madman
Super Moderator
Pharmacologic therapeutic options for sexual dysfunction (2022)
Claire S. Burtona and Kavita Mishra
Purpose of review
Sexual problems are reported by up to 45% of individuals assigned female at birth. Although sexual function is a complex biopsychosocial construct, there are a number of pharmacologic treatment options aimed at addressing the changing vaginal hormonal milieu in postmenopausal individuals and moderating the excitatory and inhibitory aspects of the central nervous system in those with hypoactive sexual desire disorder.
Recent findings
The last decade has seen an increase in the number and type of pharmacologic treatment options for dysfunction primarily associated with menopause and hypoactive sexual desire disorder. Recent publications and systematic reviews have strengthened the safety data of existing FDA-approved medications as well as off-label therapies.
Summary
Pharmacologic treatment with local estrogen and testosterone replacement in postmenopausal individuals and with centrally-acting therapies such as flibanserin, bremelanotide, and testosterone in premenopausal individuals assigned female at birth are safe and can be used to improve sexual desire and sexual satisfaction.
INTRODUCTION
Sexual dysfunction (SD) is a broad term for a diverse set of symptoms and syndromes that impact sexual function and satisfaction. In general, sexual function is multifactorial with biologic, psychologic, and sociologic factors all playing an integral role. Despite this, there has been increased attention to the understanding of the biologic components of sexual dysfunction, which has led to the advent of medical and pharmacologic therapies.
The authors acknowledge that the literature on sexual dysfunction in individuals assigned female at birth (AFAB) is commonly referred to as female sexual dysfunction. For the purposes of this review, we will use SD in place of the female sexual dysfunction to refer to sexual function and dissatisfaction symptoms in those AFAB or of female biologic sex.
In a survey of a nationally representative sample of 31 500 adult individuals AFAB, 44% reported any sexual problem, with the most common being low desire in 39%, and 12% reported associated distress [1]. This is likely an underestimation of the true incidence, as 63% of patients presenting to a female urology practice reported any element of SD [2]. Because SD in AFAB individuals commonly occurs with other disorders frequently encountered by the urogynecologist, clinicians should be comfortable with the assessment and management of the biologic components of SD.
*This review will focus on both hormonal and nonhormonal pharmacologic treatments of SD associated with genitourinary syndrome of menopause (GSM) and hypoactive sexual desire disorder (HSDD) (Table 1). Diagnosis and pathophysiology are beyond the scope of this review and will only be briefly mentioned.
GENITOURINARY SYNDROME OF MENOPAUSE
Genitourinary syndrome of menopause (GSM) refers to symptoms associated with low estrogen states. While most commonly associated with menopause, low estrogen states can also be found in individuals who have had surgical menopause, hypothalamic amenorrhea, are lactating, have a history of chronic oral contraceptive use, who are undergoing hormonal treatment for breast cancer or sex dysphoria, who have a history of pelvic radiotherapy, or have undergone chemotherapy. An estimated 27–84% of postmenopausal individuals will experience GSM, which can present with a wide array of symptoms including vaginal dryness, burning, or irritation, dyspareunia, decreased sexual desire and arousal, and urinary symptoms [3,4&,5]. GSM also has a significant impact on quality of life, with 75% reporting that their symptoms negatively impact their lives [6]. Although vasomotor symptoms (VMS) tend to improve with time, GSM is often progressive and requires ongoing management [4& ]
NON-HORMONAL THERAPY
Moisturizers and lubricants
First-line therapy for GSM as recommended by the NorthAmericanMenopause Society (NAMS) includes moisturizers and vaginal lubricants [4& ]. Lubricants are often used at the time of intercourse, whereas vaginal moisturizers are longer acting and designed to be used regularly. Vaginal moisturizers rehydrate the vaginal lining by serving as an emollient that is absorbed into the skin. The benefits of vaginal moisturizers often last 2–3 days. Beyond enhancing vaginal moisture, some, such as Replens, have also been found to lower the pH, restoring it to premenopausal acidity [7,8]. Moisturizers can be used in place of hormonal therapy or as an adjunct to vaginal estrogen, frequently used on alternating days.
