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Neuropsychiatric side effects of hormonal contraceptives: More common than you think!
Since its introduction in 1950, the combined oral contraceptive pill has been used by countless women as a method for birth control (Liao P. Can Fam Physician. 2012 Dec; 58[12]:e757-e760).
Hormonal contraception (HC) provides women with both contraceptive and noncontraceptive benefits, most notably a method for avoiding unintended pregnancy. In addition to being an effective method of contraception, oral contraceptive pills (OCPs) are well established for treating conditions such as hirsutism, pain symptoms associated with endometriosis and adenomyosis, and pelvic inflammatory disease, among others (Schindler A. Int J Endocrinol Metab. 2013 Winter;11[1]:41-7).
Combined hormonal contraceptives are also first-line treatment for women with menstrual disorders, and in women with polycystic ovary syndrome, can offer an effective long-term method to regulate their menstrual cycle, decrease androgens, clear up oily skin and acne, and reduce facial hair while also providing them with effective contraception (de Melo et al. Open Access J Contracept. 2017;8:13-23).
Associations between ‘the pill’ and mood effects remain controversial
More than 100 million women worldwide use hormonal contraceptives today, yet despite this, the data are mixed regarding the prevalence and extent of neuropsychiatric symptoms and mood changes associated with use of “the pill.” Some studies show combined oral contraceptives are associated with a decrease in general well-being, but had no effect on depression, in women compared with placebo (Zethraeus N et al. Fertil Steril. 2017 May;107[5]:1238-45).
However, a large Danish study published in JAMA Psychiatry of more than 1 million women found a significant association between use of hormonal contraception and antidepressant use or first diagnosis of depression, with adolescents having a higher rate of first depression diagnosis and antidepressant use compared with women 20–30 years old (Skovlund C et al. JAMA Psychiatry. 2016 Nov 1;73[11]:1154-62).
Studies have also shown long-term exposure to levonorgestrel is significantly associated with anxiety and sleep problems in women without a history of these issues (Slattery J et al. Drug Saf. 2018 Oct;41[10]:951-8). A recent small nationwide cohort study in France suggests this may also be true of levonorgestrel delivered by intrauterine devices (IUD) and the association may be dose-dependent (Roland N et al. JAMA. 2023;329[3]:257-9).
Of note, a study published in the American Journal of Psychiatry found a nearly twofold risk of suicide attempt and over threefold risk of suicide among women taking hormonal contraception compared with women who had never used hormonal contraceptives (Skovlund et al. Am J Psychiatry. 2017 Nov 17:appiajp201717060616).
Knowledge gaps make drawing conclusions difficult
The latest information on use of antidepressant and antianxiety medications in women of reproductive age (18-44 years) is sparse and, in some cases, outdated. According to data from the National Health and Nutrition Examination Survey, 18.6% of adult women 18 years or older reported using antidepressant medications within the last 30 days in 2017-2018, an increase from 13.8% in 2009-2010. Among women aged 15-44 year with private employer–sponsored insurance surveyed during 2008-2013, the results showed 15.4% of women filled a prescription for an antidepressant. We must look back further to find data on antianxiety medication use among women aged 18-44 years where use of antianxiety drugs (anxiolytics, sedatives, and hypnotics) was 4.3% between 2005 and 2008.
A lack of literature in this area is likely due to significant underreporting, and an inability to select patients who are sensitive to or at risk of developing neuropsychiatric symptoms resulting from hormonal contraception use because the true pathophysiology is unknown. Existing studies tend to use varying methods to assess mood changes, and do not usually specify hormonal contraceptive use type in their analyses (Schaffir J et al. Eur J Contracept Reprod Health Care. 2016 Oct;21[5]:347-55).
Studies of this nature also require large sample sizes, but the percentage of women who develop neuropsychiatric symptoms from hormonal contraceptive use has historically been relatively small. In the late 1990s, Rosenberg and colleagues found 46% of 1,657 women discontinued oral contraceptives due to side effects within 6 months of starting a new prescription; of these women, 5% reported mood changes as their reason for discontinuing oral contraceptives (Rosenberg M et al. Am J Obstet Gynecol. 1998 Sep;179[3 Pt 1]:577-82).
One might expect that, as lower dosage combined hormonal contraceptives were developed in the 1980s, that the rate of reporting psychological side effects would continue to decrease as well. Yet greater awareness of the potential for mood changes while on “the pill” as outlined by the lay press and social media may be leading to increased reporting of neuropsychiatric effects in women. In a recent cross-sectional survey of 188 women in New York, 43.6% said they experienced mood changes while on hormonal contraceptives, and 61.2% of women with histories of psychiatric illness reported mood changes they attributed to hormonal contraceptives (Martell S et al. Contracept Reprod Med. 2023;8:9).
Martell and colleagues found 48.3% of women cited side effects as a reason for discontinuing hormonal contraception, and 43 participants mentioned psychological side effects unprompted, including 2 patients with suicidal thoughts. The authors said this suggests “psychological side effects, at least in part, may have impacted” HC users’ decisions to switch from OCPs to an alternative method of contraception.
It is also not clear what risk factors exist for women who develop neuropsychiatric symptoms from hormonal contraceptive use. First, it is important to note that both progestin-only contraceptives and combined hormonal contraceptives are classified by the Centers for Disease Control and Prevention’s US Medical Eligibility Criteria for Contraceptive Use, 2016 as having no restrictions for use, including among patients with depression. While women in a smaller subgroup have significant neuropsychiatric symptoms related to their hormonal contraceptives, the underlying mechanism is unknown, and is thought to be largely related to the progestogen component of combined hormonal contraceptives or progestogen-only contraceptives (Mu E. Aust Prescr. 2022 Jun; 45[3]:75-9). We know that some women are hormone sensitive, while others are less so, and some not at all. Progestogens could affect mood as a direct action of the progestogen, because progestogens can be neurosteroids, or the progestogen effect could be mediated secondarily through a change in that woman’s own production of or bioavailability of androgens or naturally occurring estrogens (Giatti S. J Mol Endocrinol. 2016 Aug;57[2]:R109-26).
Here, we also find that currently available evidence limits our ability to draw firm conclusions. A study by Berry-Bibee and colleagues found a “low concern for clinically significant interactions” between hormonal contraception and psychotropic drugs, but was limited by quality/quantity of evidence (Berry-Bibee E et al. Contraception. 2016 Dec;94[6]:650-67). Interestingly, a study by Robinson and colleagues from the mid-2000s posited based on low evidence that “psychological response to the practice of contraception” was a potential explanation for the side effect profile of hormonal contraception (Robinson S et al. Med Hypotheses. 2004;63[2]:268-73).
Further, it may be that women with premenstrual dysphoric disorder (PMDD) might be selected for oral contraceptives, and they are predisposed to other neuropsychiatric problems. Estimates have placed the prevalence of comorbid psychiatric disorders such as anxiety, major depression, bipolar disorder, and posttraumatic stress disorder as high as 70% for women with PMDD (Sepede G et al. Neuropsychiatr Dis Treat. 2020;16:415-26). This phenomenon is not new, having been characterized in the lay literature nearly 20 years ago, by endocrinologist Geoffrey P. Redmond, MD (Redmond GP. The Hormonally Vulnerable Woman. New York: HarperCollins; 2005).
While the cause is not exactly idiosyncratic, They tend to have an entire spectrum of responses to the progestogens in combined or progestin-only contraceptives, ranging from just a flattened affect – which could easily be explained by their flattened level of endogenous hormones – to frank depression. Their frank depression, in turn, can be demonstrated to include suicidal ideation and actual suicide.
Compounding this issue is a woman’s perception of her sexuality. Some women with low sexual desire or sexual problems who are younger may have more distress about their problems compared with women of older reproductive age. While the reason for that is not clear, it may be that in the sexual arena, it is more important for some younger women to be a sexual person than in perimenopausal women, or that women who are younger are more likely to be partnered than women of older reproductive age. While the European Society of Sexual Medicine concluded in a 2019 position statement that there is inconclusive evidence whether hormonal contraception may be contributing to changes in sexual desire and sexual dysfunction, it appears that “a minority of women” experience “better or worse sexual functioning” from taking combined oral contraceptives (Both S et al. J Sex Med. 2019 Nov;16[11]:1681-95), suggesting that the majority of women report no significant changes.
Practitioners should discuss mood effects during consultation
An ob.gyn., primary care physicians, or others with prescriptive authority (i.e. nurse practitioners and physician assistants) in clinical practice may encounter a patient who seems to have mood side effects owing to progestogen-containing contraceptives that they prescribe. However, many ob.gyns. are likely unaware of the prevalence, or that some of those same patients can have such significant mood effects that they would become or are suicidal.
I believe questioning patients about mood effects during consultation and particularly during follow-up following the initiation of any hormonal contraceptive is worth a passing comment for every patient, which should include mood effects in broader discussion for anyone currently using an antidepressant, patients with a history of antidepressant use, and patients who have considered suicide. As we do with other drugs, these questions can be posed in the form of a questionnaire followed up by the practitioner in counseling.
Practitioners who encounter a patient with mood changes as a result of hormonal contraceptive use can consider changing to a nonhormonal method of birth control, or recommending the patient use a barrier method during sexual activity, as none of these options have neuropsychiatric side effects.
Ultimately, practitioners of all types need to engage in shared decision-making to identify the key benefits and risks of hormonal contraceptive use for each patient, which may involve trial and error to determine the ideal treatment. It is critical that practitioners of all types strike a balance between alleviating patient concerns about potential mood changes, monitoring patients with an appreciable risk of mood changes, and continuing patients on hormonal contraception for whom the benefits outweigh the risks.
Dr. Simon is a clinical professor at George Washington University and the medical director and founder of IntimMedicine Specialists in Washington, which provides patient-focused care for women across the reproductive life cycle. He is a past president of the International Society for the Study of Women’s Sexual Health and the North American Menopause Society. Dr. Simon has been a consultant to, received grant and research support from, and served on the speakers bureau for various pharmaceutical companies that develop combination hormonal contraceptives. Email Dr. Simon at obnews@mdedge.com.
Since its introduction in 1950, the combined oral contraceptive pill has been used by countless women as a method for birth control (Liao P. Can Fam Physician. 2012 Dec; 58[12]:e757-e760).
Hormonal contraception (HC) provides women with both contraceptive and noncontraceptive benefits, most notably a method for avoiding unintended pregnancy. In addition to being an effective method of contraception, oral contraceptive pills (OCPs) are well established for treating conditions such as hirsutism, pain symptoms associated with endometriosis and adenomyosis, and pelvic inflammatory disease, among others (Schindler A. Int J Endocrinol Metab. 2013 Winter;11[1]:41-7).
Combined hormonal contraceptives are also first-line treatment for women with menstrual disorders, and in women with polycystic ovary syndrome, can offer an effective long-term method to regulate their menstrual cycle, decrease androgens, clear up oily skin and acne, and reduce facial hair while also providing them with effective contraception (de Melo et al. Open Access J Contracept. 2017;8:13-23).
Associations between ‘the pill’ and mood effects remain controversial
More than 100 million women worldwide use hormonal contraceptives today, yet despite this, the data are mixed regarding the prevalence and extent of neuropsychiatric symptoms and mood changes associated with use of “the pill.” Some studies show combined oral contraceptives are associated with a decrease in general well-being, but had no effect on depression, in women compared with placebo (Zethraeus N et al. Fertil Steril. 2017 May;107[5]:1238-45).
However, a large Danish study published in JAMA Psychiatry of more than 1 million women found a significant association between use of hormonal contraception and antidepressant use or first diagnosis of depression, with adolescents having a higher rate of first depression diagnosis and antidepressant use compared with women 20–30 years old (Skovlund C et al. JAMA Psychiatry. 2016 Nov 1;73[11]:1154-62).
Studies have also shown long-term exposure to levonorgestrel is significantly associated with anxiety and sleep problems in women without a history of these issues (Slattery J et al. Drug Saf. 2018 Oct;41[10]:951-8). A recent small nationwide cohort study in France suggests this may also be true of levonorgestrel delivered by intrauterine devices (IUD) and the association may be dose-dependent (Roland N et al. JAMA. 2023;329[3]:257-9).
