About a third of women in the United States experience decreased sexual desire (DSD), a symptom that may be part of a more complex diagnosis. The author discusses DSD with respect to background information, screening, and diagnosis, and then focuses on treatment of this common, oftentimes perplexing, problem.
Decreased sexual desire (DSD), also known as low sex drive or low libido, may be a symptom of a diagnosable female sexual dysfunction (FSD). When DSD in a woman is severe, resulting in a complete or substantial lack of sexual interest/arousal, an absence of sexual/erotic thoughts, a disinclination to initiate sexual encounters, and an absence of pleasure during sex—and has persisted for at least 6 months, resulting in distress, with no evidence of a physical, biological, or substance-induced origin—then this FSD meets criteria for the Diagnostic and Statistical Manual for Mental Disorders, 5th Edition (DSM-5), diagnosis of female sexual interest/arousal disorder (FSIAD).1 In this latest edition of the DSM, the American Psychiatric Association merged the more familiar diagnoses of hypoactive sexual desire disorder (HSDD) and female sexual arousal disorder into one new diagnosis: FSIAD.2*
In this article, decreased sexual desire or its abbreviation DSD is used as an umbrella term to cover all of the clinical and lay terms for the symptom, and the term hypoactive sexual desire disorder or its abbreviation HSDD is used when specifically referring to the DSM diagnosis. FSDs such as female orgasmic disorder and genitopelvic pain/penetration disorder, the latter of which itself is a DSM-5 amalgam of dyspareunia and vaginismus, are beyond the scope of this paper.
*Sexual medicine providers remain divided on the acceptance of this new DSM-5 terminology because many of them appreciate the unique attributes associated with HSDD and female sexual arousal disorder. In addition, most recent studies and publications utilize the DSM-IV-TR terminology of HSDD, including the recently published HSDD Process of Care.3
Although HSDD has likely plagued millions of women over the course of human history, it was not discussed in medical literature in the United States until 1974,4 and it was first included in the DSM—the DSM-III-TR to be exact—in 1987.5 Likewise, the topic of DSD in women did not receive much attention in the media until the past few decades. It was not until 2015 that the first prescription medication was approved by the FDA to treat HSDD in premenopausal women. And, now, in the spring of 2019, another medication is nearing FDA approval for this same indication in the same population. No medication has yet been approved to treat HSDD in postmenopausal women despite published evidence supporting the efficacy of some compounds.
This article covers the prevalence of DSD—both as a symptom and as part of a more complex psychiatric diagnosis, HSDD—as well as its underlying causes, and the assessment and treatment of women who present with this problem. Much of the article is devoted to a wide variety of non-medicinal, medicinal, and alternative treatments that healthcare providers (HCPs) can offer to women who have DSD or HSDD.
In a landmark study reported almost 20 years ago, Laumann et al.6 found that 43% of 1,486 U.S. women aged 18-59 years experienced some type of sexual dysfunction. The most common FSD was a lack of interest in sex, reported by about one-third of respondents overall. FSDs such as anorgasmia, dyspareunia, lack of pleasure during sex, anxiety about performance, and difficulty lubricating affected smaller proportions of the sample.
More recently, a cross-sectional study of more than 1,900 U.S. women aged 30-70 years and in stable relationships who were interviewed by telephone showed that the overall prevalence of DSD was 36.2%.7 The overall prevalence of HSDD, characterized by distress about one’s DSD, was 8.3%. A survey of more than 31,000 U.S. women revealed that 38.7% experienced DSD.8 Age stratification revealed a sharp increase in the prevalence of DSD by age group (22.2% among women aged 18-44, 38.9% among those aged 45-64, and 74.8% among those 65 or older), whereas distress about DSD was greater among middle-aged women (12.3%) than among their younger (8.9%) or older (7.4%) counterparts. The consensus among experts is that HSDD affects about 10% of women.9
Female sexual response
Why do about a third of U.S. women, at least according to these studies, experience DSD? In order to understand the causes of DSD, HCPs must be familiar with two models of thought about female sexual response. According to the biopsychosocial model, female sexual response is affected by multiple etiologic factors, including10,11 :
• Biological factors such as physical health, neurobiologic status, and endocrine functional status;
• Psychological factors such as body image, performance anxiety, and mood;
• Sociocultural factors such as upbringing, educational background, and cultural norms; and
• Interpersonal factors such as quality of current and past relationships, intervals of abstinence, life stressors, and economic status.