TOPICAL HORMONE THERAPY
Vaginal estrogen
Vaginal estrogen remains the mainstay of treatment for GSM. Formulations include 17-b-estradiol cream or ring, conjugated equine estrogen cream, and estradiol vaginal tablets or gel capsules. Low-dose vaginal estrogen is sufficient for the treatment of symptoms of GSM and numerous studies have demonstrated no change in systemic estrogen levels above normal postmenopausal levels [13,14].
Vaginal estrogen is generally applied daily for two weeks followed by administration 2–3 times per week. The estradiol ring is changed every 3 months but may be challenging to maintain for women with pelvic organ prolapse. Although it may take several months to achieve the maximal benefit, improvements in dyspareunia may be seen even within the first 2 weeks of treatment [15].
Vaginal estrogen is generally considered to be safe, even in individuals with a history of breast cancer [16,17& ].
The American College of Obstetrics & Gynecology consensus statement on vaginal estrogen in individuals with breast cancer, including those currently on tamoxifen or aromatase inhibitors, notes that vaginal estrogen may be used if nonhormonal vaginal moisturizers are insufficient and the patient undergoes shared decision-making with their providers [17& ].
Vaginal androgen therapy
*VAGINAL PRASTERONE (DHEA)
Androgens are important in sexual health, and testosterone has been implicated in desire, arousal, genital blood flow, vaginal lengthening, and lubrication in AFAB individuals [19,20].
Additionally, androgen receptors are present in female genital tissue. Dehydroepiandrosterone (DHEA) is produced physiologically by the adrenal glands, subsequently metabolized to androgens (androstenedione and testosterone), and then further aromatized to estrogens (estrone, estradiol) [21&,22]. Vaginally administered DHEA 6.5 mg (prasterone, FDA approved in 2016) is converted locally in vaginal tissues to testosterone, dihydrotestosterone (DHT), and estradiol. Similarly to vaginal estrogen, systemic levels of estrogen and androgens do not rise with vaginal DHEA and it appears to be safe in individuals with breast cancer [22,23]. Vaginal DHEA has also been found to improve both objective and subjective symptoms of GSM along with improvement in sexual function [24].
Vaginal DHEA is an alternative treatment for 12–15% of individuals with persistent symptoms despite estrogen use [13].
*VAGINAL TESTOSTERONE
Though not FDA-approved in the United States, vaginal testosterone therapy (0.1%) can be compounded for use in GSM.
Because of limited available data, the NAMS does not recommend vaginal testosterone for the treatment of GSM [4& ].
SYSTEMIC HORMONE THERAPY
Systemic estrogen/progesterone
Individuals with both GSM and VMS may opt for systemic hormone replacement therapy, with either estrogen alone (after hysterectomy) or a combination of estrogen/progesterone.
It should be noted, however, that systemic therapy may not provide sufficient resolution of GSM symptoms. In that case, it is advisable to combine both vaginal and systemic estrogens. If systemic estrogen therapy is used, the lowest possible dose for resolution of symptoms should be administered [4& ]. Additionally, as VMS symptoms tend to improve with time, women may be able to discontinue systemic hormone use and transition to vaginal estrogen, which carries far fewer adverse effects.
Ospemifene
Ospemifene, FDA approved since 2013, is a selective estrogen receptor agonist/antagonist, and is the only oral therapy specifically approved for the treatment of GSM.
Ospemifene remains an excellent option for those who cannot tolerate vaginal estrogen.
Although there is an overlap between GSM and disorders of desire and arousal, the following section will address therapeutic options beyond hormonal replacement as described above. Pharmacologic management may be considered in premenopausal individuals with normal estrogen states or in postmenopausal individuals with persistent bothersome symptoms.
