e6-12: Low Sexual Desire in Women

While the DSM-5 has reclassified female sexual function disorders, clinical practice related to screening and management remains largely based on the prior classification of hypoactive sexual desire disorder (HSDD). HSDD is the most prevalent sexual disorder in women. Affected women report at least 6 months of low motivation or desire for sexual activity with associated significant personal distress. The Decreased Sexual Desire Screener (found as Figure 2 in Clayton article referenced below) is a validated self-administered questionnaire that can aid clinicians in diagnosing this disorder.

Pathophysiologically, HSDD is related to an imbalance of central sexual excitatory and inhibitory pathways. Excitatory pathways involve the action of dopamine, melatonin, oxytocin, vasopressin, and norepinephrine, whereas inhibitory pathways utilize opioid, serotonin, and endocannabinoid systems. Psychological comorbidities, stressors, medications, medical comorbidities, cultural and religious factors, or partner and relationship concerns further contribute to sexual dysfunction.

Several medical conditions (eg, depression, anxiety, diabetes, urinary incontinence, and multiple sclerosis) and certain medications (eg, antidepressants, hormonal therapy, antihypertensives) can contribute to low sexual desire, so a detailed history is essential for eliciting potentially modifiable risk factors. In certain women, it may be appropriate to perform a gynecologic examination to identify areas of tenderness or discomfort that might be associated with painful intercourse and reduced sexual desire. Laboratory evaluation is not necessary for making the diagnosis, although prolactin and thyroid hormone levels can be measured in select patients where other symptoms raise concern for hormonal abnormalities. Notably, testosterone levels do not correlate with female sexual function and should not be routinely measured.

Treatment for low sexual desire includes office-based counseling, psychological therapy, and medications. Office-based counseling can be facilitated using an approach based on the PLISSIT model employed in sex therapy. (The letters of the model's name refer to the four different levels of intervention that a sex therapist can use: permission [P], limited information [LI], specific suggestions [SS], and intensive therapy [IT].) In addition to sex therapy, intensive psychological therapy may include cognitive-behavioral training and mindfulness-based stress reduction training (see Chapter e4-06).

Based on the understanding of sexual excitatory and inhibitory pathways, medications that increase dopamine or decrease serotonin release or binding may be effective in increasing sexual desire. Two medications are currently FDA-approved for low sexual desire: flibanserin and bremelanotide. Flibanserin, which is a full agonist of the 5-HT_1A receptor and, with lower affinity, an antagonist of the 5-HT_2A receptor, was the first FDA-approved medication for the treatment of low sexual desire in premenopausal women. A 2016 systematic review evaluated the efficacy of flibanserin in 5914 premenopausal and postmenopausal women. Compared with women taking placebo, women who were taking flibanserin had a small increase in the number of satisfying sexual events and sexual desire intensity but were four times more likely to experience the side effects of dizziness and somnolence. Flibanserin is prescribed in a single daily oral dose of 100 mg, administered at bedtime. Women who have consumed three or more alcoholic beverages are advised to skip their daily dose of flibanserin since alcohol can potentiate side effects.

Bremelanotide, a melanocortin receptor agonist, is also FDA-approved for the treatment of HSDD in premenopausal women; the mechanism by which it improves sexual desire is unknown. In two randomized controlled trials, including 1247 women, patients had modest improvements in sexual function scales when compared with placebo (25% versus 17%). The medication is a subcutaneous injection (1.75 mg) dosed as needed, 45 minutes prior to sexual activity and it may be taken no more than once a day or eight times per month; pricing in the United States is approximately $100–300 per autoinjector. Side effects include nausea (in 40% of patients, including some requiring antiemetics), vomiting, and skin darkening (1%). Women with uncontrolled hypertension should not take bremelanotide since it may cause transient blood pressure elevations. Additionally, patients taking naltrexone should not take bremelanotide since it may decrease naltrexone levels to the subtherapeutic range.

Several studies have investigated the efficacy of testosterone for the management of HSDD. The results of a systematic review of seven randomized trials involving more than 3000 menopausal women showed that the testosterone patch, compared to placebo, resulted in a significant increase in the number of sexually satisfying encounters and sexual activity as well as sexual desire and orgasms. Side effects included increased acne and hair growth, although there was no significant difference in serious adverse events. However, the lack of FDA-approved testosterone formulations for women with sexual dysfunction (because of insufficient long-term safety data) limits off-label use of this medication for treatment. Bupropion is commonly used as an adjunct when SSRI-associated decreases in desire are present, and it has also been shown to improve desire in premenopausal women. However, bupropion is not FDA-approved for these indications.