacious in the treatment of vulvovaginal atrophy, additional data are needed to confirm the favorable outcomes observed with laser therapy for the treatment of lichen sclerosus, and a significant amount of data are needed to evaluate the efficacy of laser treatment for urinary incontinence.

Until such evidence is available, fractionated CO2 vaginal laser therapy will remain a fee-for-service treatment option and will be inaccessible to patients who cannot afford the cost of treatment.

Continue to: Hydrogel urethral bulking...

Urethral bulking agents have been used for 5 decades in the treatment of stress urinary incontinence (SUI) in women. Unlike midurethral slings, in which many medical device companies use the same implant material (microporous, monofilament polypropylene mesh), the material for bulking agents has varied greatly. A 2017 Cochrane review of urethral bulking listed these agents used for this indication: autologous fat, carbon beads, calcium hydroxylapatite, ethylene vinyl alcohol copolymer, glutaraldehyde cross-linked bovine collagen, hyaluronic acid with dextranomer, porcine dermal implant, polytetrafluoroethylene, and silicone particles.¹⁴ These agents can be injected through a transurethral or periurethral technique. The review failed to find superiority of one material or injection technique over another.

New bulking agent available

In January 2020, the FDA approved the premarket application for a new bulking agent. This new agent is a permanently implanted, nonresorbable hydrogel that consists of cross-linked polyacrylamide (2.5%) and water (97.5%). It is intended to be used with a transurethral bulking system that includes a rotatable sheath and two 23-guage needles; a total of 1.5 to 2.0 mL of the hydrogel is injected in 3 locations in the proximal urethra per session. Patients may undergo an additional 2 sessions, if needed, at least 4 weeks after the previous session.

Polyacrylamide hydrogel has been used as a bulking agent in cosmetic and ophthalmic surgery for many years, and it was first approved for medical use in Europe in 2001. The initial European data on its use as a urethral bulking agent was published in 2006.¹⁵ The first North American data came in 2014 from a multicenter, randomized trial that compared polyacrylamide hydrogel with collagen gel.¹⁶ This investigation followed 345 women for 12 months and concluded that the safety and efficacy of polyacrylamide hydrogel was not inferior to collagen, with a little over half of both cohorts demonstrating a 50% or greater decrease in incontinence episodes.

Since these initial studies, 3-year¹⁷ and 7-year safety and efficacy data¹⁸ have been reported, with reassuring findings, but both studies experienced significant attrition of the original group of patients. The most commonly reported adverse events associated with the procedure are pain at the injection site (4%–14%) and urinary tract infection (3%–7%); transient urinary retention rates range in incidence from 1.5% to 15%.¹⁹

Short procedure, long-term results

Given that a urethral bulking procedure can be done in less than 10 minutes in the office under local analgesia, this treatment may lend itself to use in more brittle patient populations. One study of women aged 80 or older showed a greater than 50% decrease in the number of daily pads used for up to 2 years after initial injection.²⁰ Another study found the greatest treatment success in women aged 60 years or older with fewer than 2.5 episodes of SUI per day.²¹

Platelet-rich plasma therapy

Platelet-rich plasma (PRP) therapy has been used in multiple disciplines for more than 2 decades as a treatment to regenerate damaged tissue, particularly in sports medicine for treating tendonitis as well as in plastic surgery, gynecology, urology, and ophthalmology, and good outcomes have been demonstrated with no serious adverse effects. PRP is a natural product in which high levels of platelets are concentrated through centrifugation with bioactive growth factors, including platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), fibroblast growth factor (FGF), and insulin growth factor (IGF).²² The activated platelets are then injected autologously back into the patient’s tissue. This process releases activated growth factors that accelerate tissue healing by stimulating the number of reparative cells to create collagen production, angiogenesis, and neurogenesis while fighting infection and downregulating the autoimmune system.

Continue to: Uses for PRP in gynecology...

In gynecology, dating back to 2007 PRP was shown to facilitate wound healing, when Fanning and colleagues reported PRP applications in gynecologic operative wounds, such as hysterectomies and urogynecologic procedures, to reduce postoperative pain.²³ In the last decade, there has been a dramatic increasing trend in the application of PRP injections as an alternative therapy in gynecology to improve intimate health. PRP has been used to treat lichen sclerosus, atrophic vaginitis, SUI, and female sexual dysfunction; however, there is a dearth of studies that compare PRP with traditional therapies.

Runels and colleagues described the effects of localized injections of autologous PRP for the treatment of sexual dysfunction early in 2014.²⁴ Those authors pioneered PRP use in women with dyspareunia and other symptoms related to sexual dysfunction. Women were offered PRP injections into the periurethral area of the Skene glands and the clitoris. Sexual satisfaction and pain were improved but results did not reach statistical significance. The results of this pilot study of 11 patients suggested that PRP injections could perhaps be an effective method to treat certain types of female sexual dysfunction, including desire, arousal, lubrication, and orgasm.

In another pilot study, Long and colleagues looked at the effectiveness of local injection of PRP for treating women with SUI.²⁵ In that study, younger patients with mild severity of SUI had promising results, with up to 75% cured or improved. Results in the older group, with 50% cured or improved, did not reach statistical significance. Other small, limited studies have been conducted under the hypothesis that PRP as an “O-shot” may be a promising treatment that is a safe, effective, nonsurgical, and nonhormonal option for women with dyspareunia from lack of lubrication and related sexual dysfunction, such as decreased libido or arousal.^26-29 A pilot study by Behnia-Willison and colleagues demonstrated clinical improvement in PRP use as an alternative to topical steroids for lichen sclerosus.³⁰ Several other studies also have shown efficacy for the treatment of lichen sclerosus.^31-34

More evidence of efficacy needed

To date, preliminary studies suggest that PRP holds promise for a host of gynecologic conditions. Since PRP is autologous, there are no significant contraindications, and thus far there have been no known serious adverse effects. However, most health insurers still do not cover this therapy, so for now patients must pay out-of-pocket fees for these treatments.

As we continue to investigate therapies in regenerative medicine, the continued efforts of our discipline are required to conduct well-designed prospective, randomized controlled studies. While initial series suggest that PRP is safe, it is unlikely that this therapy will be embraced widely in the paradigm as an alternative treatment option for many genitourinary symptoms of menopause and vulvar disorders until efficacy is better established.

Radiofrequency therapy

For the past 20 years, radiofrequency (RF) energy has been used through the vagina, urethra, and periurethral tissues for the treatment of genitourinary symptoms, with limited success. More recently, because some patients hesitate to receive mesh implants for treatment of urinary incontinence,³⁵ there has been gravitation to office-based procedures.

In contrast to lasers, which transmit energy through light, RF waves (measured in hertz) transform the kinetic energy of the intracellular atoms, which move and collide, generating thermal energy.^36,37 RF therapy has been shown to increase the proportion of smooth muscle and connective tissue; stimulate proliferation of the epithelium, neovascularization, and collagen formation in the lamina propria; and improve natural lubrication.^36,38 In addition, RF is:

• ablative when the heat is capable of generating ablation and/or necrosis of the epidermis and dermis
• microablative when energy fractionation produces microscopic columns of ablative thermal lesions in the epidermis and upper dermis, resulting in microscopic columns of treated tissue interspersed with areas of untreated skin,³⁹ and
• nonablative when trauma occurs only in the dermis by heating without causing ablation of the epidermis.³⁹

The RF devices discussed below are used with settings for microablation in the treatment of SUI and sexual health/vaginal laxity, and with nonablative settings in the treatment of GSM.

RF for the treatment of urinary incontinence

Studies with RF have shown its benefits in urinary symptoms as secondary outcomes, such as improvement of SUI.^38,40 One theory that favors energy devices as a treatment for SUI is that the treatment strengthens suburethral and pubocervical support, thereby decreasing urethral mobility.⁴¹

In 2016, the Viveve system (Viveve) received FDA 510(k) clearance for “use in general surgical procedures for electrocoagulation and hemostasis.” A single-site, randomized, nonblinded pilot study compared 1 treatment (group 1) versus 2 treatments (group 2) with the Viveve system for SUI in 35 participants.⁴² At 12 months, only for group 2 did mean scores on the Incontinence Impact Questionnaire Short Form (IIQ-7) and the International Consultation on Incontinence Modular Questionnaire-Urinary Incontinence-Short Form (ICIQ-UI-SF) decrease by the minimum clinically important difference of 16 and 2.52 points, respectively, compared with baseline.

The ThermiVa device (ThermiGen, LLC) received FDA clearance for “use in dermatological and general surgical procedures for electrocoagulation and hemostasis” in 2017. A single-site, prospective, double-blind, randomized controlled pilot trial evaluated the efficacy of this device for the treatment of SUI in 20 participants randomly assigned in a 1:1 fashion to active and sham groups.⁴³ At 12 weeks, mean scores of the Urogenital Distress Inventory (UDI-6) and the ICIQ-UI-SF decreased by the minimal clinically important difference only in the treatment group arm. Additionally, 70% of treatment group participants had a negative stress test at 12 weeks compared with 0% of control group participants.⁴³ In another study of 48 patients who were followed longitudinally for 5 months, a substantial improvement in genital appearance was observed.⁴⁴ Assessment based on validated instruments demonstrated significant improvements in sexual function and SUI.⁴⁴

A microablative RF device (Wavetronic 6000 Touch Device, Megapulse HF FRAXX system; Loktal Medical Electronics) consists of a vaginal probe with 64 microneedles at the tip, each capable of penetrating to a depth of 1 mm. During activation, delivery of RF energy, which results in vaporization of tissue at 100 °C, occurs in a preset sequence of 8 needles at a time, preventing the overheating of intervening tissue between adjacent needles.