Of note, a study published in the American Journal of Psychiatry found a nearly twofold risk of suicide attempt and over threefold risk of suicide among women taking hormonal contraception compared with women who had never used hormonal contraceptives (Skovlund et al. Am J Psychiatry. 2017 Nov 17:appiajp201717060616).
Knowledge gaps make drawing conclusions difficult
The latest information on use of antidepressant and antianxiety medications in women of reproductive age (18-44 years) is sparse and, in some cases, outdated. According to data from the National Health and Nutrition Examination Survey, 18.6% of adult women 18 years or older reported using antidepressant medications within the last 30 days in 2017-2018, an increase from 13.8% in 2009-2010. Among women aged 15-44 year with private employer–sponsored insurance surveyed during 2008-2013, the results showed 15.4% of women filled a prescription for an antidepressant. We must look back further to find data on antianxiety medication use among women aged 18-44 years where use of antianxiety drugs (anxiolytics, sedatives, and hypnotics) was 4.3% between 2005 and 2008.
A lack of literature in this area is likely due to significant underreporting, and an inability to select patients who are sensitive to or at risk of developing neuropsychiatric symptoms resulting from hormonal contraception use because the true pathophysiology is unknown. Existing studies tend to use varying methods to assess mood changes, and do not usually specify hormonal contraceptive use type in their analyses (Schaffir J et al. Eur J Contracept Reprod Health Care. 2016 Oct;21[5]:347-55).
Studies of this nature also require large sample sizes, but the percentage of women who develop neuropsychiatric symptoms from hormonal contraceptive use has historically been relatively small. In the late 1990s, Rosenberg and colleagues found 46% of 1,657 women discontinued oral contraceptives due to side effects within 6 months of starting a new prescription; of these women, 5% reported mood changes as their reason for discontinuing oral contraceptives (Rosenberg M et al. Am J Obstet Gynecol. 1998 Sep;179[3 Pt 1]:577-82).
One might expect that, as lower dosage combined hormonal contraceptives were developed in the 1980s, that the rate of reporting psychological side effects would continue to decrease as well. Yet greater awareness of the potential for mood changes while on “the pill” as outlined by the lay press and social media may be leading to increased reporting of neuropsychiatric effects in women. In a recent cross-sectional survey of 188 women in New York, 43.6% said they experienced mood changes while on hormonal contraceptives, and 61.2% of women with histories of psychiatric illness reported mood changes they attributed to hormonal contraceptives (Martell S et al. Contracept Reprod Med. 2023;8:9).
Martell and colleagues found 48.3% of women cited side effects as a reason for discontinuing hormonal contraception, and 43 participants mentioned psychological side effects unprompted, including 2 patients with suicidal thoughts. The authors said this suggests “psychological side effects, at least in part, may have impacted” HC users’ decisions to switch from OCPs to an alternative method of contraception.
It is also not clear what risk factors exist for women who develop neuropsychiatric symptoms from hormonal contraceptive use. First, it is important to note that both progestin-only contraceptives and combined hormonal contraceptives are classified by the Centers for Disease Control and Prevention’s US Medical Eligibility Criteria for Contraceptive Use, 2016 as having no restrictions for use, including among patients with depression. While women in a smaller subgroup have significant neuropsychiatric symptoms related to their hormonal contraceptives, the underlying mechanism is unknown, and is thought to be largely related to the progestogen component of combined hormonal contraceptives or progestogen-only contraceptives (Mu E. Aust Prescr. 2022 Jun; 45[3]:75-9). We know that some women are hormone sensitive, while others are less so, and some not at all. Progestogens could affect mood as a direct action of the progestogen, because progestogens can be neurosteroids, or the progestogen effect could be mediated secondarily through a change in that woman’s own production of or bioavailability of androgens or naturally occurring estrogens (Giatti S. J Mol Endocrinol. 2016 Aug;57[2]:R109-26).
Here, we also find that currently available evidence limits our ability to draw firm conclusions. A study by Berry-Bibee and colleagues found a “low concern for clinically significant interactions” between hormonal contraception and psychotropic drugs, but was limited by quality/quantity of evidence (Berry-Bibee E et al. Contraception. 2016 Dec;94[6]:650-67). Interestingly, a study by Robinson and colleagues from the mid-2000s posited based on low evidence that “psychological response to the practice of contraception” was a potential explanation for the side effect profile of hormonal contraception (Robinson S et al. Med Hypotheses. 2004;63[2]:268-73).
Further, it may be that women with premenstrual dysphoric disorder (PMDD) might be selected for oral contraceptives, and they are predisposed to other neuropsychiatric problems. Estimates have placed the prevalence of comorbid psychiatric disorders such as anxiety, major depression, bipolar disorder, and posttraumatic stress disorder as high as 70% for women with PMDD (Sepede G et al. Neuropsychiatr Dis Treat. 2020;16:415-26). This phenomenon is not new, having been characterized in the lay literature nearly 20 years ago, by endocrinologist Geoffrey P. Redmond, MD (Redmond GP. The Hormonally Vulnerable Woman. New York: HarperCollins; 2005).
While the cause is not exactly idiosyncratic, They tend to have an entire spectrum of responses to the progestogens in combined or progestin-only contraceptives, ranging from just a flattened affect – which could easily be explained by their flattened level of endogenous hormones – to frank depression. Their frank depression, in turn, can be demonstrated to include suicidal ideation and actual suicide.
Compounding this issue is a woman’s perception of her sexuality. Some women with low sexual desire or sexual problems who are younger may have more distress about their problems compared with women of older reproductive age. While the reason for that is not clear, it may be that in the sexual arena, it is more important for some younger women to be a sexual person than in perimenopausal women, or that women who are younger are more likely to be partnered than women of older reproductive age. While the European Society of Sexual Medicine concluded in a 2019 position statement that there is inconclusive evidence whether hormonal contraception may be contributing to changes in sexual desire and sexual dysfunction, it appears that “a minority of women” experience “better or worse sexual functioning” from taking combined oral contraceptives (Both S et al. J Sex Med. 2019 Nov;16[11]:1681-95), suggesting that the majority of women report no significant changes.
Practitioners should discuss mood effects during consultation
An ob.gyn., primary care physicians, or others with prescriptive authority (i.e. nurse practitioners and physician assistants) in clinical practice may encounter a patient who seems to have mood side effects owing to progestogen-containing contraceptives that they prescribe. However, many ob.gyns. are likely unaware of the prevalence, or that some of those same patients can have such significant mood effects that they would become or are suicidal.
I believe questioning patients about mood effects during consultation and particularly during follow-up following the initiation of any hormonal contraceptive is worth a passing comment for every patient, which should include mood effects in broader discussion for anyone currently using an antidepressant, patients with a history of antidepressant use, and patients who have considered suicide. As we do with other drugs, these questions can be posed in the form of a questionnaire followed up by the practitioner in counseling.
Practitioners who encounter a patient with mood changes as a result of hormonal contraceptive use can consider changing to a nonhormonal method of birth control, or recommending the patient use a barrier method during sexual activity, as none of these options have neuropsychiatric side effects.
Ultimately, practitioners of all types need to engage in shared decision-making to identify the key benefits and risks of hormonal contraceptive use for each patient, which may involve trial and error to determine the ideal treatment. It is critical that practitioners of all types strike a balance between alleviating patient concerns about potential mood changes, monitoring patients with an appreciable risk of mood changes, and continuing patients on hormonal contraception for whom the benefits outweigh the risks.
Dr. Simon is a clinical professor at George Washington University and the medical director and founder of IntimMedicine Specialists in Washington, which provides patient-focused care for women across the reproductive life cycle. He is a past president of the International Society for the Study of Women’s Sexual Health and the North American Menopause Society. Dr. Simon has been a consultant to, received grant and research support from, and served on the speakers bureau for various pharmaceutical companies that develop combination hormonal contraceptives. Email Dr. Simon at obnews@mdedge.com.
Since its introduction in 1950, the combined oral contraceptive pill has been used by countless women as a method for birth control (Liao P. Can Fam Physician. 2012 Dec; 58[12]:e757-e760).
Hormonal contraception (HC) provides women with both contraceptive and noncontraceptive benefits, most notably a method for avoiding unintended pregnancy. In addition to being an effective method of contraception, oral contraceptive pills (OCPs) are well established for treating conditions such as hirsutism, pain symptoms associated with endometriosis and adenomyosis, and pelvic inflammatory disease, among others (Schindler A. Int J Endocrinol Metab. 2013 Winter;11[1]:41-7).
Combined hormonal contraceptives are also first-line treatment for women with menstrual disorders, and in women with polycystic ovary syndrome, can offer an effective long-term method to regulate their menstrual cycle, decrease androgens, clear up oily skin and acne, and reduce facial hair while also providing them with effective contraception (de Melo et al. Open Access J Contracept. 2017;8:13-23).
Associations between ‘the pill’ and mood effects remain controversial
More than 100 million women worldwide use hormonal contraceptives today, yet despite this, the data are mixed regarding the prevalence and extent of neuropsychiatric symptoms and mood changes associated with use of “the pill.” Some studies show combined oral contraceptives are associated with a decrease in general well-being, but had no effect on depression, in women compared with placebo (Zethraeus N et al. Fertil Steril. 2017 May;107[5]:1238-45).
However, a large Danish study published in JAMA Psychiatry of more than 1 million women found a significant association between use of hormonal contraception and antidepressant use or first diagnosis of depression, with adolescents having a higher rate of first depression diagnosis and antidepressant use compared with women 20–30 years old (Skovlund C et al. JAMA Psychiatry. 2016 Nov 1;73[11]:1154-62).
Studies have also shown long-term exposure to levonorgestrel is significantly associated with anxiety and sleep problems in women without a history of these issues (Slattery J et al. Drug Saf. 2018 Oct;41[10]:951-8). A recent small nationwide cohort study in France suggests this may also be true of levonorgestrel delivered by intrauterine devices (IUD) and the association may be dose-dependent (Roland N et al. JAMA. 2023;329[3]:257-9).
Of note, a study published in the American Journal of Psychiatry found a nearly twofold risk of suicide attempt and over threefold risk of suicide among women taking hormonal contraception compared with women who had never used hormonal contraceptives (Skovlund et al. Am J Psychiatry. 2017 Nov 17:appiajp201717060616).
Knowledge gaps make drawing conclusions difficult
The latest information on use of antidepressant and antianxiety medications in women of reproductive age (18-44 years) is sparse and, in some cases, outdated. According to data from the National Health and Nutrition Examination Survey, 18.6% of adult women 18 years or older reported using antidepressant medications within the last 30 days in 2017-2018, an increase from 13.8% in 2009-2010. Among women aged 15-44 year with private employer–sponsored insurance surveyed during 2008-2013, the results showed 15.4% of women filled a prescription for an antidepressant. We must look back further to find data on antianxiety medication use among women aged 18-44 years where use of antianxiety drugs (anxiolytics, sedatives, and hypnotics) was 4.3% between 2005 and 2008.
A lack of literature in this area is likely due to significant underreporting, and an inability to select patients who are sensitive to or at risk of developing neuropsychiatric symptoms resulting from hormonal contraception use because the true pathophysiology is unknown. Existing studies tend to use varying methods to assess mood changes, and do not usually specify hormonal contraceptive use type in their analyses (Schaffir J et al. Eur J Contracept Reprod Health Care. 2016 Oct;21[5]:347-55).
Studies of this nature also require large sample sizes, but the percentage of women who develop neuropsychiatric symptoms from hormonal contraceptive use has historically been relatively small. In the late 1990s, Rosenberg and colleagues found 46% of 1,657 women discontinued oral contraceptives due to side effects within 6 months of starting a new prescription; of these women, 5% reported mood changes as their reason for discontinuing oral contraceptives (Rosenberg M et al. Am J Obstet Gynecol. 1998 Sep;179[3 Pt 1]:577-82).
One might expect that, as lower dosage combined hormonal contraceptives were developed in the 1980s, that the rate of reporting psychological side effects would continue to decrease as well. Yet greater awareness of the potential for mood changes while on “the pill” as outlined by the lay press and social media may be leading to increased reporting of neuropsychiatric effects in women. In a recent cross-sectional survey of 188 women in New York, 43.6% said they experienced mood changes while on hormonal contraceptives, and 61.2% of women with histories of psychiatric illness reported mood changes they attributed to hormonal contraceptives (Martell S et al. Contracept Reprod Med. 2023;8:9).
