Hormone replacement therapy in postmenopausal women

BACKGROUND: For many years, hormone replacement therapy (HRT) was considered an effective method of restoring the relative protection from coronary artery disease enjoyed by premenopausal women compared with men of similar age. This view has been supported by a substantial number of basic science and observational studies. DATA SOURCES: Results of recent randomized controlled trials have seriously challenged the concept of the protective value of HRT by showing that rather than decreasing the risk of coronary artery disease, HRT actually appears to increase it. In addition, it increases the risk for breast cancer, stroke, venous thromboembolism, and cholecystitis. RESULTS: Despite some benefits such as increased bone mineral density and decreased risk of fracture and colorectal cancer, these data suggest that the risks of HRT outweigh the benefits. CONCLUSIONS: HRT is no longer routinely recommended for prevention of chronic disease. We present the current scientific data, benefits, risks, and consequent clinical recommendations regarding HRT use in postmenopausal women.     

Hormone replacement therapy and venous disease

Hormone replacement therapy was first proposed as a magic solution to all the health problems of middle aged women, however, recently a great number of side effects were proven, including an increased incidence of thromboembolic events. In the last decades, a great number of women around the world were in use of HRT, believing that they would have fewer heart attacks and hip fractures. Nevertheless, large clinical trials failed to show the benefits attributed to the use of estrogen and progestin. They proved that not only HRT exposed its users to a higher risk of thromboembolic events, breast cancer and gall bladder disease, but also did not protect the women against heart attacks as it was first thought, although fewer hip fractures occurred. The truth is that we do not know the precise mechanisms by which hormones act, as we do not know all the aspects concerning coagulation and fibrinolysis. We already know that the vessel wall, as well as other target organs, have a large number of estrogen and progestagen receptors which distribution is variable from person to person, rendering a reasonably number of persons more sensitive to the hormone effects. There are still questions about the risks and benefits of the hormone replacement therapy, including its action on the chronic venous disease. Despite the impact of the recent clinical trials, many women still remained on HRT and a great number are under treatment with tamoxifene and raloxifene, for breast cancer and osteoporosis prevention.     

中国有关绝经后激素替代治疗的研究

自1942年结合雌激素上市开始,绝经后激素治疗（hormone therapy,HT）在西方国家经历了两起两落的过程。我国HT的起步较晚,但对其认知程度及使用情况有逐年增加的趋势。为了解中国妇女对HT的态度和使用情况,对近20年中国学者对HT的相关临床研究进行综述。     

Hormone replacement therapy and longevity

To assess whether hormone replacement therapy influences longevity, an analysis was made of published life tables allowing for the calculation of the relative benefit of hormone replacement therapy on longevity in men with late onset hypogonadism and in post‐menopausal women. It was found that testosterone replacement therapy of men suffering from late onset hypogonadism increased survival rate by 9–10% in 5 years, similar to that of eugonadal, non‐LOH men with normal endogenous testosterone secretion. Oestrogen replacement therapy resulted in increased survival by 2.6% in 5 years. It is concluded that hormone replacement therapy increases longevity.     

Hormone replacement therapy and hypertension

Hypertension, particularly systolic hypertension, affects postmenopausal women and is an important risk factor for cardiovascular disease in this group. In the last year, several papers have better defined the mechanisms by which hormone replacement therapy influences blood pressure in postmenopausal women, including effects on nitric oxide, angiotensin II and vascular stiffness (compliance). Currently, data concerning the influence of hormone replacement therapy on blood pressure in postmenopausal women are inconclusive because of the limitations of published studies. It is clear, however, that hypertension is not a contraindication to starting hormone replacement therapy.     

再析绝经妇女激素替代治疗

近60年来HT(Hormone therapy)的应用已在很多国家展开,并已成为当前研究绝经后妇女生活质量和健康状态的热点,对 HT的安全性,医患双方都极为关注,在临床医生中仍有不同观点,甚至仍然是个争论的焦点.我们今天讨论的重点不再是绝经后妇女该不该用HT,而是HT可以预防什么病,谁需要用HT、谁能用HT以及如何有效、安全地使用HT.理想的HT应该是能有效缓解绝经前后出现的症状,预防泌尿生殖器官萎缩、预防骨丢失加速、保护心血管、促进心理健康,提高社会交往能力;无不规则的阴道出血;不增加癌的危险.对所有需要用又没有禁忌证的妇女给予规范化、个体化、系统化的HT治疗以及定期监测,可以保证所有使用HT的妇女冒最小的风险得到最大的利益.     

Hormone replacement therapy and breast cancer risk in California

Numerous studies have documented increased breast cancer risks with hormone replacement therapy (HRT), but these do not give a woman her specific absolute risk for the remainder of her life. This article estimates the magnitude of the effect of HRT on breast cancer incidence in California and calculates a woman's cumulative risk of breast cancer with different formulations and durations of HRT use. The effects of HRT on the underlying breast cancer incidence were estimated using the attributable fraction method, applying HRT prevalence data from the 2001 California Health Interview Survey and published rates of higher relative risk (RR) from HRT use from the Women's Health Initiative (WHI) study and Million Women's Survey (MWS). The annual number of breast cancers potentially attributable to HRT in California was estimated, along with individual cumulative risk of breast cancer for various ages to 79 years according to HRT use, duration, and formulation. Using the WHI data, 829 of 19,000 breast cancers (4.3%) in California may be attributable to HRT. This figure increases to 3401 (17.4%) when the MWS RRs are applied. Use of estrogen-only HRT or short-term (approximately 5 years) use of combined HRT has a minimal effect on the cumulative risk calculated to the age of 79 years; application of the MWS data to a Californian woman commencing HRT at the age of 50 years (no HRT, 8.5%; estrogen only, 8.6%; combined, 9.1%). Prolonged (approximately 10 years) use of combined HRT increases the cumulative risk to 10.3%. This article demonstrates that HRT will generate a small additional risk of breast cancer in an individual. The reduction in perimenopausal symptoms may be considered sufficient to warrant this extra risk. However, this view needs to be balanced because the small increases in individual risk will be magnified, producing a noticeable change in population cancer caseload where HRT use is high.     

