Although female sexual arousal disorder (FSAD) is prevalent, it is often not well defined or understood. The current definition of FSAD discussed below is based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Revised (DSM-IV-TR), which includes a requirement that the woman has concomitant distress. According to the DSM-IV , the diagnostic criteria to define sexual arousal disorder are (1) persistent or recurrent inability to attain, or to maintain until completion of the sexual activity, an adequate lubrication-swelling response of sexual excitement, (2) the disturbance causes marked distress or interpersonal difficulty, and (3) the sexual dysfunction is not better accounted for by another axis I disorder (except another sexual dysfunction) and is not due exclusively to the
direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition. Oftentimes medications such as selective serotonin reuptake inhibitors (SSRIs) can lead to such sexual dysfunctions including arousal and desire dysfunction. Thus, the DSM definition of arousal disorder may be limited in its ability to appropriately classify some of these patients.

Nonhormonal Supplementation

Sexual motivation is encouraged, sustained, and ended by a number of central nervous system neurotransmitter and receptor changes induced, in part, by the action of the central neurotransmitter dopamine. The activation of dopamine receptors may be a key intermediary in the stimulation of incentive sexual motivation and sexual reward. These neurotransmitters and receptor changes in turn activate central sexual arousal and desire. Contemporary animal research reveals that dopamine neurotransmitter systems may play a critical intermediary role in the central regulation of sexual arousal and excitation, mood, and incentive- related sexual behavior. Nonhormonal neuropeptides like oxytocin and prolactin have also been utilized in this clinical setting with good success.

Vasoactive agents including phosphodiesterase inhibitors (PDEi’s) have been investigated in several studies for treatment of FSAD. In a small proportion of the studies, women with FSAD endorsed a beneficial effect on arousal, while in most of the studies, vasoactive agents had no effect when compared with placebo. Smaller studies in populations with other medical conditions have shown more consistent effects. As such, PDEi’s may be beneficial in specific groups of women with FSAD.

Bupropion , which is a noradrenaline and dopamine reuptake inhibitor with nicotinic antagonist properties originally marketed as an antidepressant, may have a beneficial effect on women with sexual arousal disorder. In one placebocontrolled trial, bupropion produced an increase in desire and frequency of sexual activity when compared with placebo. Segraves et al. investigated the role of sustained release bupropion in a randomized, double-blind, placebo-controlled, multiple-site escalating-dose 112-day trial. Outcomes were measured by investigatorrating and self- administered questionnaires. The changes in sexual functioning questionnaire (CSFQ) indicated that bupropion had significant effects on increasing measures of sexual arousal, orgasm, and sexual satisfaction. Traditional antidepressant dosing starts at 150 mg twice a day; however, low-dose bupropion at 75 mg twice a day can achieve an optimal improvement in sexual arousal potential.

Other dopamine agonists used are cabergoline administered at 0.5 mg up to three times per week and ropinirole 0.25 mg administered daily. Oxytocin lozenges, linked to improved arousal and desire, are administered at 250 IU sublingually 30 min to 1 h before sexual activity. Research with oxytocin has shown marked improvement in a number of components of sexual function, including arousal and orgasm. Lastly, amphetamine salts including dextroamphetamine/amphetamine (Adderall) and other drugs used to treat attention deficit disorder have been increasingly useful in helping women to concentrate and thus improving arousal.

Lastly, flibanserin and bremelanotide , two drugs in development, may show promise for the future of FSAD treatments. Flibanserin is a nonhormonal treatment for premenopausal women with HSDD. Flibanserin is a 5-HT1A receptor agonist and 5-HT2A receptor antagonist that was initially investigated as an antidepressant. Preclinical evidence suggested that flibanserin targets the above receptors preferentially in selective brain areas, restores a balance between inhibitory and excitatory effects, and may show benefit in the treatment of FSAD.

Bremelanotide is a drug under development for female sexual dysfunction, hemorrhagic shock, and reperfusion injury. It functions by activating the melanocortin receptors MC1R and MC4R, to modulate inflammation and limit ischemia. Bremelanotide was originally tested for intranasal administration in treating female sexual dysfunction, but this application was temporarily discontinued in 2008 after concerns were raised over adverse side effects including elevated blood pressure. As of December 2014, the company is conducting a human phase 3 study using a subcutaneous drug delivery system that appears to have little effect on blood pressure.



Seth D. Cohen and Irwin Goldstein Springer Science+Business Media New York 2016