Dehydroepiandrosterone (DHEA) Against Vaginal Atrophy

• Placebo (Drug): Placebo vaginal suppository
• DHEA (Drug), also known as Prasterone, Dehydroepiandrosterone: Vaginal suppository containing 0.25% (3.25 mg) DHEA
• DHEA (Drug), also known as Prasterone, Dehydroepiandrosterone: Vaginal suppository containing 0.5% (6.5 mg) DHEA

Primary outcomes

• Change From Baseline to Week 12 in Percentage of Parabasal Cells in the Maturation Index of the Vaginal Smear [Baseline and Week 12]: The percentage of parabasal cells was determined from the vaginal smears collected during the study. A 100-cell count was performed by a central laboratory to classify cells as parabasal (P) (including basal), intermediate (I), and superficial (S) squamous cell types. Data obtained at Baseline and Week 12 as well as the change from Baseline to Week 12 are presented.
• Change From Baseline to Week 12 in Percentage of Superficial Cells in the Maturation Index of the Vaginal Smear [Baseline and Week 12]: The percentage of superficial cells was determined from the vaginal smears collected during the study. A 100-cell count was performed by a central laboratory to classify cells as parabasal (P) (including basal), intermediate (I), and superficial (S) squamous cell types. Data obtained at Baseline and Week 12 as well as the change from Baseline to Week 12 are presented.
• Change From Baseline to Week 12 in Vaginal pH [Baseline and Week 12]: A pH strip fixed on an Ayre spatula (or equivalent) was applied directly to the lateral wall of the vagina. The change in color of the pH indicator strip was compared to the color chart for pH evaluation. The corresponding pH value (with one decimal) was recorded. Data obtained at Baseline and Week 12 as well as the change from Baseline to Week 12 are presented.
• Change From Baseline to Week 12 in Severity of the Most Bothersome Symptom of Vaginal Dryness [Baseline and Week 12]: The severity of vaginal dryness was evaluated by a questionnaire filled out by women. The severity of dryness recorded as none, mild, moderate or severe was analyzed using the score values of 0, 1, 2 or 3, respectively. Data obtained at Baseline and Week 12 as well as the change from Baseline to Week 12 are presented.

Secondary outcomes

• Change From Baseline to Week 12 in Severity of Dyspareunia [Baseline and Week 12]: The severity of dyspareunia was evaluated by a questionnaire filled out by women. The severity of dyspareunia recorded as none, mild, moderate or severe was analyzed using the score values of 0, 1, 2 or 3, respectively. Data obtained at Baseline and Week 12 as well as the change from Baseline to Week 12 are presented.
• Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Secretions [Baseline and Week 12]: To evaluate the aspect of the mucosa and the local tolerance to prasterone ovules, the vaginal secretions (one of the four main signs of vaginal atrophy) evaluated by the physician/gynecologist as corresponding to none, mild, moderate, or severe atrophy were analyzed using the score values of 1, 2, 3 and 4, respectively. Data obtained at Baseline and Week 12 as well as the change from Baseline to Week 12 are presented.
• Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Epithelial Integrity [Baseline and Week 12]: To evaluate the aspect of the mucosa and the local tolerance to prasterone ovules, the vaginal epithelial integrity (one of the four main signs of vaginal atrophy) evaluated by the physician/gynecologist as corresponding to none, mild, moderate, or severe atrophy was analyzed using the score values of 1, 2, 3 and 4, respectively. Data obtained at Baseline and Week 12 as well as the change from Baseline to Week 12 are presented.
• Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Epithelial Surface Thickness [Baseline and Week 12]: To evaluate the aspect of the mucosa and the local tolerance to prasterone ovules, the vaginal epithelial surface thickness (one of the four main signs of vaginal atrophy) evaluated by the physician/gynecologist as corresponding to none, mild, moderate, or severe atrophy was analyzed using the score values of 1, 2, 3 and 4, respectively. Data obtained at Baseline and Week 12 as well as the change from Baseline to Week 12 are presented.
• Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Color [Baseline and Week 12]: To evaluate the aspect of the mucosa and the local tolerance to prasterone ovules, the vaginal color (one of the four main signs of vaginal atrophy) evaluated by the physician/gynecologist as corresponding to none, mild, moderate, or severe atrophy was analyzed using the score values of 1, 2, 3 and 4, respectively. Data obtained at Baseline and Week 12 as well as the change from Baseline to Week 12 are presented.