According to the Dual Control Model, sexual response involves an interaction between excitatory factors and inhibitory factors.12 Individuals vary in their propensity for both sexual excitation and sexual inhibition. For most people, these propensities are adaptive and non-problematic. However, individuals with an unusually high tendency for excitation or a low propensity for inhibition are more likely to engage in high-risk or otherwise troublesome sexual behavior. Conversely, individuals with a low propensity for sexual excitation or a high propensity for sexual inhibition are more likely to experience an impairment of sexual response (i.e., sexual dysfunction). The causes of these propensities are themselves multifactorial. In terms of neurobiologic factors that affect female sexual response, sex steroids, dopamine, oxytocin, melanocortin, and norepinephrine are excitatory, whereas serotonin, endogenous opioids, endocannabinoids, and prolactin are inhibitory.9
Causes of female sexual dysfunction
The aforementioned models are thought provoking and certainly have applications in the real world. For example, subnormal sex steroid levels may be the main etiologic factor in a postmenopausal woman presenting with DSD.3 But before an HCP begins a physical assessment and possibly orders laboratory tests, with the aim of identifying the cause of a woman’s DSD, it is helpful to consider aspects of her daily life that may be contributing to her problem. For example, FSD may be related to a physical condition such as chronic pain, thyroid dysfunction, or chronic fatigue; a mental illness such as depression or anxiety; her life-stage status (e.g., pregnancy, infertility, menopause); smoking, excessive alcohol consumption, or illicit drug use; poor body image; or life stressors. In addition, many women are simply naïve about sexual physiology and sexual response.
For many medications, DSD is a common side effect. Typical offenders include psychotropic agents such as selective serotonin reuptake inhibitors (SSRIs), serotonin/ norepinephrine reuptake inhibitors, tricyclic antidepressants, and benzodiazepines; antiepileptic agents; cardiovascular agents such as beta blockers, diuretics, and lipid-lowering agents; hormonal agents such as oral contraceptives, fertility drugs, estrogens, and gonadotropin-releasing hormone agonists; cancer treatments; and histamine-2 receptor blockers.13 SSRIs are particularly well-known culprits in terms of their adverse effect on sexual function in both men and women.14
The recently published HSDD Process of Care offers an easy-to-follow algorithmB (via a link to the author’s June 2018 column on this topic) for facilitating the proper identification, diagnosis, and treatment of DSD and HSDD in pre- and postmenopausal women.3,15 The Decreased Sexual Desire ScreenerC is a validated, diagnostic tool that allows HCPs to quickly and efficiently diagnose generalized, acquired HSDD. After DSD is identified in a given woman, HCPs should take a thorough history to determine whether any of the aforementioned aspects of her daily life are causing or exacerbating her DSD.3 Other questionnaires that can help assess DSD are the Female Sexual Function Index (FSFI)D and the Female Sexual Distress Scale-Revised (FSDS-R)E.
The physical examination should include evaluation of the patient’s vital signs; general presentation; gait/posture; skin, including mucosal surfaces; and neurologic and musculoskeletal status in order to identify problems not revealed during history taking that may play a role in DSD. With regard to the vulvovaginal exam in particular, HCPs should note the woman’s skin/tissue integrity, neurologic status, vaginal/pelvic muscle strength and tone, and urogenital health. HCPs may consider blood testing, as indicated, for levels of estradiol, follicle-stimulating hormone, luteinizing hormone, testosterone, dihydrotestosterone, sex hormone-binding globulin (SHBG), prolactin, and thyroid hormones.3
The first step in treating DSD is education and revision of any identified modifiable biopsychosocial factors such as underlying health conditions, medications, and relationship discord.3 The intervention may be as simple as stopping an SSRI and switching to another antidepressant or educating the woman about female sexual response. For appropriate candidates, the next step is to initiate counseling or psychotherapy to modify thoughts, beliefs, behaviors, emotions, and relationship communication/behaviors that may be interfering with sexual desire.9 In many cases, especially when DSD is chronic and/or distressing, another non-medicinal approach and/or a medicinal approach may be advisable.
Some women with DSD can experience improvement in their sex drive by participating in talk therapy or by using devices marketed as sexual aids or toys. However, over-the-counter products marketed as sexual performance enhancers should be approached with caution. For instance, many arousal creams and lotions contain caustic ingredients that can irritate sensitive vulvovaginal tissue.
