Am. Heikkinen et al., LONG-TERM VITAMIN-D-3 SUPPLEMENTATION MAY HAVE ADVERSE-EFFECTS ON SERUM-LIPIDS DURING POSTMENOPAUSAL HORMONE REPLACEMENT THERAPY, European journal of endocrinology, 137(5), 1997, pp. 495-502
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.