Sex: Female, ages: 40 Years to 75 Years

Inclusion Criteria:

* Postmenopausal women (non-hysterectomized or hysterectomized)
* Women between 40 and 75 years of age
* Willing to participate in the study and sign an informed consent
* Women who have self-identified symptom(s) of vaginal atrophy
* For non-hysterectomized women, willing to have endometrial biopsy at baseline and end of study

Exclusion Criteria:

* Undiagnosed abnormal genital bleeding
* Hypertension equal to or above 140/90 mm Hg
* The administration of any investigational drug within 30 days of screening visit
* Endometrial hyperplasia, cancer or endometrial histology showing proliferative, secretory or menstrual type characteristics at histologic evaluation of endometrial biopsy performed at screening

Participant flow

Outcome results

• Change From Baseline to Week 12 in Percentage of Parabasal Cells in the Maturation Index of the Vaginal Smear (Primary), Mean, percentage of parabasal cells: Placebo 60.66 +/- 3.40; 0.25% DHEA 56.74 +/- 3.69; 0.50% DHEA 59.54 +/- 3.41
• Change From Baseline to Week 12 in Percentage of Superficial Cells in the Maturation Index of the Vaginal Smear (Primary), Mean, percentage of superficial cells: Placebo 0.97 +/- 0.13; 0.25% DHEA 1.12 +/- 0.13; 0.50% DHEA 0.93 +/- 0.11
• Change From Baseline to Week 12 in Vaginal pH (Primary), Mean, pH units: Placebo 6.34 +/- 0.05; 0.25% DHEA 6.27 +/- 0.06; 0.50% DHEA 6.29 +/- 0.06
• Change From Baseline to Week 12 in Severity of the Most Bothersome Symptom of Vaginal Dryness (Primary), Mean, Severity score: Placebo 2.38 +/- 0.04; 0.25% DHEA 2.37 +/- 0.04; 0.50% DHEA 2.35 +/- 0.04
• Change From Baseline to Week 12 in Severity of Dyspareunia (Secondary), Mean, Severity score: Placebo 2.56 +/- 0.05; 0.25% DHEA 2.58 +/- 0.05; 0.50% DHEA 2.60 +/- 0.05
• Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Secretions (Secondary), Mean, Severity score: Placebo 2.71 +/- 0.05; 0.25% DHEA 2.55 +/- 0.06; 0.50% DHEA 2.55 +/- 0.06
• Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Epithelial Integrity (Secondary), Mean, Severity score: Placebo 2.32 +/- 0.07; 0.25% DHEA 2.19 +/- 0.07; 0.50% DHEA 2.19 +/- 0.08
• Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Epithelial Surface Thickness (Secondary), Mean, Severity score: Placebo 2.78 +/- 0.06; 0.25% DHEA 2.66 +/- 0.06; 0.50% DHEA 2.72 +/- 0.06
• Change From Baseline to Week 12 in Severity of Vaginal Atrophy as Evaluated From Vaginal Color (Secondary), Mean, Severity score: Placebo 2.66 +/- 0.05; 0.25% DHEA 2.60 +/- 0.06; 0.50% DHEA 2.65 +/- 0.06

Adverse events

Time frame: From Baseline to Week 12 (+ 30-day follow-up period after last dose)

Serious adverse events by term

Other adverse events by term

• Results publication: Bouchard C, Labrie F, Archer DF, Portman DJ, Koltun W, Elfassi E, Grainger DA, Ayotte N, Cooper TA, Martens M, Waldbaum AS, Labrie C, Cote I, Lavoie L, Martel C, Balser J; VVA Prasterone Group. Decreased efficacy of twice-weekly intravaginal dehydroepiandrosterone on vulvovaginal atrophy. Climacteric. 2015;18(4):590-607. doi: 10.3109/13697137.2014.992012. Epub 2015 Mar 3. PMID 25511551
• Results publication: Portman DJ, Labrie F, Archer DF, Bouchard C, Cusan L, Girard G, Ayotte N, Koltun W, Blouin F, Young D, Wade A, Martel C, Dube R; other participating members of VVA Prasterone Group. Lack of effect of intravaginal dehydroepiandrosterone (DHEA, prasterone) on the endometrium in postmenopausal women. Menopause. 2015 Dec;22(12):1289-95. doi: 10.1097/GME.0000000000000470. PMID 25968836

• David Archer, MD, Principal investigator, Clinical Research Center, Eastern Virginia Medical School, Norfolk, VA