Long-term effects of continuous combined HRT on bone turnover and lipid metabolism in postmenopausal women

This study was undertaken to investigate the effect of 10 years of hormone replacement therapy (HRT) on bone turnover and lipid metabolism in postmenopausal women. The single-centre trial was initiated as a 1-year, double-masked, randomized, parallel-group study of continuous combined HRT with 2 mg 17 beta-estradiol and 1 mg norethisterone acetate administered once daily with or without 1 mg estriol. Following preliminary results which showed no difference between the addition and omission of estriol, patients continued on an open-label extension phase of continuous combined HRT without estriol for a further 9 years. Of the 52 women who entered the original double-masked study, 32 entered the open-label extension phase. The 10-year analysis was based on 27 patients. Major increases in bone mineral density (BMD) of the lumbar spine were seen during the first 3 years of treatment, remaining statistically significant compared with baseline at all visits throughout the 10-year followup (p less than or equal to 0.025). Statistical modelling confirmed that there were no decreases in BMD after these initial increases. BMD remained 5.5% higher than baseline values after 10 years of continuous combined HRT, Mean total cholesterol levels were significantly reduced after 10 years of therapy (p = 0.012), with no significant changes in serum triglyceride and low-density lipoprotein (LDL)-cholesterol levels from baseline values at this time. High-density lipoprotein (HDL)-cholesterol levels, however, were reduced by 15.4% (p < 0.001). In conclusion, 10 years of continuous combined HRT resulted in a significant and sustained increase in BMD. This treatment regimen therefore appears to be well suited for the long-term prevention of osteoporosis in postmenopausal women.