INTRODUCTION — Sexual problems are highly prevalent in females. In the United States, approximately 40 percent of females have sexual concerns, and 12 percent report distressing sexual problems [1]. Female sexual dysfunction takes different forms, including lack of sexual desire, impaired arousal, inability to achieve orgasm, pain with sexual activity, or a combination of these issues. Treatment must be tailored to the sexual dysfunction diagnosis or diagnoses and to underlying physical, psychological, and relationship factors.
The management of female sexual dysfunction will be reviewed here. The epidemiology, risk factors, and evaluation of female sexual dysfunction and evaluation and treatment of sexual pain disorders are discussed separately. The epidemiology, pathogenesis, clinical manifestations, course, assessment, diagnosis, and treatment of sexual pain and of female orgasmic disorder are also described separately. (See "Overview of sexual dysfunction in females: Epidemiology, risk factors, and evaluation" and "Female sexual pain: Evaluation" and "Female sexual pain: Differential diagnosis" and "Female orgasmic disorder: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis" and "Treatment of female orgasmic disorder".)
CLINICAL APPROACH — Female sexual dysfunction is multifactorial, often with several different etiologies contributing to the problem. Nonetheless, careful evaluation and use of available therapies can improve sexual function for many patients.
Complete the evaluation and diagnosis — Evaluate the patient for the range of sexual issues and physical, psychological, and relationship factors associated with their concerns before starting treatment. Most patients with sexual concerns have clinical issues that impact more than one aspect of sexual function. The problem may involve more than one phase of the normal sexual response cycle (desire, arousal, orgasm), sexual pain, or a general decrease in sexual satisfaction. As an example, if a patient complains of decreased libido, a full evaluation may also reveal issues with arousal or pain. (See "Overview of sexual dysfunction in females: Epidemiology, risk factors, and evaluation", section on 'Diagnostic evaluation'.)
Sexual dysfunction is defined as a sexual problem that is persistent or recurrent and causes marked personal distress or interpersonal difficulty. It must not be better accounted for by a medical or psychiatric condition (ie, anxiety and depression) or due exclusively to the direct physiologic effects of a substance or medication. Intervention is warranted when a patient presents with a distressing sexual concern, even if it does not strictly meet DSM-5 criteria.
Assess patient goals — Assess a patient's goals prior to starting treatment, and use their goals to evaluate progress. Improvement may also be tracked using a validated sexual function questionnaire, such as the Female Sexual Distress Scale [2]. This also gives the clinician the opportunity to set realistic patient expectations. While some patients may desire modest improvements in their sexual life, others may expect that treatment will allow them to achieve an ideal based on past experience or cultural or media images of sexuality.
Counsel the patient — Patients may be hesitant to discuss sexual concerns and feel anxious or embarrassed. Reassure the patient that they are not alone, sexual problems are common in patients, and effective treatment interventions are available. Inform them that just sharing a concern and wanting improvement is a good first step.
Discuss that sexual problems are usually multifactorial. Review the management plan with the patient and engage in shared decision-making. Let the patient know that most sexual issues do not have an easy or immediate treatment and that there may be a period of trial and error with management approaches before their sexual function improves.
Discuss with the patient that the principal factors associated with a satisfying sex life are physical and psychological well-being and the quality of the relationship with one's partner. Therefore, measures a patient takes to improve their health and relationship will likely have a positive impact on their sex life. Lifestyle changes that increase physical and emotional well-being, reduce fatigue and stress, and strengthen the partnership often result in positive effects on sexual function.
Address partner issues — For patients with sexual partners, the partner must be considered in the treatment plan. This may include treatment of the partner's sexual dysfunction, if present. The clinician should also discuss with the patient involving the partner in setting common goals and expectations, improving communication, and addressing relationship issues.
If relationship conflict is identified, couples counseling may be helpful. Sex therapy with a certified therapist is also an effective intervention for many patients and couples by providing education about sexuality, improving communication, and prescribing specific exercises and interventions to help couples focus on greater intimacy and pleasure. Often, a patient is satisfied with their current level of interest and response but distressed by discord stemming from discrepant levels of interest within a relationship. Let them know that that this is not their sexual problem but rather a relationship problem that is often effectively managed by couples counseling and sex therapy.
For patients without a sexual partner, the clinician should address the patient's goals and concerns. For some patients, sexual function issues deter them from seeking out relationships. Other patients may be dissatisfied with their sexual function during masturbation or other partner-independent activities.
Treat associated conditions — Assess the medical history and current conditions and medications to ensure associated conditions are treated before or during sexual dysfunction therapy. Many physical and psychological conditions are associated with sexual dysfunction. Sometimes a sexual problem can be ameliorated by diagnosing and treating an underlying problem or by adjusting therapy to minimize sexual side effects. As an example, patients with depression who are experiencing low libido or anorgasmia on a selective serotonin reuptake inhibitor can sometimes eliminate these side effects by switching to a different antidepressant. Treating arthritis pain, urinary incontinence, or anemia may improve sexual interest and response. In addition, identification and treatment of a substance use disorder, as well as the underlying factors that precipitated it, often results in greater sexual function and overall quality of life. (See "Overview of sexual dysfunction in females: Epidemiology, risk factors, and evaluation", section on 'Risk factors' and "Sexual dysfunction caused by selective serotonin reuptake inhibitors (SSRIs): Management".)
Use a multidisciplinary and multimodal approach — Sexual disorders can be complex, and their treatment can be time intensive and require special expertise. With the patient's consent, communication and management decisions should be shared between the treating clinician and the patient's other health care providers (eg, cardiologist, psychiatrist, oncologist). Also, referrals to clinicians who specialize in sexual function, psychotherapists, sex therapists, and pelvic physical therapists are often needed to address specific aspects of treatment.
Treatment approaches may include lifestyle changes, counseling, physical therapy, or medication. We restrict use of pharmacologic therapy to patients who meet diagnostic criteria for a sexual disorder and for whom nonpharmacologic interventions have proven ineffective.
EVIDENCE REGARDING MANAGEMENT — There are limited data to guide interventions for female sexual function issues. The barriers to clear and consistent guidance regarding these issues include:
●Inconsistent measures to assess efficacy – Studies have used varying measures to evaluate the efficacy of sexual function interventions. One measure that can be quantified and compared among studies is an event log, which is the frequency of sexually satisfying events. However, an event log does not typically assess qualitative changes in sexual function, such as sexual interest or level of distress.
Most studies of sexual dysfunction treatment use validated questionnaire scores as an outcome measure. There are multiple questionnaires, which use different questions and scales. This makes it difficult to compare data between studies and treatments.
