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 bone in postmenopausal women, particularly in combination with estrogen, although these studies have used derivatives that may have estrogenic and androgenic 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), absorption of progesterone preparations was too low to be clinically useful. MP has similar protective effects on the uterus and fewer effects on the lipid profile than other preparations, but its effects on bone are unknown. We tested the hypothesis that MP would alter bone turnover, as measured by serum and urine biochemical markers, in postmenopausal women. Fourteen women aged 65 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 urine 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 urinary free deoxypyridinoline cross-linked N-telopeptides and C-telopeptides of type I collagen. Markers of bone formation were serum osteocalcin, bone alkaline phosphatase, and type I C-terminal and N-terminal procollagen peptides. Using repeated measures analysis of variance, markers of bone formation and resorption did not change with MP treatment in spite of an increase in progesterone levels in all women. We conclude that 6-week treatment with MP alone does not have an effect on bone turnover in postmenopausal women in spite of high physiological levels. These data suggest that effects on bone demonstrated using other progestogen preparations might be due to androgenic or estrogenic effects or that progesterone may not affect bone in estrogen-deficient women.