Slongo and colleagues conducted a 3-arm randomized clinical trial that included 117 climacteric women with SUI.⁴⁵ In group 1, treatment consisted of 3 monthly sessions of RF; group 2 received 12 weekly sessions of pelvic floor muscle training (PFMT); and group 3 received RF treatment plus PFMT simultaneously. Assessments were conducted at baseline and 30 days after the end of therapy using validated questionnaires and scales for urinary, vaginal, and sexual functions, and cytology was used to assess vaginal atrophy. The association between RF and PFMT showed significant improvement in the SUI symptoms assessed by questionnaire. The vaginal symptoms and dryness showed more substantial improvement with the RF treatment, and vaginal laxity showed similar improvement in the 3 treatment groups.⁴⁵

Continue to: RF for the treatment of GSM...

RF for the treatment of GSM

For women who are not candidates for localized hormone therapy, as well as others who simply do not wish to use hormones, nonablative RF laser therapy may be an alternative for the management of GSM.

The VIVEVE I trial was one of the largest randomized, sham-controlled trials performed to determine the efficacy of vaginal rejuvenation using surface-cooled RF; 174 women received either RF treatment (90 J/cm²) or sham treatment (1 J/cm²).⁴⁶ Treated participants had a significant improvement in perception of vaginal laxity/looseness and sexual function up to 6 months posttreatment.⁴⁶ Overall, participants were satisfied with the treatment (77.8%–100%) and reported significant improvements in vaginal laxity and symptoms of atrophy. RF was well tolerated with minimal adverse effects, such as procedure-related erythema and edema of treated tissue, and vaginal discharge. One patient discontinued treatment because of procedural pain.^47,48

The ThermiVa system also was evaluated for efficacy in the treatment of GSM in a single-site, double-blind randomized controlled pilot study, the methods of which were previously described above.⁴³ GSM symptoms were evaluated at baseline and 12 weeks using the Vaginal Health Index (VHI) and visual analog scale (VAS). At the 12-week follow-up, compared with baseline scores, VHI scores were unchanged in the control group and improved in the treatment group. Additionally, VAS scores for dyspareunia decreased in the treatment group compared with baseline while VAS for dyspareunia in the sham group did not change from baseline to 12 weeks.

RF treatment for sexual health

The efficacy of the Viveve RF system for female sexual dysfunction was evaluated in an international, randomized, controlled, single-blinded study (n = 154) that compared 6-month outcomes of RF treatment versus sham treatment.⁴⁶ Although there was a statistically significant improvement in patient-reported sexual dysfunction on validated instruments, it is essential to note that the study was powered for the primary outcome of vaginal laxity. In addition, the study was not adequately powered to evaluate safety; however, the adverse events reported were mild, and the most frequently reported adverse event was vaginal discharge.

Microablative monopolar RF treatment for GSM has been evaluated in 2 single-arm clinical trials that included a total of 70 patients.^39,49 Pre- and posttreatment outcomes were analyzed after delivery of 3 treatment sessions 28 to 40 days apart. Although the only significant improvement in quality of life was in the health domain of the World Health Organization Quality of Life Adapted Questionnaire (P = .04), significant improvements in sexual functioning were seen in terms of the desire (P = .002), lubrication (P = .001), satisfaction (P = .003), and pain (P = .007) domains of the Female Sexual Function Index (FSFI) questionnaire except for excitation and orgasm.³⁹ Overall, 100% of participants reported being satisfied or very satisfied with treatments, and 13 of 14 women felt “cured” or “much better.”³⁹ After treatment, significant increases in vaginal Lactobacillus (P<.001), decreases in vaginal pH (P<.001), improvements in maturation of vaginal cellularity (decreased parabasal cells, P<.001; increased superficial cells, P<.001), and increased VHI score (P<.001) alone occurred.⁴⁹ No adverse events beyond self-limited vaginal burning and redness were reported.^39,49 In another study mentioned above, the combination of RF and PFMT in sexual function does not offer benefits superior to those achieved by the therapies alone.⁴⁵

Evidence on RF treatment does not support marketing efforts

Radiofrequency devices have been marketed for a variety of genitourinary problems in women, with limited high-quality, randomized, comparative evidence of efficacy and durability in the literature. It is unfortunate that RF treatment continues to be promoted by practitioners around the world who cite small, short-term studies that lack biostatistical rigor in their reporting of protocols and results. Statements from both AUGS and the International Urogynecological Association have heeded caution on the use of lasers but they could not even evaluate RF devices due to lack of evidence.^2,41

Informed counseling and shared decision making remain the bottom line

By the year 2025, all members of the Baby Boom generation will be aged 60 or older. While in the past there has been a reluctance to discuss women’s sexual health, urinary incontinence, and GSM, the need for open discussion and a variety of treatment options for these conditions has never been more critical.

Many patients prefer office-based therapies over hospital-based procedures, and others are leery of synthetic implants. These concerns are leading toward great interest in the types of treatments covered in this article. However, it is paramount that clinicians are aware of the evidence-based data behind these emerging options so that we can openly and accurately counsel our patients.

As we have shown, the quality of the data behind these officed-based therapies varies significantly. Until a greater body of research data is available, we must carefully balance our desire to meet patient wishes with solid, informed counseling and shared decision making. ●

A workplace environment conducive to success includes equal access to resources and opportunities, work-life integration, freedom from gender discrimination and sexual harassment, and supportive leadership. With focused leadership that is accountable for actionable interventions through measurable outcomes, it is possible to create an equitable, safe, and dignified workplace for all ObGyns.

Recently, obstetrics and gynecology has become the only surgical specialty in which a majority of practitioners are women. Since the 1990s, women in ObGyn have composed the majority of trainees, and 2012 marked the first year that more than half of the American College of Obstetricians and Gynecologists (ACOG) Fellows in practice were women.¹

Despite the large proportion of women within the specialty, ongoing gender-based inequities continue. Many of these inequities are rooted in our pervasive societal views of behavioral norms based on biologic or perceived sex, otherwise known as “gender,” roles.² The cultural gender role for men embodies characteristics that are bold, competitive, decisive, analytical; qualities for women include modesty, nurturing, and accommodating in interactions with others. Such male-typed traits and behaviors are termed “agentic” because they involve human agency, whereas female-typed traits and behaviors are termed “communal.”³

Gender biases remain widespread, even among health care providers.⁴ When gender roles are applied to medical specialties, there is an assumption that women tend toward “communal” specialties, such as pediatrics or family practice, whereas men are better suited for technical or procedural specialties.⁵ ObGyn is an outlier in this schema because its procedural and surgical aspects would characterize the specialty as “agentic,” yet the majority of ObGyn trainees and physicians are women.

Biases related to gender impact many aspects of practice for the ObGyn, including:

• surgical education and training
• the gender wage gap
• interpersonal interactions and sexual harassment
• advancement and promotion.

Surgical education and training

The message that desirable characteristics for leadership and autonomy are aligned with masculinity is enforced early in medical culture, and it supports the ubiquity of deep-seated stereotypes about gender roles in medicine. For example, the language used for letters of recommendation for women applying to residency and fellowship highlight communal language (nurturing, warm), whereas those for men more typically use agentic terms (decisive, strong, future leader).⁶ During ObGyn surgical training, women residents receive more negative evaluations than men from nurses throughout training, and they report spending more effort to nurture these relationships, including changing communication in order to engage assistance from nurses.⁷

Similarly, women trainees receive harsher and more contradictory feedback from attending physicians.⁸ For example, a woman resident may be criticized for failing to develop independence and execute complete plans for patient care; later, she might be labeled as “rogue” and told that she should engage with and seek input from supervising faculty when independently executing a treatment plan.

Even when attempting to apply feedback in the operating room, women trainees are afforded less surgical autonomy than men trainees.⁹ These factors contribute to lower surgical confidence in women trainees despite their having the same technical skills as men, as measured by the Fundamentals of Laparoscopic Surgery skills exam.¹⁰

Continue to: The gender wage gap...