●Diagnoses and therapies are multifaceted – Female sexual dysfunction typically affects more than one aspect of sexuality (eg, desire, arousal), and most therapies also impact several aspects. Thus, it is not generally possible to identify an isolated sexual issue and select a therapy that specifically targets that concern.
The management approaches discussed below are based on the best available data and our clinical experience.
MANAGEMENT OVERALL AND BY SEXUAL FUNCTION ISSUE — Patients often have issues in more than one sexual domain (ie, desire, interest/arousal, orgasm, pain). Thus, clinicians should identify all current issues and prioritize and coordinate treatments.
Improvement of one sexual problem may result in improvement in another. For example, successful management of sexual pain often improves sexual interest/arousal and orgasm. Thus, in a patient with postmenopausal dyspareunia and low libido, the optimal approach is to treat the genitourinary syndrome of menopause (GSM; vulvovaginal atrophy) first and then reassess the status of sexual desire concerns.
Nonpharmacologic options should be the initial treatment for most patients. All currently available pharmacologic therapies for female sexual dysfunction are of limited efficacy and associated with side effects and potential risks. As the principal predictors of sexual satisfaction are physical and psychological health and the quality of the relationship with the partner, the focus of therapy should be on interventions that optimize health, well-being, and the partner relationship.
The management approaches here do not specifically address multiple partner relationships or transgender individuals, but many of the approaches are likely to be applicable. Health care for transgender people is discussed separately. (See "Primary care of transgender individuals", section on 'Sexual function'.)
Interventions that address multiple issues — Some interventions are low risk and may improve sexual function overall. Barriers to accessing counselors and sex therapists with appropriate expertise include limited insurance coverage of these services, cost, and lack of experts in all geographic regions.
Counseling — Psychological and relationship issues often underlie, exacerbate, or are amplified by sexual dysfunction in one or both partners. As an example, a major cause of decreased sexual desire and response is a relationship with limited communication or underlying conflict. Patients should be screened for a history of physical, sexual, or emotional abuse and intimate partner violence. (See "Intimate partner violence: Diagnosis and screening".)
Couples therapy and sex therapy — Patients with sexual dysfunction and their partners will often benefit from referral to a sex and/or couples therapist.
Couples counselors are psychiatrists, psychologists, or social workers who see both members of the couple. This type of counseling is effective when there is relationship conflict or limited communication.
Sex therapists are highly trained counselors with special expertise in human sexuality. They often are psychologists or social workers with additional training and experience in sexual function and dysfunction. Certified sex therapists may be located through the website of the American Association of Sexuality Educators, Counselors, and Therapists. Their services are often covered by insurers.
Many clinicians are uncertain of whether to refer a patient to a couples counselor or sex therapist or both; some of this is due to being uncertain about the services sex therapists provide [3]. In our practice, we refer to a sex therapist if the concerns are specifically related to sex. We refer to a couples counselor if the concerns are about improving communication and reducing conflict.
Sex therapy typically includes: educating patients and male or female partners about the normal sexual response cycle, addressing cultural or religious concerns regarding sexuality, helping negotiate a mutually acceptable frequency of sexual activity when disparate levels of sexual interest are present and causing discord, and assigning specific exercises to aid many patients and couples with sexual dysfunction. They may direct patients to a wide range of helpful resources, including book lists, visual aids, and devices.
Examples of a sex therapy exercise include instruction in the appropriate use of vaginal dilators, which is highly effective in treating most cases of provoked pelvic floor hypertonus (vaginismus) and dyspareunia. Another approach is sensate focus exercises to help couples increase mutual sexual pleasure, and minimizing the importance of intercourse with orgasm as the principal goal of sexual encounters.
In one study, 65 percent of 365 couples undergoing sex therapy for a range of sexual dysfunctions described their treatment as successful [4].
Given the efficacy and high degree of safety of sex therapy, we consider consultation with a sex therapist generally to be a prerequisite to a trial of pharmacologic therapy for most patients with sexual dysfunction.
Psychotherapy and psychopharmacology — Psychiatric disorders, especially depression and anxiety, are associated with an increased likelihood of sexual dysfunction, although the majority of patients with sexual dysfunction do not have a psychiatric diagnosis. Treatment of the underlying psychiatric problem, with appropriate medications and/or psychotherapy, can lead to an improved sexual life. Prior physical, emotional, or sexual abuse or substance abuse disorders also affect sexual function and may be addressed effectively in this setting. (See "Overview of sexual dysfunction in females: Epidemiology, risk factors, and evaluation", section on 'Psychiatric disorders and medications'.)
Pharmacologic treatment of psychiatric illness, particularly with selective serotonin reuptake inhibitors (SSRI), may reduce libido and impair orgasmic response. If medically appropriate, switching to bupropion, or adding this agent to SSRI treatment, often improves SSRI-related sexual dysfunction. Bupropion is also an option for the treatment of sexual dysfunction in patients without depression. (See "Sexual dysfunction caused by selective serotonin reuptake inhibitors (SSRIs): Management" and 'Bupropion' below.)
Anxiolytic and antipsychotic medications also may adversely affect sexual function. For some patients, the expertise of a psychopharmacologist may be required if sexual problems are exacerbated by these medications or additional psychiatric medications may be part of the treatment plan.
Lifestyle changes — Fatigue and stress contribute significantly to low libido and sexual problems. Treating an underlying sleep problem, adjusting work hours, and engaging assistance with childcare and household responsibilities often improve sexual function. Reducing stress through exercise, yoga, and other relaxation techniques may result in improved sexual interest and satisfaction [5]. Lack of privacy can contribute to sexual problems, and couples may benefit from simply placing a lock on their bedroom door.
Encouraging couples to establish a regular "date night" and to spend a minimum of one or two nights per month away from family responsibilities can contribute to improved sexual interest and response.
Research on sexual function consistently demonstrates increased libido and pleasure in new relationships. Although patients in existing relationships should not be advised to improve their sex lives by seeking out new partners, they should be encouraged to bring novelty to their current relationships. Reading books about sexuality (both educational material and erotica), visiting a store with items designed to increase sexual pleasure, and expanding the typical sexual repertoire effectively increase libido and response.
Improving body image — A patient's view of their own body affects their sexual interest and satisfaction [6]. Negative body image may be impacted by many factors. Patients who are overweight and in whom body image issues are contributing to sexual dysfunction should be assisted with weight loss. Several studies confirm improved sexual function in patients with obesity following weight loss surgery [7]. In addition, many patients note improvements in their sex lives when they initiate a regular exercise program.
