MAGNITUDE AND PATTERN OF SKELETAL RESPONSE TO LONG-TERM CONTINUOUS AND CYCLIC SEQUENTIAL OESTROGEN/PROGESTIN TREATMENT

Objective To investigate the magnitude and pattern of the changes in bone mass during five years of continuous and cyclic sequential oestrogen/progestin treatment. Design Prospective study of normal, early postmenopausal women, initially a double-blind, placebo controlled trial, subsequently an open, controlled investigation. Setting Clinical physiology unit of a general hospital. Subjects Sixty-eight normal, early postmenopausal women. Results 1. Continuous treatment resulted in significantly higher lumbar spine bone density than did sequential treatment (P < 0.001). Lumbar spine bone density was 19% and 15%, respectively, above that of untreated women after three years and onwards, and 10% and 6%, respectively, above the initial value; 2. Both regimens induced a more pronounced rise in lumbar spine bone density than in forearm bone mineral content (P < 0.001); 3. The spontaneous decline (without treatment) in lumbar spine bone density and forearm bone mineral content averaged 1.86% and 1.90% per year, respectively. 4. There was a significant bone loss from the lumbar spine during the last year of active treatment (P < 0.001). This would suggest that lumbar spine bone density rises to a certain level and subsequently declines. However, neither data pooled before computation nor data processed individually for each patient over five years allowed for any definite conclusions regarding the pattern of the long term skeletal response to combined oestrogen/progestin treatment. Conclusion Five years treatment with oestradiol/norethisterone resulted in a substantial gain in bone mass. The highest values were found in the axial skeleton with daily administration of 2 mg oestradiol and 1 mg norethisterone. It is likely that bone mass after an absolute rise begins to decline after about four years of treatment.