The gender wage gap

The mean salary for women ObGyns remains lower than that for men at every academic rank, with the differences ranging from $54,700 at the assistant professor rank to $183,200 for the department chair position.¹¹ Notably, the pay discrepancy persists after adjustments are made for common salary-influencing metrics, such as experience, practice construct, and academic productivity.¹² The gender salary gap is further identified for women subspecialists, as women reproductive endocrinology and infertility specialists and gynecologic oncologists earn $67,000 and $120,000 less, respectively, than men colleagues.^13,14

While the gender wage gap often is attributed to women’s desire to work part time, similar rates of graduating women and men medical students in 2018 ranked schedule flexibility as important, suggesting that work-life balance is related to an individual’s generation rather than gender.¹¹

Parenting status specifically adversely affects women physicians, with an ascribed “motherhood penalty” and “fatherhood bonus” phenomenon: women physicians who became parents lost an additional 6% salary, whereas men physicians saw a salary increase of 4% with parenthood.¹⁵

Most worrisome for the specialty is evidence of declining wages for ObGyns relative to other fields. “Occupational segregation”¹⁶ refers to the pronounced negative effect on earnings as more women enter a given field, which has been described in other professions.¹⁷ Overall, ObGyn salaries are the lowest among surgical specialties¹⁸ and show evidence of decline corresponding to the increasing numbers of women in the field.¹⁶

Interpersonal interactions and sexual harassment

In the workplace, women in ObGyn face more interpersonal relationship friction than men. Practicing women ObGyns report differing treatment by nurses as compared to men,¹⁹ noting that additional time and effort are required to nurture professional relationships. Additionally, nurses and trainees²⁰ evaluate practicing women ObGyns more harshly than they evaluate men. Further, women gynecologic surgeons experience gender bias from patients, as patients endorse a preference to have a woman gynecologist but prefer a man gynecologic surgeon.²¹

In addition to gender bias, the experience of gender harassment, including sexual harassment, is common, as two-thirds of women gynecologists report workplace harassment, 90% of which is attributed to gender.²² This rate is 3 times higher than that for men, with a senior colleague in a position of power within the same organization reported to be the harasser to women in 91% of occurrences.

Advancement and promotion

Within academia, women faculty face specific career-limiting barriers related to gender. Rates of academic promotion and leadership opportunities remain lower for women than for men faculty. Although there has been more women representation in ObGyn over the past 20 years, the number of women serving as department chairs, cancer center directors, editors-in-chief, or on a board of directors remains lower than what would be expected by representation ratios.²³ (Representation ratios were calculated as the proportion of ObGyn department-based leadership roles held by women in 2019 divided by the proportion of women ObGyn residents in 1990; representation ratios <1.0 indicate underrepresentation of women). This lag in attainment of leadership roles is compounded by the difficulties women faculty experience in finding mentorship and sponsorship,²⁴ which are known benefits to career advancement.

Having fewer women hold leadership roles also negatively influences those in training. For example, a survey of emergency medicine and ObGyn residents identified an implicit gender bias that men and women residents favored men for leadership roles.²⁵ This difference, however, was not significant when division chiefs and department chairs were women, which suggests that visibility of women leaders positively influences the stereotype perception of men and women trainees.⁴

Continue to: Blueprint for change...

While the issues surrounding gender bias are widespread, solutions exist to create gender equity within ObGyn. Efforts to change individual behavior and organizational culture should start with an understanding of the current environment.

Multiple studies have promoted the concept of “culture change,”^26,27 which parallels a standard change process. A critical aspect of change is that individuals and organizations maintain the status quo until something prompts a desire to achieve a different way of being. As data regarding the breadth and impact of gender bias emerge and awareness is raised, there is recognition that the status quo is not achieving the goals of the department or institution. This may occur through the result of loss of physician talent, reduced access for vulnerable patient populations, or lower financial productivity.

Once change is considered, it must deliberately be pursued through a specific process. The first actionable step is to assess the existing state and then identify prior barriers to and current opportunities for success. A validated instrument that has been applied for this purpose is the Diversity Engagement Survey, a 22-item questionnaire that assesses 8 domains of organizational inclusion on a 5-point Likert scale (see TABLE).²⁸ This tool not only provides a measure of institutional culture but also obtains characteristics of the respondents so that it additionally assesses how engaged specific groups are within the organization. Once baseline data are obtained, an action plan can be formulated and enacted. This cycle of assessment, system influences, plan, and act should be continued until the desired changes are achieved.

It is critically important to identify objective, measurable outcomes to assure that the interventions are moving the culture toward enhanced gender equity. As the ideal state is achieved, development of practices and enforceable policies help to ensure the longevity of cultural changes. Furthermore, periodic re-evaluation of the existing organizational culture will confirm the maintenance of gender equity objectives.

Solutions toward gender equity

Gender inequity may arise from societal gender roles, but it is incumbent on health care organizations to create an environment free from gender bias and gender harassment. An imperative first step is to identify the occurrence of gender discrimination.

The HITS (Hurt, Insulted, Threatened with harm, or Screamed at) screening tool has been used effectively with surgical residents to identify the prevalence of and most common types of abuse.²⁹ This instrument could be adapted and administered to ObGyns in practice or in training. These data should inform the need for system-level antisexist training as well as enforcement of zero-tolerance policies.

Organizations have the ability to create a salary-only compensation model for physicians within the same specialty regardless of academic rank or academic productivity, which has been demonstrated to eliminate gender pay disparity.³⁰ Additional measures to achieve gender equity involve antisexist hiring processes³¹ and transparency in metrics for job performance, salary, and promotion.³²

While health care organizations are obliged to construct a gender-equitable culture, efforts can be made on the individual level. Implicit bias is ascribed to the unconscious attitudes and stereotypes people conclude about groups. The Implicit Association Test (IAT) is a validated instrument that provides the respondent with information about one’s own implicit biases. By uncovering gender bias “blind spots,” an individual can work to consciously overcome these stereotypes. Extending from the mental reframing required for overturning implicit biases, individuals can learn to identify and intervene in real-world situations. This concept of “being an upstander” denotes stepping in and standing up when an inappropriate situation arises³³ (see “Case example: Being an upstander”). The targeted individual may not have the ability or safety to navigate through a confrontation, but an upstander might be able to assist the target with empowerment, verbalization of needs, and support.

Lastly, mentorship and sponsorship are critical factors for professional development and career advancement. Bidirectional mentorship identifies benefit for the mentee and the mentor whereby the junior faculty obtain career development and support and the senior faculty may learn new teaching or communication skills.³⁴

A final word

As recognized advocates for women’s health, we must intentionally move toward a workplace that is equitable, safe, and dignified for all ObGyns. Ensuring gender equity within obstetrics and gynecology is everyone’s responsibility. ●

A workplace environment conducive to success includes equal access to resources and opportunities, work-life integration, freedom from gender discrimination and sexual harassment, and supportive leadership. With focused leadership that is accountable for actionable interventions through measurable outcomes, it is possible to create an equitable, safe, and dignified workplace for all ObGyns.

Recently, obstetrics and gynecology has become the only surgical specialty in which a majority of practitioners are women. Since the 1990s, women in ObGyn have composed the majority of trainees, and 2012 marked the first year that more than half of the American College of Obstetricians and Gynecologists (ACOG) Fellows in practice were women.¹

Despite the large proportion of women within the specialty, ongoing gender-based inequities continue. Many of these inequities are rooted in our pervasive societal views of behavioral norms based on biologic or perceived sex, otherwise known as “gender,” roles.² The cultural gender role for men embodies characteristics that are bold, competitive, decisive, analytical; qualities for women include modesty, nurturing, and accommodating in interactions with others. Such male-typed traits and behaviors are termed “agentic” because they involve human agency, whereas female-typed traits and behaviors are termed “communal.”³

Gender biases remain widespread, even among health care providers.⁴ When gender roles are applied to medical specialties, there is an assumption that women tend toward “communal” specialties, such as pediatrics or family practice, whereas men are better suited for technical or procedural specialties.⁵ ObGyn is an outlier in this schema because its procedural and surgical aspects would characterize the specialty as “agentic,” yet the majority of ObGyn trainees and physicians are women.

Biases related to gender impact many aspects of practice for the ObGyn, including:

• surgical education and training
• the gender wage gap
• interpersonal interactions and sexual harassment
• advancement and promotion.

Surgical education and training

The message that desirable characteristics for leadership and autonomy are aligned with masculinity is enforced early in medical culture, and it supports the ubiquity of deep-seated stereotypes about gender roles in medicine. For example, the language used for letters of recommendation for women applying to residency and fellowship highlight communal language (nurturing, warm), whereas those for men more typically use agentic terms (decisive, strong, future leader).⁶ During ObGyn surgical training, women residents receive more negative evaluations than men from nurses throughout training, and they report spending more effort to nurture these relationships, including changing communication in order to engage assistance from nurses.⁷

Similarly, women trainees receive harsher and more contradictory feedback from attending physicians.⁸ For example, a woman resident may be criticized for failing to develop independence and execute complete plans for patient care; later, she might be labeled as “rogue” and told that she should engage with and seek input from supervising faculty when independently executing a treatment plan.

Even when attempting to apply feedback in the operating room, women trainees are afforded less surgical autonomy than men trainees.⁹ These factors contribute to lower surgical confidence in women trainees despite their having the same technical skills as men, as measured by the Fundamentals of Laparoscopic Surgery skills exam.¹⁰

Continue to: The gender wage gap...