Treating pelvic floor dysfunction — Pelvic floor dysfunction, including urinary or fecal incontinence, pelvic organ prolapse, or chronic pelvic pain, may cause or exacerbate sexual function issues.
Pelvic physical therapy — Physical therapists with subspecialty training in pelvic anatomy and function are very helpful for patients with dyspareunia, pelvic floor hypertonus (vaginismus), pelvic pain, incontinence, and pelvic organ prolapse. (See "Myofascial pelvic pain syndrome in females: Pelvic floor physical therapy for management".)
Incontinence or prolapse treatment — Both urinary and fecal incontinence are associated with sexual dysfunction, likely because of fear of involuntary loss of urine or stool during sexual activity. Incontinence also may be a symptom of a pelvic floor problem that is contributing to sexual pain. It is important to ask about incontinence in patients presenting with sexual concerns, as effective treatments are available. (See "Female urinary incontinence: Treatment".)
Pelvic organ prolapse may adversely affect sexual function due to embarrassment regarding a visible bulge and physical discomfort during sex resulting from sexual contact with the cervix or sensation of fullness or pressure in the vagina. Surgery and pessaries effectively treat prolapse. Pessary use may contribute to a sexual problem, as pessaries need to be removed prior to penetrative sexual activities, which can be difficult for patients with limited mobility. (See "Pelvic organ prolapse in females: Epidemiology, risk factors, clinical manifestations, and management", section on 'Approach to management'.)
Sexual interest/arousal disorder — Low libido is the most common sexual problem for females. As it is difficult for researchers to distinguish between sexual interest and arousal, the past diagnosis of sexual desire disorder has been replaced in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) by sexual interest/arousal disorder. Desire for sexual activity is significantly reduced or absent, often including an absence of sexual thoughts or fantasies. Low libido affects patients of all ages, with a peak in associated distress at midlife.
When relationship factors are contributing to low sexual desire, counseling the patient about changes the couple can make in their sexual relationship can lead to improvement. Discuss with the patient that sexual interest typically decreases with relationship duration, so encourage interventions that increase novelty. These may include spending a night away from home, trying a new sexual position, incorporating a device, or having sex in an unusual location or at a different time of day. Establishing a regular "date night" often improves sexual satisfaction, as couples that enjoy time together outside of the bedroom often have more pleasure in the bedroom.
Hormone therapy
Androgens
Use and limitations — Levels of endogenous androgens do not predict sexual function for females; however, androgen therapy that increases serum concentrations to the upper limit of normal has been shown to improve female sexual function in selected populations of postmenopausal patients [8,9]. The testosterone production rate for premenopausal patients is approximately 10 percent of the testosterone production in males [10]; therefore, for postmenopausal patients, a dose of testosterone should be 10 percent or less of the standard male dose. Androgen treatments that increase serum concentrations to supraphysiologic levels in the low male range may significantly increase sexual desire and frequency in females but are not advised due to potential risks and side effects [11]. (See "Overview of sexual dysfunction in females: Epidemiology, risk factors, and evaluation", section on 'Role of androgens'.)
Discussion of androgen therapy with a patient must include a full explanation of the potential benefits and risks. Patients should understand that data on safety and efficacy are limited, including data on long-term use, or use without concomitant estrogen therapy. In addition, they must be informed that none of the commonly used androgen therapies are approved by the US Food and Drug Administration (FDA) for treating female sexual dysfunction because of limited clinical trial data, limited efficacy compared with placebo, or concerns about long-term safety. The clinician should document this discussion in the medical record.
In our practice, we rarely use testosterone, but will prescribe it when greatly desired by a peri- or postmenopausal patient with low libido associated with distress who has no contraindications to testosterone therapy, is otherwise physically and psychologically healthy, and is in a stable relationship. Typically, the patient has already tried other safer interventions prior to the testosterone prescription, including low-dose vaginal estrogen, relationship interventions (eg, sex therapy, date nights, use of sexual aids such as vibrators, books), and adjustment of antidepressant medication [12]. At least one visit with a sex therapist is strongly advised prior to pharmacologic treatment, as this safe and effective intervention may make androgen therapy unnecessary or enhance the response to treatment. Testosterone levels should not be used in determining the etiology of a sexual problem or in assessing efficacy of treatment, as several large, well-designed studies confirm the absence of a significant association between androgen levels and sexual function. (See "Overview of sexual dysfunction in females: Epidemiology, risk factors, and evaluation", section on 'Role of androgens'.)
Effectiveness
●Postmenopausal patients – Testosterone therapy is the most commonly studied androgen treatment for female sexual dysfunction. The addition of testosterone to postmenopausal estrogen (with or without progestin) therapy in patients who undergo menopause naturally or as a result of oophorectomy (surgical menopause) has been shown to improve sexual function in systematic reviews of randomized trials and in most, but not all, subsequent randomized trials [8,13-20]. Testosterone is primarily used to treat issues with sexual desire, although all aspects of sexual function generally improve, including arousal and orgasmic response.
Formulations (testosterone, methyltestosterone) and delivery methods (oral, transdermal patch, topical gel) vary across studies. The largest randomized trials utilized a transdermal testosterone patch delivering 300 mcg/day testosterone in postmenopausal patients with hypoactive sexual desire disorder (HSDD) [15,18]. The diagnostic category HSDD was used in the study but has been replaced by female sexual interest/arousal disorder [21] (see "Overview of sexual dysfunction in females: Epidemiology, risk factors, and evaluation", section on 'Diagnostic criteria'). Patients enrolled in these trials were physically and psychologically healthy with a satisfying sexual life prior to menopause and no other etiology for their HSDD, such as depression or antidepressant use.
Regarding dosing, in general, trials indicate that a transdermal testosterone dose of 300 mcg/day for six months is safe and effective in females who are receiving concomitant estrogen therapy. Benefits were reported for many aspects of sexuality, including desire, responsiveness, orgasm, and satisfaction. Pooled data from trials in surgically and naturally menopausal patients show that, compared with patients who received placebo, patients who were treated with testosterone reported a small increase in sexually satisfying events (SSEs) per four weeks (an increase of 1.9 versus 0.9 events over a baseline of approximately three events) [22]. By contrast, results of two randomized trials reported by the manufacturer of a topical testosterone gel (LibiGel) showed no significant increase in sexual desire, the number of SSEs, or any sexual function endpoint compared with placebo, despite achieving testosterone blood levels similar to those seen in clinical trials of the testosterone patch [20].
These data do not address use in patients who are not taking postmenopausal hormone therapy. This is clinically important, since postmenopausal estrogen (with or without progestin) therapy is no longer universally recommended. (See "Menopausal hormone therapy: Benefits and risks".)
