Serum steroid levels during 12-week intravaginal dehydroepiandrosterone administration.
OBJECTIVE
Because a previous 1-week study has shown no or minimal changes in the serum levels of dehydroepiandrosterone (DHEA) and its metabolites after up to daily 1.8% (23.4 mg) intravaginal DHEA, the objective of the present study was to investigate the serum steroid levels during a 12-week daily intravaginal administration of 0%, 0.25%, 0.5%, and 1.0% DHEA (Prasterone) 1.3 mL ovules.


METHODS
In a double-blind, placebo-controlled phase III study, 218 postmenopausal women (age range, 42-74 y) were randomized to receive daily one of four DHEA concentrations intravaginally. Serum steroids were measured by a Good Laboratory Practice-validated mass spectrometry technology in samples obtained at time of visit.


RESULTS
The serum levels of DHEA and 11 of its metabolites measured at screening, day 1, and weeks 2, 4, 8, and 12 in women showed no or minimal changes during the whole observation period, with all values remaining well within the limits of normal postmenopausal women. No accumulation of the steroid metabolites nor change in DHEA bioavailability was detected.


CONCLUSIONS
The present data show that local daily intravaginal DHEA administration at DHEA doses of 3.25-13 mg was able to rapidly and efficiently achieve correction of all the signs and symptoms of vaginal atrophy and improve sexual function and caused no or minimal changes in serum sex steroid levels, which all remain within the normal postmenopausal range, thus avoiding the risks of all estrogen formulations.
Laval University Hospital Research Center and Laval University, Quebec, Canada. Fernand.Labrie@endoceutics.com
Fernand
F
Labrie
David
D
Archer
Céline
C
Bouchard
Michel
M
Fortier
Leonello
L
Cusan
José-Luis
JL
Gomez
Ginette
G
Girard
Mira
M
Baron
Normand
N
Ayotte
Michèle
M
Moreau
Robert
R
Dubé
Isabelle
I
Côté
Claude
C
Labrie
Lyne
L
Lavoie
René
R
Bérubé
Patrick
P
Bélanger
Louise
L
Berger
Lucy
L
Gilbert
Céline
C
Martel
John
J
Balser
D000282:Administration, Intravaginal; D000368:Aged; D001284:Atrophy; D001682:Biological Availability; D003687:Dehydroepiandrosterone / Q000008:administration & dosage* / Q000172:deficiency / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016903:Drug Monitoring / Q000379:methods; D004958:Estradiol / Q000097:blood*; D005260:Female; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry; D008875:Middle Aged; D017698:Postmenopause / Q000187:drug effects / Q000502:physiology; D011446:Prospective Studies; D012735:Sexual Dysfunction, Physiological / Q000188:drug therapy* / Q000209:etiology; D013997:Time Factors; D014621:Vagina / Q000187:drug effects* / Q000473:pathology
D003687:Dehydroepiandrosterone; D004958:Estradiol