Hormone Replacement Therapy Shortens QT Dispersion in Healthy Postmenopausal Women

Background: The aim of the study was to investigate the effects of hormone replacement therapy (HRT) on myocardial repolarization characteristics in postmenopausal women without coronary artery disease. Methods: Fifty‐one consecutive healthy postmenopausal women (age 48 ±; 5) with negative exercise stress testing were prospectively enrolled into the study. Standard 12‐lead electrocardiograms were obtained to evaluate the effects of 6 months of HRT on QT intervals, corrected QT intervals (QTcmax and QTcmin), QT dispersion (QTd), and corrected QTd (QTcd). Hormone regimens were continuous 0.625 mg/day conjugated equine estrogen (CEE) plus 2.5 mg/day medroxyprogesterone acetate (MPA) or 0.625 mg/day CEE alone depending on the hysterectomy status. Results: Although not statistically significant, CEE alone or in combination with MPA increased QTmax and QTmin values. However, the increase in QTmin was greater than the increase in QTmax, which resulted in statistically significant shortening of QTd (P = 0.007 in CEE and P < 0.001 in CEE + MPA groups). There was a significant prolongation of QTcmin values after 6 months in patients assigned to the CEE group (P = 0.001). The QTcd values were significantly shortened by HRT with both regimens (for CEE group 49 ±; 13 ms vs 38 ±; 13 ms, P = 0.01; for CEE + MPA group 49 ±; 14 ms vs 36 ±; 13, P < 0.001). Conclusion: HRT significantly decreased the QTd and QTcd in postmenopausal women without coronary artery disease, independent of the addition of MPA to the regimen. This improvement in myocardial repolarization may be one of the mechanisms of the favorable effects of HRT on cardiovascular system. However, the clinical implications of the shortening of QTd in postmenopausal women with HRT must be clarified. A.N.E. 2001; 6(3):193–197     

The Cost-effectiveness of Hormone Therapy in Younger and Older Postmenopausal Women

Purpose

To evaluate the health and economic outcomes of hormone therapy in younger and older postmenopausal women.

Methods

We developed a cost-effectiveness model to evaluate outcomes associated with hormone therapy in younger and older postmenopausal women, using data sources from published literature through March 2008. The target population was 50-year-old and 65-year-old women given hormone therapy or no therapy, and then followed over their lifetime. Primary outcomes measured were quality-adjusted life-years (QALYs) and incremental cost per QALY gained.

Results

For the base-case analysis, hormone therapy for 15 years in the younger cohort resulted in a gain of 1.49 QALYs with an incremental cost of $2438 per QALY gained, compared with no therapy. The results for younger women were robust to all sensitivity analyses, and treatment remained highly cost-effective (<$10,000 per QALY gained) within the range of individual assumptions used. Treatment durations of 5 years and 30 years also were highly cost-effective. In the older cohort, treatment for 15 years resulted in a net gain of 0.11 QALYs with a cost of $27,953 per QALY gained. However, a loss of QALYs was seen in the first 9 years. The results for older women were sensitive to many of the assumptions used.

Conclusions

Hormone therapy for 5 to 30 years in younger postmenopausal women increases quality-adjusted life-years and is cost-effective. Hormone therapy started in later years results in a loss of quality-adjusted life for several years before a net gain can be realized.     

Bayesian Meta-analysis of Hormone Therapy and Mortality in Younger Postmenopausal Women

Background

There is uncertainty over the risks and benefits of hormone therapy. We performed a Bayesian meta-analysis to evaluate the effect of hormone therapy on total mortality in younger postmenopausal women. This analysis synthesizes evidence from different sources, taking into account varying views on the issue.

Methods

A comprehensive search from 1966 through January 2008 identified randomized controlled trials of at least 6 month's duration that evaluated hormone therapy in women with mean age <60 years and reported at least one death, and prospective observational cohort studies that evaluated the relative risk of mortality associated with hormone therapy after adjustment for confounding variables.

Results

The results were synthesized using a hierarchical random-effects Bayesian meta-analysis. The pooled results from 19 randomized trials, with 16,000 women (mean age 55 years) followed for 83,000 patient-years, showed a mortality relative risk of 0.73 (95% credible interval 0.52-0.96). When data from 8 observational studies were added to the analysis, the resultant relative risk was 0.72 (credible interval 0.62-0.82). The posterior probability that hormone therapy reduces total mortality in younger women is almost 1.

Conclusions

The synthesis of data using Bayesian meta-analysis indicates a reduction in mortality in younger postmenopausal women taking hormone therapy compared with no treatment. This finding should be interpreted taking into account the potential benefits and harms of hormone therapy.     

