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 replacement therapy (HRT) on serum lipids are well known, but it has been suggested that they vanish with time. Cholecalciferol (vitamin D-3) is widely used to prevent postmenopausal osteoporosis but the influence of vitamin D-3 on serum lipids is poorly known. The long-term effects of HRT and vitamin D-3 on the concentrations of serum lipids were studied in a population-based prospective 3-year study. Design and methods: 464 women were randomized into four treatment groups: (i) HRT (sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate), (ii) Vit D-3 (vitamin D-3 300 IU/day), (iii) HRT+Vit D-3, (both as above), (iv) placebo (calcium lactate 500 mg/day). Results: 320 women completed the study. After three years of treatment, serum concentrations of low density lipoprotein (LDL) cholesterol decreased in the 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 unchanged 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 HRT+Vit D-3 group (P = 0.023), but did not change in the other two groups. Serum concentrations of high density lipoprotein (HDL) cholesterol decreased 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 change 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 long-term effect of HRT with sequential estradiol valerate and cyproterone acetate on serum lipid concentrations. In addition, the results suggest that vitamin D-3 supplementation may have unfavorable effects on lipids in postmenopausal women. Pure vitamin Dg treatment was associated with increased serum LDL cholesterol, Furthermore, the beneficial effects of HRT on serum LDL cholesterol content were reduced when estradiol valerate was combined with vitamin D-3. However, the relevance of these associations to cardiovascular morbidity remains to be established.