HYPOACTIVE SEXUAL DESIRE DISORDER AND FEMALE SEXUAL AROUSAL DISORDER
Hypoactive sexual desire disorder (HSDD) was classified in the DSM-IV as a decrease or absent spontaneous sexual desire, response to erotic cures, inability to maintain desire throughout sexual activity or a loss of previously present desire that is associated with distress [33]. Controversially, in the DSM-V this diagnosis was combined with female sexual arousal disorder (FSAD) and has been merged into a new diagnosis titled female sexual interest/ arousal disorder (FSIAD) [34]. Because the literature on pharmacologic therapies continues to differentiate between HSDD and FSAD, they will continue to be referred to separately in this review. Development to date has been primarily aimed at the centrally acting excitatory (dopamine, noradrenaline, melanocortin) and inhibitory (serotonin, endocannabinoid, opioid) receptors to augment the sexual desire response [35]. Although our understanding of the neurochemical basis for HSDD is poor, the prevailing hypothesis is that an interplay between the serotoninergic system and other neurochemical pathways leads to increased inhibition or decreased excitation, and pharmaceutical development has been aimed at these pathways [36].
NON-HORMONAL THERAPY
Flibanserin
Flibanserin (Addyi1) was FDA-approved in 2015 for the treatment of HSDD in premenopausal individuals. Flibanserin acts as a multifunctional serotonin agonist and antagonist, which ultimately leads to an increase in dopamine and norepinephrine in the prefrontal cortex and an overall decrease in inhibitory serotonin [37]. It is taken as a 100 mg tablet nightly. I
The most common reported side effects are dizziness, somnolence, nausea, and headache [38–40].
Currently, there remains a black box warning to avoid alcohol consumption within two hours of taking the medication. Flibanserin is safe to use with SSRIs and SNRIs. It is metabolized by cytochrome p450, so prescribers should exercise caution in patients taking other CYP450 inhibitors as they may be at increased risk of somnolence and hypotension [42]. Patients who do not notice improvement after 8 weeks should discontinue the medication.
Bremelanotide
Bremelanotide (Vyleesi1) is the second FDA-approved medication (approved in 2019) for HSDD in premenopausal individuals [43]. It is a melanocortin receptor agonist, with an affinity for MC4R in presynaptic neurons of the hypothalamus, which activates the release of dopamine and enhances the excitatory pathways in arousal and desire [36]. It is administered subcutaneously approximately 45 min prior to intercourse and can be used once per 24 h up to 8 times per month.
The most commonly reported side effects include nausea in 40%, flushing in 20%, and headache in 12% of individuals [38]. Unlike flibanserin, there is no black box warning related to alcohol usage and no significant interactions with other medications [45].
*Although there are no studies to date investigating the combined usage of flibanserin, bremelanotide, and testosterone, their mechanisms of action are each distinct and there is no theoretical reason why they cannot be combined.
Other non-hormonal agents
Buproprion, currently approved as an antidepressant and smoking cessation aid, has shown efficacy in several studies as a treatment for HSDD in both pre-and postmenopausal women [46,47].
Buspirone, another antidepressant, and trazodone, which is pharmacologically similar to flibanserin, have also been described as having some benefits in the treatment of HSDD [49,50]. These may be attractive options for individuals with concurrent depression and HSDD.
Sildenafil, a PDE-5 inhibitor, has been shown to increase vaginal and clitoral blood flow [51].
HORMONAL THERAPY
Transdermal testosterone
In 2019, 12 international societies authored the Global Consensus Statement on the use of Testosterone Therapy for Women to standardize recommendations for its use in postmenopausal individuals [54]. Additionally, in 2021 the International Society for the Study of Women’s Sexual Health (ISSWSH) published a practice guideline for the use of testosterone in AFAB individuals with HSDD [21].
Though there is no established link between HSDD and testosterone levels, transdermal testosterone has been used off-label in postmenopausal individuals to increase sexual desire [54].
A meta-analysis of 36 RCTs of all preparations of systemic testosterone in over 8000 postmenopausal individuals found that testosterone significantly increased sexual desire, pleasure, arousal, and orgasm and reduced distress compared to placebo or estrogen ± progesterone [56]. This study also reaffirmed that nonoral administration was preferred due to significant rises in cholesterol and triglycerides in orally administered testosterone.
