This study aims to evaluate the effects of intravaginal dehydroepiandrosterone (DHEA, prasterone) on the endometrium in postmenopausal women.
Intravaginal DHEA (6.5 mg) was administered daily for 52 weeks to 422 women who had endometrial biopsy at baseline and end of study, whereas 15 women were similarly treated for 26 to 52 weeks. Participants in three other studies received 3.25 mg (n = 126), 6.5 mg (n = 129), or 13 mg (n = 30) of DHEA for 12 weeks; women similarly had baseline and end-of-study biopsies. Endometrial biopsy samples were available for 668 women at baseline and end of study, with sufficient material for analysis.
Endometrial atrophy or inactive endometrium (668 women) was found in all women treated with intravaginal DHEA. Similar atrophy was observed in 119 of 121 participants with sufficient material for analysis who received placebo.
After cessation of estradiol secretion by the ovaries at menopause, the estrogens made by mechanisms of intracrinology are inactivated intracellularly at their site of formation and action, thus maintaining serum estradiol at biologically inactive concentrations to avoid stimulation of the endometrium. The absence of enzymes that are able to transform DHEA into estrogens in the endometrium explains the typical endometrial atrophy in all normal postmenopausal women in the presence of variable concentrations of circulating endogenous DHEA. According to these mechanisms, the inactive sex steroid precursor DHEA administered intravaginally acts exclusively in the vagina, whereas all serum sex steroids remain well within the biologically inactive postmenopausal reference range, thus avoiding any stimulation of the already atrophic endometrium.
1Columbus Center for Women's Health Research, Columbus, OH
2EndoCeutics Inc, Quebec City, QC, Canada
3CONRAD Clinical Research Center, Norfolk, VA
4Clinique de Recherche en Santé des Femmes, Quebec City, QC, Canada
5Clinique de Recherche en Traitements Hormonaux, Quebec City, QC, Canada
6Diex Recherche Montréal Inc, Montreal, QC, Canada
7Clinique de Gynécologie, Shawinigan, QC, Canada
8Medical Center for Clinical Research, San Diego, CA
9Pro-Recherche, St-Romuald, QC, Canada
10Northern Califonia Research, Sacramento, CA
11Maritime Research Center, Bathurst, NB, Canada
12Centre Hospitalier Universitaire de Quebec, Quebec City, QC, Canada.
Address correspondence to: Fernand Labrie, MD, PhD, EndoCeutics, 2795 Laurier Blvd, Suite 500, Quebec City, QC, Canada G1 V 4M7. E-mail: Fernand.Labrie@endoceutics.com
Received 31 October, 2014
Revised 5 March, 2015
Accepted 5 March, 2015
Funding/support: This research was sponsored by EndoCeutics.
Financial disclosure/conflicts of interest: All authors received financial support from EndoCeutics. F.L. and C.M. are employees of EndoCeutics. D.J.P. reports consultancy for TherapeuticsMD, Shionogi, Actavis, Pfizer, Teva, Sprout, and Palatin, and membership in speakers bureau for Pfizer, Shionogi, and Actavis. D.F.A. reports consultancy for Abbvie, Agile Therapeutics, Ascend Therapeutics, CHEMO, Exceltis, Shionogi, and TherapeuticsMD, and grants from Abbvie, Bayer Healthcare, Merck, and TherapeuticsMD. C.B. reports grants from Bayer and membership in speakers bureau for Merck and Actavis.