Low Sexual Desire in Women: What Are the Options?

Pam Harrison

Disclosures

July 09, 2018

Asking Women About Sex

"How's your sex life?" is not a question asked of most women during a routine women's health visit.

But it should be, sexual health experts agree. Women who find themselves distressed by low sexual desire must be encouraged to raise the topic with their healthcare providers. An unsatisfying sexual life caused by physical or emotional problems can be treated.

If physicians and other clinicians don't ask, many women will never verbalize their concerns. These reticent women may think their provider will be embarrassed by the question, or won't know how to treat the condition.

"Many doctors are uncomfortable with this topic, and they haven't been well trained in it," explained Anita Clayton, MD, chair of psychiatry and neurobehavioral sciences, University of Virginia, Charlottesville, Virginia "But there is no reason for women to settle for an unsatisfying sexual life, especially when there are more than 20 drugs out there for different types of sexual dysfunction in men," she added.

Hypoactive Sexual Desire Disorder

Officially, the disorder known to clinicians as "hypoactive sexual desire disorder" (HSDD) has been changed, in the latest Diagnostic and Statistical Manual of Mental Disorders, to "female sexual interest/arousal disorder." Unofficially, clinicians still refer to this condition as "HSDD," and the acronym is still widely used in the literature on this topic.

HSDD is characterized by reduced or absence of interest in sexual activity and, crucially, is distressing to the affected woman.[1] In other words, if a woman has no sex drive but isn't concerned about it, she does not have HSDD.

How prevalent HSDD is depends on the patient population and how it is measured. In a large epidemiologic study,[2] Sue Davis, MD, president of the International Menopause Society and professor of women's health at Monash University in Melbourne, Australia, and colleagues found that almost one third of women between the ages of 40 and 64 years had HSDD, irrespective of menopausal status, and an equivalent proportion were distressed by it.

"We don't know the prevalence of HSDD in premenopausal women because all the interest has been in postmenopausal women," Davis continued. That said, the literature suggests that about 1 in 10 women meets the criteria for HSDD.[3] Because sexual desire and related distress both decline with age, the prevalence of HSDD is probably fairly steady across the adult lifespan, as Clayton pointed out in a recent review.[1] Low sexual desire has biological, psychological, and cultural causes, so teasing out the prime contributor can be daunting, sexual health experts acknowledge.

Dyspareunia

Among the more straightforward biological causes of HSDD is painful sex, a hallmark of the genitourinary syndrome of menopause.[4] "If a woman is having pain with intercourse, she's going to have low desire," said Maureen Whelihan, MD, a practicing gynecologist and sexual health expert in Palm Beach County, Florida.

Vulvovaginal atrophy, along with vaginal dryness and other symptoms caused by the loss of estrogen associated with postmenopausal status, are major contributors to dyspareunia.[4] Fortunately, a range of effective treatments are available. For women who want to avoid systemic hormone therapy, intravaginal estrogens come in several formulations. "There is also a new nonestrogen vaginal product called prasterone (Intrarosa®)—a good solution for women who don't want estrogen," Whelihan added. Prasterone is a synthetic dehydroepiandrosterone, a hormone precursor that is converted peripherally to androgens, which exert local effects on the vaginal mucosa. Prasterone has been shown to improve symptoms, including vaginal atrophy, dyspareunia, burning, itching, and dryness, compared with placebo.[5]

Another alternative to hormone therapy is ospemifene (Osphena®), approved in 2013 for treatment of moderate to severe dyspareunia associated with vulvar and vaginal atrophy of menopause. Ospemifene is an oral selective estrogen receptor modulator that acts on the vaginal epithelium to address painful sex associated with genitourinary syndrome of menopause. In phase 3 studies, ospemifene demonstrated efficacy in vaginal dryness and dyspareunia by regenerating vaginal cells, improving lubrication, and reducing pain during sexual intercourse. Symptoms improved in the first 4 weeks of use, and lasted up to 1 year.[6]

A nondrug option has recently joined the field. In observational studies, the pulsed CO2 laser (MonaLisa Touch [Deka; Manchester, New Hampshire]), which directly treats the vaginal tissue, was shown to increase collagen and extracellular matrix production and increase the thickness of the vaginal epithelium with the formation of new papilla.[7] Three 5-minute treatments are given at 6-week intervals, and no anesthesia is required. However, the CO2 laser has not yet been tested in a randomized controlled trial.

The HSDD Pharmaceutical Arsenal

Flibanserin. Only one drug has been approved to date in North America for use in the treatment of HSDD, and only in premenopausal women. Flibanserin (Addyi®) is a nonhormonal agent that decreases serotonin—a sexual killjoy—and increases sexual desire stimulants norepinephrine and dopamine. Flibanserin must be taken daily at night, because its main side effect is sleepiness.