Counseling or psychotherapy
Office-based counseling using the PLISSIT model (Permission, Limited Information, Specific Suggestions, and Intensive Therapy), a stepped approach specifically for general HCPs caring for women with sexual concerns, may be helpful.16 If psychotherapy is indicated, the woman can be referred to a mental health specialist or sex therapist.
Clitoral stimulators, vibrating pumps, and similar devices marketed as sexual aids or toys can enhance sexual arousal in women. These products are available at websites such as buywomanizer.com, pureromance.com, and goodvibes.com/s/. Although sexual arousal typically follows sexual desire, some women who use these products to achieve sexual arousal find that their sex drive increases as a side benefit.
Not all women are receptive to the idea of using devices to enhance their sex drive. HCPs need to use their judgment to select appropriate candidates. At the same time, some women who seem reticent at first may be more interested in trying a product if their HCP normalizes the use of sexual aids and toys by describing them as physical therapy for the vagina.
These approaches include one FDA-approved medication for HSDD (flibanserin), one drug nearing FDA approval for HSDD (bremelanotide [BMT]), hormonal agents, and various pharmaceuticals used off label to treat DSD and HSDD.
Flibanserin is the first and only medication approved by the FDA to treat HSDD in premenopausal women. Flibanserin is dosed at 100 mg once daily at bedtime. This agent is a full agonist at postsynaptic serotonin 5HT1A receptors and an antagonist at postsynaptic 5HT2A receptors,17 although its exact mechanism of action in treating HSDD is unknown. Its safety and efficacy, as evidenced by an improvement in desire, a reduction in distress, and the experience of more satisfying sexual events, was demonstrated in three pivotal placebo-controlled trials.18-20
In these three trials, common side effects of flibanserin were dizziness, somnolence, nausea, and fatigue. The package insert for flibanserin warns against ingestion of alcoholic beverages, which may increase the risk for severe hypotension and syncope.21 This warning was based on results of a phase I study of 25 subjects—23 men and 2 women—in whom the incidence of hypotension and syncope increased when flibanserin was co-administered with ethanol.22 However, a postmarketing, randomized, double-blind, placebo-controlled, single-dose, crossover study conducted on 96 premenopausal women showed that mild/moderate consumption of alcohol did not affect the adverse event profile of flibanserin with respect to dizziness, hypotension, or somnolence, and that no instances of syncope were observed.23 The FDA may consider removing the boxed warning if results of additional postmarketing studies support those reported by Sicard et al.23
In June 2018, the FDA accepted a New Drug Application for BMT, a peptide melanocortin receptor agonist, for the treatment of HSDD, with a Prescription Drug User Fee Act date set for March 23, 2019. Unlike flibanserin, which is taken orally, on a daily basis at bedtime, BMT is administered subcutaneously and is used only as needed. BMT 1.75 mg is administered into the anterior thigh or abdomen via a disposable auto-injector.
Two 2015 reviews of agents undergoing development and testing indicated that BMT showed promise.24,25 A 2016 phase IIB trial demonstrated that BMT doses of 1.25 mg and 1.75 mg, but not 0.75 mg or placebo, were safe, effective, and well tolerated in increasing the number of sexually satisfying events per month, the main outcome measure.26
The RECONNECT trial, whose 52-week open-label treatment phase is ongoing, included a 24-week, randomized, double-blind, placebo-controlled treatment phase evaluating the safety and efficacy of BMT in 1,247 premenopausal women who had HSDD for at least 6 months.27 In this 24-week segment of the trial, BMT recipients, compared with placebo recipients, experienced statistically significant and clinically meaningful improvement as gauged by FSFI desire domain scores and the FSDS desire/arousal/orgasm tool. Scores for item 13 of the FSDS-R showed a significant reduction in DSD-related distress for women using BMT versus those using placebo. The most frequent BMT-related treatment emergent adverse events (TEAEs) were mild/moderate nausea, facial flushing, and headache. TEAEs led to treatment discontinuation or interruption in approximately 18% of BMT users versus 2% of placebo users.
Randomized, double-blind, placebo-controlled studies have demonstrated the efficacy of transdermal testosterone (T), alone or with estrogen or estrogen/progestogen therapy, in relieving HSDD symptoms in menopausal women.28 Although supported by evidence, T is used off label for DSD. An Endocrine Society Practice Guideline suggests a 3- to 6-month trial of T in postmenopausal women who request this therapy and in whom it is not contraindicated.3,29 T should be prescribed in a non-oral formulation such as a transdermal patch, gel, or cream—either an FDA-approved product for men or a product prepared by a compounding pharmacy—at a dosage that is about one-tenth of that used in men.