The gender wage gap

The mean salary for women ObGyns remains lower than that for men at every academic rank, with the differences ranging from $54,700 at the assistant professor rank to $183,200 for the department chair position.¹¹ Notably, the pay discrepancy persists after adjustments are made for common salary-influencing metrics, such as experience, practice construct, and academic productivity.¹² The gender salary gap is further identified for women subspecialists, as women reproductive endocrinology and infertility specialists and gynecologic oncologists earn $67,000 and $120,000 less, respectively, than men colleagues.^13,14

While the gender wage gap often is attributed to women’s desire to work part time, similar rates of graduating women and men medical students in 2018 ranked schedule flexibility as important, suggesting that work-life balance is related to an individual’s generation rather than gender.¹¹

Parenting status specifically adversely affects women physicians, with an ascribed “motherhood penalty” and “fatherhood bonus” phenomenon: women physicians who became parents lost an additional 6% salary, whereas men physicians saw a salary increase of 4% with parenthood.¹⁵

Most worrisome for the specialty is evidence of declining wages for ObGyns relative to other fields. “Occupational segregation”¹⁶ refers to the pronounced negative effect on earnings as more women enter a given field, which has been described in other professions.¹⁷ Overall, ObGyn salaries are the lowest among surgical specialties¹⁸ and show evidence of decline corresponding to the increasing numbers of women in the field.¹⁶

Interpersonal interactions and sexual harassment

In the workplace, women in ObGyn face more interpersonal relationship friction than men. Practicing women ObGyns report differing treatment by nurses as compared to men,¹⁹ noting that additional time and effort are required to nurture professional relationships. Additionally, nurses and trainees²⁰ evaluate practicing women ObGyns more harshly than they evaluate men. Further, women gynecologic surgeons experience gender bias from patients, as patients endorse a preference to have a woman gynecologist but prefer a man gynecologic surgeon.²¹

In addition to gender bias, the experience of gender harassment, including sexual harassment, is common, as two-thirds of women gynecologists report workplace harassment, 90% of which is attributed to gender.²² This rate is 3 times higher than that for men, with a senior colleague in a position of power within the same organization reported to be the harasser to women in 91% of occurrences.

Advancement and promotion

Within academia, women faculty face specific career-limiting barriers related to gender. Rates of academic promotion and leadership opportunities remain lower for women than for men faculty. Although there has been more women representation in ObGyn over the past 20 years, the number of women serving as department chairs, cancer center directors, editors-in-chief, or on a board of directors remains lower than what would be expected by representation ratios.²³ (Representation ratios were calculated as the proportion of ObGyn department-based leadership roles held by women in 2019 divided by the proportion of women ObGyn residents in 1990; representation ratios <1.0 indicate underrepresentation of women). This lag in attainment of leadership roles is compounded by the difficulties women faculty experience in finding mentorship and sponsorship,²⁴ which are known benefits to career advancement.

Having fewer women hold leadership roles also negatively influences those in training. For example, a survey of emergency medicine and ObGyn residents identified an implicit gender bias that men and women residents favored men for leadership roles.²⁵ This difference, however, was not significant when division chiefs and department chairs were women, which suggests that visibility of women leaders positively influences the stereotype perception of men and women trainees.⁴

Continue to: Blueprint for change...

While the issues surrounding gender bias are widespread, solutions exist to create gender equity within ObGyn. Efforts to change individual behavior and organizational culture should start with an understanding of the current environment.

Multiple studies have promoted the concept of “culture change,”^26,27 which parallels a standard change process. A critical aspect of change is that individuals and organizations maintain the status quo until something prompts a desire to achieve a different way of being. As data regarding the breadth and impact of gender bias emerge and awareness is raised, there is recognition that the status quo is not achieving the goals of the department or institution. This may occur through the result of loss of physician talent, reduced access for vulnerable patient populations, or lower financial productivity.

Once change is considered, it must deliberately be pursued through a specific process. The first actionable step is to assess the existing state and then identify prior barriers to and current opportunities for success. A validated instrument that has been applied for this purpose is the Diversity Engagement Survey, a 22-item questionnaire that assesses 8 domains of organizational inclusion on a 5-point Likert scale (see TABLE).²⁸ This tool not only provides a measure of institutional culture but also obtains characteristics of the respondents so that it additionally assesses how engaged specific groups are within the organization. Once baseline data are obtained, an action plan can be formulated and enacted. This cycle of assessment, system influences, plan, and act should be continued until the desired changes are achieved.

It is critically important to identify objective, measurable outcomes to assure that the interventions are moving the culture toward enhanced gender equity. As the ideal state is achieved, development of practices and enforceable policies help to ensure the longevity of cultural changes. Furthermore, periodic re-evaluation of the existing organizational culture will confirm the maintenance of gender equity objectives.

Solutions toward gender equity

Gender inequity may arise from societal gender roles, but it is incumbent on health care organizations to create an environment free from gender bias and gender harassment. An imperative first step is to identify the occurrence of gender discrimination.

The HITS (Hurt, Insulted, Threatened with harm, or Screamed at) screening tool has been used effectively with surgical residents to identify the prevalence of and most common types of abuse.²⁹ This instrument could be adapted and administered to ObGyns in practice or in training. These data should inform the need for system-level antisexist training as well as enforcement of zero-tolerance policies.

Organizations have the ability to create a salary-only compensation model for physicians within the same specialty regardless of academic rank or academic productivity, which has been demonstrated to eliminate gender pay disparity.³⁰ Additional measures to achieve gender equity involve antisexist hiring processes³¹ and transparency in metrics for job performance, salary, and promotion.³²

While health care organizations are obliged to construct a gender-equitable culture, efforts can be made on the individual level. Implicit bias is ascribed to the unconscious attitudes and stereotypes people conclude about groups. The Implicit Association Test (IAT) is a validated instrument that provides the respondent with information about one’s own implicit biases. By uncovering gender bias “blind spots,” an individual can work to consciously overcome these stereotypes. Extending from the mental reframing required for overturning implicit biases, individuals can learn to identify and intervene in real-world situations. This concept of “being an upstander” denotes stepping in and standing up when an inappropriate situation arises³³ (see “Case example: Being an upstander”). The targeted individual may not have the ability or safety to navigate through a confrontation, but an upstander might be able to assist the target with empowerment, verbalization of needs, and support.

Lastly, mentorship and sponsorship are critical factors for professional development and career advancement. Bidirectional mentorship identifies benefit for the mentee and the mentor whereby the junior faculty obtain career development and support and the senior faculty may learn new teaching or communication skills.³⁴

A final word

As recognized advocates for women’s health, we must intentionally move toward a workplace that is equitable, safe, and dignified for all ObGyns. Ensuring gender equity within obstetrics and gynecology is everyone’s responsibility. ●

A workplace environment conducive to success includes equal access to resources and opportunities, work-life integration, freedom from gender discrimination and sexual harassment, and supportive leadership. With focused leadership that is accountable for actionable interventions through measurable outcomes, it is possible to create an equitable, safe, and dignified workplace for all ObGyns.

Recently, obstetrics and gynecology has become the only surgical specialty in which a majority of practitioners are women. Since the 1990s, women in ObGyn have composed the majority of trainees, and 2012 marked the first year that more than half of the American College of Obstetricians and Gynecologists (ACOG) Fellows in practice were women.¹

Despite the large proportion of women within the specialty, ongoing gender-based inequities continue. Many of these inequities are rooted in our pervasive societal views of behavioral norms based on biologic or perceived sex, otherwise known as “gender,” roles.² The cultural gender role for men embodies characteristics that are bold, competitive, decisive, analytical; qualities for women include modesty, nurturing, and accommodating in interactions with others. Such male-typed traits and behaviors are termed “agentic” because they involve human agency, whereas female-typed traits and behaviors are termed “communal.”³

Gender biases remain widespread, even among health care providers.⁴ When gender roles are applied to medical specialties, there is an assumption that women tend toward “communal” specialties, such as pediatrics or family practice, whereas men are better suited for technical or procedural specialties.⁵ ObGyn is an outlier in this schema because its procedural and surgical aspects would characterize the specialty as “agentic,” yet the majority of ObGyn trainees and physicians are women.

Biases related to gender impact many aspects of practice for the ObGyn, including:

• surgical education and training
• the gender wage gap
• interpersonal interactions and sexual harassment
• advancement and promotion.

Surgical education and training

The message that desirable characteristics for leadership and autonomy are aligned with masculinity is enforced early in medical culture, and it supports the ubiquity of deep-seated stereotypes about gender roles in medicine. For example, the language used for letters of recommendation for women applying to residency and fellowship highlight communal language (nurturing, warm), whereas those for men more typically use agentic terms (decisive, strong, future leader).⁶ During ObGyn surgical training, women residents receive more negative evaluations than men from nurses throughout training, and they report spending more effort to nurture these relationships, including changing communication in order to engage assistance from nurses.⁷

Similarly, women trainees receive harsher and more contradictory feedback from attending physicians.⁸ For example, a woman resident may be criticized for failing to develop independence and execute complete plans for patient care; later, she might be labeled as “rogue” and told that she should engage with and seek input from supervising faculty when independently executing a treatment plan.

Even when attempting to apply feedback in the operating room, women trainees are afforded less surgical autonomy than men trainees.⁹ These factors contribute to lower surgical confidence in women trainees despite their having the same technical skills as men, as measured by the Fundamentals of Laparoscopic Surgery skills exam.¹⁰

Continue to: The gender wage gap...

