Lack of effect of short-term micronized progesterone on bone turnover in postmenopausal women

A number of studies suggest that progestogens have beneficial effects on bo ne in postmenopausal women, particularly in combination with estrogen, alth ough these studies have used derivatives that may have estrogenic and andro genic properties in addition to effects mediated by progesterone receptors. Progesterone itself affects only progesterone and glucocorticoid receptors . However, until the development of micronized progesterone (MP), absorptio n of progesterone preparations was too low to be clinically useful. MP has similar protective effects on the uterus and fewer effects on the lipid pro file than other preparations, but its effects on bone are unknown. We teste d the hypothesis that MP would alter bone turnover, as measured by serum an d urine biochemical markers, in postmenopausal women. Fourteen women aged 6 5 or over who were not on estrogen replacement received a 6-week course of daily MP (200 mg). Markers of bone turnover were measured in serum and urin e collected at baseline, at 6 weeks on MP, and 6 weeks after termination of MP. We also measured total and high-density lipoprotein (HDL) cholesterol and progesterone levels during the study. Markers of bone resorption were u rinary free deoxypyridinoline cross-linked N-telopeptides and C-telopeptide s of type I collagen. Markers of bone formation were serum osteocalcin, bon e alkaline phosphatase, and type I C-terminal and N-terminal procollagen pe ptides. Using repeated measures analysis of variance, markers of bone forma tion and resorption did not change with MP treatment in spite of an increas e in progesterone levels in all women. We conclude that 6-week treatment wi th MP alone does not have an effect on bone turnover in postmenopausal wome n in spite of high physiological levels. These data suggest that effects on bone demonstrated using other progestogen preparations might be due to and rogenic or estrogenic effects or that progesterone may not affect bone in e strogen-deficient women.