LONG-TERM VITAMIN-D-3 SUPPLEMENTATION MAY HAVE ADVERSE-EFFECTS ON SERUM-LIPIDS DURING POSTMENOPAUSAL HORMONE REPLACEMENT THERAPY

Objective: The positive short-term effects of postmenopausal hormone r eplacement therapy (HRT) on serum lipids are well known, but it has be en suggested that they vanish with time. Cholecalciferol (vitamin D-3) is widely used to prevent postmenopausal osteoporosis but the influen ce of vitamin D-3 on serum lipids is poorly known. The long-term effec ts of HRT and vitamin D-3 on the concentrations of serum lipids were s tudied in a population-based prospective 3-year study. Design and meth ods: 464 women were randomized into four treatment groups: (i) HRT (se quential combination of 2 mg estradiol valerate and 1 mg cyproterone a cetate), (ii) Vit D-3 (vitamin D-3 300 IU/day), (iii) HRT+Vit D-3, (bo th as above), (iv) placebo (calcium lactate 500 mg/day). Results: 320 women completed the study. After three years of treatment, serum conce ntrations of low density lipoprotein (LDL) cholesterol decreased in th e HRT group (10.1%, P < 0.001) and the HRT+Vit D-3 group (5.9%, P = 0. 005), increased in the Vit D-3 group (4.1%, P = 0.035) but remained un changed in the placebo group. The concentrations of total cholesterol decreased by 5.8% in the HRT group (P < 0.001) and by 3.3% in the HRTVit D-3 group (P = 0.023), but did not change in the other two groups. Serum concentrations of high density lipoprotein (HDL) cholesterol de creased in the Vit D-3 group (5.2%, P = 0.001), HRT+Vit D-3 group (3.7 %, P = 0.046), and the placebo group (4.5%, P = 0.006) but did not cha nge significantly in the HRT group. The HDL/LDL ratio increased in the HRT group (10.5%, P = 0.006) and decreased in the Vit D-3 group (10.5 %, P < 0.001) whereas no changes occurred in the other two groups. In addition, serum triglycerides increased similarly in all groups (14.0- 18.8%, P < 0.05-0.001). Conclusion: Our results confirm the positive l ong-term effect of HRT with sequential estradiol valerate and cyproter one acetate on serum lipid concentrations. In addition, the results su ggest that vitamin D-3 supplementation may have unfavorable effects on lipids in postmenopausal women. Pure vitamin Dg treatment was associa ted with increased serum LDL cholesterol, Furthermore, the beneficial effects of HRT on serum LDL cholesterol content were reduced when estr adiol valerate was combined with vitamin D-3. However, the relevance o f these associations to cardiovascular morbidity remains to be establi shed.