Increased Arterial Distensibility in Postmenopausal Hypertensive Women with and Without Hormone Replacement Therapy after Acute Administration of the Ace Inhibitor Moexipril

Menopause and essential hypertension are associated with a decreased compliance and distensibility of the arteries. ACE inhibitors have been shown to improve arterial distensibility. Hormone replacement therapy (HRT), especially estrogens, could have a positive influence through their atheroprotective, vasodilative, and blood pressure–lowering effect. The vascular interactions of HRT and ACE inhibitors, like moexipril hydrochloride, have not been investigated so far. This trial was intended to assess the effect of combined sequential HRT for 25 days on acute changes in arterial distensibility after a single oral dose of 15 mg moexipril hydrochloride in postmenopausal women with borderline to mild essential hypertension. This study had a monocentric, randomized, parallel-group design, and was open for moexipril, and double-blind, and placebo-controlled for HRT. Assessment of arterial distensibility was by automatic noninvasive measurement of the carotid–femoral pulse wave velocity (PWV). The PWV and the pulse pressure decreased significantly after a single oral dose of 15 mg moexipril. An influence of HRT on the changes in the PWV and pulse pressure could not be seen. The plasma concentrations of renin increased and of aldosterone decreased after moexipril administration. Arterial function improves after acute administration of 15 mg moexipril in postmenopausal women with mild to moderate essential hypertension. The changes in PWV and pulse pressure are of similar magnitude in women with and without HRT.     

Hypertension in Postmenopausal Women

Blood pressure is typically lower in premenopausal women than in men. However, after menopause, the prevalence of hypertension in women is higher than it is in men. Hypertension is a major risk factor for cardiovascular disease in women and men, but cardiovascular disease is the leading cause of death in women. Furthermore, there is evidence that blood pressure may not be as well-controlled in women as in men, despite the fact that most women adhere better to their therapeutic regimens and medications than do men, and have their blood pressures measured more frequently than do men. This review describes possible mechanisms by which blood pressure may be increased in postmenopausal women.     

Spotlight on Estradiol and Norgestimate as Hormone Replacement Therapy in Postmenopausal Women

The focus of this review is hormone replacement therapy (HRT) with continuous administration of micronized, oral 17beta-estradiol 1 mg/day (herein referred to as continuous estradiol) plus micronized, oral norgestimate 90 microg/day administered for 3 days then withdrawn for 3 days in a 6-day repeating sequence (herein referred to as intermittent norgestimate). According to data from randomized, comparative trials of 1 year's duration, continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day relieves climacteric symptoms (vasomotor symptoms and vulvovaginal atrophy) in postmenopausal women. Continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day appeared as effective as estradiol 1 mg/day alone or continuous estradiol 2 mg/day plus continuous norethisterone acetate 1 mg/day in the treatment of postmenopausal women with vasomotor symptoms. Continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day was as effective as continuous estradiol 1 mg/day in causing the maturation of vaginal epithelial cells. In a randomized, double-blind study, bone mineral density (BMD) increased to a significantly greater extent and the rate of bone turnover was slower in postmenopausal women treated with continuous oral estradiol 1 mg/day plus intermittent norgestimate 90 microg/day than in placebo-treated patients. Two randomized, double-blind studies indicated that the addition of norgestimate 90 microg/day to continuous estradiol 1 mg/day did not attenuate the beneficial effects of estradiol on lipid parameters. Continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day was associated with increases in mean serum high density lipoprotein (HDL)-cholesterol levels and decreases in total cholesterol, low density lipoprotein (LDL)-cholesterol and lipoprotein (a) levels, compared with baseline. There was no statistically significant increase in triglyceride levels. In comparative trials, continuous oral estradiol 1 mg/day plus intermittent oral norgestimate 90 microg/day was well tolerated. Headache, breast pain or discomfort, abdominal pain or discomfort, uterine bleeding, dysmenorrhea, edema, nausea and depression were the most commonly reported adverse events. Continuous estradiol 1 mg/day plus intermittent oral norgestimate 90 microg/day was associated with a favorable uterine bleeding profile that improved over time. In a randomized trial, 80% of women were free from bleeding (irrespective of spotting) during month 12 of treatment. Norgestimate 90 microg/day was effective in protecting postmenopausal women against induction of endometrial hyperplasia by continuous estradiol 1 mg/day. In conclusion, data from a limited number of randomized studies indicate that HRT with continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day is effective in relieving climacteric symptoms, increasing BMD and slowing the rate of bone turnover in postmenopausal women. This HRT regimen is well tolerated and is associated with a similar incidence of adverse events to that reported in recipients of continuous estradiol 1 mg/day. The norgestimate component of the regimen provides good endometrial protection and is associated with a favorable bleeding profile. Long-term studies investigating the associated risk of breast cancer and thromboembolic events in recipients of continuous estradiol plus intermittent norgestimate are needed. In the meantime, continuous oral estradiol plus intermittent oral norgestimate can be regarded as an effective new option for HRT in postmenopausal women.     

