In Kwon Han

The changes in circulating osteoprotegerin after hormone therapy in postmenopausal women and their relationship with oestrogen responsiveness on bone

Objective  Oestrogen replacement reduces the increased rate of bone remodelling after the menopause. Osteoprotegerin (OPG) is a negative regulator of osteoclast‐mediated bone resorption. In vitro studies have shown that oestrogen stimulates OPG production. However, the role of OPG in physiological bone remodelling and its regulation by oestrogen in vivo remain controversial. In this study, we analysed the association between changes in serum OPG levels and bone turnover status before and after hormone therapy (HT) in healthy postmenopausal women.

Association of estrogen receptor α gene microsatellite polymorphism with annual changes in bone mineral density in Korean women with hormone replacement therapy

Variation in drug response to hormone replacement therapy (HRT) may reflect genetic heterogeneity in the estrogen-related genes, possibly including estrogen receptor alpha (ERα) gene. However, only a few association studies of the drug response to HRT have been reported, focusing mainly on the intronic polymorphisms of the ERα gene. We therefore examined 284 postmenopausal women (mean age, 52.2 ± 5.0 years) for the microsatellite thymine–adenine (TA) repeat polymorphism in the promoter of the ERα gene and its relationship to drug response by measuring changes in bone mineral density (BMD) after 1 year of HRT. In our study population, the most common number of TA repeats was 14, with a range of values between 11 and 27. At baseline, the number of TA repeats was neither associated with measured lumbar spine or femoral neck BMD nor with bone markers. When we categorized the subjects by the TA repeat numbers into an L group (n = 142), with a low mean number of repeats (TA < 16), and an H group (n = 142), with a high mean number of repeats (TA ≥ 16), no significant genotypic differences were noted in spinal or femoral neck BMD or in bone markers. However, the drug response on lumbar spine BMD after 1 year of HRT correlated with the mean number of TA repeats (r = −0.131, P = 0.035) after adjustment for confounding factors such as body mass index and years since menopause. This correlation was also seen with the number of TA repeats on the shorter allele (r = −0.159, P = 0.012), which was defined as the allele with the lower number of TA repeats. However, this genotypic association was not found in the femoral neck BMD (r = 0.053, P = 0.396). When we defined the nonresponder group as women who had lost BMD even with HRT, 15.9% of the subjects were included, and this group was significantly younger and had higher initial BMD than the responder group. After further adjustment for age and initial BMD, the number of TA repeats on the shorter allele remained significantly associated with drug responsiveness (P = 0.005). These data indicate significant effects of the ERα TA repeat polymorphism on the estrogen responsiveness of lumbar spine BMD after 1 year of HRT in Korean women.

A common mutation in cholesteryl ester transfer protein gene and plasma HDL cholesterol level before and after hormone replacement therapy in Korean postmenopausal women

Background Plasma cholesteryl ester transfer protein (CETP) functions to transfer cholesteryl ester from HDL to trigiyceride-rich lipoproteins and regulates plasma HDL cholesterol level. A common mutation, the exon 15 A to G substitution at codon 442 (D442G) results in reduced plasma CETP activity and increased plasma HDL cholesterol level. Meanwhile, hormone replacement therapy (HRT) in postmenopausal women increases plasma HDL cholesterol level. Methods We investigated the frequency of D442G mutation and its effect on plasma HDL cholesterol level in Korean women. We also examined if the mutation has any effect on an increase in plasma HDL cholesterol level during HRT. Results Two hundred and twenty eight women aged over 40 years were recruited in this study. Of 228 women, 22 (9.6%) were identified as having the D442G mutation; 21 heterozygotes and 1 homozygote. The subjects with the mutation had higher plasma HDL cholesterol levels than those without the mutation (61.6±17.3 vs. 55.1±14.0 mg/dL, p<0.05). After 12 month HRT, HDL cholesterol increased by 6.4% (3.6±13.2 mg/dL, p<0.05) and D442G mutation did not have any significant effect on the change of plasma HDL cholesterol level. Conclusion D442G mutation is common in Korean postmenopausal women and it is associated with increased plasma HDL cholesterol level. HRT for postmenopausal women increased plasma HDL cholesterol level in similar amounts regardless of the presence or absence of D442G mutation.