Female Sexual Interest/Arousal Disorder

The etiology of FSIAD is multifactorial, influenced by a combination of biological, psychological, interpersonal, and sociocultural factors (see figure Biopsychosocial Model).

Biopsychosocial Model

Data from Parish SJ, Hahn SR, Goldstein SW, et al. The International Society for the Study of Women's Sexual Health Process of Care for the Identification of Sexual Concerns and Problems in Women. Mayo Clin Proc. 2019;94(5):842-856. doi:10.1016/j.mayocp.2019.01.009

Biological: Few direct biological factors have been identified in low sexual desire in women, but they may include hormonal changes related to menopause, pregnancy, or breastfeeding, as well as certain medications (eg, SSRIs, SNRIs) or medical conditions (eg, endocrine or neurologic disorders). Although testosterone levels decrease with age, research connecting testosterone and sexual desire in women is sparse; thus, testosterone therapy is not routinely recommended (1).

Difficulties with arousal may be driven by reductions in estrogen and androgen resulting from medical conditions and physiological changes such as menopause, breastfeeding, primary central and peripheral nervous system disorders, infections, or vascular disorders (2). Often biological factors indirectly contribute to reduced desire and arousal, such as through fatigue, stress, or body image concerns occurring secondary to a medical condition.

Psychological: Mental health conditions, like depression or generalized anxiety disorder, may contribute to difficulty with desire and arousal. Additionally, sexual-specific cognitive-affective factors such as spectatoring (eg, viewing oneself or sexual activity as if one is viewing it from the outside) and performance anxiety can contribute to FSIAD, even in the absence of a clinical mental health condition. Sometimes, the decrease in desire and arousal develops secondary to another sexual problem, such as becoming less interested in sexual activity as a result of dyspareunia.

Interpersonal: Relationship satisfaction and dyadic cohesion and affection are positive predictors of sexual desire in women (3, 4). In contrast, relationship problems such as ongoing conflict, infidelity, or partner's sexual concerns may contribute to FSIAD. Differences between each partner's sexual desire (ie, desire discrepancy) may further contribute to distress related to low desire. Women may be more likely to experience responsive sexual desire, meaning that their sexual interest is dependent on stimuli from their partner (eg, initiation of sexual activity), environment (eg, romantic setting), or erotic stimuli (5).

Sociocultural: Religious or cultural attitudes and beliefs about sexuality, and women's sexuality in particular, can result in feelings of guilt or shame and inhibit sexual desire and expression.

The symptoms and signs of FSIAD include absent or diminished interest in sexual activity or arousal, accompanied by distress.

• History and physical examination

• Clinical criteria

A thorough evaluation of FSIAD is based on a clinical interview that focuses on current symptoms and sexual history as well as relevant aspects of the medical history, obstetric/gynecologic history, and medications. (See table Components of the Sexual History for Assessment of Female Sexual Dysfunction.) Evaluation may include a pelvic examination and laboratory testing, if needed, to evaluate associated symptoms (eg, dyspareunia). The clinical evaluation should align with Diagnostic and Statistical Manual of Mental Disorders, 5th edition, Text Revision (DSM-5-TR) diagnostic criteria, utilizing a biopsychosocial framework to identify precipitating, perpetuating, and maintaining factors.

DSM-5-TR criteria for female sexual interest/arousal disorder require an absence of or a significant decrease in ≥ 3 of the following (1):

• Interest in sexual activity

• Sexual or erotic fantasies or thoughts

• Initiation of sexual activity and responsiveness to a partner's initiation

• Excitement or pleasure during ≥ 75% of sexual encounters

• Interest or arousal in response to internal or external sexual or erotic stimuli (eg, written, verbal, visual)

• Genital or nongenital sensations during sexual activity in ≥ 75% of sexual encounters

Criteria require that these symptoms be present for ≥ 6 months; cause significant distress in the individual; and not be better explained by another psychiatric or general medical condition, significant relationship stressors, or use of a medication or substance.

Standardized measures of sexual function, such as the Female Sexual Function Index (FSFI) may be incorporated to support diagnosis (2).

• Psychological therapies

• Medications

The overall approach is multimodal, addressing both the psychological and physical factors contributing to FSIAD.

