Expert Commentary

Does sildenafil improve antidepressant-related sexual dysfunction in women?

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Female sexual dysfunction is a prevalent condition for which there is no medical intervention approved by the US Food and Drug Administration. Approval of sildenafil (Viagra) and other type-5 phosphodiesterase inhibitors (vardenafil and tadalafil) for the treatment of erectile dysfunction in men was followed by a series of studies to determine their efficacy in women. To date, those trials have demonstrated no treatment benefit for women.

Assessment of female sexual dysfunction is difficult

The four areas of potential abnormality in sexual function, as described in the Diagnostic and Statistical Manual of Mental Disorders–IV, include desire, arousal, orgasm, and pain and are more difficult to differentiate in women than in men. In addition, the variability of the hormonal environment makes it challenging to study the physiologic mechanisms of some of these conditions.

Nurnberg and colleagues sought to eliminate most of the variables by including only premenopausal women who had normal hormone levels at baseline (mean estradiol level, 67 pg/mL; FSH

Selective and nonselective SRIs have been associated with sexual side effects in up to 70% of women—specifically, delayed or absent orgasm, decreased arousal and lubrication, and diminished libido.

Details of the study

This prospective, randomized, double-blind, placebo-controlled trial aimed to assess the efficacy of 50 to 100 mg of sildenafil in reversing new-onset sexual dysfunction in women adequately treated for their underlying major depression. Ninety-eight women (average age, 37 years) were randomized, with 37 and 39 completing the 8-week trial in the placebo and active treatment arms, respectively.

Utilizing an intent-to-treat statistical analysis, the authors found that women taking an average dosage of 91.7 mg of sildenafil experienced significant improvement in overall sexual satisfaction, lubrication, and ability to reach orgasm. Four different scales of sexual function were utilized in the analysis, each of which has been well validated in previous studies. Of note, 28% of women taking sildenafil and 73% of those taking placebo reported no improvement in sexual function throughout the 8-week study.

In this study, responders had slightly (and statistically significantly) higher levels of both free testosterone (1.44 pg/mL vs 1.04 pg/mL) and thyroxine (8.83 ng/dL vs 7.75 ng/dL) than nonresponders in the treatment arm.

These findings are the first to demonstrate efficacy in women

Physiologically, these findings make sense. In estrogen-replete women, type-5 phosphodiesterase inhibitors are thought to increase blood flow, engorgement, and lubrication to the genitalia, resulting in improved sensation and arousal.

By eliminating or controlling for many of the confounders in earlier studies of sildenafil in women, this well-designed trial has demonstrated, for the first time, significant improvement in women who have sexual complaints related to antidepressant medication.


This study shows that treatment with one of the type-5 phosphodiesterase inhibitors for arousal or orgasmic problems, or both, makes sense. It is critical to ensure that baseline hormone levels are well within normal premenopausal ranges and that underlying depression or relationship issues are not contributing to low libido if you are to expect improvement.

Women who have new-onset sexual dysfunction after taking SRIs are most likely to respond. Look for subtle thyroid problems or low testosterone levels in nonresponders.—BARBARA S. LEVY, MD

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