Martell and colleagues found 48.3% of women cited side effects as a reason for discontinuing hormonal contraception, and 43 participants mentioned psychological side effects unprompted, including 2 patients with suicidal thoughts. The authors said this suggests “psychological side effects, at least in part, may have impacted” HC users’ decisions to switch from OCPs to an alternative method of contraception.
It is also not clear what risk factors exist for women who develop neuropsychiatric symptoms from hormonal contraceptive use. First, it is important to note that both progestin-only contraceptives and combined hormonal contraceptives are classified by the Centers for Disease Control and Prevention’s US Medical Eligibility Criteria for Contraceptive Use, 2016 as having no restrictions for use, including among patients with depression. While women in a smaller subgroup have significant neuropsychiatric symptoms related to their hormonal contraceptives, the underlying mechanism is unknown, and is thought to be largely related to the progestogen component of combined hormonal contraceptives or progestogen-only contraceptives (Mu E. Aust Prescr. 2022 Jun; 45[3]:75-9). We know that some women are hormone sensitive, while others are less so, and some not at all. Progestogens could affect mood as a direct action of the progestogen, because progestogens can be neurosteroids, or the progestogen effect could be mediated secondarily through a change in that woman’s own production of or bioavailability of androgens or naturally occurring estrogens (Giatti S. J Mol Endocrinol. 2016 Aug;57[2]:R109-26).
Here, we also find that currently available evidence limits our ability to draw firm conclusions. A study by Berry-Bibee and colleagues found a “low concern for clinically significant interactions” between hormonal contraception and psychotropic drugs, but was limited by quality/quantity of evidence (Berry-Bibee E et al. Contraception. 2016 Dec;94[6]:650-67). Interestingly, a study by Robinson and colleagues from the mid-2000s posited based on low evidence that “psychological response to the practice of contraception” was a potential explanation for the side effect profile of hormonal contraception (Robinson S et al. Med Hypotheses. 2004;63[2]:268-73).
Further, it may be that women with premenstrual dysphoric disorder (PMDD) might be selected for oral contraceptives, and they are predisposed to other neuropsychiatric problems. Estimates have placed the prevalence of comorbid psychiatric disorders such as anxiety, major depression, bipolar disorder, and posttraumatic stress disorder as high as 70% for women with PMDD (Sepede G et al. Neuropsychiatr Dis Treat. 2020;16:415-26). This phenomenon is not new, having been characterized in the lay literature nearly 20 years ago, by endocrinologist Geoffrey P. Redmond, MD (Redmond GP. The Hormonally Vulnerable Woman. New York: HarperCollins; 2005).
While the cause is not exactly idiosyncratic, They tend to have an entire spectrum of responses to the progestogens in combined or progestin-only contraceptives, ranging from just a flattened affect – which could easily be explained by their flattened level of endogenous hormones – to frank depression. Their frank depression, in turn, can be demonstrated to include suicidal ideation and actual suicide.
Compounding this issue is a woman’s perception of her sexuality. Some women with low sexual desire or sexual problems who are younger may have more distress about their problems compared with women of older reproductive age. While the reason for that is not clear, it may be that in the sexual arena, it is more important for some younger women to be a sexual person than in perimenopausal women, or that women who are younger are more likely to be partnered than women of older reproductive age. While the European Society of Sexual Medicine concluded in a 2019 position statement that there is inconclusive evidence whether hormonal contraception may be contributing to changes in sexual desire and sexual dysfunction, it appears that “a minority of women” experience “better or worse sexual functioning” from taking combined oral contraceptives (Both S et al. J Sex Med. 2019 Nov;16[11]:1681-95), suggesting that the majority of women report no significant changes.
Practitioners should discuss mood effects during consultation
An ob.gyn., primary care physicians, or others with prescriptive authority (i.e. nurse practitioners and physician assistants) in clinical practice may encounter a patient who seems to have mood side effects owing to progestogen-containing contraceptives that they prescribe. However, many ob.gyns. are likely unaware of the prevalence, or that some of those same patients can have such significant mood effects that they would become or are suicidal.
I believe questioning patients about mood effects during consultation and particularly during follow-up following the initiation of any hormonal contraceptive is worth a passing comment for every patient, which should include mood effects in broader discussion for anyone currently using an antidepressant, patients with a history of antidepressant use, and patients who have considered suicide. As we do with other drugs, these questions can be posed in the form of a questionnaire followed up by the practitioner in counseling.
Practitioners who encounter a patient with mood changes as a result of hormonal contraceptive use can consider changing to a nonhormonal method of birth control, or recommending the patient use a barrier method during sexual activity, as none of these options have neuropsychiatric side effects.
Ultimately, practitioners of all types need to engage in shared decision-making to identify the key benefits and risks of hormonal contraceptive use for each patient, which may involve trial and error to determine the ideal treatment. It is critical that practitioners of all types strike a balance between alleviating patient concerns about potential mood changes, monitoring patients with an appreciable risk of mood changes, and continuing patients on hormonal contraception for whom the benefits outweigh the risks.
Dr. Simon is a clinical professor at George Washington University and the medical director and founder of IntimMedicine Specialists in Washington, which provides patient-focused care for women across the reproductive life cycle. He is a past president of the International Society for the Study of Women’s Sexual Health and the North American Menopause Society. Dr. Simon has been a consultant to, received grant and research support from, and served on the speakers bureau for various pharmaceutical companies that develop combination hormonal contraceptives. Email Dr. Simon at obnews@mdedge.com.
Prior authorization abuse: It’s time for health insurance CEOs and their proxies to cease and desist the practice once and for all!
Before reading this editorial and concluding that the author (me) has lost his grip on reality, I would ask that you consider the facts I provide below and the ramifications incurred by your patients and practices, due to the misbehaviors adopted by the health insurance industry.
- Two of the most common issues discussed in today’s health care environment are revenue generation and provider/staff burnout.
While these issues are impacted by several factors, one of the most common denominators is increasing administrative workloads driven by non–revenue-generating activities. Consider this:
- A recent American Medical Association survey pointed out that during the course of the average workweek, a physician completes an average of 37 prior authorization requests. Physicians and their staff spend an average of 16.4 hours per week completing prior authorization requirements for patient medicines, procedures, and medical services that they may need.1
- While physicians report that about 65% of prior authorizations take only 1 day, they report that 26% take 3 or more days.2
The potential significance of the generated delays
While this may not seem like a long time (other than the impact it has on staff workload), consider the impact this can have on the patient if the medication being requested is: PrEP, the morning after pill, or other contraceptives? The consequences of the delay or denial could be a lifetime living with HIV, or an unintended pregnancy. This is to say nothing on the larger impact to family, partners, and the potential social stigma faced by all.
Beyond the personal costs and costs within your practice associated with the additional workload, consider the financial costs. The average cost to complete a prior authorization remains the single highest cost for the health care industry at $13.40 per manual transaction, and $7.19 per partially electronic web portal transaction,3 meaning that if I did only one prescription per week, I probably would not mind, but at $13.40 per prior authorization, this burden amounts to millions, actually $767 million by recent estimates.3 Additionally, if you factor in the number of denials and potential follow-ups, this creates a significant amount of waste and spending.
Ultimately, in my experience, I have found that most prior authorizations are simply unnecessary. Here, I’ve picked key examples from just my own recent experiences:
- My patient was denied access to a particular birth control pill she had been on successfully before, and my office was told she needed to try and fail on 5 different generic pills before she could be approved. However, the Affordable Care Act’s (ACA; aka Obamacare) Contraceptive Mandate requires coverage of all contraceptives determined to be most appropriate between a patient and their provider (see below).
- A menopausal patient was denied coverage twice (electronically) for generic micronized progesterone, and I was asked to write a letter of appeal because the insurance company wanted me to use medroxyprogesterone acetate instead. Polling my nearby retail independent pharmacy, the total cost difference per year was $19.96 savings/year ($47.01 ‒ $27.05 = $19.96). My pharmacist did note it could have been a different amount at a large chain pharmacy. Really? I had to write a letter, following two denials, to save less than $20, for a full year!
- A 78-year-old patient using Prolia for severe osteoporosis and preexisting fractures was delayed in getting her next Prolia injection due to a prior authorization snafu. She ended up with multiple additional fractures, a well-described effect of the increase in bone turnover when stopping or delaying this medication. She is now disabled.
- A 94-year-old patient was sent an email reminder to get the medical practice to authorize a refill of ileostomy bags. The email went to spam, and the patient ran out of bags prior to a holiday weekend. I got them in 2 days on Amazon Prime. But who emails a 94-year-old? And ileostomy bags! When does anyone stop needing ileostomy bags?
- I requested a prior authorization for Orilissa (clearly off label) because a severely progestogen-sensitive patient (augmented depression) with severe premenstrual dysphoric disorder requiring hospitalization was thought by her psychiatrist to be better off without menstrual periods. I completed the proper paperwork, two electronic appeals, and a letter of explanation including available references on the use of gonadotropin-releasing hormone analogues for such patients. I was then told I would need to have a peer-to-peer discussion, so I filled out that paperwork, which clearly noted that I am a board-certified reproductive endocrinologist. I got a phone call a few days later by a pleasant, young-sounding pediatric rheumatologist. Our interaction did not go well for him. This was not peer-to-peer!
Let us be clear, prior authorizations have nothing to do with patient care. In fact, they are solely about the money. We in ObGyn have mostly inexpensive and generic products, but even that fact has not lowered the excessive burden of the prior authorization process. In the case of contraception, whether you like the ACA or not it is the law, and it contains specific provisions regarding contraception. With the goals of providing broad access to patients and incentives to developers for new and novel contraceptive methods, these provisions require insurers to cover, without cost-sharing, women’s preventive services including the full range of FDA-approved contraceptives (currently 18 different method categories), and additional methods identified by the FDA as they become available. Further, providers must have an easily accessible, transparent, and sufficiently expedient exceptions process that is not unduly burdensome on the individual or a provider (or other individuals acting as a patient’s authorized representative).
And while I can regale you with chapter and verse and citations of the legal precedent and language, it boils down to this:
- The AMA reported that medical practices spend an average of 2 business days a week per physician to comply with health plans’ inefficient and overused prior-authorization protocols.4 To keep up with the administrative burden, 2 out of 5 physicians (40%) employ staff members who work exclusively on tasks associated with prior authorization.4
- About 86% of practices reported an increased burden of prior authorizations in the last 5 years.5
Continue to: What is to be done?
What is to be done?
I do have suggested solutions. Given the insurance industry’s complete lack of progress in voluntarily reducing the burdens of prior authorizations agreed to in their consensus statement with the AMA, American Hospital Association, America’s Health Insurance Plans, American Pharmacists Association, Blue Cross Blue Shield Association, and the Medical Group Management Association, I say, why not fine them? The AMA is calling on Congress to pass legislation that would codify much of the agreement, in which the above parties had already agreed that reforms were needed to reduce prior authorization burdens and enhance patient-centered care.6
A good model for enforcement via fines could be based on the old “incident to” rules of Medicare. These state that a physician needs to be “in the space” when advanced practice nurses or physician assistants see Medicare recipients. If they are not actually “in the space” they are subject to a fine. As a completely theoretical example, let’s say the claim was for $100. The practitioner would have to pay it back plus triple that amount in damages, or $400. They can also be fined up to $11,000 per claim and kick you out of Medicare and Medicaid. Take my example of Prolia from above…a single shot of Prolia is about $1,000. The insurer would theoretically have to pay $14,000/claim (the claim + triple damages + $11,000) if it was determined that the prior authorization was unnecessary. Seems about right to me. Or we could just sit the health insurance CEOs and their proxies in the corner on 2-foot-tall plastic Little Tikes® chairs for a “timeout” (dunce cap optional), like the outset of the article says.
Until the detrimental prior authorization process is challenged at all levels, we will continue to see and feel the effects of the harm it causes. Being able to drive change through advocacy and education is the best way we as clinicians can impact not just the future of health care but provide for the daily care of our patients who depend on and trust us to provide for their medical needs. We must be the impactors of change for ourselves, colleagues, staff, and profession if we are to really make advancements into the future.
