Nomegestrol acetate may enhance the skeletal effects of estradiol on biochemical markers of bone turnover in menopausal women after a 12-week treatment period

Objective To compare the effects of a 12-week treatment with 17β-estradiol given alone and in sequential combination with 3.75 mg of nomegestrol acetate (Naemis®), or a placebo on biochemical markers of bone turnover in menopausal women.Patients and methods A double-blind, randomized, placebo and estradiol-controlled multicenter study was conducted. A total of 176 patients who had been menopausal for 1–10 years, hysterectomized or not, having no contraindications to hormone replacement therapy, without any risks factors for osteoporosis, received one of these treatments during 12 weeks: placebo, 1.5 mg estradiol (E2) or 1.5 mg E2/3.75 mg nomegestrol acetate (E2/NOMAC). The primary efficacy variables were the change in bone markers (total alkaline phosphatase, bone alkaline phosphatase and osteocalcin; urinary type-I collagen peptides).Results The four biochemical markers decreased only in the E2/NOMAC group. Bone alkaline phosphatase, osteocalcin and urinary type-I collagen peptides decreased in the E2group. For both active treatment groups compared to the placebo group, the changes were statistically significant after a 12-week treatment. There were no statistically significant differences between the E2and the E2/NOMAC groups except for total serum alkaline phosphatase, whose mean value decreased in the E2/NOMAC group but increased slightly in the E2group (p<0.001). Furthermore, after a 6-week treatment, the changes in biochemical markers of bone turnover were similar to those found after 12 weeks. Safety data were satisfactory with regard to estradiol given alone or in combination with nomegestrol acetate.Conclusion These results demonstrated that 1.5 mg E2is effective in reducing bone turnover in postmenopausal women and proved that the combination of 1.5 mg E2and 3.75 mg nomegestrol acetate has no deleterious effect on bone remodelling.