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Labrie F.,EndoCeutics Inc | Archer D.F.,Eastern Virginia Medical School | Bouchard C.,Clinique de Recherche en Sante des Femmes | Girard G.,Diex Recherche Inc. | And 15 more authors.
Maturitas | Year: 2015

Objective An objective was to analyze the time course of efficacy of daily intravaginal administration of 0.5% (6.5 mg) DHEA (prasterone) for 52 weeks on the moderate to severe (MS) symptoms and signs of vulvovaginal atrophy (VVA). Method Five hundred twenty-one postmenopausal women were enrolled and received daily intravaginal administration of 0.5% DHEA in an open-label phase III study. The severity of the VVA symptoms examined in detail in the different groups. Results A parallel improvement of pain at sexual activity was observed in women who had moderate to severe (MS) dyspareunia as their most bothersome symptom (MBS) (n = 183) or not MBS (n = 240) and MS without being MBS (n = 57) with a 1.70 severity unit change in the MBS group for a decrease of 66.1% from baseline (p < 0.0001 versus baseline) over 52 weeks. A further improvement of dyspareunia, namely 0.33 severity unit (19.4%), was observed with continuing treatment from 12 weeks to 52 weeks. Similar results were observed on vaginal dryness and irritation/itching. Highly significant beneficial effects (p < 0.0001 versus baseline for all) were observed at gynecological examination on vaginal secretions, color, epithelial integrity and epithelial surface thickness. Conclusion The present study shows, in addition to the parallel benefits on the three symptoms of VVA, that the choice of any of the MS symptoms as being or not being MBS by women has no influence on the observed therapeutic effect (NCT01256671). © 2015 Elsevier Ireland Ltd. All rights reserved.

Archer D.F.,Eastern Virginia Medical School | Labrie F.,EndoCeutics Inc | Bouchard C.,Clinique de Recherche en Sante des Femmes | Portman D.J.,Columbus Center for Womens Health Research | And 7 more authors.
Menopause | Year: 2015

Objective: This study aims to confirm the local effects of intravaginal prasterone on moderate to severe dyspareunia, a symptom of vulvovaginal atrophy (VVA) associated with menopause. Methods: In a prospective, randomized, double-blind, placebo-controlled phase III clinical trial, we examined the effects of daily intravaginal prasterone (6.5mg) on four co-primary objectives, namely, percentage of vaginal parabasal cells, percentage of vaginal superficial cells, vaginal pH, and moderate to severe dyspareunia identified by women as the most bothersome VVA symptom. Results: After daily intravaginal prasterone administration for 12 weeks, the percentage of parabasal cells decreased by 45.8% compared with placebo (P<0.0001), the percentage of superficial cells increased by 4.7% over placebo (P<0.0001), and vaginal pH decreased by 0.83 pH units compared with placebo (P<0.0001). The severity of most bothersome dyspareunia decreased by 46% over placebo (P=0.013) at 12 weeks, whereas moderate to severe vaginal dryness decreased by 0.43 severity score units (or 42%) compared with placebo (P=0.013). On gynecologic evaluation, a 14.4% to 21.1% improvement in vaginal secretions, epithelial integrity, epithelial surface thickness, and color over placebo (P=0.0002 to P<0.0001) was observed. Serum steroids, in agreement with the physiology of intracrinology and menopause, remained well within reference postmenopausal concentrations. All endometrial biopsies at 12 weeks have shown atrophy. Conclusions: Daily intravaginal prasterone (0.50%; 6.5mg) treatment has clinically and statistically significant beneficial effects on the four co-primary objectives of VVA, according to US Food and Drug Administration guidelines. No significant drug-related adverse effect in line with the strictly local action of treatment has been reported, thus providing a high benefit-to-risk ratio for intravaginal prasterone. © 2015 by The North American Menopause Society.

Reid R.L.,Queens University | Fortier M.P.,Clinique de Recherche en Sante des Femmes | Smith L.,Pfizer | Mirkin S.,Pfizer | And 2 more authors.
Contraception | Year: 2010

Background: The study was conducted to evaluate bleeding profile and safety of continuous oral contraceptive (OC) containing levonorgestrel (LNG) 90 mcg/ethinyl estradiol (EE) 20 mcg. Study Design: Healthy women who participated at seven Canadian sites in 1-year open-label study of LNG 90 mcg/EE 20 mcg daily were eligible for this second-year extension study. Primary end points included bleeding profile and adverse events. Results: Seventy-nine women enrolled without interrupting pill taking; 62 (78.5%) completed. Adverse events were comparable to cyclic OC regimens, except unscheduled vaginal bleeding. Amenorrhea and absence of bleeding increased to about 80% and 90%, respectively, by Pill Pack 18. Mean (median) number of bleeding days for the last two 90-day intervals was 1.1 (0) and 0.7 (0) days, respectively. Conclusions: Continuous LNG 90 mcg/EE 20 mcg had a safety profile similar to low-dose cyclic OCs. Short-term safety profile remained excellent, with increasing rates of amenorrhea and decreasing incidence of unscheduled bleeding and/or spotting. © 2010 Elsevier Inc.

Endrikat J.,Bayer AG | Endrikat J.,Universitatskliniken des Saarlandes | Vilos G.,University of Western Ontario | Muysers C.,Bayer AG | And 3 more authors.
Archives of Gynecology and Obstetrics | Year: 2012

Objectives Idiopathic menorrhagia (IM) is an important clinical challenge. The levonorgestrel-releasing intrauterine system (LNG IUS) provides an effective treatment option as shown by multiple small clinical studies. In this analysis of combined data, we describe the time course of relative change in menstrual blood loss (MBL) from baseline up to 5 years. The results of two different methods to assess MBL were merged. Methods We pooled and analyzed five prospective, randomized clinical studies investigating the effect of the LNG IUS on IM in a total of 230 women. Four studies assessed MBL by using the pictorial blood loss assessment chart (PBAC) and one study used the alkaline hematin method. We gathered data on percentage change from baseline after 3 and 6 months, and annually up to 5 years. In addition we analyzed results on hemoglobin (Hb) and serum ferritin (S-Fe). Results MBL data was available after 3 and 6 months from 165 and 152 patients, respectively, and after 1 year from 51 patients. Long-term data up to 3 and 5 years was available for 28 and 10 patients, respectively. Not all studies provided data for all time points. Median (interquartile range) MBL decreased from baseline by -84.5% (-93.3; -63.6%) after 3 months, by -92.9% (-97.6; -81.1%) and by -93.8% (-98.8; -81.1%) after 6 months and 1 year, respectively (p < 0.0001, all time points). After 2 and 5 years the decrease was more than 96%. In parallel, Hb and S-Fe increased significantly. Conclusion The LNG IUS rapidly induced clinically and statistically significant long-term reductions in MBL, paralleled by increases in Hb and S-Fe levels. © Springer-Verlag 2011.

Portman D.J.,Columbus Center for Womens Health Research | Labrie F.,EndoCeutics Inc | Archer D.F.,Clinical Research Center | Bouchard C.,Clinique de Recherche en Sante des Femmes | And 9 more authors.
Menopause | Year: 2015

Objective: This study aims to evaluate the effects of intravaginal dehydroepiandrosterone (DHEA, prasterone) on the endometrium in postmenopausal women. Methods: 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. Results: 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. Conclusions: 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. © 2015 by The North American Menopause Society.

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