For postmenopausal patients who are not using concurrent estrogen therapy, one large, controlled trial reported similar results as discussed above. In this trial, 814 naturally or surgically postmenopausal patients with HSDD were randomly assigned to receive transdermal testosterone (daily dose of 150 or 300 mcg) or a placebo patch [16]. The testosterone 300 mcg group reported significantly more SSEs than the placebo group (an increase of 2.1 versus 0.7 episodes per four weeks); this was not true for the 150 mcg dose (increase of 1.2 episodes). However, both testosterone doses were associated with significant improvements in desire and reduction in distress about sexual dysfunction.
There were no differences in treatment efficacy between patients with natural versus surgical menopause. Regarding safety, breast cancer was diagnosed in four patients who received testosterone compared with none who received placebo. Although two of the cases likely were present prior to testosterone administration, the authors concluded that long-term effects of testosterone, including effects on the breast, remain uncertain.
Another androgen, dehydroepiandrosterone (DHEA), administered systemically, has been shown to improve sexual interest and satisfaction in some studies of females with adrenal insufficiency but was ineffective in patients who were perimenopausal or naturally postmenopausal [23]. DHEA has not been studied for treatment of sexual dysfunction in patients with surgical menopause. Although systemic DHEA does not appear to be an effective treatment for sexual dysfunction in otherwise healthy patients, a vaginally administered DHEA (1%) insert compared with placebo improved sexual desire, arousal, lubrication, orgasm, and satisfaction, while reducing pain during intercourse in a randomized trial of 554 postmenopausal patients with moderate to severe vaginal atrophy [24,25]. As systemic androgen and estrogen levels are minimally elevated with low-dose vaginal DHEA, sexual function benefits likely reflect the effective treatment of menopausal vaginal atrophy and dyspareunia.
●Premenopausal patients – Testosterone levels in females decline with age and do not change abruptly at the time of natural menopause. Thus, patients in their late 30s and 40s have lower androgen levels than younger patients.
However, data regarding androgen treatment of premenopausal patients are few and inconclusive [26,27]. As an example, in the best designed randomized trial, 261 females aged 35 to 46 years who complained of decreased sexual satisfaction were assigned to testosterone (180, 90, or 45 microL transdermal metered spray) versus placebo [26]. Improvements in number of SSEs compared with placebo were found only in patients treated with 90 microL but not with other testosterone doses. There were no significant improvements in any other measure of sexuality, including desire, pleasure, or orgasm. Despite repeated warnings to use contraception, one patient was found to be pregnant at week 20 of the study. When considering androgen therapy in females of reproductive age, inadvertent exposure of a developing fetus must be considered a significant potential risk.
Available androgen preparations and limitations — Prescribing a testosterone preparation to females has many limitations. Available preparations vary in ability to deliver an appropriate and consistent dose and have not been tested to confirm safety, efficacy, and serum testosterone levels. When prescribing a formulation approved for use in males, the goal is to approximate hormone concentrations of premenopausal patients, which are approximately 10 percent of male levels [10,12]. Various products in use include:
●Female testosterone patch – As the majority of controlled data on the efficacy and safety of testosterone therapy for postmenopausal patients with female sexual interest/arousal disorder were obtained using a testosterone transdermal patch (Intrinsa 300 mcg), these patches would be the preferred product for females electing testosterone therapy but are no longer available, even in Europe. In the United States, no androgen therapies for female sexual dysfunction are approved by the FDA, which declined approval of a testosterone patch for females pending additional long-term safety data.
●Topical compounded testosterone cream, ointment, or gel
The most convenient testosterone formulation currently available is topical compounded 1% testosterone cream, ointment, or gel. The patient applies approximately 0.5 grams daily to the skin of the arms, legs, or abdomen. The Global Consensus Statement on androgens for females [28] recommends against compounded testosterone, unless an authorized equivalent preparation is unavailable. As of 2020, there is no government-approved testosterone formulation for females, so options are limited.
Despite the many limitations of compounded hormones, this approach may be preferable to using testosterone products approved for males, although not all experts agree [12]. Topical cream or gel should be applied in approximately one-tenth the male prescribed dose, as testosterone levels in females are approximately 10 percent those of males. This is very difficult to do accurately with available gels dosed for males in pumps and packets. In addition, the FDA has issued a warning regarding testosterone gels due to reports of adverse effects in children due to secondary exposure to the skin of an adult who had recently applied the medication [29].
Limitations of prescription custom-compounded topical testosterone formulations include inconsistent concentrations of testosterone with variable absorption and bioavailability. Product quality and purity are a concern given limited regulatory oversight of the compounded hormone industry. Compounding pharmacies typically supply these products in a marked, needleless syringe to allow for more accurate dosing, although these controlled administration methods do not overcome the significant inconsistency in delivered dose between pharmacies or even between separate lots of product from the same pharmacy. Clinical trials have not evaluated the safety or efficacy of this product for any indication, including improvement of female sexual function. If compounded testosterone is used, the compounding pharmacy should be compliant with purity of Active Pharmaceutical Ingredients (API) and Good Manufacturing Practice (GMP) to meet industry standards for quality and safety.
●Male testosterone patch – Transdermal formulations created for males, such as skin patches (eg, Androderm) and gels (eg, AndroGel), should be prescribed for females with caution. If they are used, careful dose adjustment is required, as excessive dosing will result from standard doses prescribed for males. Cutting patches is not advised as no data are available on dose delivered in cut patches, product stability, or resulting serum testosterone levels.
●Oral formulations – Use of oral formulations is limited by the potential for adverse changes in lipids and liver function tests following first-pass hepatic metabolism [12,30]. Methyltestosterone is available by prescription in the United States in a fixed-dose combination with a high dose of oral estrogen. Oral DHEA is available without a prescription; doses of 25 to 50 mg/day raise circulating androgen levels into the physiologic range [31]. As this product is subject to minimal regulatory oversight, hormone content is highly variable [32].
●Injectable or implantable preparations – Use of injectable or implantable preparations ("pellets") of testosterone are available but not advised for females [12]. Administration is uncomfortable and inconvenient, and dosing is almost always supraphysiologic. In addition, if side effects occur, removal of the implanted or injected testosterone is not possible. Testosterone levels remain elevated for a minimum of one month and often longer.
Adverse effects and contraindications — Androgen therapy in females can potentially result in androgenic, metabolic, or other adverse health effects [8]. These medications should not be used in patients with cardiovascular disease, hepatic disease, endometrial hyperplasia or cancer, or breast cancer and should be used with caution in patients at high risk for these disorders. Even in the absence of these concerns, androgen therapy should rarely be used in reproductive-age females, given a low likelihood that decreased testosterone levels are a principal etiologic factor, the limited data on efficacy, and the potential for inadvertent exposure of a developing fetus.