The transdermal route (300 mcg/day patch or 5mg/0.5ml gel) allows for more accurate dosing, with a goal of achieving premenopausal testosterone levels. . In a systematic review of transdermal testosterone, both surgically and naturally postmenopausal women with HSDD, with and without adjuvant estrogen replacement had an increase in the number of SSEs, orgasms, and desire vs. placebo [57].
The most common side effects are androgenic, including hirsutism and acne. In short-term safety trials of transdermal testosterone, metabolic markers, renal, and liver function tests were similar to controls and longer-term studies similarly demonstrated no increased adverse events [56,58]. Testosterone can be prescribed as the FDA-approved male-formulation products (at one-tenth the dose), and it is recommended to monitor free and total testosterone levels after 3–6 weeks of therapy to ensure that the value is not above the upper limit of the normal range for premenopausal AFAB individuals (approx. 40 ng/dl) [21&,54]. Because testosterone is currently off-label for AFAB individuals, informed consent should be obtained.
CONCLUSION
SD is common, with multiple forms and etiologies. Many individuals never seek care or even discuss their concerns with a clinician, leading to both underdiagnosis and undertreatment of the disease. Despite this, we know that SD has a significant impact on quality of life. Therefore, it is incumbent upon clinicians to discuss sexual activity to both recognize and manage the disease. At this time, there are many hormonal and nonhormonal treatment options for AFAB individuals with SD that are well tolerated and efficacious and do not require extensive monitoring, with recent publications further highlighting their safety. Both urologists and gynecologists should consider this within their scope of practice, as referrals to sexual medicine specialists may not be immediately available in the majority of geographic areas [59].
Additionally, pharmacologic therapy only addresses one element of the complex biopsychosocial triad that governs sexual satisfaction. Referral to adjunct and supportive care from pelvic floor physical therapists, psychologists or psychiatrists, and sexual health therapists are also often required for maximum benefit. Sexual health is important to all individuals and clinicians should become familiar with the available treatment options.
Claire S. Burtona and Kavita Mishra
Purpose of review
Sexual problems are reported by up to 45% of individuals assigned female at birth. Although sexual function is a complex biopsychosocial construct, there are a number of pharmacologic treatment options aimed at addressing the changing vaginal hormonal milieu in postmenopausal individuals and moderating the excitatory and inhibitory aspects of the central nervous system in those with hypoactive sexual desire disorder.
Recent findings
The last decade has seen an increase in the number and type of pharmacologic treatment options for dysfunction primarily associated with menopause and hypoactive sexual desire disorder. Recent publications and systematic reviews have strengthened the safety data of existing FDA-approved medications as well as off-label therapies.
Summary
Pharmacologic treatment with local estrogen and testosterone replacement in postmenopausal individuals and with centrally-acting therapies such as flibanserin, bremelanotide, and testosterone in premenopausal individuals assigned female at birth are safe and can be used to improve sexual desire and sexual satisfaction.
INTRODUCTION
Sexual dysfunction (SD) is a broad term for a diverse set of symptoms and syndromes that impact sexual function and satisfaction. In general, sexual function is multifactorial with biologic, psychologic, and sociologic factors all playing an integral role. Despite this, there has been increased attention to the understanding of the biologic components of sexual dysfunction, which has led to the advent of medical and pharmacologic therapies.
The authors acknowledge that the literature on sexual dysfunction in individuals assigned female at birth (AFAB) is commonly referred to as female sexual dysfunction. For the purposes of this review, we will use SD in place of the female sexual dysfunction to refer to sexual function and dissatisfaction symptoms in those AFAB or of female biologic sex.
In a survey of a nationally representative sample of 31 500 adult individuals AFAB, 44% reported any sexual problem, with the most common being low desire in 39%, and 12% reported associated distress [1]. This is likely an underestimation of the true incidence, as 63% of patients presenting to a female urology practice reported any element of SD [2]. Because SD in AFAB individuals commonly occurs with other disorders frequently encountered by the urogynecologist, clinicians should be comfortable with the assessment and management of the biologic components of SD.