The gender wage gap

The mean salary for women ObGyns remains lower than that for men at every academic rank, with the differences ranging from $54,700 at the assistant professor rank to $183,200 for the department chair position.¹¹ Notably, the pay discrepancy persists after adjustments are made for common salary-influencing metrics, such as experience, practice construct, and academic productivity.¹² The gender salary gap is further identified for women subspecialists, as women reproductive endocrinology and infertility specialists and gynecologic oncologists earn $67,000 and $120,000 less, respectively, than men colleagues.^13,14

While the gender wage gap often is attributed to women’s desire to work part time, similar rates of graduating women and men medical students in 2018 ranked schedule flexibility as important, suggesting that work-life balance is related to an individual’s generation rather than gender.¹¹

Parenting status specifically adversely affects women physicians, with an ascribed “motherhood penalty” and “fatherhood bonus” phenomenon: women physicians who became parents lost an additional 6% salary, whereas men physicians saw a salary increase of 4% with parenthood.¹⁵

Most worrisome for the specialty is evidence of declining wages for ObGyns relative to other fields. “Occupational segregation”¹⁶ refers to the pronounced negative effect on earnings as more women enter a given field, which has been described in other professions.¹⁷ Overall, ObGyn salaries are the lowest among surgical specialties¹⁸ and show evidence of decline corresponding to the increasing numbers of women in the field.¹⁶

Interpersonal interactions and sexual harassment

In the workplace, women in ObGyn face more interpersonal relationship friction than men. Practicing women ObGyns report differing treatment by nurses as compared to men,¹⁹ noting that additional time and effort are required to nurture professional relationships. Additionally, nurses and trainees²⁰ evaluate practicing women ObGyns more harshly than they evaluate men. Further, women gynecologic surgeons experience gender bias from patients, as patients endorse a preference to have a woman gynecologist but prefer a man gynecologic surgeon.²¹

In addition to gender bias, the experience of gender harassment, including sexual harassment, is common, as two-thirds of women gynecologists report workplace harassment, 90% of which is attributed to gender.²² This rate is 3 times higher than that for men, with a senior colleague in a position of power within the same organization reported to be the harasser to women in 91% of occurrences.

Advancement and promotion

Within academia, women faculty face specific career-limiting barriers related to gender. Rates of academic promotion and leadership opportunities remain lower for women than for men faculty. Although there has been more women representation in ObGyn over the past 20 years, the number of women serving as department chairs, cancer center directors, editors-in-chief, or on a board of directors remains lower than what would be expected by representation ratios.²³ (Representation ratios were calculated as the proportion of ObGyn department-based leadership roles held by women in 2019 divided by the proportion of women ObGyn residents in 1990; representation ratios <1.0 indicate underrepresentation of women). This lag in attainment of leadership roles is compounded by the difficulties women faculty experience in finding mentorship and sponsorship,²⁴ which are known benefits to career advancement.

Having fewer women hold leadership roles also negatively influences those in training. For example, a survey of emergency medicine and ObGyn residents identified an implicit gender bias that men and women residents favored men for leadership roles.²⁵ This difference, however, was not significant when division chiefs and department chairs were women, which suggests that visibility of women leaders positively influences the stereotype perception of men and women trainees.⁴

Continue to: Blueprint for change...

While the issues surrounding gender bias are widespread, solutions exist to create gender equity within ObGyn. Efforts to change individual behavior and organizational culture should start with an understanding of the current environment.

Multiple studies have promoted the concept of “culture change,”^26,27 which parallels a standard change process. A critical aspect of change is that individuals and organizations maintain the status quo until something prompts a desire to achieve a different way of being. As data regarding the breadth and impact of gender bias emerge and awareness is raised, there is recognition that the status quo is not achieving the goals of the department or institution. This may occur through the result of loss of physician talent, reduced access for vulnerable patient populations, or lower financial productivity.

Once change is considered, it must deliberately be pursued through a specific process. The first actionable step is to assess the existing state and then identify prior barriers to and current opportunities for success. A validated instrument that has been applied for this purpose is the Diversity Engagement Survey, a 22-item questionnaire that assesses 8 domains of organizational inclusion on a 5-point Likert scale (see TABLE).²⁸ This tool not only provides a measure of institutional culture but also obtains characteristics of the respondents so that it additionally assesses how engaged specific groups are within the organization. Once baseline data are obtained, an action plan can be formulated and enacted. This cycle of assessment, system influences, plan, and act should be continued until the desired changes are achieved.

It is critically important to identify objective, measurable outcomes to assure that the interventions are moving the culture toward enhanced gender equity. As the ideal state is achieved, development of practices and enforceable policies help to ensure the longevity of cultural changes. Furthermore, periodic re-evaluation of the existing organizational culture will confirm the maintenance of gender equity objectives.

Solutions toward gender equity

Gender inequity may arise from societal gender roles, but it is incumbent on health care organizations to create an environment free from gender bias and gender harassment. An imperative first step is to identify the occurrence of gender discrimination.

The HITS (Hurt, Insulted, Threatened with harm, or Screamed at) screening tool has been used effectively with surgical residents to identify the prevalence of and most common types of abuse.²⁹ This instrument could be adapted and administered to ObGyns in practice or in training. These data should inform the need for system-level antisexist training as well as enforcement of zero-tolerance policies.

Organizations have the ability to create a salary-only compensation model for physicians within the same specialty regardless of academic rank or academic productivity, which has been demonstrated to eliminate gender pay disparity.³⁰ Additional measures to achieve gender equity involve antisexist hiring processes³¹ and transparency in metrics for job performance, salary, and promotion.³²

While health care organizations are obliged to construct a gender-equitable culture, efforts can be made on the individual level. Implicit bias is ascribed to the unconscious attitudes and stereotypes people conclude about groups. The Implicit Association Test (IAT) is a validated instrument that provides the respondent with information about one’s own implicit biases. By uncovering gender bias “blind spots,” an individual can work to consciously overcome these stereotypes. Extending from the mental reframing required for overturning implicit biases, individuals can learn to identify and intervene in real-world situations. This concept of “being an upstander” denotes stepping in and standing up when an inappropriate situation arises³³ (see “Case example: Being an upstander”). The targeted individual may not have the ability or safety to navigate through a confrontation, but an upstander might be able to assist the target with empowerment, verbalization of needs, and support.

Lastly, mentorship and sponsorship are critical factors for professional development and career advancement. Bidirectional mentorship identifies benefit for the mentee and the mentor whereby the junior faculty obtain career development and support and the senior faculty may learn new teaching or communication skills.³⁴

A final word

As recognized advocates for women’s health, we must intentionally move toward a workplace that is equitable, safe, and dignified for all ObGyns. Ensuring gender equity within obstetrics and gynecology is everyone’s responsibility. ●

Turok DK, Gero A, Simmons RG, et al. Levonorgestrel vs copper intrauterine devices for emergency contraception. N Engl J Med. 2021;384:335-344.

EXPERT COMMENTARY

Emergency contraception refers to therapies used to prevent pregnancy after inadequately protected intercourse.¹ Evidence-based forms of EC available in the United States include oral LNG, oral ulipristal acetate, and the copper IUD. The copper IUD provides not only EC but also highly effective contraception after placement.² The LNG-IUD has a favorable side effect profile compared with the copper IUD and is theorized to act as EC through direct interference with sperm and oviduct transport.³ Recently, Turok and colleagues conducted a noninferiority trial designed to investigate the EC effectiveness of the LNG-IUD compared with the copper IUD.³

Details of the study

Turok and colleagues recruited participants aged 18 to 35 who requested EC from 6 family planning clinics in Utah from 2016 to 2019. Participants who reported unprotected intercourse within the past 120 hours and who desired an IUD to prevent pregnancy for at least 1 year were randomly assigned to receive either the LNG-IUD or the copper IUD. Individuals were excluded from the trial if they had contraindications to IUD placement, were breastfeeding, had abnormal uterine bleeding, had irregular menses, were currently using highly effective contraception, or had recent EC use. Researchers determined pregnancy status at 1 month through a pregnancy test or clinical records review.

Results. Of 711 participants randomly assigned, 317 who received the LNG-IUD and 321 who received the copper IUD provided 1-month outcome data. Pregnancy 1 month after IUD placement occurred in 1 participant (0.3%) in the LNG-IUD group and in no participants in the copper IUD group (0%). The between-group difference of 0.3 percentage points was within the margin of noninferiority and was not significant.

Study strengths and limitations

This large, multicenter randomized controlled trial contributes novel information about the effectiveness and noninferiority of the LNG-IUD as EC. Unlike prior studies of oral EC, which commonly limited participants to 1 episode of unprotected intercourse, this trial enrolled women at potentially higher risk of pregnancy with multiple episodes of intercourse and found fewer pregnancies than expected. Randomization ensured equivalence between groups, with the exception of the reason for needing EC.

Study limitations include a higher than expected rate of loss to follow-up, requiring clinical records and survey data to confirm pregnancy status. After randomization, clinicians were unable to place IUDs in more than 5% of participants in both groups; noninferiority was demonstrated nonetheless. This study did not include participants receiving oral EC, so direct comparison of effectiveness is not possible. Pregnancy rates among IUD users in this study were favorable to rates reported in previous studies of oral EC.⁴

When choosing an IUD for contraception, more women select the LNG-IUD for its favorable side effect profile and reduction in menstrual bleeding. In this randomized IUD study, only 7% of eligible participants enrolled, potentially introducing selection bias. The majority who declined enrollment did not want an IUD. Previous studies that allowed participants to choose their IUD had higher enrollment rates. ● 

Turok DK, Gero A, Simmons RG, et al. Levonorgestrel vs copper intrauterine devices for emergency contraception. N Engl J Med. 2021;384:335-344.