Major issues regarding side effects include:
●Cosmetic, androgenic side effects, such as hirsutism and acne, are usually mild; irreversible, virilizing changes (eg, voice deepening, clitoromegaly) are rare and occur only with excessive dosing.
●Serum high-density lipoprotein cholesterol concentrations decline slightly in postmenopausal patients receiving oral testosterone therapy, but it is not known if the change substantially affects overall cardiovascular risk. Nonoral administration is lipid neutral.
●Most androgens are aromatized to estrogens; thus, risks of estrogen therapy are also possible with androgen treatment. A possible association between testosterone administration and breast cancer risk has been reported [16]. Also, some patients on testosterone develop abnormal uterine bleeding. Although there is no evidence of an increased risk of endometrial hyperplasia or cancer [16,33,34], data on long-term use and use in naturally menopausal patients not receiving concurrent progestin therapy are very limited.
Evaluation of the adverse effects of androgens is limited by the lack of data on females taking testosterone alone (without estrogen). Also, the duration of studies is generally from 3 to 12 months; therefore, the long-term safety of testosterone therapy cannot be assured.
Risks of androgen therapy in females are discussed in detail separately. (See "Overview of androgen deficiency and therapy in women", section on 'Risks and side effects' and "Menopausal hormone therapy and the risk of breast cancer", section on 'Effect of testosterone'.)
Monitoring androgen therapy — Patients on androgen therapy should be monitored for potential adverse effects. Some effects are cosmetic (eg, hirsutism, acne) and so are easily detected by the patient. Given potential effects on lipids and liver function, normal values should be confirmed prior to initiating androgen therapy, reassessed approximately six months after starting treatment, and then annually thereafter.
Testosterone is metabolized to estrogen, and thus, abnormal uterine bleeding or breast symptoms (eg, lump, nipple discharge) may result and require appropriate evaluation. Annual mammograms should be performed in females receiving androgen therapy. (See "Overview of the evaluation of the endometrium for malignant or premalignant disease" and "Breast imaging for cancer screening: Mammography and ultrasonography".)
Measuring a free testosterone level or free androgen index (total testosterone/sex hormone binding globulin) in females using topical testosterone therapies may be used as a safety measure, with the goal of keeping the value within the normal range for reproductive-aged females provided by the testing laboratory.
Estrogens — The Women's Health Initiative, a set of randomized trials in over 27,000 postmenopausal patients, found that systemic estrogen with or without progestin therapy did not improve sexual satisfaction and may be harmful [35]. (See "Menopausal hormone therapy: Benefits and risks", section on 'Health-related quality of life'.)
Although evidence does not support a role for systemic, postmenopausal hormone therapy in the treatment of sexual problems, if a patient with a previously satisfying sex life presents with sexual problems concurrent with the onset of hot flashes, night sweats, sleep disruption, and resulting fatigue, treatment of menopausal symptoms with systemic postmenopausal hormone therapy may lead to improvement in the sexual problem. (See "Treatment of menopausal symptoms with hormone therapy".)
Tibolone — Tibolone is a synthetic steroid whose metabolites have estrogenic, progestogenic, and androgenic properties. It was not approved by the FDA due to concerns about risk of breast cancer, endometrial cancer, and stroke [22] but is used by postmenopausal patients in Europe and other countries.
In randomized trials, tibolone appears more effective than estrogen/progestin therapy for treatment of sexual dysfunction in postmenopausal patients [36-38]. However, the beneficial effects of tibolone on sexuality are modest and may not outweigh the risks. Comparative trials of tibolone versus testosterone have not been performed.
Adverse effects associated with tibolone are discussed in detail separately. (See "Preparations for menopausal hormone therapy", section on 'Tibolone'.)
Serotonergic or dopaminergic agents — Some psychotropic agents may have a benefit for female sexual function.
Flibanserin — Flibanserin is the first drug approved by the FDA for female sexual dysfunction in premenopausal patients [39,40]. Daily use results in small increases in the frequency of SSEs and sexual desire in premenopausal patients with low sexual desire that is associated with distress. The clinical role of flibanserin may be limited by the need for daily dosing, common adverse effects (eg, somnolence, dizziness), and safety concerns regarding combining flibanserin with alcohol or certain medications (eg, fluconazole, antidepressants) [41]; hypersensitivity reactions (eg, anaphylaxis, angioedema) have also been reported [42].
Flibanserin is a centrally acting serotonin receptor agonist/antagonist that results in transient decreases in serotonin and increases in dopamine and norepinephrine in certain regions of the brain [43,44]. It was initially studied as a potential antidepressant, and although it was ineffective for depression, it appeared to increase sex drive.
Flibanserin was rejected twice for approval by the FDA due to concerns regarding both efficacy and safety. It was approved by the FDA in August 2015 for premenopausal patients with HSDD after review of additional safety information and efforts by consumer groups. The diagnostic category HSDD was used in the FDA report and in the associated studies, but is no longer used and has been replaced by the term female sexual interest/arousal disorder [21]. (See "Overview of sexual dysfunction in females: Epidemiology, risk factors, and evaluation", section on 'Diagnostic criteria'.)
Flibanserin results in small increases in sexual desire and the frequency of SSEs in females with low sexual desire associated with distress. The best available evidence regarding flibanserin is from a meta-analysis of trials comparing flibanserin (oral, 100 mg daily) with placebo in premenopausal and postmenopausal patients with HSDD. This meta-analysis included eight double-blind, randomized trials (three unpublished) with a total of 5914 patients [45]. Flibanserin compared with placebo resulted in a small but statistically significant increase in SSEs per month (pooled mean difference 0.49, 95% CI 0.32-0.67). In terms of absolute benefit, in two trials, there were 0.4 to 1.0 additional SSEs per month with flibanserin from an average baseline of 2.0 to 3.0 per month [46,47]. In the meta-analysis, measures of sexual desire (Female Sexual Function Index desire, eDiary desire) showed statistically significant improvement, but these changes were modest, and the clinical significance appears small [45]. Scores on the validated measure Patient's Global Impression of Improvement showed minimal improvement to no change. Data from one trial suggest that onset of efficacy with flibanserin starts at four weeks of use [47].