*This review will focus on both hormonal and nonhormonal pharmacologic treatments of SD associated with genitourinary syndrome of menopause (GSM) and hypoactive sexual desire disorder (HSDD) (Table 1). Diagnosis and pathophysiology are beyond the scope of this review and will only be briefly mentioned.
GENITOURINARY SYNDROME OF MENOPAUSE
Genitourinary syndrome of menopause (GSM) refers to symptoms associated with low estrogen states. While most commonly associated with menopause, low estrogen states can also be found in individuals who have had surgical menopause, hypothalamic amenorrhea, are lactating, have a history of chronic oral contraceptive use, who are undergoing hormonal treatment for breast cancer or sex dysphoria, who have a history of pelvic radiotherapy, or have undergone chemotherapy. An estimated 27–84% of postmenopausal individuals will experience GSM, which can present with a wide array of symptoms including vaginal dryness, burning, or irritation, dyspareunia, decreased sexual desire and arousal, and urinary symptoms [3,4&,5]. GSM also has a significant impact on quality of life, with 75% reporting that their symptoms negatively impact their lives [6]. Although vasomotor symptoms (VMS) tend to improve with time, GSM is often progressive and requires ongoing management [4& ]
NON-HORMONAL THERAPY
Moisturizers and lubricants
First-line therapy for GSM as recommended by the NorthAmericanMenopause Society (NAMS) includes moisturizers and vaginal lubricants [4& ]. Lubricants are often used at the time of intercourse, whereas vaginal moisturizers are longer acting and designed to be used regularly. Vaginal moisturizers rehydrate the vaginal lining by serving as an emollient that is absorbed into the skin. The benefits of vaginal moisturizers often last 2–3 days. Beyond enhancing vaginal moisture, some, such as Replens, have also been found to lower the pH, restoring it to premenopausal acidity [7,8]. Moisturizers can be used in place of hormonal therapy or as an adjunct to vaginal estrogen, frequently used on alternating days.
TOPICAL HORMONE THERAPY
Vaginal estrogen
Vaginal estrogen remains the mainstay of treatment for GSM. Formulations include 17-b-estradiol cream or ring, conjugated equine estrogen cream, and estradiol vaginal tablets or gel capsules. Low-dose vaginal estrogen is sufficient for the treatment of symptoms of GSM and numerous studies have demonstrated no change in systemic estrogen levels above normal postmenopausal levels [13,14].
Vaginal estrogen is generally applied daily for two weeks followed by administration 2–3 times per week. The estradiol ring is changed every 3 months but may be challenging to maintain for women with pelvic organ prolapse. Although it may take several months to achieve the maximal benefit, improvements in dyspareunia may be seen even within the first 2 weeks of treatment [15].
Vaginal estrogen is generally considered to be safe, even in individuals with a history of breast cancer [16,17& ].
The American College of Obstetrics & Gynecology consensus statement on vaginal estrogen in individuals with breast cancer, including those currently on tamoxifen or aromatase inhibitors, notes that vaginal estrogen may be used if nonhormonal vaginal moisturizers are insufficient and the patient undergoes shared decision-making with their providers [17& ].
Vaginal androgen therapy
*VAGINAL PRASTERONE (DHEA)
Androgens are important in sexual health, and testosterone has been implicated in desire, arousal, genital blood flow, vaginal lengthening, and lubrication in AFAB individuals [19,20].
Additionally, androgen receptors are present in female genital tissue. Dehydroepiandrosterone (DHEA) is produced physiologically by the adrenal glands, subsequently metabolized to androgens (androstenedione and testosterone), and then further aromatized to estrogens (estrone, estradiol) [21&,22]. Vaginally administered DHEA 6.5 mg (prasterone, FDA approved in 2016) is converted locally in vaginal tissues to testosterone, dihydrotestosterone (DHT), and estradiol. Similarly to vaginal estrogen, systemic levels of estrogen and androgens do not rise with vaginal DHEA and it appears to be safe in individuals with breast cancer [22,23]. Vaginal DHEA has also been found to improve both objective and subjective symptoms of GSM along with improvement in sexual function [24].
