Open-label pilot, prospective vulvoscopic study of daily administration of prasterone vaginal inserts in women with moderate to severe dyspareunia

INTRODUCTION AND OBJECTIVE: Prasterone (DHEA), a daily 6.5 mg vaginal insert, is FDA approved for moderate to severe dyspareunia, a symptom of vulvovaginal atrophy due to menopause. Prasterone is converted intracellularly in vaginal wall layers into active androgens and estrogens with blood values maintained within normal post-menopausal range. In Phase III clinical trials the mean pretreatment dyspareunia score was 2.57, falling to 1.20, 0.97 and 0.87 at weeks 12, 26 and 52, respectively (0 = none, 1 = mild, 2 = moderate, 3 = severe). Although prasterone is a vaginal insert, the significant reduction of pain suggests improvement of the vestibular, endodermal genital tissue associated with dyspareunia in androgen and estrogen deficient states like menopause. The primary objective was to use vulvoscopic photographs to document changes to the vestibule and vaginal region in menopausal women with moderate to severe dyspareunia using prasterone daily for 20 weeks. Secondary objectives included changes in pain on the cotton-tipped swab test and sexual function by subject diary. METHODS: This prospective study involves photography at screening, baseline and every four weeks for twenty weeks. Blinded photographs were assessed independently using a 4-point Likert scale, with lower scores representing healthier appearance. Vestibular tissue appearance (VestTA) assessed severity of 5 items: urethral meatal prolapse, introital stenosis, pallor, erythema, mucosa inflammation. Vaginal tissue appearance (VagTA) assessed severity of loss of vaginal rugae. Changes in pain based on cotton-tipped swab test results and responses on subject diaries completed at each sexual event were examined for each visit and compared. Semi-quantitative data were analyzed by repeated measures ANOVA and mean differences between treatment visits and 95% CI of VestTA scores, VagTA scores and cotton swab test scores were calculated. Adverse events were recorded. RESULTS: Eleven subjects completed the study. VestTA and VagTA scores were significantly reduced from baseline after active treatment by week 4 (mean change from baseline = -0.53; 95% CI [-0.82, -0.24] and -0.49; 95% CI [-0.79, -0.20], respectively) and maintained through week 20 (-0.58; 95% CI [-0.87, -0.29] and -0.80; 95% CI [-1.09, -0.51], respectively), suggesting improved vestibular and vaginal tissue health. Cotton-tipped swab test scores were significantly reduced from baseline after week 8 (mean change = -0.65; 95% CI [-1.02, -0.28]) through week 20 (mean change = -1.04; 95% CI [-1.41, -0.67]), suggesting decreased pain. Diary results showed decrease in pain as well. No prasterone related adverse events were reported. CONCLUSIONS: Significant improvements were revealed in VestTA, VagTA and cotton-tipped swab test scores. This is the first prospective vulvoscopic study to show that an intravaginal hormone therapy significantly improves the photographic appearance of 5 vestibular health parameters. This observation may explain the robust effect on prasterone in lowering dyspareunia in menopausal women with moderate to severe dyspareunia.