Oh…and health insurance CEOs and their proxies, to get out of their “time-out” would still be entitled to one phone call to beg forgiveness from their mommies/daddies, priest/ rabbi/pastor, psychologist/psychiatrist/mystic healer, etc., but alas, the average wait time is an hour, and if anyone answers the phone, they have a grade school education used in following an irrelevant algorithm. ●
- Corder JC. Streamlining the insurance prior authorization debacle. Mo Med. 2018;115:312-314.
- Prior authorization hurdles have led to serious adverse events. American Medical Association website. February 5, 2019. https://www.ama-assn .org/press-center/press-releases/prior-author ization-hurdles-have-led-serious-adverse -events. Accessed November 29, 2021.
- Council for Affordable Quality Healthcare. 2020 CAQH INDEX. https://www.caqh.org/sites /default/files/explorations/index/2020-caqh -index.pdf. Accessed November 22, 2021.
- Most physicians had little relief from prior authorization as COVID cases soared. American Medical Association website. April 7, 2021. https:// www.ama-assn.org/press-center/press-releases /most-physicians-had-little-relief-prior-author ization-covid-cases. Accessed November 29, 2021.
- Robeznieks A. 1 in 4 doctors say prior authorization has led to a serious adverse event. American Medical Association website. February 5, 2019. https://www .ama-assn.org/practice-management/sustainability /1-4-doctors-say-prior-authorization-has-led-serious -adverse. Accessed November 29, 2021.
- Physicians call on Congress to address prior authorization reform. American Medical Association website. May 14, 2021. https://www .ama-assn.org/press-center/press-releases /physicians-call-congress-address-prior-author ization-reform. Accessed November 29, 2021.
Before reading this editorial and concluding that the author (me) has lost his grip on reality, I would ask that you consider the facts I provide below and the ramifications incurred by your patients and practices, due to the misbehaviors adopted by the health insurance industry.
- Two of the most common issues discussed in today’s health care environment are revenue generation and provider/staff burnout.
While these issues are impacted by several factors, one of the most common denominators is increasing administrative workloads driven by non–revenue-generating activities. Consider this:
- A recent American Medical Association survey pointed out that during the course of the average workweek, a physician completes an average of 37 prior authorization requests. Physicians and their staff spend an average of 16.4 hours per week completing prior authorization requirements for patient medicines, procedures, and medical services that they may need.1
- While physicians report that about 65% of prior authorizations take only 1 day, they report that 26% take 3 or more days.2
The potential significance of the generated delays
While this may not seem like a long time (other than the impact it has on staff workload), consider the impact this can have on the patient if the medication being requested is: PrEP, the morning after pill, or other contraceptives? The consequences of the delay or denial could be a lifetime living with HIV, or an unintended pregnancy. This is to say nothing on the larger impact to family, partners, and the potential social stigma faced by all.
Beyond the personal costs and costs within your practice associated with the additional workload, consider the financial costs. The average cost to complete a prior authorization remains the single highest cost for the health care industry at $13.40 per manual transaction, and $7.19 per partially electronic web portal transaction,3 meaning that if I did only one prescription per week, I probably would not mind, but at $13.40 per prior authorization, this burden amounts to millions, actually $767 million by recent estimates.3 Additionally, if you factor in the number of denials and potential follow-ups, this creates a significant amount of waste and spending.
Ultimately, in my experience, I have found that most prior authorizations are simply unnecessary. Here, I’ve picked key examples from just my own recent experiences:
- My patient was denied access to a particular birth control pill she had been on successfully before, and my office was told she needed to try and fail on 5 different generic pills before she could be approved. However, the Affordable Care Act’s (ACA; aka Obamacare) Contraceptive Mandate requires coverage of all contraceptives determined to be most appropriate between a patient and their provider (see below).
- A menopausal patient was denied coverage twice (electronically) for generic micronized progesterone, and I was asked to write a letter of appeal because the insurance company wanted me to use medroxyprogesterone acetate instead. Polling my nearby retail independent pharmacy, the total cost difference per year was $19.96 savings/year ($47.01 ‒ $27.05 = $19.96). My pharmacist did note it could have been a different amount at a large chain pharmacy. Really? I had to write a letter, following two denials, to save less than $20, for a full year!
- A 78-year-old patient using Prolia for severe osteoporosis and preexisting fractures was delayed in getting her next Prolia injection due to a prior authorization snafu. She ended up with multiple additional fractures, a well-described effect of the increase in bone turnover when stopping or delaying this medication. She is now disabled.
- A 94-year-old patient was sent an email reminder to get the medical practice to authorize a refill of ileostomy bags. The email went to spam, and the patient ran out of bags prior to a holiday weekend. I got them in 2 days on Amazon Prime. But who emails a 94-year-old? And ileostomy bags! When does anyone stop needing ileostomy bags?
- I requested a prior authorization for Orilissa (clearly off label) because a severely progestogen-sensitive patient (augmented depression) with severe premenstrual dysphoric disorder requiring hospitalization was thought by her psychiatrist to be better off without menstrual periods. I completed the proper paperwork, two electronic appeals, and a letter of explanation including available references on the use of gonadotropin-releasing hormone analogues for such patients. I was then told I would need to have a peer-to-peer discussion, so I filled out that paperwork, which clearly noted that I am a board-certified reproductive endocrinologist. I got a phone call a few days later by a pleasant, young-sounding pediatric rheumatologist. Our interaction did not go well for him. This was not peer-to-peer!
Let us be clear, prior authorizations have nothing to do with patient care. In fact, they are solely about the money. We in ObGyn have mostly inexpensive and generic products, but even that fact has not lowered the excessive burden of the prior authorization process. In the case of contraception, whether you like the ACA or not it is the law, and it contains specific provisions regarding contraception. With the goals of providing broad access to patients and incentives to developers for new and novel contraceptive methods, these provisions require insurers to cover, without cost-sharing, women’s preventive services including the full range of FDA-approved contraceptives (currently 18 different method categories), and additional methods identified by the FDA as they become available. Further, providers must have an easily accessible, transparent, and sufficiently expedient exceptions process that is not unduly burdensome on the individual or a provider (or other individuals acting as a patient’s authorized representative).
And while I can regale you with chapter and verse and citations of the legal precedent and language, it boils down to this:
- The AMA reported that medical practices spend an average of 2 business days a week per physician to comply with health plans’ inefficient and overused prior-authorization protocols.4 To keep up with the administrative burden, 2 out of 5 physicians (40%) employ staff members who work exclusively on tasks associated with prior authorization.4
- About 86% of practices reported an increased burden of prior authorizations in the last 5 years.5
Continue to: What is to be done?
What is to be done?
I do have suggested solutions. Given the insurance industry’s complete lack of progress in voluntarily reducing the burdens of prior authorizations agreed to in their consensus statement with the AMA, American Hospital Association, America’s Health Insurance Plans, American Pharmacists Association, Blue Cross Blue Shield Association, and the Medical Group Management Association, I say, why not fine them? The AMA is calling on Congress to pass legislation that would codify much of the agreement, in which the above parties had already agreed that reforms were needed to reduce prior authorization burdens and enhance patient-centered care.6
A good model for enforcement via fines could be based on the old “incident to” rules of Medicare. These state that a physician needs to be “in the space” when advanced practice nurses or physician assistants see Medicare recipients. If they are not actually “in the space” they are subject to a fine. As a completely theoretical example, let’s say the claim was for $100. The practitioner would have to pay it back plus triple that amount in damages, or $400. They can also be fined up to $11,000 per claim and kick you out of Medicare and Medicaid. Take my example of Prolia from above…a single shot of Prolia is about $1,000. The insurer would theoretically have to pay $14,000/claim (the claim + triple damages + $11,000) if it was determined that the prior authorization was unnecessary. Seems about right to me. Or we could just sit the health insurance CEOs and their proxies in the corner on 2-foot-tall plastic Little Tikes® chairs for a “timeout” (dunce cap optional), like the outset of the article says.
Until the detrimental prior authorization process is challenged at all levels, we will continue to see and feel the effects of the harm it causes. Being able to drive change through advocacy and education is the best way we as clinicians can impact not just the future of health care but provide for the daily care of our patients who depend on and trust us to provide for their medical needs. We must be the impactors of change for ourselves, colleagues, staff, and profession if we are to really make advancements into the future.
Oh…and health insurance CEOs and their proxies, to get out of their “time-out” would still be entitled to one phone call to beg forgiveness from their mommies/daddies, priest/ rabbi/pastor, psychologist/psychiatrist/mystic healer, etc., but alas, the average wait time is an hour, and if anyone answers the phone, they have a grade school education used in following an irrelevant algorithm. ●
Before reading this editorial and concluding that the author (me) has lost his grip on reality, I would ask that you consider the facts I provide below and the ramifications incurred by your patients and practices, due to the misbehaviors adopted by the health insurance industry.
- Two of the most common issues discussed in today’s health care environment are revenue generation and provider/staff burnout.
While these issues are impacted by several factors, one of the most common denominators is increasing administrative workloads driven by non–revenue-generating activities. Consider this:
- A recent American Medical Association survey pointed out that during the course of the average workweek, a physician completes an average of 37 prior authorization requests. Physicians and their staff spend an average of 16.4 hours per week completing prior authorization requirements for patient medicines, procedures, and medical services that they may need.1
- While physicians report that about 65% of prior authorizations take only 1 day, they report that 26% take 3 or more days.2
The potential significance of the generated delays
While this may not seem like a long time (other than the impact it has on staff workload), consider the impact this can have on the patient if the medication being requested is: PrEP, the morning after pill, or other contraceptives? The consequences of the delay or denial could be a lifetime living with HIV, or an unintended pregnancy. This is to say nothing on the larger impact to family, partners, and the potential social stigma faced by all.
Beyond the personal costs and costs within your practice associated with the additional workload, consider the financial costs. The average cost to complete a prior authorization remains the single highest cost for the health care industry at $13.40 per manual transaction, and $7.19 per partially electronic web portal transaction,3 meaning that if I did only one prescription per week, I probably would not mind, but at $13.40 per prior authorization, this burden amounts to millions, actually $767 million by recent estimates.3 Additionally, if you factor in the number of denials and potential follow-ups, this creates a significant amount of waste and spending.
Ultimately, in my experience, I have found that most prior authorizations are simply unnecessary. Here, I’ve picked key examples from just my own recent experiences:
- My patient was denied access to a particular birth control pill she had been on successfully before, and my office was told she needed to try and fail on 5 different generic pills before she could be approved. However, the Affordable Care Act’s (ACA; aka Obamacare) Contraceptive Mandate requires coverage of all contraceptives determined to be most appropriate between a patient and their provider (see below).
- A menopausal patient was denied coverage twice (electronically) for generic micronized progesterone, and I was asked to write a letter of appeal because the insurance company wanted me to use medroxyprogesterone acetate instead. Polling my nearby retail independent pharmacy, the total cost difference per year was $19.96 savings/year ($47.01 ‒ $27.05 = $19.96). My pharmacist did note it could have been a different amount at a large chain pharmacy. Really? I had to write a letter, following two denials, to save less than $20, for a full year!
- A 78-year-old patient using Prolia for severe osteoporosis and preexisting fractures was delayed in getting her next Prolia injection due to a prior authorization snafu. She ended up with multiple additional fractures, a well-described effect of the increase in bone turnover when stopping or delaying this medication. She is now disabled.
- A 94-year-old patient was sent an email reminder to get the medical practice to authorize a refill of ileostomy bags. The email went to spam, and the patient ran out of bags prior to a holiday weekend. I got them in 2 days on Amazon Prime. But who emails a 94-year-old? And ileostomy bags! When does anyone stop needing ileostomy bags?
- I requested a prior authorization for Orilissa (clearly off label) because a severely progestogen-sensitive patient (augmented depression) with severe premenstrual dysphoric disorder requiring hospitalization was thought by her psychiatrist to be better off without menstrual periods. I completed the proper paperwork, two electronic appeals, and a letter of explanation including available references on the use of gonadotropin-releasing hormone analogues for such patients. I was then told I would need to have a peer-to-peer discussion, so I filled out that paperwork, which clearly noted that I am a board-certified reproductive endocrinologist. I got a phone call a few days later by a pleasant, young-sounding pediatric rheumatologist. Our interaction did not go well for him. This was not peer-to-peer!
