Phentolamine

Two controlled studies have investigated the effect of the alpha-1 and alpha-2 adrenergic receptor antagonist phentolamine on the basis of the hypothesis that, as in men, the smooth muscle surrounding the vaginal arterial vascular bed is mainly alpha adrenergically innervated. In the first study, an oral application was used that showed a positive effect on subjective and genital sexual arousal (VPA) in postmenopausal women with sexual arousal difficulties. A second placebo-controlled study studied both oral and vaginal applications in estrogenized and nonestrogenized postmenopausal women. Genital response was higher with the highest dose of vaginally applied phentolamine than with placebo, in estrogenized postmenopausal women only. Subjective sexual arousal was higher with the highest doses of both applications of phentolamine than with placebo, again in the estrogenized women only.

Dopamine Agonists

Dopaminergic drugs might be interesting because unlike the previously discussed drugs, they have a direct effect on the brain and may therefore have a positive influence on sexual arousal and desire. The only controlled study published to date found an enhancing effect of levodopa on an index of somatic motor preparation, the Achilles tendon reflex, in men, but not in women. Sumanirole is a dopamine agonist that specifically targets D2-receptors. We investigated the effect of this drug in women with complaints of sexual arousal and desire in a placebo-controlled laboratory study, but found no effects on genital or subjective sexual arousal (data not published). Buproprion was used in one uncontrolled study to counteract the sexual side-effects of selective serotonine reuptake inhibitors. Keeping in mind that no adequate control was used, the authors conclude that the results point to relief of the sexual complaints.

Androgens

Several companies have begun to study the effects of various androgen products and androgen–estrogen combinations. The relationship between declining androgens and sexual response has not been clarified. Sexual problems related to androgen deficiency are to be expected only when there is a real deficiency of biologically available testosterone. Recently, a consensus conference has tried to establish clear criteria for such an androgen insufficiency syndrome. Fourcroy recently published a detailed overview of androgen treatments that are being developed, and concluded that it remains to be seen whether these products will show promise in female sexual dysfunction. Besides efficacy, there are increasing concerns about safety.