Sildenafil cream for female sexual arousal disorder may benefit only a subset of women

Topical sildenafil cream appears to deliver promising outcomes for premenopausal women with sexual arousal disorder with or without concomitant decreased sexual desire, with increased arousal and reduced sexual distress, according to the results of an exploratory post hoc efficacy analysis of a phase IIb trial.

In the intention-to-treat population, 12 weeks of topical sildenafil cream application did not yield significant improvements in the coprimary endpoints of the Arousal Sensation domain of the Sexual Function Questionnaire (SFQ28) and question 14 of the Female Sexual Distress Scale—Desire, Arousal, Orgasm (FSDS-DAO; “How often in the past 30 days did you feel concerned by difficulties with sexual arousal?”) as compared with placebo cream. [Obstet Gynecol 2024;doi:10.1097/AOG.0000000000005648]

However, in an exploratory post hoc subset of women with or without concomitant decreased desire, those who received sildenafil cream vs placebo cream reported significantly greater improvements in their SFQ28 Arousal Sensation domain score (mean change, 2.03 vs 0.08; p=0.04), the investigators reported.

“Although [this] subset of women randomized to sildenafil cream … did not demonstrate statistically significant decreased sexual distress as measured by the coprimary endpoint of FSDS-DAO question 14 (p=0.95), which assesses concern about difficulties with sexual arousal, we found that several other FSDS-DAO questions, which asked about generalized feelings related to sexual distress and interpersonal difficulties, showed significant improvement with sildenafil cream compared with placebo cream (question 3*: mean change, −0.73 vs −0.23; question 5**: mean change, −0.50 vs −0.02; question 10⁺: mean change, −0.51 vs 0.00; p≤0.04 for all),” they added.

Numerical improvements with sildenafil cream were also observed in the SFQ28 Desire domain score (mean change, 1.27 vs –0.89; p=0.06) and Orgasm domain score (mean change, 1.12 vs 0.18; p=0.19).

Meanwhile, “participants with female sexual arousal disorder with concomitant orgasmic dysfunction did not derive as much benefit from sildenafil cream use. [This] was expected, because orgasmic dysfunction is often associated with neurologic problems or other comorbid medical or psychological conditions that would not be treated by the mechanism of action of sildenafil citrate (ie, increased blood flow to the genital tissue) and can be challenging to distinguish from female sexual arousal disorder temporally in terms of onset,” the investigators explained.

“Although we recognize that exploratory post hoc subset analyses must be interpreted with caution and can introduce type I errors, we believe that the trends observed in the subset of women with female sexual arousal disorder with or without concomitant decreased desire are promising, are clinically meaningful, and warrant further study because an important objective of this exploratory phase IIb study was to identify which women with female sexual arousal disorder are most likely to benefit from the mechanism of action of sildenafil citrate to increase genital blood flow,” they continued.

In the study, 200 women were randomly assigned to treatment with topical sildenafil cream (n=101) or placebo cream (n=99) for 12 weeks. All of them had a main diagnosis of female sexual arousal disorder and were categorized according to the presence or absence of concomitant sexual dysfunction diagnoses or symptoms, including decreased desire, orgasmic dysfunction, and genital pain. A total of 174 women completed the study (sildenafil n=90, placebo n=84). 

The mean age of the total safety population (n=233) was 36.3 years, with most being White (83.3 percent) and all identifying as cisgender female (100 percent). The mean baseline BMI was 27.2 kg/m². Of the 174 women who completed the study, 5.2 percent had female sexual arousal disorder only, 32.2 percent had concomitant decreased desire, 59.2 percent had concomitant orgasmic dysfunction, and 3.4 had concomitant genital pain.

*How often in the past 30 days did you feel guilty about sexual difficulties?

**How often in the past 30 days did you feel stressed about sex?

⁺How often in the past 30 days did you feel embarrassed about sexual problems?