Let us be clear, prior authorizations have nothing to do with patient care. In fact, they are solely about the money. We in ObGyn have mostly inexpensive and generic products, but even that fact has not lowered the excessive burden of the prior authorization process. In the case of contraception, whether you like the ACA or not it is the law, and it contains specific provisions regarding contraception. With the goals of providing broad access to patients and incentives to developers for new and novel contraceptive methods, these provisions require insurers to cover, without cost-sharing, women’s preventive services including the full range of FDA-approved contraceptives (currently 18 different method categories), and additional methods identified by the FDA as they become available. Further, providers must have an easily accessible, transparent, and sufficiently expedient exceptions process that is not unduly burdensome on the individual or a provider (or other individuals acting as a patient’s authorized representative).
And while I can regale you with chapter and verse and citations of the legal precedent and language, it boils down to this:
- The AMA reported that medical practices spend an average of 2 business days a week per physician to comply with health plans’ inefficient and overused prior-authorization protocols.4 To keep up with the administrative burden, 2 out of 5 physicians (40%) employ staff members who work exclusively on tasks associated with prior authorization.4
- About 86% of practices reported an increased burden of prior authorizations in the last 5 years.5
Continue to: What is to be done?
What is to be done?
I do have suggested solutions. Given the insurance industry’s complete lack of progress in voluntarily reducing the burdens of prior authorizations agreed to in their consensus statement with the AMA, American Hospital Association, America’s Health Insurance Plans, American Pharmacists Association, Blue Cross Blue Shield Association, and the Medical Group Management Association, I say, why not fine them? The AMA is calling on Congress to pass legislation that would codify much of the agreement, in which the above parties had already agreed that reforms were needed to reduce prior authorization burdens and enhance patient-centered care.6
A good model for enforcement via fines could be based on the old “incident to” rules of Medicare. These state that a physician needs to be “in the space” when advanced practice nurses or physician assistants see Medicare recipients. If they are not actually “in the space” they are subject to a fine. As a completely theoretical example, let’s say the claim was for $100. The practitioner would have to pay it back plus triple that amount in damages, or $400. They can also be fined up to $11,000 per claim and kick you out of Medicare and Medicaid. Take my example of Prolia from above…a single shot of Prolia is about $1,000. The insurer would theoretically have to pay $14,000/claim (the claim + triple damages + $11,000) if it was determined that the prior authorization was unnecessary. Seems about right to me. Or we could just sit the health insurance CEOs and their proxies in the corner on 2-foot-tall plastic Little Tikes® chairs for a “timeout” (dunce cap optional), like the outset of the article says.
Until the detrimental prior authorization process is challenged at all levels, we will continue to see and feel the effects of the harm it causes. Being able to drive change through advocacy and education is the best way we as clinicians can impact not just the future of health care but provide for the daily care of our patients who depend on and trust us to provide for their medical needs. We must be the impactors of change for ourselves, colleagues, staff, and profession if we are to really make advancements into the future.
Oh…and health insurance CEOs and their proxies, to get out of their “time-out” would still be entitled to one phone call to beg forgiveness from their mommies/daddies, priest/ rabbi/pastor, psychologist/psychiatrist/mystic healer, etc., but alas, the average wait time is an hour, and if anyone answers the phone, they have a grade school education used in following an irrelevant algorithm. ●
- Corder JC. Streamlining the insurance prior authorization debacle. Mo Med. 2018;115:312-314.
- Prior authorization hurdles have led to serious adverse events. American Medical Association website. February 5, 2019. https://www.ama-assn .org/press-center/press-releases/prior-author ization-hurdles-have-led-serious-adverse -events. Accessed November 29, 2021.
- Council for Affordable Quality Healthcare. 2020 CAQH INDEX. https://www.caqh.org/sites /default/files/explorations/index/2020-caqh -index.pdf. Accessed November 22, 2021.
- Most physicians had little relief from prior authorization as COVID cases soared. American Medical Association website. April 7, 2021. https:// www.ama-assn.org/press-center/press-releases /most-physicians-had-little-relief-prior-author ization-covid-cases. Accessed November 29, 2021.
- Robeznieks A. 1 in 4 doctors say prior authorization has led to a serious adverse event. American Medical Association website. February 5, 2019. https://www .ama-assn.org/practice-management/sustainability /1-4-doctors-say-prior-authorization-has-led-serious -adverse. Accessed November 29, 2021.
- Physicians call on Congress to address prior authorization reform. American Medical Association website. May 14, 2021. https://www .ama-assn.org/press-center/press-releases /physicians-call-congress-address-prior-author ization-reform. Accessed November 29, 2021.
- Corder JC. Streamlining the insurance prior authorization debacle. Mo Med. 2018;115:312-314.
- Prior authorization hurdles have led to serious adverse events. American Medical Association website. February 5, 2019. https://www.ama-assn .org/press-center/press-releases/prior-author ization-hurdles-have-led-serious-adverse -events. Accessed November 29, 2021.
- Council for Affordable Quality Healthcare. 2020 CAQH INDEX. https://www.caqh.org/sites /default/files/explorations/index/2020-caqh -index.pdf. Accessed November 22, 2021.
- Most physicians had little relief from prior authorization as COVID cases soared. American Medical Association website. April 7, 2021. https:// www.ama-assn.org/press-center/press-releases /most-physicians-had-little-relief-prior-author ization-covid-cases. Accessed November 29, 2021.
- Robeznieks A. 1 in 4 doctors say prior authorization has led to a serious adverse event. American Medical Association website. February 5, 2019. https://www .ama-assn.org/practice-management/sustainability /1-4-doctors-say-prior-authorization-has-led-serious -adverse. Accessed November 29, 2021.
- Physicians call on Congress to address prior authorization reform. American Medical Association website. May 14, 2021. https://www .ama-assn.org/press-center/press-releases /physicians-call-congress-address-prior-author ization-reform. Accessed November 29, 2021.
Cervical cancer screening: National snapshot reveals confusion over optimal intervals
Results of a recent survey of provider and patient attitudes toward and behaviors surrounding cervical cancer screening indicate there is much confusion, among both practitioners and patients, about the optimal screening interval for cervical cancer. Only 48% of women understood that HPV can cause cervical cancer.
The survey, of 2000 women and 750 providers, was conducted by the National Association of Nurse Practitioners in Women’s Health and Healthy Women.
This special audiocast is an interview with James S. Simon, MD, panel member for the survey release event in Washington, DC.
Listen to hear the survey results and Dr. Simon discuss:
• The roots of the highlighted confusion around cervical cancer screening among women and practitioners
• How often he screens patients for cervical cancer and what tests he employs
• His patient counseling strategy regarding HPV and other sexually transmitted infections
Dr. James A. Simon reports having served (within the last year) or currently serving as a consultant to or on the advisory boards of: AbbVie, Inc. (North Chicago, IL), Actavis, PLC. (Dublin, Ireland), Amgen Inc. (Thousand Oaks, CA), Amneal Pharmaceuticals (Bridgewater, NJ), Apotex, Inc. (Toronto, Canada), Ascend Therapeutics (Herndon, VA), Dr. Reddy Laboratories, Ltd. (Hyderabad, India), Everett Laboratories, Inc. (West Orange, NJ), Lupin Pharmaceuticals, (Baltimore, MD), Merck & Co., Inc. (Whitehouse Station, NJ), Novartis Pharmaceuticals Corporation (East Hanover, NJ), Noven Pharmaceuticals, Inc. (New York, NY), Novo Nordisk (Bagsvrerd, Denmark), Pfizer Inc. (New York, NY), Shionogi Inc. (Florham Park, NJ), Shippan Point Advisors LLC (Upper Saddle River, NJ), Sprout Pharmaceuticals (Raleigh, NC), and TherapeuticsMD (Boca Raton, FL).
He reports having received grant/research support in the last year or currently from: AbbVie, Inc. (North Chicago, IL), Actavis, PLC. (Dublin, Ireland), Agile Therapeutics (Princeton, NJ), Bayer Healthcare LLC., (Tarrytown, NY), New England Research Institute, Inc. (Watertown, MA), Novo Nordisk (Bagsvrerd, Denmark), Palatin Technologies (Cranbury, NJ), and Teva Pharmaceutical Industries Ltd (Jerusalem, Israel), and TherapeuticsMD (Boca Raton, FL).
He also reports having served or currently serving on the speakers' bureaus of: Amgen Inc. (Thousand Oaks, CA), Eisai, Inc. (Woodcliff Lake, NJ), Merck (Whitehouse Station, NJ), Noven Pharmaceuticals, Inc. (New York, NY), Novo Nordisk (Bagsvrerd, Denmark), and Shionogi Inc. (Florham Park, NJ).
Results of a recent survey of provider and patient attitudes toward and behaviors surrounding cervical cancer screening indicate there is much confusion, among both practitioners and patients, about the optimal screening interval for cervical cancer. Only 48% of women understood that HPV can cause cervical cancer.
The survey, of 2000 women and 750 providers, was conducted by the National Association of Nurse Practitioners in Women’s Health and Healthy Women.
This special audiocast is an interview with James S. Simon, MD, panel member for the survey release event in Washington, DC.
Listen to hear the survey results and Dr. Simon discuss:
• The roots of the highlighted confusion around cervical cancer screening among women and practitioners
• How often he screens patients for cervical cancer and what tests he employs
• His patient counseling strategy regarding HPV and other sexually transmitted infections
Dr. James A. Simon reports having served (within the last year) or currently serving as a consultant to or on the advisory boards of: AbbVie, Inc. (North Chicago, IL), Actavis, PLC. (Dublin, Ireland), Amgen Inc. (Thousand Oaks, CA), Amneal Pharmaceuticals (Bridgewater, NJ), Apotex, Inc. (Toronto, Canada), Ascend Therapeutics (Herndon, VA), Dr. Reddy Laboratories, Ltd. (Hyderabad, India), Everett Laboratories, Inc. (West Orange, NJ), Lupin Pharmaceuticals, (Baltimore, MD), Merck & Co., Inc. (Whitehouse Station, NJ), Novartis Pharmaceuticals Corporation (East Hanover, NJ), Noven Pharmaceuticals, Inc. (New York, NY), Novo Nordisk (Bagsvrerd, Denmark), Pfizer Inc. (New York, NY), Shionogi Inc. (Florham Park, NJ), Shippan Point Advisors LLC (Upper Saddle River, NJ), Sprout Pharmaceuticals (Raleigh, NC), and TherapeuticsMD (Boca Raton, FL).
He reports having received grant/research support in the last year or currently from: AbbVie, Inc. (North Chicago, IL), Actavis, PLC. (Dublin, Ireland), Agile Therapeutics (Princeton, NJ), Bayer Healthcare LLC., (Tarrytown, NY), New England Research Institute, Inc. (Watertown, MA), Novo Nordisk (Bagsvrerd, Denmark), Palatin Technologies (Cranbury, NJ), and Teva Pharmaceutical Industries Ltd (Jerusalem, Israel), and TherapeuticsMD (Boca Raton, FL).
He also reports having served or currently serving on the speakers' bureaus of: Amgen Inc. (Thousand Oaks, CA), Eisai, Inc. (Woodcliff Lake, NJ), Merck (Whitehouse Station, NJ), Noven Pharmaceuticals, Inc. (New York, NY), Novo Nordisk (Bagsvrerd, Denmark), and Shionogi Inc. (Florham Park, NJ).
Results of a recent survey of provider and patient attitudes toward and behaviors surrounding cervical cancer screening indicate there is much confusion, among both practitioners and patients, about the optimal screening interval for cervical cancer. Only 48% of women understood that HPV can cause cervical cancer.
The survey, of 2000 women and 750 providers, was conducted by the National Association of Nurse Practitioners in Women’s Health and Healthy Women.
This special audiocast is an interview with James S. Simon, MD, panel member for the survey release event in Washington, DC.