Vaginal DHEA is an alternative treatment for 12–15% of individuals with persistent symptoms despite estrogen use [13].
*VAGINAL TESTOSTERONE
Though not FDA-approved in the United States, vaginal testosterone therapy (0.1%) can be compounded for use in GSM.
Because of limited available data, the NAMS does not recommend vaginal testosterone for the treatment of GSM [4& ].
SYSTEMIC HORMONE THERAPY
Systemic estrogen/progesterone
Individuals with both GSM and VMS may opt for systemic hormone replacement therapy, with either estrogen alone (after hysterectomy) or a combination of estrogen/progesterone.
It should be noted, however, that systemic therapy may not provide sufficient resolution of GSM symptoms. In that case, it is advisable to combine both vaginal and systemic estrogens. If systemic estrogen therapy is used, the lowest possible dose for resolution of symptoms should be administered [4& ]. Additionally, as VMS symptoms tend to improve with time, women may be able to discontinue systemic hormone use and transition to vaginal estrogen, which carries far fewer adverse effects.
Ospemifene
Ospemifene, FDA approved since 2013, is a selective estrogen receptor agonist/antagonist, and is the only oral therapy specifically approved for the treatment of GSM.
Ospemifene remains an excellent option for those who cannot tolerate vaginal estrogen.
Although there is an overlap between GSM and disorders of desire and arousal, the following section will address therapeutic options beyond hormonal replacement as described above. Pharmacologic management may be considered in premenopausal individuals with normal estrogen states or in postmenopausal individuals with persistent bothersome symptoms.
HYPOACTIVE SEXUAL DESIRE DISORDER AND FEMALE SEXUAL AROUSAL DISORDER
Hypoactive sexual desire disorder (HSDD) was classified in the DSM-IV as a decrease or absent spontaneous sexual desire, response to erotic cures, inability to maintain desire throughout sexual activity or a loss of previously present desire that is associated with distress [33]. Controversially, in the DSM-V this diagnosis was combined with female sexual arousal disorder (FSAD) and has been merged into a new diagnosis titled female sexual interest/ arousal disorder (FSIAD) [34]. Because the literature on pharmacologic therapies continues to differentiate between HSDD and FSAD, they will continue to be referred to separately in this review. Development to date has been primarily aimed at the centrally acting excitatory (dopamine, noradrenaline, melanocortin) and inhibitory (serotonin, endocannabinoid, opioid) receptors to augment the sexual desire response [35]. Although our understanding of the neurochemical basis for HSDD is poor, the prevailing hypothesis is that an interplay between the serotoninergic system and other neurochemical pathways leads to increased inhibition or decreased excitation, and pharmaceutical development has been aimed at these pathways [36].
NON-HORMONAL THERAPY
Flibanserin
Flibanserin (Addyi1) was FDA-approved in 2015 for the treatment of HSDD in premenopausal individuals. Flibanserin acts as a multifunctional serotonin agonist and antagonist, which ultimately leads to an increase in dopamine and norepinephrine in the prefrontal cortex and an overall decrease in inhibitory serotonin [37]. It is taken as a 100 mg tablet nightly. I
The most common reported side effects are dizziness, somnolence, nausea, and headache [38–40].
Currently, there remains a black box warning to avoid alcohol consumption within two hours of taking the medication. Flibanserin is safe to use with SSRIs and SNRIs. It is metabolized by cytochrome p450, so prescribers should exercise caution in patients taking other CYP450 inhibitors as they may be at increased risk of somnolence and hypotension [42]. Patients who do not notice improvement after 8 weeks should discontinue the medication.
Bremelanotide
Bremelanotide (Vyleesi1) is the second FDA-approved medication (approved in 2019) for HSDD in premenopausal individuals [43]. It is a melanocortin receptor agonist, with an affinity for MC4R in presynaptic neurons of the hypothalamus, which activates the release of dopamine and enhances the excitatory pathways in arousal and desire [36]. It is administered subcutaneously approximately 45 min prior to intercourse and can be used once per 24 h up to 8 times per month.