EXPERT COMMENTARY

Emergency contraception refers to therapies used to prevent pregnancy after inadequately protected intercourse.¹ Evidence-based forms of EC available in the United States include oral LNG, oral ulipristal acetate, and the copper IUD. The copper IUD provides not only EC but also highly effective contraception after placement.² The LNG-IUD has a favorable side effect profile compared with the copper IUD and is theorized to act as EC through direct interference with sperm and oviduct transport.³ Recently, Turok and colleagues conducted a noninferiority trial designed to investigate the EC effectiveness of the LNG-IUD compared with the copper IUD.³

Details of the study

Turok and colleagues recruited participants aged 18 to 35 who requested EC from 6 family planning clinics in Utah from 2016 to 2019. Participants who reported unprotected intercourse within the past 120 hours and who desired an IUD to prevent pregnancy for at least 1 year were randomly assigned to receive either the LNG-IUD or the copper IUD. Individuals were excluded from the trial if they had contraindications to IUD placement, were breastfeeding, had abnormal uterine bleeding, had irregular menses, were currently using highly effective contraception, or had recent EC use. Researchers determined pregnancy status at 1 month through a pregnancy test or clinical records review.

Results. Of 711 participants randomly assigned, 317 who received the LNG-IUD and 321 who received the copper IUD provided 1-month outcome data. Pregnancy 1 month after IUD placement occurred in 1 participant (0.3%) in the LNG-IUD group and in no participants in the copper IUD group (0%). The between-group difference of 0.3 percentage points was within the margin of noninferiority and was not significant.

Study strengths and limitations

This large, multicenter randomized controlled trial contributes novel information about the effectiveness and noninferiority of the LNG-IUD as EC. Unlike prior studies of oral EC, which commonly limited participants to 1 episode of unprotected intercourse, this trial enrolled women at potentially higher risk of pregnancy with multiple episodes of intercourse and found fewer pregnancies than expected. Randomization ensured equivalence between groups, with the exception of the reason for needing EC.

Study limitations include a higher than expected rate of loss to follow-up, requiring clinical records and survey data to confirm pregnancy status. After randomization, clinicians were unable to place IUDs in more than 5% of participants in both groups; noninferiority was demonstrated nonetheless. This study did not include participants receiving oral EC, so direct comparison of effectiveness is not possible. Pregnancy rates among IUD users in this study were favorable to rates reported in previous studies of oral EC.⁴

When choosing an IUD for contraception, more women select the LNG-IUD for its favorable side effect profile and reduction in menstrual bleeding. In this randomized IUD study, only 7% of eligible participants enrolled, potentially introducing selection bias. The majority who declined enrollment did not want an IUD. Previous studies that allowed participants to choose their IUD had higher enrollment rates. ● 

Turok DK, Gero A, Simmons RG, et al. Levonorgestrel vs copper intrauterine devices for emergency contraception. N Engl J Med. 2021;384:335-344.

EXPERT COMMENTARY

Emergency contraception refers to therapies used to prevent pregnancy after inadequately protected intercourse.¹ Evidence-based forms of EC available in the United States include oral LNG, oral ulipristal acetate, and the copper IUD. The copper IUD provides not only EC but also highly effective contraception after placement.² The LNG-IUD has a favorable side effect profile compared with the copper IUD and is theorized to act as EC through direct interference with sperm and oviduct transport.³ Recently, Turok and colleagues conducted a noninferiority trial designed to investigate the EC effectiveness of the LNG-IUD compared with the copper IUD.³

Details of the study

Turok and colleagues recruited participants aged 18 to 35 who requested EC from 6 family planning clinics in Utah from 2016 to 2019. Participants who reported unprotected intercourse within the past 120 hours and who desired an IUD to prevent pregnancy for at least 1 year were randomly assigned to receive either the LNG-IUD or the copper IUD. Individuals were excluded from the trial if they had contraindications to IUD placement, were breastfeeding, had abnormal uterine bleeding, had irregular menses, were currently using highly effective contraception, or had recent EC use. Researchers determined pregnancy status at 1 month through a pregnancy test or clinical records review.

Results. Of 711 participants randomly assigned, 317 who received the LNG-IUD and 321 who received the copper IUD provided 1-month outcome data. Pregnancy 1 month after IUD placement occurred in 1 participant (0.3%) in the LNG-IUD group and in no participants in the copper IUD group (0%). The between-group difference of 0.3 percentage points was within the margin of noninferiority and was not significant.

Study strengths and limitations

This large, multicenter randomized controlled trial contributes novel information about the effectiveness and noninferiority of the LNG-IUD as EC. Unlike prior studies of oral EC, which commonly limited participants to 1 episode of unprotected intercourse, this trial enrolled women at potentially higher risk of pregnancy with multiple episodes of intercourse and found fewer pregnancies than expected. Randomization ensured equivalence between groups, with the exception of the reason for needing EC.

Study limitations include a higher than expected rate of loss to follow-up, requiring clinical records and survey data to confirm pregnancy status. After randomization, clinicians were unable to place IUDs in more than 5% of participants in both groups; noninferiority was demonstrated nonetheless. This study did not include participants receiving oral EC, so direct comparison of effectiveness is not possible. Pregnancy rates among IUD users in this study were favorable to rates reported in previous studies of oral EC.⁴

When choosing an IUD for contraception, more women select the LNG-IUD for its favorable side effect profile and reduction in menstrual bleeding. In this randomized IUD study, only 7% of eligible participants enrolled, potentially introducing selection bias. The majority who declined enrollment did not want an IUD. Previous studies that allowed participants to choose their IUD had higher enrollment rates. ● 

When gonadotropin-releasing hormone (GnRH) agonist and antagonist peptide medications were first approved for use in the 1980s and 1990s, the available agents could only be administered by injection or nasal spray. The innovative development of orally active, nonpeptide GnRH antagonists, including relugolix and elagolix (FIGURE 1), is a major breakthrough in women’s health. Orally active GnRH antagonists provide gynecologists with a unique way to regulate hypothalamic-pituitary-ovarian-uterus function. GnRH antagonists bind to the pituitary GnRH receptor, reducing pituitary secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In turn, reduction in LH and FSH suppresses ovarian follicle development, reducing ovarian secretion of estradiol and progesterone. The uterine endometrium becomes less active in response to low levels of estradiol and progesterone, resulting in oligomenorrhea or amenorrhea. The hypoestrogenic adverse effects of GnRH antagonist treatment, including bone loss and vasomotor symptoms can be minimized by adding back a low dose of estrogen and progestin, such as oral estradiol 1 mg and norethindrone acetate 0.5 mg.

Recently, the US Food and Drug Administration (FDA) approved oral relugolix combination therapy (Myfembree, Myovant Sciences and Pfizer Inc; relugolix 40 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg) once daily for the treatment of abnormal uterine bleeding (AUB) associated with uterine leiomyomata (fibroids) in premenopausal women for up to 24 months.¹ This editorial will focus on key clinical issues when using relugolix combination therapy.

Relugolix combination treatment is superior to placebo for AUB from fibroids

In 2 clinical trials, 770 women with symptomatic uterine fibroids were randomly assigned to 1 of 3 groups²:

• placebo for 24 weeks
• relugolix combination therapy (consisting of relugolix 40 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg) daily for 24 weeks
• relugolix monotherapy (40 mg daily for 12 weeks) followed by relugolix combination therapy for 12 additional weeks (delayed combination therapy group).

The women’s mean age was approximately 42 years, and they had a mean menstrual blood loss at baseline of approximately 230 mL and mean uterine volume by ultrasound measurement of 408 cm³.² Prior to entry into the study all the women had an endometrial biopsy and a transvaginal ultrasound study of the pelvis. Women with a baseline bone mineral density Z-score of less than -2.0 at the spine, total hip, or femoral neck were excluded from the study because of low bone mass.²

At 24 weeks of treatment, approximately 72% of the women in the relugolix combination therapy groups had less than 80 mL of menstrual blood volume loss and ≥50% reduction in menstrual blood loss from baseline compared with 17% of women in the placebo group.² At 8 weeks of treatment mean percent changes in menstrual blood loss from baseline were approximately 80% and 20% for the women receiving relugolix combination and placebo, respectively. Those differences persisted from 8 weeks through 24 weeks of treatment.¹ In the last 35 days of treatment, amenorrhea was reported by approximately 51% and 4.5% of women receiving relugolix combination or placebo treatment, respectively.² Compared with the placebo group, the relugolix combination groups reported significant improvement in bleeding and pelvic discomfort and had a higher hemoglobin concentration. Compared with placebo, relugolix combination treatment resulted in a greater percentage decrease in uterine volume (-12.9% vs +2.2%, respectively; P< .001).²

Continue to: Relugolix combination treatment is associated with fewer side effects than relugolix monotherapy...

