Markers of Bone Turnover and Rates of Bone Loss During Three Yearsʼ Combined Hormone Replacement Therapy

Seventy-five women who had had their last menstrual period 6 months to 3 years previously were randomized to continuous treatment with 2 mg estradiol valerate (E2V) and 1 mg cyproterone acetate (CPA), sequential treatment with 2 mg E2V and 75 mg levonorgestrel (LNG). or placebo. Both treatment regimens prevented bone loss from the axial and peripheral skeleton, and the effect was maintained throughout the entire study period. The 3-year changes in bone loss in the two bone compartments were significantly related (r = 0.56; p < 0.001). The 3-year changes in bone mass of both bone compartments were furthermore significantly related to the changes after 6 and 12 months in both a specific bone resorption marker (fasting urinary cross-links corrected for creatinine) (r = -0.75 to -0.79, p < 0.001 for the forearm; r ∽--0.31 to -0.34. p < 0.05 to 0.07 for the spine) and a bone formation marker (BGP) (r = -0.40 to -0.46, p < 0.05 to 0.01 for the forearm; r = -0.40 to -0.45, p < 0.05 to 0.01 for the spine). Stratification of the participants according to reduction in bone turnover markers showed significant differences in rates of bone loss from both the forearm (p < 0.001 to 0.01) and the spine (p < 0.01 to 0.05). Menopausal complaints were reduced with both treatments, but the reduction was unrelated to the response in the skeleton. In conclusion, continuous treatment with 2 mg E2V/1 mg CPA and sequential treatment with 2 mg E2V and 75 mg LNG are effective in preventing postmenopausal bone loss for >3 years and in reducing menopausal symptoms, Furthermore, the responses in the axial and peripheral skeleton are highly correlated, and follow-up can be done accurately by taking measurements in one bone compartment only. The skeletal response is reflected by changes in markers of bone turnover, but measurements of a few markers are not clinically useful in monitoring the effects of hormone replacement therapy.