A Phase III Randomized, Double-Blind, Placebo-Controlled Study of Pilocarpine for Vaginal Dryness: North Central Cancer Treatment Group Study N04CA

Abstract

Purpose Vaginal dryness is a common problem, for which effective and safe non-estrogenic treatments are needed. Based on preliminary promising data that pilocarpine attenuated vaginal dryness, the current trial was conducted. Methods A double-blind, placebo-controlled, randomized trial design was used to compare pilocarpine, at target doses of 5 mg twice daily and 5 mg four times daily, to a placebo. Vaginal dryness was recorded by patient-completed questionnaires at baseline and weekly for 6 weeks after study initiation. The primary endpoint for this study was the area under the curve (AUC) summary statistic comprised of the longitudinal responses obtained at baseline and through the six weeks of treatment to a numerical analogue scale asking patients to rate their perceived amount of vaginal dryness. The primary analysis was carried out by a single t-test using a two-sided alternative to compare the collective pilocarpine treatment arms versus the collective placebo arms. Results A total of 201 patients enrolled in this trial. The primary analysis, comparing vaginal dryness symptoms in the collective pilocarpine arms against the placebo arm, did not reveal any benefit for the pilocarpine treatment. This finding was confirmed by other secondary analyses. Toxicity evaluation revealed more nausea, sweating, rigors, and urinary frequency with the pilocarpine arms compared to the placebo arm. Conclusion Pilocarpine did not alleviate vaginal dryness.

Efficacy of Hormonal and Nonhormonal Approaches to Vaginal Atrophy and Sexual Dysfunctions in Postmenopausal Women: A Systematic Review

“…A total of 55 studies were deemed eligible for inclusion ( Table 1, Supplementary material ). The approaches tested to treat vaginal atrophy and sexual dysfunction were as follows: lubricants and moisturizers (18 studies, 14 15 16 17 18 19 20 21 22 23 24 25 26 5 27 28 29 30 31 of which evaluated hyaluronic acid); phytoestrogens (14 studies); 30 32 33 34 35 36 37 38 39 40 41 42 43 44 dehydroepiandrosterone (DHEA; 8 studies); 27 45 46 47 48 49 50 51 ospemifene (5 studies); 52 53 54 55 56 vaginal testosterone (4 studies); 16 19 57 58 pelvic floor muscle exercises (2 studies); 59 60 oxytocin (2 studies); 61 62 vaginal CO 2 laser (2 studies); 63 64 lidocaine (1 study);…”

“…Regarding side effects, the results for lubricants and moisturizers indicated that all adverse events (AEs) were considered mild in severity and self-limited. 14 15 16 17 18 19 20 21 22 23 24 25 26 The most common AEs were burn on the application site, discomfort on the application site, vulvovaginal pruritus, and general pruritus. The compound hyaluronic acid has been shown to be well tolerated without side effects among most patients tested.…”

Management of genitourinary syndrome of menopause in breast cancer survivors: An update

“…The authors did not find improvements invaginal dryness compared with placebo. Thus, pilocarpine cannot be recommended for use in the treatment of vaginal dryness, despite the preliminary pilot information that suggested that it might have been beneficial[ 211 ].…”

Concise Synthesis of Both Enantiomers of Pilocarpine

“…Pilocarpine (+)-1 ( Figure 1 ) is the main alkaloid of the South American tree Pilocarpus jaborandi , and it is usually isolated from its leaves. Pilocarpine is used as a cholinergic [ 1 , 2 , 3 ] parasympathomimetic [ 4 , 5 , 6 , 7 , 8 ], hidrotic and miotic agent [ 9 , 10 ]; in ophthalmology, it is used against glaucoma [ 11 , 12 , 13 ] and also acts as an antagonist [ 14 , 15 , 16 ] to atropine and as an inhibitor of the enzyme carbonic anhydrase II [ 17 , 18 , 19 ]. Moreover, a deficiency of carbonic anhydrase in humans is linked to osteopetrosis; thereby, osteoclasts are unable to perform bone resorption in a normal way [ 20 ].…”