A randomized, placebo- and active-controlled trial of bazedoxifene/conjugated estrogens for treatment of moderate to severe vulvar/vaginal atrophy in postmenopausal women.
OBJECTIVE
The primary objective of the Selective estrogen Menopause And Response to Therapy 3 (SMART-3) trial was to compare the efficacy and safety of two doses of bazedoxifene (BZA)/conjugated estrogens (CE) versus placebo for the treatment of moderate to severe vulvar/vaginal atrophy (VVA) associated with menopause.


METHODS
This was a phase 3, multicenter, double-blind, randomized, placebo-controlled, and active comparator-controlled study. Healthy postmenopausal women (n = 664; aged 40-65 y) were randomized to BZA 20 mg/CE 0.625 mg, BZA 20 mg/CE 0.45 mg, BZA 20 mg, or placebo once daily for 12 weeks. Changes in vaginal maturation, vaginal pH, and severity of the most bothersome symptom of VVA from baseline were assessed at screening and at weeks 4 and 12. Adverse events were recorded throughout the study.


RESULTS
BZA 20 mg/CE 0.625 or CE 0.45 mg significantly (P < 0.01) increased superficial cells and decreased parabasal cells compared with placebo. Vaginal pH and most bothersome symptom significantly improved with BZA 20 mg/CE 0.625 mg compared with placebo (P < 0.05). Improvements in vaginal dryness were also observed with both BZA/CE doses (P G 0.05). The incidence of treatment-related adverse events were similar across treatment groups.


CONCLUSIONS
BZA/CE is effective in treating moderate to severe VVA and vaginal symptoms. These data further support the use of a tissue-selective estrogen complex containing BZA/CE as a new menopausal therapy for postmenopausal women.
Kagan
Risa
R
Foundation for Osteoporosis Research and Education, Oakland, CA, USA. kaganr@sutterhealth.org
Williams
R Stan
RS
Pan
Kaijie
K
Mirkin
Sebastian
S
Pickar
James H
JH
D000282:Administration, Intravaginal; D000328:Adult; D000368:Aged; D001284:Atrophy / Q000188:drug therapy / Q000473:pathology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004967:Estrogens / Q000009:adverse effects / Q000627:therapeutic use*; D004966:Estrogens, Conjugated (USP) / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D017698:Postmenopause; D016896:Treatment Outcome; D014621:Vagina / Q000187:drug effects* / Q000473:pathology; D014623:Vaginal Diseases / Q000188:drug therapy* / Q000473:pathology; D014844:Vulva / Q000187:drug effects* / Q000473:pathology
D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D007211:Indoles; C447119:bazedoxifene