Effects of Hormone Replacement Therapy on Heart Rate Variability in Postmenopausal Women

Background: Hormone replacement therapy (HRT) is associated with reduced cardiovascular risk, but the underlying mechanism(s) are not fully understood. This study investigated the effects of a 6‐month course of HRT on cardiac autonomic function parameters assessed by heart rate variability (HRV) in postmenopausal women. Methods: Forty‐six healthy postmenopausal women (age 48 ± 5, range 40–60) with normal baseline electrocardiogram and negative exercise testing were enrolled. HRT, which was either 0.625 mg/day conjugated equine estrogen (CEE) plus 2.5 mg/day medroxyprogesterone acetate or 0.625 mg/day CEE alone were administered depending on hysterectomy status. Power spectral analysis of HRV was performed to calculate the low frequency component in absolute (LF) and normalized units (LF nu), high frequency component in absolute (HF), and normalized units (HF nu), and the LF/HF ratio. The standard deviation of RR intervals (SDNN) was calculated from the time series of RR intervals. Results: A 6‐month course of HRT did not significantly alter resting heart rate (P > 0.05). The LF/HF ratio and LF nu significantly decreased after HRT (P = 0.022 and P = 0.032), whereas a significant increase was noted in the HF component of HRV (P = 0.043), indicating an improvement in cardiac autonomic function. The SDNN value, which was 28.8 ± 11.8 ms before HRT significantly increased to 35.4 ± 16.7 ms after 6 months (P = 0.011). Conclusion: Our results indicate that a 6‐month course of HRT may significantly improve cardiac autonomic function parameters, a finding that could at least partly explain the potential cardiopro‐tective effect(s) of HRT. A.N.E. 2001;6(4):280–284     

雌激素替代治疗对绝经后妇女血管内皮舒张功能的影响

为了探讨雌激素抗动脉粥样硬化和降低冠心病发病危险的机制 ,采用无创性高分辨超声法观察雌激素替代治疗对绝经后妇女血管内皮依赖性舒张功能的影响 ,于治疗前后测量血清雌二醇、一氧化氮和血脂水平。结果发现 ,绝经后妇女较绝经前妇女血清雌二醇和一氧化氮下降 (P <0 .0 0 1) ,肱动脉血流介导的舒张反应较绝经前明显下降 (3.84 %± 2 .18%比 10 .0 5 %± 3.18% ,P <0 .0 0 1) ;短期雌激素替代治疗后雌二醇和一氧化氮水平较治疗前极显著升高 (P <0 .0 0 1) ,肱动脉血流介导的舒张反应也显著改善 (9.16 %± 3.0 2 % ,P <0 .0 0 1) ,而雌激素替代治疗并未使血脂发生明显改善 (P >0 .0 5 )。相关分析发现肱动脉血流介导的舒张反应与雌二醇和一氧化氮呈正相关(r值分别为 0 .5 6 4和 0 .72 9,P <0 .0 0 1) ,与总胆固醇呈负相关 (r为 - 0 .36 9,P <0 .0 5 )。结果提示短期雌激素替代治疗可明显改善绝经后妇女内皮依赖性舒血管功能障碍 ,且与血脂的改善无关 ,可能与雌激素的直接血管保护作用有关。     

Evaluation of Arterial Compliance in Humans

Compliance is a measure of the elastic properties of arterial vessels and is a function of blood pressure. In recent years new techniques have been developed which allow to measure arterial compliance non invasively and continuously over the range of existing blood pressure values. It has been thus possible to investigate the alterations of arterial compliance in a variety of diseases and to address the physiological factors involved in arterial compliance modulation. This article will focus on the new data available on these issues.     

动脉顺应性的研究进展

动脉顺应性是动脉血管壁的内在弹性特性,顺应性的降低为血管性疾病发生、发展的早期表现。现就动脉顺应性的定义、影响因素、检测方法、临床意义作一综述。     

Isoflavones and Postmenopausal Women

Isoflavonic phytoestrogens, or isoflavones, constitute a class of phytoestrogens that have properties similar to selective estrogen receptor modulators, and have attracted a substantial degree of attention in recent years, particularly as a possible alternative to the conventional hormone replacement therapy regimens used by postmenopausal women. Despite great promise, it is difficult to make many specific recommendations about their use at the current time, in light of the many outstanding questions that hopefully will be answered in the future by focused interventional studies involving humans. Studies to date indicate that the use of isoflavones to address vasomotor symptoms provides at most small benefits beyond a placebo effect, and no benefit for genital atrophy. As for postmenopausal women whose primary concern is cardiovascular disease, the recommendation of the American Heart Association to include soy protein foods as part of an otherwise healthy diet is well justified, and similarly the substitution of supplements containing soy protein for animal protein can also be recommended. The use of purified isoflavone supplements not containing soy protein may have some cardiovascular benefits, but these appear to be less substantial in degree than those provided by soy protein with isoflavones. In particular, more research is needed to assess the effects of isoflavones on osteoporosis, for which no recommendation regarding isoflavones can be made based on the current data. Also, isoflavones should not be taken by postmenopausal women for the specific purpose of decreasing their risk of breast or endometrial cancer, although, at least for those without pre-existing disease or at high risk, it seems quite unlikely that isoflavone use is harmful in this regard.     

Hormonal Replacement Therapy

Reviews in Endocrine and Metabolic Disorders -