Hormonal Agents

Androgens are known to increase libido, but their exact role in erectile function remains unclear. Normal levels of testosterone appear to be important for erectile function, particularly in older males. It has been shown that androgen replacement therapy can improve depressed erectile function when ED is secondary to hypogonadism. As such, it is not surprising that any drug that interferes with testosterone production or action might lead to sexual dysfunction. Estrogens, GnRH agonists, LHRH agonists, and corticosteroids can cause ED by suppressing gonadotropin production. Certain drugs like spironolactone, cypoterone acetate, ketoconazole, aminoglutethimide, and other similar drugs have also been shown to have antiandrogen activity and have each been linked to drug-induced sexual dysfunction. These agents often resemble the molecular structure of testosterone and compete with native testosterone for binding to androgen receptors; they have also been shown to induce hyperprolactinemia. Multiple reports have linked H₂ blockers to sexual dysfunction. Ranitidine and cimetidine have both been shown to increase prolactin levels and act as antiandrogens.

5a (alpha)-reductase inhibitors

The potential sexual side effects, including ED, decreased libido and ejaculatory problems, which have been reported with 5a-reductase inhibitors (dutasteride and finasteride) are of particular relevance to the urology patient. These drugs block the con-version of testosterone to the more potent androgen, dihydrotestosterone (DHT). Animal models have demonstrated decreased NOS activity with decreased DHT, and thus, it has been proposed that 5a-reductase inhibitors elicit sexual dysfunction by indirectly attenuating NOS activity. Sexual adverse events have been reported in clinical trials at rates of 2.1–38%. The most common complaint is ED, followed by ejaculatory dysfunction and decreased libido. It appears that these effects occur early in the initiation of therapy and decrease over time. The results of these studies, however, have been questioned as the high incidence of drug-induced sexual dysfunction reported in some clinical tri-als does not seem to correlate with clinician experience. In a more recent study, two groups of blinded, randomized patients received 5 mg of finasteride with and without counseling regarding the potential for sexual side effects. The incidence of ED, decreased libido and ejaculatory problems were significantly reduced in patients who did not receive sexual side effect counseling. The authors conclude that a “nocebo” effect, an adverse effect that is not a direct result of the specific pharmacological action of the drug, should be taken into account when managing patients with reported sexual side effects. This latter study elucidates a common problem encountered by any physician attempting to counsel their patients regarding the potential side effects caused by the drugs mentioned in this chapter. This psychological priming can be a particularly difficult challenge in the management of sexual dysfunction in the setting of drug use.

HIV therapy

HIV and the polypharmacy standardin the care of HIV patients have been associated with sexual dysfunction. A recent cross­sectional study of HIV patients in England estimated the prevalence of moderate to severe ED to be 33% and moderate to severe impairment of sexual desire to be 24%. While multivariate analysis found sexual dysfunction to be common in both patients receiving antiretroviral therapy and those naïve to the drugs, ED was found to be associated with long duration of HIV therapy. A survey among a different group of HIV patients from ten different European countries demonstrated decreased libido and potency in men receiving drug regimens containing protease inhibitors as compared to protease inhibitor naïve patients, specifically identifying protease inhibitors as a drug leading to sexual dysfunction among HIV patients. Studies have shown that antiretroviral therapy is associated with increased aromatization of testosterone leading to increases serum levels of estradiol in men. It is hypothesized that the sexual dysfunction reported by patients taking antiretrovirals is secondary to these hormonal imbalances. Various hormonal replacement strategies have recently been under investigation. While testosterone has been well studied in the treatment of HIV-related wasting syndromes several more recent reports specifically address sexual function. Letrozole, an aromatase inhibitor, and both parenteral and topical forms of testosterone have both been shown not only to increase serum levels of testosterone, but also to improve patient reported sexual function.