Serum levels of sex steroids and metabolites following 12 weeks of intravaginal 0.50% DHEA administration. Issue 154 (November 2015)

• Record Type: Journal Article
• Authors: Ke, Yuyong; Labrie, Fernand; Gonthier, Renaud; Simard, Jean-Nicolas; Bergeron, Danielle; Martel, Céline; Vaillancourt, Mario; Montesino, Marlene; Lavoie, Lyne; Archer, David F.; Balser, John; Moyneur, Erick
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 154(2015)
• Page Start: 186
• Page End: 196
• Publication Date: 2015-11
• Subjects: Liquid chromatography tandem mass spectrometry -- Intracrinology -- Menopause -- dehydroepiandrosterone -- Prasterone -- Vulvovaginal atrophy; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2015.08.016
• Languages: English
• ISSNs: 0960-0760

Abstract

Highlights: Intravaginal 0.50% DHEA was administered daily for 12 weeks in postmenopausal women with VVA. Eleven steroids were measured in serum by validated mass spectrometry-based assays. All serum sex steroids remained well within normal postmenopausal values, thus excluding systemic exposure. At 12 weeks, serum estradiol was 22% below average normal postmenopausal values. Such data are in line with the physiology of sex steroids after menopause or midlife gynecological symptoms. Abstract: The objective of the present phase III, placebo-controlled, double-blind, prospective and randomized study was to confirm the efficacy of daily intravaginal administration of 0.50% dehydroepiandrosterone (DHEA; prasterone) ovules for 12 weeks on moderate to severe dyspareunia (or pain at sexual activity) as most bothersome symptom of vulvovaginal atrophy (VVA) while having serum steroid concentrations within normal postmenopausal values. To this end, serum levels of DHEA, DHEA-sulfate (DHEA-S), Androst-5-ene-diol-3β, 17β-diol (5-diol), testosterone, dihydrotestosterone (DHT), androstenedione (4-dione), estrone (E1 ), estradiol (E2 ), estrone sulfate (E1 -S), androsterone glucuronide (ADT-G), and androstane-3α, 17β-diol 17-glucuronide (3α-diol-17G) were measured by validated liquid chromatography–tandem mass spectrometry (LC–MS/MS). In agreement with the mechanisms of intracrinology, all serum sex steroids and metabolites concentrations after 12 weeks of daily intravaginal administration of 0.50% DHEA remain well within the limits of normal postmenopausal women. More specifically, the 12-week serum E2 concentration was measured at 22% below the average normal postmenopausal value (3.26 versus 4.17 pg/ml), thus eliminating any fear of E2 exposure outside the vagina. In addition, serum E1 -S, a particularly reliable indicator of global estrogenic activity, shows serum levels practically superimposable to the value observed in normal postmenopausal women (219 versus 220 pg/ml). Similarly, serum ADT-G, the major metabolite of androgens, remains within normal postmenopausal values. The present data confirm the intracellular transformation of DHEA in the vagina resulting in local efficacy without any systemic exposure to sex steroids, observations which are in agreement with the physiological mechanisms of menopause.