Healthcare providers who prescribe T off label for a woman with DSD should measure her T levels at baseline, after 3-6 weeks of treatment, and then every 6 months thereafter to monitor for overuse and signs of androgen excess. At all these checkpoints, a woman’s bioavailable T level should be determined via a mathematical formula (total T x 3.47/ SHBG) or with use of an online calculator available at issam.ch/freetesto.htm. The goal for calculated free T in women is 0.6-0.8 ng/dL.30
A systematic review evaluating the effect of DHEA on aspects of sexual function showed that treatment with this endogenous steroid hormone improved sexual interest, lubrication, pain, arousal, orgasm, and sexual frequency.31 Like T, DHEA is used off label to treat HSDD.
Anecdotal evidence suggests that a psychostimulant such as dextroamphetamine/amphetamine or methylphenidate may help treat HSDD in select cases, particularly if a woman has co-existing attention deficit disorder that may or may not have been diagnosed.32 A short course of a short-acting psychostimulant, used off label in this fashion, may help a woman who has difficulty “shutting down” and “focusing” to enjoy sex.
Buspirone, a serotonin 1A partial agonist, is approved as an anxiolytic for the treatment of generalized anxiety disorder and for short-term relief of anxiety symptoms, and it is used off label to treat HSDD.24 Bupropion, a norepinephrine-dopamine reuptake inhibitor, is approved for the treatment of depression and for smoking cessation, but it is used off label to treat HSDD.33
Other medicinal options
If none of the aforementioned treatments are effective in a given woman, other medicinal options are available. Depending on her needs, preferences, and health status, she can try compounded oxytocin troches/lozenges (10-50 IU) or nasal spray (100 IU/mL; 1 spray into nostril at time of coitus), a phosphodiesterase type 5 inhibitor such as sildenafil, or a topical arousal cream. These creams, used to enhance clitoral stimulation and sexual arousal, contain active ingredients such as aminophylline, L-arginine, sildenafil, nitroglycerin, or phentolamine. Zestra cream includes borage oil, evening primrose oil, angelica root extract, coleus root extract, and cocoa seed powder. Oral sildenafil and the cream formulations are used mainly to enhance sexual arousal, as opposed to sexual desire—but, as with the aforementioned sexual devices, increased sexual arousal may lead to increased sexual desire.
A woman who wants to avoid using conventional medications may find that an alternative remedy improves her sexual function. A double-blind, placebo-controlled study was conducted to determine the effect of a dietary supplement, ArginMax, which contains L-arginine (shown to enhance blood flow and nerve conduction in the genitals), other herbs, vitamins, and minerals on sexual function in women.34 Active treatment, compared with placebo, had significantly beneficial effects on level of sexual desire, satisfaction with overall sex life, and frequency of sexual intercourse in premenopausal women; on frequency of intercourse, satisfaction with one’s sexual relationship,and vaginal dryness in perimenopausal women; and on sexual desire in postmenopausal women.
The causes of DSD and HSDD in women are complex and multifactorial; as such, the approach to treatment is often multifaceted. After a physical exam and lab tests rule in or out other treatable causes (and those causes are addressed as indicated), HCPs can try non-medicinal, medicinal, or alternative approaches that are individually tailored to a woman’s needs and preferences.
As of this writing, only one medication, flibanserin, is FDA approved to treat HSDD in premenopausal women, although BMT may soon be granted this same approval. Testosterone is used off label to treat HSDD in postmenopausal women. Other medications and herbal remedies have been used safely and effectively for this indication in women of any age. Women can avail themselves of a course of psychotherapy or sex therapy to shed light on the cause of their DSD and to learn strategies for enhancing their sex drive. They can use devices that increase sexual arousal and that have the side benefit of increasing sexual desire. DSD is a common, often distressing problem, but it can be improved, if not fully overcome, with a wide variety of treatment options.
Brooke M. Faught, DNP, WHNP-BC, NCMP, IF, is a women’s health nurse practitioner and Clinical Director of the Women’s Institute for Sexual Health (WISH), A Division of Urology Associates, in Nashville, Tennessee.
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