Listen to hear the survey results and Dr. Simon discuss:
• The roots of the highlighted confusion around cervical cancer screening among women and practitioners
• How often he screens patients for cervical cancer and what tests he employs
• His patient counseling strategy regarding HPV and other sexually transmitted infections
Dr. James A. Simon reports having served (within the last year) or currently serving as a consultant to or on the advisory boards of: AbbVie, Inc. (North Chicago, IL), Actavis, PLC. (Dublin, Ireland), Amgen Inc. (Thousand Oaks, CA), Amneal Pharmaceuticals (Bridgewater, NJ), Apotex, Inc. (Toronto, Canada), Ascend Therapeutics (Herndon, VA), Dr. Reddy Laboratories, Ltd. (Hyderabad, India), Everett Laboratories, Inc. (West Orange, NJ), Lupin Pharmaceuticals, (Baltimore, MD), Merck & Co., Inc. (Whitehouse Station, NJ), Novartis Pharmaceuticals Corporation (East Hanover, NJ), Noven Pharmaceuticals, Inc. (New York, NY), Novo Nordisk (Bagsvrerd, Denmark), Pfizer Inc. (New York, NY), Shionogi Inc. (Florham Park, NJ), Shippan Point Advisors LLC (Upper Saddle River, NJ), Sprout Pharmaceuticals (Raleigh, NC), and TherapeuticsMD (Boca Raton, FL).
He reports having received grant/research support in the last year or currently from: AbbVie, Inc. (North Chicago, IL), Actavis, PLC. (Dublin, Ireland), Agile Therapeutics (Princeton, NJ), Bayer Healthcare LLC., (Tarrytown, NY), New England Research Institute, Inc. (Watertown, MA), Novo Nordisk (Bagsvrerd, Denmark), Palatin Technologies (Cranbury, NJ), and Teva Pharmaceutical Industries Ltd (Jerusalem, Israel), and TherapeuticsMD (Boca Raton, FL).
He also reports having served or currently serving on the speakers' bureaus of: Amgen Inc. (Thousand Oaks, CA), Eisai, Inc. (Woodcliff Lake, NJ), Merck (Whitehouse Station, NJ), Noven Pharmaceuticals, Inc. (New York, NY), Novo Nordisk (Bagsvrerd, Denmark), and Shionogi Inc. (Florham Park, NJ).
Your postmenopausal patient reports a history of migraine
Brought to you by the menopause experts
| Andrew M. Kaunitz, MD |
| JoAnn V. Pinkerton, MD |
| James A. Simon, MD |
Disclosures
Dr. Kaunitz reports that his institution receives grant or research support from Bayer, Teva, Medical Diagnostic Laboratories, and Noven, and that he is a consultant to Bayer, Actavis, and Teva.
Dr. Pinkerton reports that her institution receives consulting fees from Pfizer, DepoMed, Shionogi, and Noven and multicenter research fees from DepoMed, Endoceutics, and Bionova.
Dr. Simon reports being a consultant to or on the advisory boards of Abbott Laboratories, Agile Therapeutics, Amgen, Ascend Therapeutics, BioSante, Depomed, Lelo, MD Therapeutics, Meda Pharmaceuticals, Merck, Noven, Novo Nordisk, Novogyne, Pfizer, Shionogi, Shippan Point Advisors LLC, Slate Pharmaceuticals, Sprout Pharmaceuticals, Teva, Warner Chilcott, and Watson. He also reports receiving (currently or in the past year) grant/research support from BioSante, EndoCeutics, Novo Nordisk, Novogyne, Palatin Technologies, Teva, and Warner Chilcott. He reports serving on the speakers bureaus of Amgen, Merck, Novartis, Noven, Novo Nordisk, Novogyne, Teva, and Warner Chilcott. Dr. Simon is currently the Chief Medical Officer for Sprout Pharmaceuticals.
CASE: Menopausal symptoms and a history of migraine with aura
Your new patient is a 52-year-old woman (G2P2) who reports a long history of two types of migraine: menstrually related migraine without aura and nonmenstrually related migraine with aura (usually involving visual scotomata). Other than the history of migraine, her health is good. Now postmenopausal, she has been referred to you by her primary care physician (PCP) for management of severe vasomotor symptoms and sleep disturbance.
Because of this patient’s history of migraine, her PCP declined to prescribe oral contraceptives (OCs) in the past over concern of increasing her risk of stroke. For her vasomotor symptoms, her PCP prescribed a trial of venlafaxine (Effexor) 75 mg daily, but her orgasms, which always had been difficult to achieve, became impossible. In addition, the patient began to perspire heavily unrelated to her hot flashes. As a result, she describes her mood as “terrible,” her energy level as “miniscule,” and she reports losing interest in sex completely (“I am just too tired”). She and her referring physician wonder whether it would be safe to try hormone therapy (HT).
A physical examination, including funduscopic assessment, reveals no abnormalities. Her blood pressure is 126/70 mm Hg, and blood chemistry results, including C-reactive protein, 25-hydroxy vitamin D, a complete blood count, and lipid profile, are all normal.
Would you offer this patient the option of HT?
Migraine affects roughly twice as many women as men.1 During the reproductive years, rapid fluctuations in ovarian hormones—both increases at midcycle and, to a greater extent, decreases during the premenstrual phase—are believed to be migraine “triggers.” Women who experience menstrually related migraine before menopause typically have an increased risk of migraine during perimenopause, with a significant reduction of migraine symptoms following menopause.2
Side effects of SSRIs and SNRIs
Most providers are aware that selective serotonin reuptake inhibitors (SSRIs) cause sexual side effects in as many as 80% of users. There is a dose-related pattern to reports of sexual problems among SSRI users, with higher doses causing more problems. The most common sexual symptoms associated with SSRIs are delayed ejaculation and absent or delayed orgasm.3
What is not as widely known is that even serotonin-norepinephrine reuptake inhibitors (SNRIs) can cause sexual dysfunction. For example, in a prospective, multicenter study from Spain involving more than
1,000 outpatients, all of whom were taking an antidepressant, the overall rate of sexual dysfunction was 59%.4 Sexual dysfunction was most common among users of SSRIs and venlafaxine, an SNRI.5
Another common side effect of venlafaxine, sweating, is unrelated to hot flashes.5 So two of this patient’s concerns—orgasmic difficulties and profuse sweating unrelated to hot flashes—may have been caused or worsened by her antidepressant.
Another nonhormonal option
In June 2013, the US Food and Drug Administration (FDA) approved paroxetine mesylate (Brisdelle), an SSRI, for the treatment of moderate to severe menopausal vasomotor symptoms. Because the drug is a strong CYP2D6 inhibitor, it should not be given to women taking another medication that is metabolized by CYP2D6—most notably, tamoxifen.
Preliminary data on this drug suggest that, at the recommended dose (7.5 mg/d), it has no effect on sexual function.6 For this reason, it is another option for our patient to consider.
Related article: The gynecologist's role in managing menstrual migraine Anne H. Calhoun, MD
Migraine and the risk of stroke
Migraine with aura has been associated with an increased risk of stroke and other cerebral vascular events,7 and that risk is further elevated in patients treated with OCs.8 Although migraine without aura also may be associated with an elevated risk of stroke, OCs do not further increase that risk.
Some practitioners assume that the data on the risk of stroke associated with OC use also applies to hormone therapy, but there is no evidence that HT, in which doses of estrogen are far lower than in OCs, increases the risk of stroke in migraineurs to any greater degree than would be expected in unselected populations (ie, as noted in the Women’s Health Initiative, Nurses Health Study, or other large investigations). Therefore, HT would be an appropriate option for this patient if her very slight risk of stroke on HT would be acceptable to the practitioner and patient.
Choosing an HT formulation
Consider the pharmacokinetic profile. Many oral estrogen HT products have rapid-release characteristics that make them likely to contribute to rapid rises and falls in the user’s estrogen level. Oral estrogens also are associated with procoagulant properties that may increase the risk of thrombosis and thromboembolism. Nonoral estrogens do not appear to increase these risks.13
Nonoral estrogens (patches, gels, sprays, lotions, and vaginal rings) provide a more stable pharmacokinetic profile, as do some oral products with controlled-release properties.
As for progestins, some formulations (medroxyprogesterone acetate) tend to cause vasoconstriction, whereas others (micronized progesterone) tend to be vasodilators. Whether these properties affect the rate of migraine or risk of stroke is unclear.
My management approach for this patient
In the absence of any systematic data on the use of HT in this clinical setting, and without any concrete suggestions from migraine experts, I would take the following three-step approach:
1. I would begin with a low-dose nonoral estradiol formulation, prescribing it without a progestin even in a woman who still has a uterus. My aim: to determine the lowest effective dose of HT for this particular patient. I would follow the patient on this dose for 3 months.
JoAnn V. Pinkerton, MD:
Another goal is to determine whether transdermal estradiol increases headaches. Before settling on a therapy, however, I would ask how long this patient has been postmenopausal, how long she has been experiencing vasomotor symptoms, and how severe those symptoms are. For example, is she having 7 or 8 hot flashes per day and waking from night sweats once or twice per night? I also would ask her how long she remained on the venlafaxine. The additional information would allow me to fine-tune her treatment.
2. If this formulation is tolerated, I would add micronized progesterone (oral or vaginal) for endometrial protection.
JoAnn V. Pinkerton, MD:
I would give oral progesterone if it is FDA approved for postmenopausal use, vaginal progesterone if it isn’t.
3. I would follow the patient’s clinical response—specifically, her vasomotor symptoms and rate of migraine with or without aura.
Hormone therapy is one option for postmenopausal migraineurs with bothersome vasomotor symptoms
Many women with a history of migraine move into menopause expecting their condition to improve, says headache expert Anne H. Calhoun, MD, a founder of the Carolina Headache Institute in Chapel Hill, North Carolina.
“Over the years, these women have heard that things get better with menopause.”
For women with a history of episodic migraine, that expectation is realistic, Calhoun says. “But for women with chronic migraine, who may experience a low-grade headache on a daily, or almost daily basis, with 10 or 12 severe headaches in a month, things usually get worse after menopause because the sleep issues of menopause are superimposed on the migraine.”
Dr. Calhoun observes that hormone therapy (HT) has never been contraindicated in women with migraine, although many neurologists are hesitant to prescribe any hormones for this population.
Before prescribing HT to a postmenopausal migraineur, Dr. Calhoun considers a range of variables, including sleep patterns, current medications, anxiety, frequency and severity of vasomotor symptoms, and any other problems the patient may be experiencing.
“It’s basically the same assessment as with any postmenopausal patient—to determine whether HT is a reasonable option,” she says.
And when she determines that HT is appropriate, “I almost exclusively use transdermal HT. I also am more likely to prescribe continuous use of a transdermal patch or skin gel, as I want to achieve very consistent hormone levels, day in and day out,” she says.
My bottom line
No systematic data on the use of HT in migraineurs has been published. In the absence of such data, some practitioners have extrapolated data on the use of OCs in this population and decline to prescribe HT to women with migraine. However, HT and OCs are vastly different in formulation, dose, and risks. Rather than make assumptions on the basis of irrelevant data, we should conduct studies of HT use in migraineurs.
Related article: Update on Menopause Andrew M. Kaunitz, MD (June 2013)
Women who have menstrually related migraine typically have an increased risk of migraine during perimenopause and a significant reduction in migraine following menopause. If hot flashes are bothersome, these women certainly can use HT. I recommend prescribing HT in a continuous fashion that maintains stable hormone levels in the blood, as fluctuating hormones tend to trigger migraines.
Andrew M. Kaunitz, MD:
I would just add that transdermal estradiol is preferred, to be given at the lowest effective dose.
Do you have a troubling case in menopause? Suggest it to the expert panel: obg@frontlinemedcom.com. They may address your management dilemma in a future issue.
We want to hear from you! Send us your Letter to the Editor
1. Shuster LT, Faubion SS. Sood R, Casey PM. Hormonal manipulation strategies in the management of menstrual migraine and other hormonally related headaches. Curr Neurol Neurosci Rep. 2011;11(2):131–138.
2. Loder E, Rizzoli P, Golub J. Hormonal management of migraine associated with menses and the menopause: a clinical review. Headache. 2007;47(2):329–340.