In the meta-analysis, the risk of adverse events was significantly higher with flibanserin compared with placebo: dizziness (relative risk [RR] 4.00, 95% CI 2.56-6.27), somnolence (RR 3.97, 95% CI 3.01-5.24), nausea (RR 2.35, 95% CI 1.85-2.98), and fatigue (RR 1.64, 95% CI 1.27-2.13). Alcohol has been found to increase the risk of adverse events, based on data provided by the manufacturer [48]. Eight to 13 percent of patients treated with flibanserin discontinued the drug due to adverse effects. Severe adverse effects that may occur with flibanserin include syncope or hypotension; in one trial, the rates of sedation or hypotension-related events were 29 percent on flibanserin versus 9 percent on placebo, and syncope occurred in 0.5 versus 0.3 percent [48].
Patients on antidepressants and antiestrogens were excluded from the randomized trials, and thus safety and efficacy in patients on these medications has not been evaluated [44,46,47,49]. The safety of flibanserin in pregnancy is not known; among the few patients in the trials who became pregnant, no congenital anomalies were reported [46,47,49].
The FDA approved flibanserin for premenopausal patients with low sexual desire with associated distress at a daily dose of 100 mg at bedtime with several cautionary notes (including a black box warning) [50]. Flibanserin is not indicated for the treatment of sexual dysfunction in postmenopausal patients. Flibanserin can cause hypotension and syncope. These risks are increased when combined with alcohol or cytochrome P450 3A4 (CYP3A4) inhibitors (eg, fluconazole). Flibanserin ingestion should be delayed by at least two hours after alcohol ingestion; patients who consume three or more alcoholic beverages are advised to skip their evening flibanserin dose [41]. Oral contraceptives and antibiotics commonly used to treat urinary tract infections in patients also might affect the drug's metabolism. Use of either alcohol or CYP3A4 inhibitors in combination with flibanserin is contraindicated.
Flibanserin availability is limited in countries other than the United States and Canada.
Bupropion — If a patient with a distressing sexual problem greatly desires a pharmacologic intervention, after nonpharmacologic treatments have been tried, bupropion is often the first choice in our practice. Bupropion is FDA approved to treat depression and assist with smoking cessation; use for SSRI-induced sexual dysfunction is an off-label indication. As a centrally acting agent, the mechanism of action is likely similar to that of flibanserin. Long-term safety data are available, and risks and side effects are well characterized. Generic formulations are available, so cost is low. Bupropion should be dosed in the morning, and patients should be observed for increased anxiety, insomnia, and hypertension. Patients must be informed of potential risks and side effects and off-label nature of use.
One randomized trial of 75 premenopausal patients with HSDD and without underlying depression reported increased sexual pleasure, arousal, and orgasm with bupropion (sustained release 300 mg/day) compared with placebo [51].
Use of bupropion in patients with depression and SSRI-associated sexual dysfunction is discussed separately. (See "Sexual dysfunction caused by selective serotonin reuptake inhibitors (SSRIs): Management", section on 'Females'.)
Buspirone — Some data suggest that buspirone (typically used as an antianxiety medication) is helpful for decreased libido. Use of buspirone in patients with SSRI-associated sexual dysfunction is discussed separately. (See "Sexual dysfunction caused by selective serotonin reuptake inhibitors (SSRIs): Management", section on 'Treatments with little to no demonstrated benefit'.)
Other — Apomorphine is a dopamine agonist that has been used for the treatment of male erectile dysfunction, although it is not FDA approved for this indication. One small study of limited quality reported improved sexual function in premenopausal patients. Use of this drug is not advised due to limited data on efficacy and significant side effects, including nausea, vomiting, dizziness, and hypotension [52].
Bremelanotide — Bremelanotide, a melanocortin receptor agonist, was approved by the FDA in June 2019 for treatment of HSDD in premenopausal patients [53]. The medication is administered as a subcutaneous injection (1.75 mg) at least 45 minutes before anticipated sexual activity. Two randomized trials in a total of 1247 premenopausal patients with HSDD found that 24 weeks of bremelanotide compared with placebo resulted in more patients with a meaningful increase in sexual desire (51 versus 21 percent) and improvement in sexual satisfaction (57 versus 26 percent) [53-55]. There was no significant difference in number of satisfying sexual events. Serious adverse reactions occurred in 1.1 percent of patients treated with bremelanotide (compared with 0.5 percent with placebo). Common adverse reactions included nausea (40 percent; mostly with first injection; 13 percent of patients required anti-emetic medications), vomiting (5 percent), flushing (20 percent), headache (11 percent), and hyperpigmentation (1 percent; possibly permanent). Some patients had a transient increase in blood pressure, and bremelanotide should not be used in patients with uncontrolled hypertension or known cardiovascular disease. Concomitant use decreases blood levels of oral naltrexone. Bremelanotide is associated with fetal harm in animal studies, so patients must use effective contraception.
An advantage of bremelanotide compared with flibanserin is that it is taken prior to anticipated sexual activity rather than every day, potentially reducing risks and side effects and avoiding the need to take a daily medication. Associated nausea and vomiting may limit acceptability for some patients. Although not currently approved for postmenopausal patients, there is no physiologic reason that bremelanotide would not be similarly effective, although potential cardiovascular adverse events may be more likely in an older population. Similar to other pharmacologic agents, use should be limited to patients who experience distress due to low libido with no other etiology for the sexual problem after other nonpharmacologic interventions have proven ineffective.
Phosphodiesterase inhibitors — Phosphodiesterase (PDE-5) inhibitors effectively treat male erectile dysfunction but generally have not proven effective in females.
Studies of sildenafil for treatment of females with sexual dysfunction have reported inconsistent results [56-60]. The best available evidence is a randomized trial of nearly 800 pre- and postmenopausal patients with disorders of desire, arousal, orgasm, and/or dyspareunia treated with 10 to 100 mg of sildenafil for 12 weeks [56]. Sildenafil was no more effective than placebo in increasing the frequency of enjoyable sexual events or improving any aspect of sexual function.
However, positive effects of sildenafil on sexual arousal and orgasm have been demonstrated in premenopausal patients with SSRI-associated sexual dysfunction. A randomized trial of sildenafil 50 or 100 mg in 98 females with major depression in remission on SSRIs and new-onset sexual dysfunction found that sildenafil for eight weeks, compared with placebo, significantly improved scores for global sexual function and orgasmic response [61]. Sildenafil use did not impact sexual desire and had no effect on hormone levels or measures of depression. (See "Sexual dysfunction caused by selective serotonin reuptake inhibitors (SSRIs): Management", section on 'Females'.)
Although there have been no studies on the use of other PDE-5 inhibitors, such as tadalafil and vardenafil, on SSRI-induced sexual dysfunction, it is likely that they have similar effectiveness due to their shared mechanism of action.
