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Am J Obstet Gynecol. 2005 Apr;192(4):1316-23; discussion 1323-4.

The effects of progestins on bone density and bone metabolism in postmenopausal women: a randomized controlled trial.

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Department of Obstetrics and Gynecology, University of Cincinnati School of Medicine, Cincinnati, Ohio, USA.



The purpose of this study was to evaluate the action of progestins on bone metabolism in early menopausal women.


One hundred thirty-two menopausal women were randomized into a 2-year double-blinded, placebo-controlled clinical trial. There were 6 treatment groups: micronized progesterone (P 4 ) 300 mg/day; medroxyprogesterone acetate (MPA) 10 mg/day; norethindrone (NET) 1 mg/day; micronized estradiol (E 2 ) 1 mg/day; E 2 1 mg/day + MPA 10 mg/day; and placebo. All subjects received 1000 mg of calcium and 400 IU of vitamin D/day. Primary outcome variables were bone mineral density (BMD) changes at the spine and hip. Secondary variables were bone turnover markers.


With E 2 or E 2 +MPA treatment, BMD at L2-L4 increased by 2% to 4% over 2 years. Bone mineral density (BMD) at the spine followed a decreasing trend with MPA, P 4 , and placebo treatments. With NET treatment, BMD did not change from baseline. At the femoral neck site, BMD did not change significantly for any treatment group. Bone resorption and bone formation markers decreased with E 2 or E 2 +MPA treatment, and did not change appreciably with all 3 progestin-alone treatments. There were no vertebral or hip fractures observed during the trial.


Estrogen remains the primary bone active agent in hormone therapy, while progestins have significantly less activity. The selection of the appropriate progestin in hormone therapy should be based on criteria other than bone activity.

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