The most commonly reported side effects include nausea in 40%, flushing in 20%, and headache in 12% of individuals [38]. Unlike flibanserin, there is no black box warning related to alcohol usage and no significant interactions with other medications [45].
*Although there are no studies to date investigating the combined usage of flibanserin, bremelanotide, and testosterone, their mechanisms of action are each distinct and there is no theoretical reason why they cannot be combined.
Other non-hormonal agents
Buproprion, currently approved as an antidepressant and smoking cessation aid, has shown efficacy in several studies as a treatment for HSDD in both pre-and postmenopausal women [46,47].
Buspirone, another antidepressant, and trazodone, which is pharmacologically similar to flibanserin, have also been described as having some benefits in the treatment of HSDD [49,50]. These may be attractive options for individuals with concurrent depression and HSDD.
Sildenafil, a PDE-5 inhibitor, has been shown to increase vaginal and clitoral blood flow [51].
HORMONAL THERAPY
Transdermal testosterone
In 2019, 12 international societies authored the Global Consensus Statement on the use of Testosterone Therapy for Women to standardize recommendations for its use in postmenopausal individuals [54]. Additionally, in 2021 the International Society for the Study of Women’s Sexual Health (ISSWSH) published a practice guideline for the use of testosterone in AFAB individuals with HSDD [21].
Though there is no established link between HSDD and testosterone levels, transdermal testosterone has been used off-label in postmenopausal individuals to increase sexual desire [54].
A meta-analysis of 36 RCTs of all preparations of systemic testosterone in over 8000 postmenopausal individuals found that testosterone significantly increased sexual desire, pleasure, arousal, and orgasm and reduced distress compared to placebo or estrogen ± progesterone [56]. This study also reaffirmed that nonoral administration was preferred due to significant rises in cholesterol and triglycerides in orally administered testosterone.
The transdermal route (300 mcg/day patch or 5mg/0.5ml gel) allows for more accurate dosing, with a goal of achieving premenopausal testosterone levels. . In a systematic review of transdermal testosterone, both surgically and naturally postmenopausal women with HSDD, with and without adjuvant estrogen replacement had an increase in the number of SSEs, orgasms, and desire vs. placebo [57].
The most common side effects are androgenic, including hirsutism and acne. In short-term safety trials of transdermal testosterone, metabolic markers, renal, and liver function tests were similar to controls and longer-term studies similarly demonstrated no increased adverse events [56,58]. Testosterone can be prescribed as the FDA-approved male-formulation products (at one-tenth the dose), and it is recommended to monitor free and total testosterone levels after 3–6 weeks of therapy to ensure that the value is not above the upper limit of the normal range for premenopausal AFAB individuals (approx. 40 ng/dl) [21&,54]. Because testosterone is currently off-label for AFAB individuals, informed consent should be obtained.
CONCLUSION
SD is common, with multiple forms and etiologies. Many individuals never seek care or even discuss their concerns with a clinician, leading to both underdiagnosis and undertreatment of the disease. Despite this, we know that SD has a significant impact on quality of life. Therefore, it is incumbent upon clinicians to discuss sexual activity to both recognize and manage the disease. At this time, there are many hormonal and nonhormonal treatment options for AFAB individuals with SD that are well tolerated and efficacious and do not require extensive monitoring, with recent publications further highlighting their safety. Both urologists and gynecologists should consider this within their scope of practice, as referrals to sexual medicine specialists may not be immediately available in the majority of geographic areas [59].
Additionally, pharmacologic therapy only addresses one element of the complex biopsychosocial triad that governs sexual satisfaction. Referral to adjunct and supportive care from pelvic floor physical therapists, psychologists or psychiatrists, and sexual health therapists are also often required for maximum benefit. Sexual health is important to all individuals and clinicians should become familiar with the available treatment options.
