Effect of two different progestins (cyproterone acetate and norgestrel), administered in a cyclical estradiol valerate regimen, on markers of bone turnover

Abstract

It has been suggested that some progestogens could have a stimulating effect on bone formation. This study was therefore undertaken in order to compare the influence of cyproterone acetate and norgestrel on bone metabolism when administered in a discontinuous, sequentially combined regimen with estradiol valerate. Twenty healthy early postmenopausal women were randomly assigned to treatment with either Cyclo-Progynova® containing 0.5 mg of norgestrel, or Climen® containing 1 mg of cyproterone acetate (CPA), over two 28-day cycles. Markers of bone resorption -fasting urinary hydroxypro-line / creatinine and calcium / creatinine ratios - and of bone formation - serum alkaline phosphatase and osteocalcin - were determined initially, before the start of treatment and thereafter twice weekly (a total of 17 assessments for each woman) during the 8-week treatment period. Serum osteocalcin concentrations were slightly but not significantly higher throughout the study period in women receiving Climen, compared to those taking Cyclo-Progynova. Cyclical fluctuation of serum osteocalcin levels were more pronounced in women with a high baseline level of osteocalcin. During the period of progestogen administration, osteocalcin concentrations were either similar to or even lower than those in the phase of administration of estradiol valerate alone. Serum calcium and alkaline phosphatase concentrations were relatively stable during the study period with both treatment regimens. Urinary excretion of calcium and hydroxyproline varied during the cycle but the variation was unrelated to either type or time of progestogen administration. Mean urinary hydroxyproline excretion during the 8-week study period was similar for both preparations, although the mean decrease in the urinary hydroxyproline /creatinine ratio was insignificantly higher for the CPA-containing preparation. Women with a high baseline osteocalcin level, however, showed significantly lower hydroxyproline excretion when treated with Climen than with a norgestrel-containing preparation. The significantly lower hydroxyproline excretion suggests a favorable effect on bone turnover of the preparation containing CPA. This effect was particularly obvious in women with a high bone turnover and was most probably the result of a potentiating effect of CPA on the anti-resorptive effect of estradiol valerate. © 1994 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.