Systemic effects of conjugated equine estrogen vaginal cream on bone turnover markers in postmenopausal women

Objective To evaluate the systemic effect of therapy with conjugated equine estrogen (CEE) vaginal cream on bone turnover markers in postmenopausal women. Methods This study was conducted in 40 spontaneously menopausal women aged 40-60 years who complained of vulvovaginal symptoms. Subjects were instructed to self-administer 1 g CEE vaginal cream (CEE 0.625 mg) once daily for 12 weeks (continuous phase), then twice weekly for the next 12 consecutive weeks (intermittent phase). Serum levels of bone turnover markers and estradiol and the vaginal maturation index were evaluated at baseline, 12 and 24 weeks after treatment initiation. Results Levels of C-terminal cross-linked telopeptide of type I collagen (CTx) were significantly decreased at 12 weeks and 24 weeks when compared to baseline values (median (range) 0.435 (0.171-0.859) and 0.391 (0.122-0.714) vs. 0.562 (0.250-1.290) ng/ml (p < 0.001 and < 0.001), respectively), but there was no significant difference between the levels at 12 and 24 weeks. Levels of procollagen type I N-terminal propeptide (P1NP) and osteocalcin levels were significantly decreased after 24 weeks when compared to pretreatment levels (mean (standard deviation) 41.74 (11.76) vs. 50.02 (17.71) ng/ml (p = 0.002) for P1NP and 23.91 (7.11) vs. 27.54 (8.67) ng/ml (p < 0.001) for osteocalcin, respectively). Estradiol levels were significantly increased and the vaginal maturation index was significantly improved after 12 and 24 weeks when compared to baseline. Conclusions CEE vaginal cream significantly decreased the bone resorption marker (CTx) in postmenopausal women after completion of the continuous-treatment phase. There was no significant further decrease after the intermittent phase. The effects on the markers of bone formation and bone turnover (P1NP and osteocalcin) were apparent only at 24 weeks. The two treatment phases moderately increased serum estradiol levels and significantly improved the vaginal maturation index.