Compared with relugolix combination therapy, women treated with relugolix monotherapy for 12 weeks followed by 12 weeks of relugolix combination therapy lost more bone density as measured by dual-energy X-ray absorptiometry and reported more vasomotor symptoms. This is an expected finding because GnRH antagonist monotherapy is known to significantly reduce ovarian estradiol and progesterone levels, causing bone loss and vasomotor symptoms. Relugolix combination treatment minimizes bone density loss and vasomotor symptoms because the combination of estradiol and norethindrone helps to preserve bone density and reduce hot flashes. Based on these and other findings, the FDA approved relugolix combination therapy for up to 24 months of treatment.¹

Contraindications

Contraindications to relugolix combination therapy include: 1) pregnancy, 2) undiagnosed abnormal uterine bleeding, 3) current or personal history of breast cancer or other hormone-sensitive cancer, 4) known osteoporosis, 5) liver disease, 6) high risk of thrombosis, and 7) hypersensitivity to components of the medication.¹

Adverse reactions

Serious adverse reactions were reported by 3.1% and 2.3% of women treated with the relugolix combination and placebo, respectively. Women taking relugolix combination reported the following adverse effects: 10.6% hot flashes, 6.3% AUB, 3.5% alopecia, and 3.1% decreased libido. Women taking placebo reported the following adverse effects: 6.6% hot flashes, 1.2% AUB, 0.8% alopecia, and 0.4% decreased libido. Among women taking relugolix combination, the following events occurred, each reported once by different women: myoma expulsion with menorrhagia, myoma prolapse without menorrhagia, cholecystitis, and pelvic pain.¹

Bone loss

In women taking relugolix combination or placebo for 6 months, lumbar spine bone density change from baseline, as measured by DEXA, were -0.23% and +0.18%, respectively.¹ After 12 months of relugolix combination treatment, lumbar spine bone density had decreased by -0.8% from baseline. These changes in lumbar bone density are minimal, and in my opinion of no clinical importance.

Reported mental health effects

Compared with placebo, more women taking relugolix combination reported depression, depressed mood, or mood swings (2.4% vs 0.8%), irritability (2.4% vs 0%), and anxiety (1.2% vs 0.8%).¹

Continue to: Options for the treatment of AUB caused by fibroids...

There are many options for the treatment of AUB caused by fibroids, including surgical, hormonal, and nonhormonal therapies. Women with bothersome fibroids strongly prefer to be involved in the decision-making process and select the treatment plan that is best for their situation.³ The patient’s preferences can be explored by discussing the main benefits and common complications and side effects of each treatment option.

Surgical options for the treatment of AUB caused by fibroids include, but are not limited to, hysterectomy (laparoscopic, vaginal, or laparotomy), myomectomy (hysteroscopic, laparoscopic, or laparotomy), uterine artery embolization, focused ultrasound surgery, radiofrequency ablation, cryomyolysis, endometrial ablation, and occlusion of the uterine arteries.⁴ The FIGO classification system provides a consensus nomenclature for describing fibroid location (see FIGURE 2).⁵ The selection of a treatment option is greatly influenced by the location of the fibroids in the uterus.⁶ Most experts recommend hysteroscopic myomectomy to treat Type 0 and Type 1 fibroids causing AUB.⁶ For Type 2 fibroids, hysteroscopic myomectomy, if technically feasible, is associated with a high rate of resolution of AUB with minimal complications. Hormonal treatment of Type 0 and Type 1 fibroids may result in red degeneration of the fibroid with significant menorrhagia.^7,8 In my practice, I generally advise patients that hysteroscopic myomectomy is the first-line treatment option for Types 0, 1, and 2 fibroids causing AUB.

New hormonal treatment adds options for women

Fibroids are the most common pelvic tumor of women. Women with fibroids often present for clinical care due to AUB, pelvic pain, and/or lower abdominal discomfort. For women with symptomatic fibroids it may be difficult to effectively complete employment-related tasks and home responsibilities. In one study, women with symptomatic fibroids reported that their symptoms negatively impacted approximately 20 hours per month of employment-related work and 12 hours per month of home responsibilities, reducing productivity in both settings.¹⁹ Relugolix combination therapy adds another important option for the hormonal treatment of the problems caused by these prevalent and bothersome tumors, improving health and the quality of contributions at work and home. ●

When gonadotropin-releasing hormone (GnRH) agonist and antagonist peptide medications were first approved for use in the 1980s and 1990s, the available agents could only be administered by injection or nasal spray. The innovative development of orally active, nonpeptide GnRH antagonists, including relugolix and elagolix (FIGURE 1), is a major breakthrough in women’s health. Orally active GnRH antagonists provide gynecologists with a unique way to regulate hypothalamic-pituitary-ovarian-uterus function. GnRH antagonists bind to the pituitary GnRH receptor, reducing pituitary secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In turn, reduction in LH and FSH suppresses ovarian follicle development, reducing ovarian secretion of estradiol and progesterone. The uterine endometrium becomes less active in response to low levels of estradiol and progesterone, resulting in oligomenorrhea or amenorrhea. The hypoestrogenic adverse effects of GnRH antagonist treatment, including bone loss and vasomotor symptoms can be minimized by adding back a low dose of estrogen and progestin, such as oral estradiol 1 mg and norethindrone acetate 0.5 mg.

Recently, the US Food and Drug Administration (FDA) approved oral relugolix combination therapy (Myfembree, Myovant Sciences and Pfizer Inc; relugolix 40 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg) once daily for the treatment of abnormal uterine bleeding (AUB) associated with uterine leiomyomata (fibroids) in premenopausal women for up to 24 months.¹ This editorial will focus on key clinical issues when using relugolix combination therapy.

Relugolix combination treatment is superior to placebo for AUB from fibroids

In 2 clinical trials, 770 women with symptomatic uterine fibroids were randomly assigned to 1 of 3 groups²:

• placebo for 24 weeks
• relugolix combination therapy (consisting of relugolix 40 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg) daily for 24 weeks
• relugolix monotherapy (40 mg daily for 12 weeks) followed by relugolix combination therapy for 12 additional weeks (delayed combination therapy group).

The women’s mean age was approximately 42 years, and they had a mean menstrual blood loss at baseline of approximately 230 mL and mean uterine volume by ultrasound measurement of 408 cm³.² Prior to entry into the study all the women had an endometrial biopsy and a transvaginal ultrasound study of the pelvis. Women with a baseline bone mineral density Z-score of less than -2.0 at the spine, total hip, or femoral neck were excluded from the study because of low bone mass.²

At 24 weeks of treatment, approximately 72% of the women in the relugolix combination therapy groups had less than 80 mL of menstrual blood volume loss and ≥50% reduction in menstrual blood loss from baseline compared with 17% of women in the placebo group.² At 8 weeks of treatment mean percent changes in menstrual blood loss from baseline were approximately 80% and 20% for the women receiving relugolix combination and placebo, respectively. Those differences persisted from 8 weeks through 24 weeks of treatment.¹ In the last 35 days of treatment, amenorrhea was reported by approximately 51% and 4.5% of women receiving relugolix combination or placebo treatment, respectively.² Compared with the placebo group, the relugolix combination groups reported significant improvement in bleeding and pelvic discomfort and had a higher hemoglobin concentration. Compared with placebo, relugolix combination treatment resulted in a greater percentage decrease in uterine volume (-12.9% vs +2.2%, respectively; P< .001).²

Continue to: Relugolix combination treatment is associated with fewer side effects than relugolix monotherapy...

Compared with relugolix combination therapy, women treated with relugolix monotherapy for 12 weeks followed by 12 weeks of relugolix combination therapy lost more bone density as measured by dual-energy X-ray absorptiometry and reported more vasomotor symptoms. This is an expected finding because GnRH antagonist monotherapy is known to significantly reduce ovarian estradiol and progesterone levels, causing bone loss and vasomotor symptoms. Relugolix combination treatment minimizes bone density loss and vasomotor symptoms because the combination of estradiol and norethindrone helps to preserve bone density and reduce hot flashes. Based on these and other findings, the FDA approved relugolix combination therapy for up to 24 months of treatment.¹

Contraindications

Contraindications to relugolix combination therapy include: 1) pregnancy, 2) undiagnosed abnormal uterine bleeding, 3) current or personal history of breast cancer or other hormone-sensitive cancer, 4) known osteoporosis, 5) liver disease, 6) high risk of thrombosis, and 7) hypersensitivity to components of the medication.¹

Adverse reactions

Serious adverse reactions were reported by 3.1% and 2.3% of women treated with the relugolix combination and placebo, respectively. Women taking relugolix combination reported the following adverse effects: 10.6% hot flashes, 6.3% AUB, 3.5% alopecia, and 3.1% decreased libido. Women taking placebo reported the following adverse effects: 6.6% hot flashes, 1.2% AUB, 0.8% alopecia, and 0.4% decreased libido. Among women taking relugolix combination, the following events occurred, each reported once by different women: myoma expulsion with menorrhagia, myoma prolapse without menorrhagia, cholecystitis, and pelvic pain.¹

Bone loss

In women taking relugolix combination or placebo for 6 months, lumbar spine bone density change from baseline, as measured by DEXA, were -0.23% and +0.18%, respectively.¹ After 12 months of relugolix combination treatment, lumbar spine bone density had decreased by -0.8% from baseline. These changes in lumbar bone density are minimal, and in my opinion of no clinical importance.

Reported mental health effects

Compared with placebo, more women taking relugolix combination reported depression, depressed mood, or mood swings (2.4% vs 0.8%), irritability (2.4% vs 0%), and anxiety (1.2% vs 0.8%).¹

Continue to: Options for the treatment of AUB caused by fibroids...

There are many options for the treatment of AUB caused by fibroids, including surgical, hormonal, and nonhormonal therapies. Women with bothersome fibroids strongly prefer to be involved in the decision-making process and select the treatment plan that is best for their situation.³ The patient’s preferences can be explored by discussing the main benefits and common complications and side effects of each treatment option.