Randomized trial data also suggest that PDE-5 inhibitors may be helpful in treating sexual dysfunction in patients with diabetes, multiple sclerosis, or spinal cord injuries [62-64]. Further study is needed in these populations.
Potential side effects of PDE-5 inhibitors include headache, flushing, and nausea. These drugs are contraindicated in patients taking nitrates. Patients must be informed that PDE-5 inhibitor use for females has not been approved by the FDA. (See "Treatment of male sexual dysfunction".)
Erectile dysfunction is very common in aging males, and females may experience reduced sexual interest, arousal, and pleasure secondary to a partner's sexual dysfunction. In this setting, PDE-5 inhibitor use by a male partner with erectile dysfunction may result in improved sexual function and satisfaction for both members of the couple.
Orgasmic disorder — Treatment for female orgasmic disorder consists principally of education, psychosocial interventions, and the use of devices, including vibrators. Vibrators may improve the ability to achieve orgasm by increasing clitoral blood flow; they can be purchased at stores and websites specializing in products for sexual pleasure, but patients should be informed that most chain pharmacy stores also carry vibrators in the section where lubricants and moisturizers are sold. Some patients may be more comfortable purchasing these devices without going into a sexual device store.
Female orgasmic disorder is discussed in detail separately. (See "Treatment of female orgasmic disorder".)
Sexual pain — Sexual pain (also referred to as dyspareunia or genitopelvic pain/penetration disorder) is managed based on the etiology. Three common causes of sexual pain in females are GSM, which includes hypoestrogenic vulvovaginal atrophy; provoked pelvic floor hypertonus (including vaginismus); and vulvodynia. There are also many other etiologies of sexual pain. (See "Female sexual pain: Evaluation".)
Genitourinary syndrome of menopause — Hypoestrogenism due to menopause is the main cause of GSM. Menopause may occur naturally around age 50 years or may occur earlier due to a genetic mutation, autoimmune process, surgery, chemotherapy, or radiation. Anti-estrogen therapy, including aromatase inhibitors, results in profound estrogen deficiency and is increasingly used for estrogen-dependent tumors and even for chemoprevention. Management options for sexual pain associated with GSM include vaginal lubricants and moisturizers, low-dose vaginal estrogen, vaginal DHEA, and oral ospemifene (an estrogen agonist/antagonist). Vaginal laser or radiofrequency devices have been developed, but their safety/efficacy is not established. The FDA issued a warning regarding the use of these devices for the treatment of gynecologic problems, including vulvovaginal atrophy [65]. Dyspareunia with GSM is discussed in detail separately. (See "Genitourinary syndrome of menopause (vulvovaginal atrophy): Treatment".)
Provoked pelvic floor hypertonus — Provoked pelvic floor hypertonus (vaginismus) may be effectively treated with physical therapy by a therapist with expertise in managing disorders of the pelvic floor. Specific techniques may include the use of vaginal dilators and myofascial release of muscle tension in muscles of the pelvic floor, thighs, and abdomen, with or without biofeedback. Desensitization techniques are then applied to give the patient control over muscle tonicity/relaxation.
Other therapeutic approaches include sex therapy, progressive relaxation, sensate focus, electromyography, use of benzodiazepines, hypnotherapy, and botulinum toxin type A injections [66]. This is discussed in detail separately. (See "Myofascial pelvic pain syndrome in females: Treatment".)
Vulvar pain syndromes — Vulvar pain syndromes are a common cause of dyspareunia. Contact dermatitis from products applied to the vulva, incontinence, and daily pad use contribute to vulvar pain. Identifying and avoiding the irritant and effective management of incontinence improves pain from these causes. Management of general or local vulvodynia without a clear etiology includes pelvic physical therapy, psychotherapy, and topical or systemic medications. This is discussed in detail separately. (See "Vulvar pain of unknown cause (vulvodynia): Treatment".)
Treatments that are not recommended
Herbal supplements — Many patients are interested in trying over-the-counter herbal supplements, which are advertised widely and claim to increase sexual desire and pleasure. Patients should be informed that the safety and efficacy of these products are unproven, there is minimal regulatory oversight, and they are often costly. Nonetheless, given a 30 percent predicted placebo response and few reported side effects, patients may elect a trial of these alternatives.
One such product is a proprietary blend of herbal supplements (Avlimil). Many of the components of Avlimil are estrogenic, and animal study data suggest that the product may stimulate growth of estrogen-dependent breast tumors [67].
Another product, a botanical feminine massage oil (Zestra), is applied to the clitoris, labia, and vagina. A randomized, double-blind crossover trial in 20 patients reported increased sexual arousal, orgasm, and pleasure compared with a placebo oil; the only adverse effect reported was mild genital burning [68]. Other "warming" vaginal lubricants may increase sexual pleasure for some patients, but may cause vulvovaginal discomfort in patients with untreated GSM.
FOLLOW-UP — After initiating therapy for sexual dysfunction, patients should be seen for regular follow-up visits, approximately every three months, until effective interventions are identified and the sexual problem has improved. Patients may then be seen every 6 to 12 months, depending on the potential risks of the treatments selected. Patients using pharmacologic therapies will need to be monitored for drug-related risks and side effects at these visits. Treatment efficacy is best assessed by patient self-report of improvement of symptoms and achieving treatment goals.
SPECIAL POPULATIONS
Older adults — Clinicians are increasingly likely to encounter older patients seeking help with sexual dysfunction. More individuals are living into late life, a significant proportion of whom remain sexually active. This is discussed in detail separately. (See "Sexual dysfunction in older adults".)
Cancer survivors — Cancer treatment, including surgery, chemotherapy, radiation, and hematopoietic cell transplantation, often impacts sexual function. This is discussed in detail separately. (See "Overview of sexual dysfunction in female cancer survivors" and "Sexuality in palliative care".)
