Hypoactive sexual desire disorder (HSDD) is the most common type of female sexual dysfunction, affecting approximately 10% of all adult women. In certain populations of women that we see in our clinic, including women treated with serotonergic antidepressants and perimenopausal women, rates of sexual dysfunction are even higher.
Currently, flibanserin is the only medication approved by the Food and Drug Administration to treat women with HSDD. Flibanserin is a postsynaptic serotonin-1A (5HT-1A) receptor agonist and 5HT-2A receptor antagonist. While its precise mechanism of action is not known, it is hypothesized that flibanserin may enhance sexual desire by increasing levels of dopamine and norepinephrine while transiently decreasing serotonin levels.
The use of flibanserin has been limited as it is has been FDA-approved only for premenopausal women with acquired HSDD (which is HSDD developing in a woman who has previously had no problems with sexual desire). Furthermore, it has a long list of drug-drug interactions, including commonly used antidepressants, such as fluoxetine and sertraline. In addition, it has a black box warning regarding its use with alcohol, a combination that has been associated with hypotension and syncopal episodes.
There is another drug for HSSD coming down the pipeline. Bremelanotide is a peptide which acts as a melanocortin receptor agonist. Bremelanotide is an analog of endogenous melanocyte stimulating hormone (MSH) and is structurally related to the synthetic polypeptide melanotan II, which was initially tested as a potential sunless tanning agent. (MSH affects the function of melanin-containing melanocytes and can increase skin pigmentation.)
The initial intranasal formulation of bremelanotide caused increased blood pressure. The drug was then reformulated as an injectable drug. In subsequent trials, injectable bremelanotide was used to treat female sexual dysfunction (administered 45 minutes before sexual contact) and demonstrated only transient elevation of blood pressure. Reported side effects include nausea, flushing, headache, injection-site pain and itchiness. AMAG Pharmaceuticals has filed a New Drug Application in the first quarter of 2018 with the FDA to support the approval of bremelanotide as an “as needed” treatment for premenopausal women with HSDD.
Other treatments for female sexual dysfunction are currently under development, including Lorexys (combining bupropion and trazodone), Librido (sildenanil and testosterone), Libridos (testosterone and buspirone), and intranasal testosterone.
Ruta Nonacs, MD PhD
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