Surgical options for the treatment of AUB caused by fibroids include, but are not limited to, hysterectomy (laparoscopic, vaginal, or laparotomy), myomectomy (hysteroscopic, laparoscopic, or laparotomy), uterine artery embolization, focused ultrasound surgery, radiofrequency ablation, cryomyolysis, endometrial ablation, and occlusion of the uterine arteries.⁴ The FIGO classification system provides a consensus nomenclature for describing fibroid location (see FIGURE 2).⁵ The selection of a treatment option is greatly influenced by the location of the fibroids in the uterus.⁶ Most experts recommend hysteroscopic myomectomy to treat Type 0 and Type 1 fibroids causing AUB.⁶ For Type 2 fibroids, hysteroscopic myomectomy, if technically feasible, is associated with a high rate of resolution of AUB with minimal complications. Hormonal treatment of Type 0 and Type 1 fibroids may result in red degeneration of the fibroid with significant menorrhagia.^7,8 In my practice, I generally advise patients that hysteroscopic myomectomy is the first-line treatment option for Types 0, 1, and 2 fibroids causing AUB.

New hormonal treatment adds options for women

Fibroids are the most common pelvic tumor of women. Women with fibroids often present for clinical care due to AUB, pelvic pain, and/or lower abdominal discomfort. For women with symptomatic fibroids it may be difficult to effectively complete employment-related tasks and home responsibilities. In one study, women with symptomatic fibroids reported that their symptoms negatively impacted approximately 20 hours per month of employment-related work and 12 hours per month of home responsibilities, reducing productivity in both settings.¹⁹ Relugolix combination therapy adds another important option for the hormonal treatment of the problems caused by these prevalent and bothersome tumors, improving health and the quality of contributions at work and home. ●

When gonadotropin-releasing hormone (GnRH) agonist and antagonist peptide medications were first approved for use in the 1980s and 1990s, the available agents could only be administered by injection or nasal spray. The innovative development of orally active, nonpeptide GnRH antagonists, including relugolix and elagolix (FIGURE 1), is a major breakthrough in women’s health. Orally active GnRH antagonists provide gynecologists with a unique way to regulate hypothalamic-pituitary-ovarian-uterus function. GnRH antagonists bind to the pituitary GnRH receptor, reducing pituitary secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In turn, reduction in LH and FSH suppresses ovarian follicle development, reducing ovarian secretion of estradiol and progesterone. The uterine endometrium becomes less active in response to low levels of estradiol and progesterone, resulting in oligomenorrhea or amenorrhea. The hypoestrogenic adverse effects of GnRH antagonist treatment, including bone loss and vasomotor symptoms can be minimized by adding back a low dose of estrogen and progestin, such as oral estradiol 1 mg and norethindrone acetate 0.5 mg.

Recently, the US Food and Drug Administration (FDA) approved oral relugolix combination therapy (Myfembree, Myovant Sciences and Pfizer Inc; relugolix 40 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg) once daily for the treatment of abnormal uterine bleeding (AUB) associated with uterine leiomyomata (fibroids) in premenopausal women for up to 24 months.¹ This editorial will focus on key clinical issues when using relugolix combination therapy.

Relugolix combination treatment is superior to placebo for AUB from fibroids

In 2 clinical trials, 770 women with symptomatic uterine fibroids were randomly assigned to 1 of 3 groups²:

• placebo for 24 weeks
• relugolix combination therapy (consisting of relugolix 40 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg) daily for 24 weeks
• relugolix monotherapy (40 mg daily for 12 weeks) followed by relugolix combination therapy for 12 additional weeks (delayed combination therapy group).

The women’s mean age was approximately 42 years, and they had a mean menstrual blood loss at baseline of approximately 230 mL and mean uterine volume by ultrasound measurement of 408 cm³.² Prior to entry into the study all the women had an endometrial biopsy and a transvaginal ultrasound study of the pelvis. Women with a baseline bone mineral density Z-score of less than -2.0 at the spine, total hip, or femoral neck were excluded from the study because of low bone mass.²

At 24 weeks of treatment, approximately 72% of the women in the relugolix combination therapy groups had less than 80 mL of menstrual blood volume loss and ≥50% reduction in menstrual blood loss from baseline compared with 17% of women in the placebo group.² At 8 weeks of treatment mean percent changes in menstrual blood loss from baseline were approximately 80% and 20% for the women receiving relugolix combination and placebo, respectively. Those differences persisted from 8 weeks through 24 weeks of treatment.¹ In the last 35 days of treatment, amenorrhea was reported by approximately 51% and 4.5% of women receiving relugolix combination or placebo treatment, respectively.² Compared with the placebo group, the relugolix combination groups reported significant improvement in bleeding and pelvic discomfort and had a higher hemoglobin concentration. Compared with placebo, relugolix combination treatment resulted in a greater percentage decrease in uterine volume (-12.9% vs +2.2%, respectively; P< .001).²

Continue to: Relugolix combination treatment is associated with fewer side effects than relugolix monotherapy...

Compared with relugolix combination therapy, women treated with relugolix monotherapy for 12 weeks followed by 12 weeks of relugolix combination therapy lost more bone density as measured by dual-energy X-ray absorptiometry and reported more vasomotor symptoms. This is an expected finding because GnRH antagonist monotherapy is known to significantly reduce ovarian estradiol and progesterone levels, causing bone loss and vasomotor symptoms. Relugolix combination treatment minimizes bone density loss and vasomotor symptoms because the combination of estradiol and norethindrone helps to preserve bone density and reduce hot flashes. Based on these and other findings, the FDA approved relugolix combination therapy for up to 24 months of treatment.¹

Contraindications

Contraindications to relugolix combination therapy include: 1) pregnancy, 2) undiagnosed abnormal uterine bleeding, 3) current or personal history of breast cancer or other hormone-sensitive cancer, 4) known osteoporosis, 5) liver disease, 6) high risk of thrombosis, and 7) hypersensitivity to components of the medication.¹

Adverse reactions

Serious adverse reactions were reported by 3.1% and 2.3% of women treated with the relugolix combination and placebo, respectively. Women taking relugolix combination reported the following adverse effects: 10.6% hot flashes, 6.3% AUB, 3.5% alopecia, and 3.1% decreased libido. Women taking placebo reported the following adverse effects: 6.6% hot flashes, 1.2% AUB, 0.8% alopecia, and 0.4% decreased libido. Among women taking relugolix combination, the following events occurred, each reported once by different women: myoma expulsion with menorrhagia, myoma prolapse without menorrhagia, cholecystitis, and pelvic pain.¹

Bone loss

In women taking relugolix combination or placebo for 6 months, lumbar spine bone density change from baseline, as measured by DEXA, were -0.23% and +0.18%, respectively.¹ After 12 months of relugolix combination treatment, lumbar spine bone density had decreased by -0.8% from baseline. These changes in lumbar bone density are minimal, and in my opinion of no clinical importance.

Reported mental health effects

Compared with placebo, more women taking relugolix combination reported depression, depressed mood, or mood swings (2.4% vs 0.8%), irritability (2.4% vs 0%), and anxiety (1.2% vs 0.8%).¹

Continue to: Options for the treatment of AUB caused by fibroids...

There are many options for the treatment of AUB caused by fibroids, including surgical, hormonal, and nonhormonal therapies. Women with bothersome fibroids strongly prefer to be involved in the decision-making process and select the treatment plan that is best for their situation.³ The patient’s preferences can be explored by discussing the main benefits and common complications and side effects of each treatment option.

Surgical options for the treatment of AUB caused by fibroids include, but are not limited to, hysterectomy (laparoscopic, vaginal, or laparotomy), myomectomy (hysteroscopic, laparoscopic, or laparotomy), uterine artery embolization, focused ultrasound surgery, radiofrequency ablation, cryomyolysis, endometrial ablation, and occlusion of the uterine arteries.⁴ The FIGO classification system provides a consensus nomenclature for describing fibroid location (see FIGURE 2).⁵ The selection of a treatment option is greatly influenced by the location of the fibroids in the uterus.⁶ Most experts recommend hysteroscopic myomectomy to treat Type 0 and Type 1 fibroids causing AUB.⁶ For Type 2 fibroids, hysteroscopic myomectomy, if technically feasible, is associated with a high rate of resolution of AUB with minimal complications. Hormonal treatment of Type 0 and Type 1 fibroids may result in red degeneration of the fibroid with significant menorrhagia.^7,8 In my practice, I generally advise patients that hysteroscopic myomectomy is the first-line treatment option for Types 0, 1, and 2 fibroids causing AUB.

New hormonal treatment adds options for women

Fibroids are the most common pelvic tumor of women. Women with fibroids often present for clinical care due to AUB, pelvic pain, and/or lower abdominal discomfort. For women with symptomatic fibroids it may be difficult to effectively complete employment-related tasks and home responsibilities. In one study, women with symptomatic fibroids reported that their symptoms negatively impacted approximately 20 hours per month of employment-related work and 12 hours per month of home responsibilities, reducing productivity in both settings.¹⁹ Relugolix combination therapy adds another important option for the hormonal treatment of the problems caused by these prevalent and bothersome tumors, improving health and the quality of contributions at work and home. ●