RESOURCES FOR CLINICIANS AND PATIENTS
●Books
•The Joy of Sex, by Alex Comfort
•Becoming Orgasmic: A Sexual and Personal Growth Program for Women, by Julia Heiman and Joseph Lopiccolo
•For Women Only: A Revolutionary Guide to Overcoming Sexual Dysfunction and Reclaiming Your Sex Life, by Jennifer Berman, Laura Berman, and Elisabeth Bumiller
•Getting the Sex You Want: A Woman's Guide to Becoming Proud, Passionate and Pleased in Bed, by Sandra Leiblum and Judith Sachs
•Come As You Are: The Surprising New Science That Will Transform Your Sex Life, by Emily Nagoski
•I [heart] Female Orgasm: An Extraordinary Orgasm Guide, by Dorian Solot and Marshall Miller
•Real Sex for Real Women: Intimacy, Pleasure & Sexual Wellbeing, by Laura Berman
•Hot Monogamy: Essential Steps to More Passionate, Intimate Lovemaking, by Patricia Love and Jo Robinson
•Dr. Ruth's Sex after 50: Revving Up the Romance, Passion & Excitement, by Ruth Westheimer
•Passionate Marriage: Keeping Love and Intimacy Alive in Committed Relationships, by David Schnarch
•Healing Painful Sex: A Woman's Guide to Confronting, Diagnosing, and Treating Sexual Pain, by Deborah Coady, MD and Nancy Fish, MSW, MPH
●Websites
•American Association of Sexuality Educators, Counselors, and Therapists
•American College of Obstetricians and Gynecologists
•American Urological Association
•North American Menopause Society – Module on "Sexual Health and Menopause"
•Sexuality Information and Education Council of the United States
•Society for Sex Therapy and Research
•Society for the Scientific Study of Sexuality
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Female sexual dysfunction".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Sex problems in females (The Basics)" and "Patient education: Sex as you get older (The Basics)")
●Beyond the Basics topics (see "Patient education: Sexual problems in females (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Clinical approach – Females who seek treatment of sexual concerns (eg, lack of sexual desire, impaired arousal, inability to achieve orgasm, pain with sexual activity) should be fully evaluated for underlying factors. Evaluation should include a physical and pelvic examination. Many patients present with multiple issues, and the etiology may be multifactorial. Medical or psychiatric conditions that may alter sexual function (eg, depression, arthritis, genitourinary syndrome of menopause [GSM], pelvic pain, anemia, sexual issues related to medications, urinary and fecal incontinence) should be assessed and treated before considering other treatments for sexual dysfunction. Partner issues should be addressed in making the management plan. (See 'Clinical approach' above.)
●Initial interventions – Initial treatment often includes nonpharmacologic options such as vaginal lubricants and moisturizers, lifestyle changes (eg, reducing stress and fatigue, increasing quality time with partners, bringing novelty to the sexual repertoire, improving body image), and couples and/or sex therapy. (See 'Interventions that address multiple issues' above.)
•Referral to a sex therapist or couples counselor is a highly effective intervention for sexual dysfunction.
•For patients with psychiatric disorders, particularly those on psychotropic medications, management of sexual function usually requires communication between the clinician managing the sexual problem and the patient's psychiatrist.
•Pelvic physical therapists are often needed to address specific problems, including pelvic floor hypertonus (vaginismus), pelvic pain, urinary or fecal incontinence, or pelvic organ prolapse. (See 'Counseling' above and 'Treating pelvic floor dysfunction' above.)
●Pharmacologic therapy – Pharmacologic therapy should be restricted to patients who meet diagnostic criteria for a sexual disorder (a sexual problem that is persistent or recurrent and causes marked distress or interpersonal difficulty) and who did not respond to nonpharmacologic interventions. The sexual dysfunction must not be better accounted for by a general medical or psychiatric condition (eg, anxiety and depression) or due exclusively to the direct physiologic effects of a substance or medication. (See 'Clinical approach' above.)
•Hormonal pharmacologic options
-For postmenopausal patients with sexual problems that begin with the onset of vasomotor symptoms (hot flashes, night sweats, sleep disruption), systemic estrogen therapy is an option for carefully selected patients. (See 'Estrogens' above.)
-For postmenopausal patients with dyspareunia due to GSM, options include vaginal lubricants and moisturizers, low-dose vaginal estrogen therapy, vaginal dehydroepiandrosterone, or ospemifene. (See 'Genitourinary syndrome of menopause' above.)
-For postmenopausal patients with hypoactive sexual desire disorder, testosterone therapy is an option for carefully selected patients. Candidates for therapy must have no contraindications to taking androgens or estrogens (as many androgens are aromatized to estrogens), be willing to accept androgenic side effects, and counseled that this therapy is not approved for females by the US Food and Drug Administration (FDA) due to a lack of long-term safety data. A commonly used preparation is compounded 1% testosterone topical cream or gel; 0.5 grams is applied daily to the skin of the arms, legs, or abdomen. (See 'Androgens' above and 'Available androgen preparations and limitations' above.)
-For premenopausal patients with sexual dysfunction, we do not prescribe androgen therapy. Androgen therapy does not significantly improve sexual function (eg, desire, pleasure, orgasm) and can lead to potential adverse events (eg, inadvertent exposure to a developing fetus if pregnancy occurs). (See 'Androgens' above and 'Available androgen preparations and limitations' above.)
•Nonhormonal pharmacologic options
-Bremelanotide – Bremelanotide is a melanocortin receptor agonist approved for the treatment of low sexual desire with associated distress in premenopausal patients. It is a subcutaneous injection used, as needed, 45 minutes prior to anticipated sexual activity. Use may increase sexual desire and sexual satisfaction. Associated nausea and vomiting may limit acceptability for some patients; hyperpigmentation, potentially permanent, occurs in 1 percent of patients. Bremelanotide may increase blood pressure and should not be used in patients with uncontrolled hypertension or known cardiovascular disease. Bremelanotide is not indicated for the treatment of sexual dysfunction in postmenopausal patients. (See 'Bremelanotide' above.)
-Flibanserin – Flibanserin is a centrally acting serotonin receptor agonist/antagonist for treatment of low sexual desire with associated distress in premenopausal patients. Daily use results in small increases in the frequency of sexually satisfying events and sexual desire compared with placebo. The clinical role of flibanserin may be limited by the need for daily dosing, common adverse effects (eg, somnolence, dizziness), and safety concerns regarding combining flibanserin with alcohol or certain medications (eg, fluconazole, antidepressants). Flibanserin is not indicated for the treatment of sexual dysfunction in postmenopausal patients. (See 'Flibanserin' above.)
-Bupropion – Bupropion may be an effective treatment for sexual dysfunction in patients with or without associated depression. Use for selective serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction is an off-label indication. (See 'Bupropion' above.)
-Phosphodiesterase inhibitors – Phosphodiesterase (PDE-5) inhibitors are ineffective for female sexual dysfunction except for patients with sexual interest/arousal or orgasm disorders associated with use of an SSRI. For patients in whom stopping the SSRI or switching to another antidepressant is not advisable, treatment with a PDE-5 inhibitor may improve sexual function; however, patients must be informed that these medications are not FDA approved for use in females. (See 'Phosphodiesterase inhibitors' above.)
-Herbal supplements – Use of over-the-counter herbal supplements for sexual dysfunction should be avoided since the safety and efficacy of these products are unproven and there is minimal regulatory oversight. (See 'Herbal supplements' above.)