3. Balon R. SSRI-associated sexual dysfunction. Am J Psychiatry. 2006;163:1504–1509.
4. Taylor MJ. Strategies for managing antidepressant-induced sexual dysfunction: a review. Curr Psychiatry Rep. 2006;8(6):431–436.
5. Effexor [package insert]. New York, NY: Pfizer; 2012.
6. Brisdelle [package insert]. Miami, FL: Noven Therapeutics; 2013.
7. Etminan M, Takkouche B, Isorna FC, Samli A. Risk of ischaemic stroke in people with migraine: systematic review and meta-analysis of observational studies. BMJ. 2005;330(7482):63–65.
8. Becker WJ. Use of oral contraceptives in patients with migraine. Neurology. 1999;53(4 Suppl 1):S19–S25.
9. WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Ischaemic stroke and combined oral contraceptives: results of an international, multicentre, case-control study. Lancet. 1996;348(9026): 498–505.
10. Petitti DB, Sidney S, Bernstein A, Wolf S, Quesenberry C, Ziel HK. Stroke in users of low-dose oral contraceptives. N Engl J Med. 1996;335(1):8-15.
11. Marjoribanks J, Farquhar C, Roberts H, Lethaby A. Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2012;7:CD004143. doi: 10.1002/14651858.CD004143.pub4
12. Renoux C, Dell’aniello S, Garbe E, Suissa S. Transdermal and oral hormone replacement therapy and the risk of stroke: a nested case-control study. BMJ. 2010;340:c2519.
13. Kaunitz AM. Update on Menopause. OBG Manag. 2013;25(6):36–43, 49.
Brought to you by the menopause experts
| Andrew M. Kaunitz, MD |
| JoAnn V. Pinkerton, MD |
| James A. Simon, MD |
Disclosures
Dr. Kaunitz reports that his institution receives grant or research support from Bayer, Teva, Medical Diagnostic Laboratories, and Noven, and that he is a consultant to Bayer, Actavis, and Teva.
Dr. Pinkerton reports that her institution receives consulting fees from Pfizer, DepoMed, Shionogi, and Noven and multicenter research fees from DepoMed, Endoceutics, and Bionova.
Dr. Simon reports being a consultant to or on the advisory boards of Abbott Laboratories, Agile Therapeutics, Amgen, Ascend Therapeutics, BioSante, Depomed, Lelo, MD Therapeutics, Meda Pharmaceuticals, Merck, Noven, Novo Nordisk, Novogyne, Pfizer, Shionogi, Shippan Point Advisors LLC, Slate Pharmaceuticals, Sprout Pharmaceuticals, Teva, Warner Chilcott, and Watson. He also reports receiving (currently or in the past year) grant/research support from BioSante, EndoCeutics, Novo Nordisk, Novogyne, Palatin Technologies, Teva, and Warner Chilcott. He reports serving on the speakers bureaus of Amgen, Merck, Novartis, Noven, Novo Nordisk, Novogyne, Teva, and Warner Chilcott. Dr. Simon is currently the Chief Medical Officer for Sprout Pharmaceuticals.
CASE: Menopausal symptoms and a history of migraine with aura
Your new patient is a 52-year-old woman (G2P2) who reports a long history of two types of migraine: menstrually related migraine without aura and nonmenstrually related migraine with aura (usually involving visual scotomata). Other than the history of migraine, her health is good. Now postmenopausal, she has been referred to you by her primary care physician (PCP) for management of severe vasomotor symptoms and sleep disturbance.
Because of this patient’s history of migraine, her PCP declined to prescribe oral contraceptives (OCs) in the past over concern of increasing her risk of stroke. For her vasomotor symptoms, her PCP prescribed a trial of venlafaxine (Effexor) 75 mg daily, but her orgasms, which always had been difficult to achieve, became impossible. In addition, the patient began to perspire heavily unrelated to her hot flashes. As a result, she describes her mood as “terrible,” her energy level as “miniscule,” and she reports losing interest in sex completely (“I am just too tired”). She and her referring physician wonder whether it would be safe to try hormone therapy (HT).
A physical examination, including funduscopic assessment, reveals no abnormalities. Her blood pressure is 126/70 mm Hg, and blood chemistry results, including C-reactive protein, 25-hydroxy vitamin D, a complete blood count, and lipid profile, are all normal.
Would you offer this patient the option of HT?
Migraine affects roughly twice as many women as men.1 During the reproductive years, rapid fluctuations in ovarian hormones—both increases at midcycle and, to a greater extent, decreases during the premenstrual phase—are believed to be migraine “triggers.” Women who experience menstrually related migraine before menopause typically have an increased risk of migraine during perimenopause, with a significant reduction of migraine symptoms following menopause.2
Side effects of SSRIs and SNRIs
Most providers are aware that selective serotonin reuptake inhibitors (SSRIs) cause sexual side effects in as many as 80% of users. There is a dose-related pattern to reports of sexual problems among SSRI users, with higher doses causing more problems. The most common sexual symptoms associated with SSRIs are delayed ejaculation and absent or delayed orgasm.3
What is not as widely known is that even serotonin-norepinephrine reuptake inhibitors (SNRIs) can cause sexual dysfunction. For example, in a prospective, multicenter study from Spain involving more than
1,000 outpatients, all of whom were taking an antidepressant, the overall rate of sexual dysfunction was 59%.4 Sexual dysfunction was most common among users of SSRIs and venlafaxine, an SNRI.5
Another common side effect of venlafaxine, sweating, is unrelated to hot flashes.5 So two of this patient’s concerns—orgasmic difficulties and profuse sweating unrelated to hot flashes—may have been caused or worsened by her antidepressant.
Another nonhormonal option
In June 2013, the US Food and Drug Administration (FDA) approved paroxetine mesylate (Brisdelle), an SSRI, for the treatment of moderate to severe menopausal vasomotor symptoms. Because the drug is a strong CYP2D6 inhibitor, it should not be given to women taking another medication that is metabolized by CYP2D6—most notably, tamoxifen.
Preliminary data on this drug suggest that, at the recommended dose (7.5 mg/d), it has no effect on sexual function.6 For this reason, it is another option for our patient to consider.
Related article: The gynecologist's role in managing menstrual migraine Anne H. Calhoun, MD
Migraine and the risk of stroke
Migraine with aura has been associated with an increased risk of stroke and other cerebral vascular events,7 and that risk is further elevated in patients treated with OCs.8 Although migraine without aura also may be associated with an elevated risk of stroke, OCs do not further increase that risk.
Some practitioners assume that the data on the risk of stroke associated with OC use also applies to hormone therapy, but there is no evidence that HT, in which doses of estrogen are far lower than in OCs, increases the risk of stroke in migraineurs to any greater degree than would be expected in unselected populations (ie, as noted in the Women’s Health Initiative, Nurses Health Study, or other large investigations). Therefore, HT would be an appropriate option for this patient if her very slight risk of stroke on HT would be acceptable to the practitioner and patient.
Choosing an HT formulation
Consider the pharmacokinetic profile. Many oral estrogen HT products have rapid-release characteristics that make them likely to contribute to rapid rises and falls in the user’s estrogen level. Oral estrogens also are associated with procoagulant properties that may increase the risk of thrombosis and thromboembolism. Nonoral estrogens do not appear to increase these risks.13
Nonoral estrogens (patches, gels, sprays, lotions, and vaginal rings) provide a more stable pharmacokinetic profile, as do some oral products with controlled-release properties.
As for progestins, some formulations (medroxyprogesterone acetate) tend to cause vasoconstriction, whereas others (micronized progesterone) tend to be vasodilators. Whether these properties affect the rate of migraine or risk of stroke is unclear.
My management approach for this patient
In the absence of any systematic data on the use of HT in this clinical setting, and without any concrete suggestions from migraine experts, I would take the following three-step approach:
1. I would begin with a low-dose nonoral estradiol formulation, prescribing it without a progestin even in a woman who still has a uterus. My aim: to determine the lowest effective dose of HT for this particular patient. I would follow the patient on this dose for 3 months.
JoAnn V. Pinkerton, MD:
Another goal is to determine whether transdermal estradiol increases headaches. Before settling on a therapy, however, I would ask how long this patient has been postmenopausal, how long she has been experiencing vasomotor symptoms, and how severe those symptoms are. For example, is she having 7 or 8 hot flashes per day and waking from night sweats once or twice per night? I also would ask her how long she remained on the venlafaxine. The additional information would allow me to fine-tune her treatment.
2. If this formulation is tolerated, I would add micronized progesterone (oral or vaginal) for endometrial protection.
JoAnn V. Pinkerton, MD:
I would give oral progesterone if it is FDA approved for postmenopausal use, vaginal progesterone if it isn’t.
3. I would follow the patient’s clinical response—specifically, her vasomotor symptoms and rate of migraine with or without aura.
Hormone therapy is one option for postmenopausal migraineurs with bothersome vasomotor symptoms
Many women with a history of migraine move into menopause expecting their condition to improve, says headache expert Anne H. Calhoun, MD, a founder of the Carolina Headache Institute in Chapel Hill, North Carolina.
“Over the years, these women have heard that things get better with menopause.”
For women with a history of episodic migraine, that expectation is realistic, Calhoun says. “But for women with chronic migraine, who may experience a low-grade headache on a daily, or almost daily basis, with 10 or 12 severe headaches in a month, things usually get worse after menopause because the sleep issues of menopause are superimposed on the migraine.”
Dr. Calhoun observes that hormone therapy (HT) has never been contraindicated in women with migraine, although many neurologists are hesitant to prescribe any hormones for this population.
Before prescribing HT to a postmenopausal migraineur, Dr. Calhoun considers a range of variables, including sleep patterns, current medications, anxiety, frequency and severity of vasomotor symptoms, and any other problems the patient may be experiencing.
“It’s basically the same assessment as with any postmenopausal patient—to determine whether HT is a reasonable option,” she says.
And when she determines that HT is appropriate, “I almost exclusively use transdermal HT. I also am more likely to prescribe continuous use of a transdermal patch or skin gel, as I want to achieve very consistent hormone levels, day in and day out,” she says.
My bottom line
No systematic data on the use of HT in migraineurs has been published. In the absence of such data, some practitioners have extrapolated data on the use of OCs in this population and decline to prescribe HT to women with migraine. However, HT and OCs are vastly different in formulation, dose, and risks. Rather than make assumptions on the basis of irrelevant data, we should conduct studies of HT use in migraineurs.
Related article: Update on Menopause Andrew M. Kaunitz, MD (June 2013)
Women who have menstrually related migraine typically have an increased risk of migraine during perimenopause and a significant reduction in migraine following menopause. If hot flashes are bothersome, these women certainly can use HT. I recommend prescribing HT in a continuous fashion that maintains stable hormone levels in the blood, as fluctuating hormones tend to trigger migraines.
Andrew M. Kaunitz, MD:
I would just add that transdermal estradiol is preferred, to be given at the lowest effective dose.
Do you have a troubling case in menopause? Suggest it to the expert panel: obg@frontlinemedcom.com. They may address your management dilemma in a future issue.
We want to hear from you! Send us your Letter to the Editor
Brought to you by the menopause experts
| Andrew M. Kaunitz, MD |
| JoAnn V. Pinkerton, MD |
| James A. Simon, MD |
Disclosures
Dr. Kaunitz reports that his institution receives grant or research support from Bayer, Teva, Medical Diagnostic Laboratories, and Noven, and that he is a consultant to Bayer, Actavis, and Teva.
Dr. Pinkerton reports that her institution receives consulting fees from Pfizer, DepoMed, Shionogi, and Noven and multicenter research fees from DepoMed, Endoceutics, and Bionova.
Dr. Simon reports being a consultant to or on the advisory boards of Abbott Laboratories, Agile Therapeutics, Amgen, Ascend Therapeutics, BioSante, Depomed, Lelo, MD Therapeutics, Meda Pharmaceuticals, Merck, Noven, Novo Nordisk, Novogyne, Pfizer, Shionogi, Shippan Point Advisors LLC, Slate Pharmaceuticals, Sprout Pharmaceuticals, Teva, Warner Chilcott, and Watson. He also reports receiving (currently or in the past year) grant/research support from BioSante, EndoCeutics, Novo Nordisk, Novogyne, Palatin Technologies, Teva, and Warner Chilcott. He reports serving on the speakers bureaus of Amgen, Merck, Novartis, Noven, Novo Nordisk, Novogyne, Teva, and Warner Chilcott. Dr. Simon is currently the Chief Medical Officer for Sprout Pharmaceuticals.
