OBJECTIVES: Dyspareunia, a symptom of genitourinary syndrome of menopause (GSM), affects approximately 60% of postmenopausal women in the U.S. Current treatment options for symptoms of GSM include over-the-counter and prescription therapies. Head-to-head randomized-control trials comparing treatments for moderate to severe dyspareunia have not been conducted which prohibits direct comparisons of efficacy or product adverse event (AE) rates. The objective of this analysis was to evaluate the relative safety of these treatments via indirect comparisons using published clinical trial literature.

METHODS: A systematic literature review was conducted to identify clinical studies of dyspareunia treatments. All AE data extracted were considered for Network meta-analysis (NMA). A Bayesian random effects model was used to estimate AE rates and odds ratios. Results focus on prasterone, a non-estrogen sex steroid precursor indicated for the treatment of moderate to severe dyspareunia due to menopause.

RESULTS: Eighteen clinical studies published between 2004 and 2018 representing 4,718 participants were included in the NMA. Data for a total of 17 AEs were extracted, and the five most comprehensively reported were analyzed: hot flush, urinary tract infection, headache, back pain, and vaginal discharge. Prasterone’s AE rates among these AEs were 2.7%, 6.5%, 5.1%, 2.7%, and 7.2%, respectively. Prasterone had a lower rate of hot flush compared with ospemifene [OR, 0.3 (95% CrI: 0.2-0.7)] and a higher vaginal discharge rate versus estradiol vaginal inserts [OR, 4.0 (95% CrI: 1.1-18.1) for 4 mcg; OR, 3.3 (95% CrI: 1.0-14.1) for 10 mcg]. Prasterone’s AE rates were statistically no different than placebo.

CONCLUSIONS: Among the five AEs evaluated, prasterone’s rates were comparable to placebo, suggesting a reasonable safety profile, not meaningfully different from AEs typically encountered among postmenopausal women with GSM. These study results may help healthcare providers assess treatment risks. Similar studies evaluating efficacy would be valuable in assessing the benefit of prescription treatments, including prasterone.