Serum levels of sex steroids and metabolites following 12 weeks of intravaginal 0.50% DHEA administration.
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.
EndoCeutics Inc., Quebec City, Quebec, QC, Canada.
Yuyong
Y
Ke
EndoCeutics Inc., Quebec City, Quebec, QC, Canada. Electronic address: fernand.labrie@endoceutics.com.
Fernand
F
Labrie
EndoCeutics Inc., Quebec City, Quebec, QC, Canada.
Renaud
R
Gonthier
EndoCeutics Inc., Quebec City, Quebec, QC, Canada.
Jean-Nicolas
JN
Simard
EndoCeutics Inc., Quebec City, Quebec, QC, Canada.
Danielle
D
Bergeron
EndoCeutics Inc., Quebec City, Quebec, QC, Canada.
Céline
C
Martel
EndoCeutics Inc., Quebec City, Quebec, QC, Canada.
Mario
M
Vaillancourt
EndoCeutics Inc., Quebec City, Quebec, QC, Canada.
Marlene
M
Montesino
EndoCeutics Inc., Quebec City, Quebec, QC, Canada.
Lyne
L
Lavoie
CONRAD Clinical Research Center, Norfolk, VA, USA.
David F
DF
Archer
Veristat, Holliston, MA, USA.
John
J
Balser
StatLog Consulting Inc., Gatineau, QC, Canada.
Erick
E
Moyneur
D000368:Aged; D003687:Dehydroepiandrosterone / Q000008:administration & dosage*; D004311:Double-Blind Method; D004333:Drug Administration Routes; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D008875:Middle Aged; D010919:Placebos; D017698:Postmenopause; D011446:Prospective Studies; D014621:Vagina
D012739:Gonadal Steroid Hormones; D010919:Placebos; D003687:Dehydroepiandrosterone
Intracrinology; Liquid chromatography tandem mass spectrometry; Menopause; Prasterone; Vulvovaginal atrophy; dehydroepiandrosterone