title: Intravaginal prasterone (DHEA) provides local action without clinically significant changes in serum concentrations of estrogens or androgens.
abstract: In order to avoid the risks of non-physiological systemic exposure, serum concentrations of estradiol (E2) and testosterone (as measured by mass spectrometry-based assays) should remain below the 95th centiles measured at 9.3pg/ml and 0.26ng/ml for these respective sex steroids in normal postmenopausal women. To document the possibility of achieving this therapeutic objective, we have measured individual 24h serum E2 and testosterone concentrations in women with vulvovaginal atrophy (VVA) receiving daily intravaginal administration of a clinically effective dose of 6.5mg prasterone (dehydroepiandrosterone, DHEA). Serum E2 and testosterone, as well as DHEA and nine of its other metabolites, were assayed at ten time intervals over 24h on the first and seventh days of daily vaginal administration of 6.5mg prasterone. No significant change from baseline of average 24h serum E2 or testosterone concentrations was observed. Moreover, average 24h serum DHEA remained within the normal postmenopausal range. Estrone sulfate and the androgen metabolites androsterone glucuronide and androstane-3α, 17β-diol glucuronide did not change, thus confirming the absence of any biologically relevant systemic exposure to estrogens and androgens, respectively. Serum concentrations of metabolites of both estrogens and androgens remain within the normal postmenopausal range following daily intravaginal administration of 6.5mg prasterone. As other studies have shown, local formation of sex steroids in peripheral tissues without significant release of E2 or testosterone in the circulation can be achieved with intravaginal prasterone. Thus, prasterone is a promising physiological and attractive solution to treating VVA symptoms.
authors: EndoCeutics Inc., Quebec City, Quebec, G1V 4M7, Canada; Research Center in Molecular Endocrinology, Oncology and Human Genomics, Laval University, Quebec City, Quebec, G1V 4G2, Canada. Electronic address: fernand.labrie@endoceutics.com.
authors: Fernand
authors: F
authors: Labrie
authors: Céline
authors: C
authors: Martel
authors: René
authors: R
authors: Bérubé
authors: Isabelle
authors: I
authors: Côté
authors: Claude
authors: C
authors: Labrie
authors: Leonello
authors: L
authors: Cusan
authors: José-Luis
authors: JL
authors: Gomez
mesh_terms: D000282:Administration, Intravaginal; D000368:Aged; D000728:Androgens / Q000097:blood*; D003687:Dehydroepiandrosterone / Q000008:administration & dosage* / Q000494:pharmacology*; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000097:blood*; D005260:Female; D006801:Humans; D008875:Middle Aged; D013739:Testosterone / Q000097:blood
chemical_list: D000728:Androgens; D004967:Estrogens; D013739:Testosterone; D003687:Dehydroepiandrosterone; D004958:Estradiol
keywords: Dehydroepiandrosterone; Dyspareunia; Intracrinology; Intravaginal prasterone; Local administration; Vulvovaginal atrophy