Medical reviews of flibanserin (sometimes labeled "female Viagra") have largely damned it with faint praise.[8] In a series of randomized, double-blind, placebo-controlled trials reviewed by experts, premenopausal women with HSDD assigned to active treatment reported an average increase of 1.6 to 2.5 additional satisfying sexual events (SSEs) per month. In comparison, women assigned to placebo had an increase of 0.8 to 1.5 additional SSEs per month, suggesting that flibanserin, at best, results in approximately one more SSE per month than placebo.[8]

That outcome might still hold appeal for some women, except that flibanserin comes with a black-box warning that the drug cannot be taken in conjunction with alcohol. Flibanserin can cause hypotension and syncope, both are which are exacerbated by alcohol.[9] (Canada has far less stringent rules around drinking for women taking flibanserin). Still, Whelihan noted that the thinking was that "nobody is going to take the drug if they can't have their wine at night." But this underestimates how desperate some women are for a solution—it turns out that "asking them to stop drinking at least while they started taking the drug was not an issue for many women," explained Whelihan.

Despite its black-box warning, both Whelihan and Clayton point out that the pivotal studies done with flibanerin did not restrict alcohol consumption in women taking the drug, so women might want to decide for themselves what they want to do about alcohol consumption if on flibanserin.

Testosterone. In some women, low levels of sexual desire are related to lower androgen (testosterone) levels. A woman's testosterone levels do not fall at menopause; rather, there is a rapid decline in testosterone between the mid-30s and the mid-40s.[10] "So if a woman gets to the menopause and her testosterone level is low, it's probably been low for 10 years," Davis noted.

The obvious conclusion is that testosterone replacement is the most direct way to treat low sexual desire in both pre- and postmenopausal women. In Australia, this is exactly what they do, with the help of a transdermal product (AndroFeme® 1% testosterone cream) that has been specifically formulated for women. According to Davis, Australian clinicians use testosterone in the treatment of HSDD because, in a nutshell, it works and it's safe.

"There is no evidence that a dose of testosterone given through the skin has any adverse metabolic or cardiovascular effects," Davis insisted. Outside of Australia, no formulation of testosterone has been approved for the treatment of HSDD, despite major efforts by industry to obtain approval for a testosterone patch that improved desire in menopausal women. That failure has not stopped physicians from prescribing testosterone products for women, although these products must be used at one tenth of the dose recommended for men.

"We know that testosterone treatments increase sexy thoughts in women," Whelihan affirmed.

HSDD Drugs in Development

Combination products. Capitalizing on the libido-boosting properties of testosterone but addressing other aspects of the psyche that can stop women from enjoying sex is a drug known as Lybridos, which contains sublingual testosterone plus buspirone, an anxiolytic, to ease any inhibition the brain might drum up against a healthy sexual response. Lybrido, from the same manufacturer, is another formulation that combines sublingual testosterone and sildenafil, the chemical found in erectile dysfunction drugs for men and which has a similar effect in women—increasing blood flow to the genitalia, which helps with lubrication and arousal.

Both formulations are intended to be taken on demand, when needed, and both have been studied in pre- and postmenopausal women. Findings to date as reported by Emotional Brain founder Andre Tuiten, PhD, and colleagues,[11] indicate that the drugs increase the number of SSEs by about one to two events over an 8-week treatment period compared with placebo, depending on the combinations and doses of the formulations used. Both treatments appear to be well tolerated.

Bremelanotide. A final candidate for HSDD in premenopausal women is a drug known as bremelanotide (no trade name yet), a melanocortin receptor 4 agonist that is believed to modulate brain pathways involved in sexual response.[12] At pooled doses of 1.25 and 1.75 mg, bremelanotide increased SSEs by 0.7 episode per month compared with 0.2 additional SSE for placebo.[12] Positive changes in sexual function index scores and significant decreases in sexual distress scores were also seen with active treatment compared with placebo. Nausea, flushing, and headache were the most commonly reported side effects.

Bremelanotide is another on-demand drug. Clayton described it as being "self-injected, like an EpiPen, but it's quick and easy and not painful. It increases the norepinephrine/dopamine [pathway] of excitation and desire, so it offers a different mechanism of action from flibanserin, and it might work better in women with diminished excitation," she added. The US Food and Drug Administration has given the company a date early in 2019 when they promise to approve the drug (or not) for HSDD in premenopausal women.

In the meantime, despite what may seem to be modest increases in desire reported for any HSDD products to date, it's important to understand that these drugs actually do have a large effect size compared with other commonly used drugs.[13] "I think the most important part of this story is to ask providers to please ask their patients about sex," Whelihan stressed.

"And to tell the women of the world to please speak up if their doctors don't ask them about their sex life, because sometimes doctors are as embarrassed as they are to raise it," she added. "So patients, please ask your providers, and providers, please ask your patients about their sexual interest or concerns. Once you get the conversation going, we have a nice tool box of ideas with which to help our patients," Whelihan said.

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