A CONTROLLED TRIAL OF RALOXIFENE (LY139481) HCL - IMPACT ON BONE TURNOVER AND SERUM-LIPID PROFILE IN HEALTHY POSTMENOPAUSAL WOMEN

This randomized, double-blind, placebo-controlled, multicenter, 8-week study evaluated short-term effects of raloxifene on bone turnover, se rum lipids, and endometrium in healthy, postmenopausal women, A total of 251 women received either placebo, raloxifene HCl 200 or 600 mg/day , or conjugated estrogens (Premarin, 0.625 mg/day), Bone turnover (ser um alkaline phosphatase, serum osteocalcin, urinary pyridinoline cross -links, urinary calcium excretion, urinary hydroxyproline) and serum l ipids (total serum cholesterol, high- and low-density lipoprotein chol esterol [HDL-C and LDL-C]) were evaluated at weeks 0; 2, 4, and 8, End ometrial biopsies were performed at weeks 0 and 8, Treatment groups we re compared for each parameter for baseline-to-endpoint changes, The e strogen and raloxifene groups experienced similar decreases in serum a lkaline phosphatase (range 10-11%), serum osteocalcin (range 21-26%), urinary pyridinoline cross-links (range 20-26%), and urinary calcium e xcretion (range 45-72%), These decreases differed significantly compar ed with placebo-treated subjects for all markers except serum osteocal cin, the raloxifene HCl 200 mg group, LDL-C decreased significantly in the estrogen and both raloxifene groups (range 5-9%) compared with pl acebo-treated subjects, HDL-C increased significantly in the estrogen group (16%) but was unchanged in the raloxifene groups, HDL-C:LDL-C ra tios increased significantly in the estrogen and raloxifene groups (ra nge 9-29%), Serum cholesterol decreased significantly in both raloxife ne groups (range 4-8%) but was unchanged in the estrogen group, Uterin e biopsies of raloxifene-treated subjects showed no change in the endo metrium during this short-term treatment, Biopsies of the estrogen gro up showed significant endometrial stimulation, The only adverse event possibly related to raloxifene was vasodilatation (hot hashes) which w as most common in the raloxifene HCl 600 mg group, Study results indic ate that raloxifene may provide beneficial effects to bone and serum l ipids in humans without uterine stimulatory effects.