Treatment starts with psychological interventions, such as education and addressing modifiable risk factors. Several psychological interventions, including individual, couples and cognitive behavioral therapy, mindfulness-based practices, and sexual skills training, have been found to be effective with or without pharmacotherapy (1).

Because selective serotonin reuptake inhibitors (SSRIs) can contribute to several types of sexual dysfunction, including low sexual interest, substituting another antidepressant that impairs sexual response less may help (eg, bupropion, moclobemide, mirtazapine, and duloxetine).

There are several pharmacologic therapy options for FSIAD. (See table Medications for Female Sexual Interest/Arousal Disorder.) Flibanserin, an oral serotonin agonist/antagonist taken daily, and bremelanotide, a subcutaneous melanocortin-4 receptor agonist, are nonhormonal pharmacotherapies approved by the U.S. Food and Drug Administration (FDA) for management of FSIAD in premenopausal women (2). The original labeling for flibanserin carried a box warning prohibiting the intake of alcohol while using flibanserin (2); the box warning has been removed based on a follow-up study that did not show an increase in the side effect profile in those who used alcohol in conjunction with flibanserin. Patients are advised to take flibanserin at bedtime and to avoid consumption of alcohol for at least 2 hours prior.

Several antidepressants have been used off-label for management of FSIAD; bupropion and buspirone have been shown to have some benefit. For sexual dysfunction as a side effect in individuals on selective serotonin reuptake inhibitors (SSRI), the addition of buspirone has been found to increase sexual desire; however, there are no studies in which FSIAD is the primary clinical outcome (2–4). There are conflicting data regarding the utility of adding bupropion for management of SSRI-induced sexual dysfunction.

Trazodone is a derivative of the serotonin receptor antagonist and reuptake inhibitor class with a similar mechanism of action as flibanserin (2). At high doses, serious sexual side effects such as persistent genital arousal can occur; however, low doses (3.5 mg/day) have shown promising clinical results in enhancing sexual desire without the side effects seen at higher doses.

While there are no FDA-approved testosterone therapy options for women, off-label use of topical testosterone at low doses has demonstrated improvement in sexual desire, arousal, and responsiveness and reduced sexual distress in some studies (5–7). Long-term safety data are lacking; therefore, it is generally recommended that treatment be discontinued if there has not been improvement in symptoms after 6 months. In addition, regular follow-up should include measuring serum liver function tests, lipids, and serum testosterone levels at baseline, and then measuring serum testosterone at 3 to 6 weeks after initiating treatment and every 6 months thereafter to ensure levels remain in the normal physiologic premenopausal range. Patients should be counseled about potential adverse effects, including acne, excess facial or body hair growth, male pattern baldness, and potentially permanent voice deepening or enlargement of the clitoris. Supraphysiologic serum concentrations, as seen with pellets and injections, can be associated with irreversible side effects (7). Use of testosterone in premenopausal women is not recommended.

Additionally, transdermal forms of systemic hormone therapy are preferred in those with sexual dysfunction, as oral forms are associated with increases in sex hormone-binding globulin and reduced bioavailability of testosterone (8). However, there is an oral formulation of 0.625 mg of esterified estrogens plus 1.25 mg of methyltestosterone approved for management of VMS that has been shown to increase the concentration of bioavailable testosterone and is associated with lower sex hormone-binding globulin (9).

Devices such as vibrators or clitoral suction stimulators may help with sexual arousal, but there is little evidence to support their effectiveness. Some of these products are available over the counter.

• Female sexual interest/arousal disorder (FSIAD) is ≥ 6 months of reduced or absent sexual interest and/or arousal with associated distress, not explained by another condition, relationship issue, or medication or substance.

• Symptoms include decreased sexual thoughts or fantasies, reduced initiation or receptivity, diminished excitement or pleasure, reduced response to sexual cues, and decreased genital or nongenital sensations.

• Causes are multifactorial and may be biological, psychological, interpersonal, or sociocultural.

• Diagnosis is based on clinical interview and criteria using a biopsychosocial framework.

• Treatment is multimodal, beginning with psychological interventions (eg, CBT, mindfulness, sex therapy) and addressing contributing factors; pharmacologic options (eg, flibanserin, bremelanotide, selected off-label therapies) may be considered in appropriate patients.