Clinical Review

UPDATE: SEXUAL DYSFUNCTION

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A dearth of approved drugs for desire and arousal disorders frustrates women and clinicians alike.


 

References

Since sildenafil (Viagra) was approved by the US Food and Drug Administration to treat erectile dysfunction, women have been calling for research and development of treatments for female sexual dysfunction.

Despite considerable research documenting improvement in sexual responsiveness, genital sensation, and overall well-being among women who were given testosterone after undergoing bilateral oophorectomy, there remains only one testosterone formulation for women. A combination of synthetic estrogen and methyl testosterone (Estratest; Abbott) is indicated for management of moderate to severe vasomotor symptoms associated with menopause in patients who do not respond to estrogens alone.

In the testing stage from BioSante is LibiGel, a transdermal testosterone product. Acrux is developing Luramist, a daily testosterone spray. Proctor & Gamble’s efforts to gain approval of a testosterone-containing transdermal patch (Intrinsa) for treatment of low libido were unsuccessful, largely because of concern about potential increases in the risks of coronary artery disease and breast cancer. Pivotal trial data did not demonstrate enhanced risk, but the numbers were too small and the timeframe too short (a maximum follow-up of 2 years) to establish an effect, so the FDA asked for long-term studies. In 2006, European regulators approved Intrinsa to treat low sexual desire in surgically menopausal women.

Then there’s flibanserin, which also failed to win approval from an FDA advisory committee after numerous concerns were raised about its safety and efficacy in premenopausal women.

The lack of approved drugs leaves gynecologists and women’s health providers with little to offer our patients who are distressed by sexual dysfunction.

In this Update, I discuss:

  • the complexity of female sexual function
  • what derailed flibanserin
  • recent findings that suggest dehydroepiandrosterone (DHEA) may be beneficial
  • recommendations for clinical practice.

As understanding of female sexual dysfunction evolves, so do its labels

The fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) divides female sexual dysfunction into four categories:

  • hypoactive sexual desire disorder (HSDD)—a persistent or recurrent deficiency or absence of sexual fantasies and desire for sexual activity
  • female sexual arousal disorder—a persistent or recurrent inability to achieve or maintain adequate vaginal lubrication or vulvar swelling (i.e., sexual excitement)
  • female orgasmic disorder—persistent or recurrent delay in or absence of orgasm following a normal sexual excitement phase
  • dyspareunia—persistent or recurrent genital pain that is associated with sexual intercourse.

These categories were revised in 2003 by an international consensus committee sponsored by the American Urological Association Foundation; arousal disorder has been subdivided into:

  • combined arousal disorder—absent feelings of sexual arousal from any type of stimulation, as well as absent or impaired genital sexual arousal (vulvar swelling and vaginal lubrication)
  • subjective arousal disorder—absent feelings of sexual excitement and pleasure from any type of stimulation in the presence of genital sexual arousal (vulvar swelling and vaginal lubrication)
  • genital arousal disorder—subjective sexual excitement from nongenital sexual stimuli with reduced sensation from genital touching and an absence of genital sexual arousal from any type of sexual stimulation.

These updated definitions will be incorporated into DSM-V, to be published in 2013.

Also likely to change in DSM-V: HSDD and female sexual arousal disorder may be subsumed into a new category, “sexual interest/arousal disorder in women”.1

The female response to sexual stimuli is complex

The complexity of sexual arousal disorders in women complicates research into the pathophysiology and potential pharmacologic treatment of these conditions. Conflicting evidence for any benefit of the phosphodiesterase type-5 (PDE5) inhibitors, such as sildenafil, in the treatment of sexual dysfunction in women likely arises from a lack of precision in defining the conditions in which and patients for whom these interventions are appropriate.

Functional magnetic resonance imaging (MRI) studies of men and women reveal differences in areas of brain activity related to sexual arousal. The neurophysiology of sexual desire and response is complex, involving multiple neurotransmitters, peptides, and hormones as well as multiple structural regions within the brain. Dopamine, norepinephrine, melanocortin, oxytocin, and serotonin (at some of its receptors) promote sexual activity, whereas prolactin, gamma amino butyric acid (GABA), and serotonin (at most of its receptors) are inhibitory.

In animal studies, both an increase in dopamine and a change in social environment can trigger increased sexual behavior. In women, a dopaminergic drug such as buproprion may increase arousability and pleasure—but so can a new partner.

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