The effect of sequential three-monthly hormone replacement therapy on several cardiovascular risk estimators in postmenopausal women

Abstract

Objective: To investigate the changes in plasma lipids and lipoproteins, low-density lipopro tein (LDL) oxidizability, and plasma homocysteine during postmenopausal sequential 3-monthly hormone replacement therapy.Design: Open longitudinal prospective study. Setting: Gynecological outpatient departm ent of a university hospital. P atient(s): Thirty-nine healthy nonhysterectomized postmenopausal women.In terv en tion (s): Oral conjugated estrogen, 0.625 mg/d, combined with oral medrogestone 10 mg/d during the last 14 days of each 84-day treatm ent cycle, The treatm ent was given for four treatm ent cycles of 84 days (1 year). M ain Outcom e Measure(s): Plasma lipids and lipoproteins, LDL oxidizability, and plasma homocysteine.R es uit (s): After 1 year of treatm ent plasma concentrations of total cholesterol and LDL cholesterol were 3.5% and 8.7% lower, respectively. High density lipoprotein cholesterol, apolipoprotein A-I, and triglycerides were 6.5%, 9.0% and 16% higher, respectively. Apolipoprotein B concentration remained unchanged. The results on LDL oxidizability were inconsistent. Plasma homocysteine decreased with 12.3% during the first 6 months of treatm ent in women with higher homocysteine concentrations at baseline. These values returned to baseline levels during the second half year of treatm ent. Conclusion(s):This sequential hormone regimen induced beneficial changes in the conven tional lipid and lipoprotein risk estimators, whereas the observed changes in the other markers remained inconclusive and/or of minor importance.Fértil in postmenopausal women (1, 2). Furthermore, it has been reported to reduce the incidence of osteopo rotic fractures (2) and of cardiovascular disease (2, 3). To accomplish the latter two preventive effects of HRT, long-term supplementation is recommended in selected groups of subjects at increased risk (2), To prevent the development of endometrial hyper plasia and carcinoma in nonhysterectomized women the addition of progestogen to the estrogen adminis tration is recommended (4). A disadvantage of se quential estrogen-progestogen therapy, however, is that it restores vaginal bleeding, which is an im portant reason for poor compliance in many women (5). Therefore, alternative treatment regimens, such as continuous combined estrogen/progestogen regi men and 3-monthly progestogen administration dur ing estrogen supplementation (6, 7), currently are

Hormone Replacement Therapy Does Not Affect Plasma Homocysteine in Postmenopausal Women with Coronary Artery Disease

“…The novelty of our study compared to previous ones is the study cohort comprising patients with high cardiovascular risk since they had angiographically verified CAD, and the use of transdermal application of 17β-estradiol as HRT. Our results are in contrast to some earlier reports [9, 10, 11, 12, 13]that claim that HRT favorably modulates homocysteine, with the most marked reduction occurring in those with the highest concentrations. Walsh et al [9]found an absolute decrease of 7% in plasma homocysteine in healthy women on conjugated equine estrogen and continuous MPA, i.e.…”

“…Although early reports consistently showed a moderate decrease in plasma homocysteine on HRT [9, 10, 11, 12, 13], more recent studies have either failed to observe such an effect or merely observed a transient decrease in homocysteine levels [10, 14, 15]. The investigations have been done in healthy postmenopausal women free of CAD, and a variety of HRT formulations have been used, including conjugated equine estrogens [10, 13], which is a less frequently used HRT regimen in Europe compared to the US.…”

“…The investigations have been done in healthy postmenopausal women free of CAD, and a variety of HRT formulations have been used, including conjugated equine estrogens [10, 13], which is a less frequently used HRT regimen in Europe compared to the US. At the time the EWA (Estrogen in Women with Atherosclerosis) study [16]was planned, there was little knowledge of the effect of HRT on homocysteine and in particular in women at high risk of CAD.…”

Mortality risk in men is associated with a common mutation in the methylenetetrahydrofolate reductase gene (MTHFR)

“…Influence of oestrogens on the methionine/ homocysteine metabolism is further refuted by the absence of a long-term effect of hormone replacement therapy on the level of plasma homocysteine. 40 Since the level of plasma folate is a critical modulator of the MTHFR mutation, differences in the level of plasma folate between men and women may also have contributed to the gender-dependent association. A previous study in elderly subjects, however, reported no difference in the level of plasma folate between men and women despite the higher folate intake of women.…”

The effects of hormone replacement therapy on homocysteine and vascular histopathological changes

“…However, the effects of gonadal steroids on homocysteine metabolism are not exactly clear. Studies are available suggesting that plasma homocysteine levels increase with natural menopause [16] and HRT in postmenopausal women and rats with surgical menopause decreases homocysteine levels by affecting homocysteine metabolism nongenetically [17][18][19]. But this effect of HRT on homocysteine levels is not always compatible with the clinical end result.…”