Restoring sexual function: Which medications show benefit?

Table 2

Duration of action of PDE-5 inhibitors

Drug	Duration
Sildenafil	4 hours
Vardenafil	4 hours
Tadalafil	24 to 36 hours
PDE-5: phosphodiesterase type 5

Cases of sudden loss of hearing or vision (nonarteritic anterior ischemic optic neuropathy) have been associated with PDE-5 inhibitor use.^10,11 To date, there is insufficient evidence to determine if these adverse events are chance associations in a population at risk for hearing and vision losses from other causes such as aging.

Other options. Other accepted options for treating ED include intracavernosal injection of vasoactive substances such as phentolamine or prostaglandin E1, or intraurethral insertion of prostaglandins.¹² Since the advent of PDE-5 inhibitors, these approaches are rarely used.

Cabergoline. Off-label use of dopaminergic agents such as cabergoline may be moderately effective in treating ED in men who do not respond adequately to PDE-5 inhibitors. Cabergoline is a dopamine D2 receptor agonist used to treat hyperprolactinemia and Parkinson’s disease.

In a randomized, double-blind, placebo- controlled study, 402 men who did not respond to sildenafil received cabergoline, 0.5 to 1 mg weekly for 6 months. Among the 370 men (92%) who completed the trial, mean weekly intercourse episodes increased from 1.4 to 2.2, compared with 1.2 to 1.4 in men who received placebo.¹³

Cabergoline also improved erectile function and sexual satisfaction in a randomized, double-blind, placebo-controlled trial of 50 men with psychogenic erectile dysfunction.¹⁴

Treatment outcomes. Most studies report positive psychological responses to ED reversal in men using PDE-5 inhibitors. Successful therapy has been associated with increased self-esteem, satisfaction, and sexual satisfaction.⁸ Some studies have found increased sexual satisfaction in the partner as well.¹⁵

Approximately 50% of PDE-5 inhibitor prescriptions are not refilled, however, and some case reports suggest that restored erectile function can result in:

• divorce and marital discord
  
• no change in partner-related activity.¹⁶
  

Given the symbolic meaning and interpersonal context of sexual activity, it is not surprising that restored sexual function does not always have a positive psychological outcome. Combined psychological and pharmacologic therapy may improve treatment outcomes in men with ED.¹⁷
Recommendation. Because erectile problems are common in psychiatric patients, most psychiatrists should feel comfortable treating ED with PDE-5 inhibitors. In general, these agents are relatively safe. Reversing drug-induced sexual dysfunction may improve patients’ adherence to psychotropics, increase self-esteem, and improve relationships with sexual partners.

Hypoactive sexual desire

PDE-5 inhibitors. The success of PDE-5 inhibitors in treating ED led to investigations into whether these agents also could treat female sexual disorders. Large multisite trials using sildenafil failed to find evidence of efficacy in treating female hypoactive sexual desire or arousal disorders, however.¹⁸ Similarly, trials of topical prostaglandin E1 and alpha blockers were unsuccessful in women.

Some small studies suggested that PDE-5 inhibitors might be useful in:

• women with normal libido but decreased arousal¹⁹
  
• young women with normal libido and inability to reach orgasm.²⁰
  

These studies used small sample sizes and have not been replicated, however.
Testosterone therapy. In the 1940s, case reports suggested increased libido as a side effect when women were treated with androgens for metastatic cancer. In a prospective study, Sherwin and Gelfand²¹ found increased sexual desire, sexual arousal, and rates of coitus and orgasm in women injected with testosterone/estrogen preparations after surgical menopausal.

More recently, Shifren et al²² showed in a randomized, placebo-controlled trial that transdermal testosterone, 150 or 300 micrograms/day for 12 weeks, improved sexual function and psychological wellbeing in women age 31 to 56 after surgical menopause. Since then, numerous large, multisite, double-blind studies have demonstrated the efficacy of transdermal testosterone in treating low sexual desire in surgically menopausal women.²³ Transdermal testosterone has been approved for this indication in the European Union but not in the United States.

Testosterone also has been reported to increase sexual desire in women who experienced natural menopause and in normal premenopausal women.²⁴ The study of the relationship of testosterone to libido in women is complicated by numerous factors, however (Box 2).^23,24

Other agents. Recent research has focused on centrally active compounds’ effect on libido. One agent in development is flibanserin, a serotonergic 5HT2 antagonist and a 5HT1a agonist. Data from large, multisite studies indicates that this compound increases libido in women with low sexual desire.

Box 2