CASE: Menopausal symptoms and a history of migraine with aura
Your new patient is a 52-year-old woman (G2P2) who reports a long history of two types of migraine: menstrually related migraine without aura and nonmenstrually related migraine with aura (usually involving visual scotomata). Other than the history of migraine, her health is good. Now postmenopausal, she has been referred to you by her primary care physician (PCP) for management of severe vasomotor symptoms and sleep disturbance.
Because of this patient’s history of migraine, her PCP declined to prescribe oral contraceptives (OCs) in the past over concern of increasing her risk of stroke. For her vasomotor symptoms, her PCP prescribed a trial of venlafaxine (Effexor) 75 mg daily, but her orgasms, which always had been difficult to achieve, became impossible. In addition, the patient began to perspire heavily unrelated to her hot flashes. As a result, she describes her mood as “terrible,” her energy level as “miniscule,” and she reports losing interest in sex completely (“I am just too tired”). She and her referring physician wonder whether it would be safe to try hormone therapy (HT).
A physical examination, including funduscopic assessment, reveals no abnormalities. Her blood pressure is 126/70 mm Hg, and blood chemistry results, including C-reactive protein, 25-hydroxy vitamin D, a complete blood count, and lipid profile, are all normal.
Would you offer this patient the option of HT?
Migraine affects roughly twice as many women as men.1 During the reproductive years, rapid fluctuations in ovarian hormones—both increases at midcycle and, to a greater extent, decreases during the premenstrual phase—are believed to be migraine “triggers.” Women who experience menstrually related migraine before menopause typically have an increased risk of migraine during perimenopause, with a significant reduction of migraine symptoms following menopause.2
Side effects of SSRIs and SNRIs
Most providers are aware that selective serotonin reuptake inhibitors (SSRIs) cause sexual side effects in as many as 80% of users. There is a dose-related pattern to reports of sexual problems among SSRI users, with higher doses causing more problems. The most common sexual symptoms associated with SSRIs are delayed ejaculation and absent or delayed orgasm.3
What is not as widely known is that even serotonin-norepinephrine reuptake inhibitors (SNRIs) can cause sexual dysfunction. For example, in a prospective, multicenter study from Spain involving more than
1,000 outpatients, all of whom were taking an antidepressant, the overall rate of sexual dysfunction was 59%.4 Sexual dysfunction was most common among users of SSRIs and venlafaxine, an SNRI.5
Another common side effect of venlafaxine, sweating, is unrelated to hot flashes.5 So two of this patient’s concerns—orgasmic difficulties and profuse sweating unrelated to hot flashes—may have been caused or worsened by her antidepressant.
Another nonhormonal option
In June 2013, the US Food and Drug Administration (FDA) approved paroxetine mesylate (Brisdelle), an SSRI, for the treatment of moderate to severe menopausal vasomotor symptoms. Because the drug is a strong CYP2D6 inhibitor, it should not be given to women taking another medication that is metabolized by CYP2D6—most notably, tamoxifen.
Preliminary data on this drug suggest that, at the recommended dose (7.5 mg/d), it has no effect on sexual function.6 For this reason, it is another option for our patient to consider.
Related article: The gynecologist's role in managing menstrual migraine Anne H. Calhoun, MD
Migraine and the risk of stroke
Migraine with aura has been associated with an increased risk of stroke and other cerebral vascular events,7 and that risk is further elevated in patients treated with OCs.8 Although migraine without aura also may be associated with an elevated risk of stroke, OCs do not further increase that risk.
Some practitioners assume that the data on the risk of stroke associated with OC use also applies to hormone therapy, but there is no evidence that HT, in which doses of estrogen are far lower than in OCs, increases the risk of stroke in migraineurs to any greater degree than would be expected in unselected populations (ie, as noted in the Women’s Health Initiative, Nurses Health Study, or other large investigations). Therefore, HT would be an appropriate option for this patient if her very slight risk of stroke on HT would be acceptable to the practitioner and patient.
Choosing an HT formulation
Consider the pharmacokinetic profile. Many oral estrogen HT products have rapid-release characteristics that make them likely to contribute to rapid rises and falls in the user’s estrogen level. Oral estrogens also are associated with procoagulant properties that may increase the risk of thrombosis and thromboembolism. Nonoral estrogens do not appear to increase these risks.13
Nonoral estrogens (patches, gels, sprays, lotions, and vaginal rings) provide a more stable pharmacokinetic profile, as do some oral products with controlled-release properties.
As for progestins, some formulations (medroxyprogesterone acetate) tend to cause vasoconstriction, whereas others (micronized progesterone) tend to be vasodilators. Whether these properties affect the rate of migraine or risk of stroke is unclear.
My management approach for this patient
In the absence of any systematic data on the use of HT in this clinical setting, and without any concrete suggestions from migraine experts, I would take the following three-step approach:
1. I would begin with a low-dose nonoral estradiol formulation, prescribing it without a progestin even in a woman who still has a uterus. My aim: to determine the lowest effective dose of HT for this particular patient. I would follow the patient on this dose for 3 months.
JoAnn V. Pinkerton, MD:
Another goal is to determine whether transdermal estradiol increases headaches. Before settling on a therapy, however, I would ask how long this patient has been postmenopausal, how long she has been experiencing vasomotor symptoms, and how severe those symptoms are. For example, is she having 7 or 8 hot flashes per day and waking from night sweats once or twice per night? I also would ask her how long she remained on the venlafaxine. The additional information would allow me to fine-tune her treatment.
2. If this formulation is tolerated, I would add micronized progesterone (oral or vaginal) for endometrial protection.
JoAnn V. Pinkerton, MD:
I would give oral progesterone if it is FDA approved for postmenopausal use, vaginal progesterone if it isn’t.
3. I would follow the patient’s clinical response—specifically, her vasomotor symptoms and rate of migraine with or without aura.
Hormone therapy is one option for postmenopausal migraineurs with bothersome vasomotor symptoms
Many women with a history of migraine move into menopause expecting their condition to improve, says headache expert Anne H. Calhoun, MD, a founder of the Carolina Headache Institute in Chapel Hill, North Carolina.
“Over the years, these women have heard that things get better with menopause.”
For women with a history of episodic migraine, that expectation is realistic, Calhoun says. “But for women with chronic migraine, who may experience a low-grade headache on a daily, or almost daily basis, with 10 or 12 severe headaches in a month, things usually get worse after menopause because the sleep issues of menopause are superimposed on the migraine.”
Dr. Calhoun observes that hormone therapy (HT) has never been contraindicated in women with migraine, although many neurologists are hesitant to prescribe any hormones for this population.
Before prescribing HT to a postmenopausal migraineur, Dr. Calhoun considers a range of variables, including sleep patterns, current medications, anxiety, frequency and severity of vasomotor symptoms, and any other problems the patient may be experiencing.
“It’s basically the same assessment as with any postmenopausal patient—to determine whether HT is a reasonable option,” she says.
And when she determines that HT is appropriate, “I almost exclusively use transdermal HT. I also am more likely to prescribe continuous use of a transdermal patch or skin gel, as I want to achieve very consistent hormone levels, day in and day out,” she says.
My bottom line
No systematic data on the use of HT in migraineurs has been published. In the absence of such data, some practitioners have extrapolated data on the use of OCs in this population and decline to prescribe HT to women with migraine. However, HT and OCs are vastly different in formulation, dose, and risks. Rather than make assumptions on the basis of irrelevant data, we should conduct studies of HT use in migraineurs.
Related article: Update on Menopause Andrew M. Kaunitz, MD (June 2013)
Women who have menstrually related migraine typically have an increased risk of migraine during perimenopause and a significant reduction in migraine following menopause. If hot flashes are bothersome, these women certainly can use HT. I recommend prescribing HT in a continuous fashion that maintains stable hormone levels in the blood, as fluctuating hormones tend to trigger migraines.
Andrew M. Kaunitz, MD:
I would just add that transdermal estradiol is preferred, to be given at the lowest effective dose.
Do you have a troubling case in menopause? Suggest it to the expert panel: obg@frontlinemedcom.com. They may address your management dilemma in a future issue.
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1. Shuster LT, Faubion SS. Sood R, Casey PM. Hormonal manipulation strategies in the management of menstrual migraine and other hormonally related headaches. Curr Neurol Neurosci Rep. 2011;11(2):131–138.
2. Loder E, Rizzoli P, Golub J. Hormonal management of migraine associated with menses and the menopause: a clinical review. Headache. 2007;47(2):329–340.
3. Balon R. SSRI-associated sexual dysfunction. Am J Psychiatry. 2006;163:1504–1509.
4. Taylor MJ. Strategies for managing antidepressant-induced sexual dysfunction: a review. Curr Psychiatry Rep. 2006;8(6):431–436.
5. Effexor [package insert]. New York, NY: Pfizer; 2012.
6. Brisdelle [package insert]. Miami, FL: Noven Therapeutics; 2013.
7. Etminan M, Takkouche B, Isorna FC, Samli A. Risk of ischaemic stroke in people with migraine: systematic review and meta-analysis of observational studies. BMJ. 2005;330(7482):63–65.
8. Becker WJ. Use of oral contraceptives in patients with migraine. Neurology. 1999;53(4 Suppl 1):S19–S25.
9. WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Ischaemic stroke and combined oral contraceptives: results of an international, multicentre, case-control study. Lancet. 1996;348(9026): 498–505.
10. Petitti DB, Sidney S, Bernstein A, Wolf S, Quesenberry C, Ziel HK. Stroke in users of low-dose oral contraceptives. N Engl J Med. 1996;335(1):8-15.
11. Marjoribanks J, Farquhar C, Roberts H, Lethaby A. Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2012;7:CD004143. doi: 10.1002/14651858.CD004143.pub4
12. Renoux C, Dell’aniello S, Garbe E, Suissa S. Transdermal and oral hormone replacement therapy and the risk of stroke: a nested case-control study. BMJ. 2010;340:c2519.
13. Kaunitz AM. Update on Menopause. OBG Manag. 2013;25(6):36–43, 49.
1. Shuster LT, Faubion SS. Sood R, Casey PM. Hormonal manipulation strategies in the management of menstrual migraine and other hormonally related headaches. Curr Neurol Neurosci Rep. 2011;11(2):131–138.
2. Loder E, Rizzoli P, Golub J. Hormonal management of migraine associated with menses and the menopause: a clinical review. Headache. 2007;47(2):329–340.
3. Balon R. SSRI-associated sexual dysfunction. Am J Psychiatry. 2006;163:1504–1509.
4. Taylor MJ. Strategies for managing antidepressant-induced sexual dysfunction: a review. Curr Psychiatry Rep. 2006;8(6):431–436.
5. Effexor [package insert]. New York, NY: Pfizer; 2012.
6. Brisdelle [package insert]. Miami, FL: Noven Therapeutics; 2013.
7. Etminan M, Takkouche B, Isorna FC, Samli A. Risk of ischaemic stroke in people with migraine: systematic review and meta-analysis of observational studies. BMJ. 2005;330(7482):63–65.
8. Becker WJ. Use of oral contraceptives in patients with migraine. Neurology. 1999;53(4 Suppl 1):S19–S25.
9. WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Ischaemic stroke and combined oral contraceptives: results of an international, multicentre, case-control study. Lancet. 1996;348(9026): 498–505.
10. Petitti DB, Sidney S, Bernstein A, Wolf S, Quesenberry C, Ziel HK. Stroke in users of low-dose oral contraceptives. N Engl J Med. 1996;335(1):8-15.
11. Marjoribanks J, Farquhar C, Roberts H, Lethaby A. Long-term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2012;7:CD004143. doi: 10.1002/14651858.CD004143.pub4
12. Renoux C, Dell’aniello S, Garbe E, Suissa S. Transdermal and oral hormone replacement therapy and the risk of stroke: a nested case-control study. BMJ. 2010;340:c2519.
13. Kaunitz AM. Update on Menopause. OBG Manag. 2013;25(6):36–43, 49.