激素替代疗法联合抗抑郁药治疗绝经后女性尿道综合征

目的 探讨绝经后女性尿道综合征的治疗方法.方法 绝经后女性52例,年龄44～87岁,平均60岁.均有尿频(排尿次数＞10次/d)、尿急、下腹胀及紧张、焦虑等症状.病程2个月～3年.均有抗生素治疗史,疗效不佳.均行尿动力学检查,除外不稳定膀胱和膀胱出口梗阻,剩余尿均＜50 ml.采用激素替代疗法(替勃龙2.5 mg/d口服)联合抗抑郁药(舍曲林50～100 mg/d口服或文拉法辛75～150 mg/d口服),3个月为1个疗程.疗效评定标准为:①显效:排尿次数＜10次/d,其他临床症状基本消失;②有效:排尿次数＜10次/d,其他临床症状明显缓解;③无效:排尿次数＞10次/d,其他临床症状基本无缓解.结果 52例患者中7例因药物不良反应(恶心、头晕、嗜睡、失眠、乳房胀痛)退出治疗.余45例中显效35例、有效7例、无效3例,总有效率93%.结论 激素替代疗法联合抗抑郁药治疗绝经后女性尿道综合征效果显著.     

Hormone replacement therapy in women with spinal cord injury - a survey with literature review

STUDY DESIGN: Postal questionnaire survey. OBJECTIVE: To examine the current use of hormone replacement therapy (HRT) in a sample of menopausal women with spinal cord injury (SCI). SETTING: National Spinal Injuries Centre (NSIC), Stoke Mandeville Hospital, Aylesbury, UK. METHOD: A postal questionnaire was sent to 94 women from the NSIC patient database who met the study inclusion criteria (wheelchair dependent, aged 49 years and above, last seen or heard from within the last 3 years). RESULTS: A total of 59 valid questionnaires were analysed. At the time of the survey, 50 women were menopausal and 11 of them were using HRT, six for menopausal symptoms and five for osteoporosis prevention. Another 11 had used HRT, eight for menopausal symptoms and three for osteoporosis prevention, but had discontinued it. The main reasons for stopping HRT were side effects. Of the 28 women who had never been on HRT, 20 had either enquired about it, or had been offered HRT, but decided against it. Of the nine women who were still premenopausal at the time of the survey, four would consider using HRT. CONCLUSIONS: Results show that 44% of the menopausal women in our sample have used HRT at some point and 22% still do, mostly for treatment of menopausal symptoms and for osteoporosis prevention. In view of the latest literature findings in able-bodied women, use of HRT for osteoporosis prevention in women with SCI may have to be reconsidered.     

Hormone replacement therapy is associated with improved survival in women undergoing coronary artery bypass grafting

OBJECTIVES: The effect of hormone replacement therapy on cardiovascular events in postmenopausal women is controversial. We investigated the roles of sex and hormone replacement status in female patients undergoing coronary artery bypass grafting. METHODS: We reviewed the records of 4259 consecutive patients aged 55 years or older who underwent primary elective isolated coronary artery bypass at our hospital between May 1996 and September 2001. RESULTS: Female sex with hormone replacement therapy was an independent predictor of decreased mortality, regardless of age. Mortality was 6.7% (61/905) for women not receiving hormone replacement therapy, 2.3% (6/256) for hormone replacement therapy recipients, and 2.7% (82/3098) for men (P <.01 for all comparisons). Of the characteristics examined, multivariate analysis indicated that independent predictors of mortality were advanced age, previous congestive heart failure, class IV angina, and female sex without hormone replacement (P <.005). Independent predictors of survival included use of an internal thoracic artery graft and white ethnicity. There were no significant intergroup differences in the incidence of nonfatal, morbid postoperative events. CONCLUSIONS: Postmenopausal women undergoing coronary artery bypass had a significantly improved in-hospital survival if they had been receiving hormone replacement therapy. The improved survival might be related to one or more of the numerous cardiovascular effects of estrogen that are considered beneficial. A prospective randomized trial is needed to validate the observation that hormone replacement therapy is protective in this setting.     

Hormone replacement therapy prevents osteoclastic hyperactivity: A histomorphometric study in early postmenopausal women.

In a randomized, double blind, clinical prospective trial comprising 35 women treated with either hormone replacement therapy (HRT) (cyclic estradiol/norethisterone acetate) or placebo we performed histomorphometric studies on paired bone biopsies obtained before and after 2 years of treatment. Untreated women developed a progressively more negative balance at individual bone multicellular units (BMUs) (i.e., wall thickness-erosion depth) (2.2 +/- 1.7 microm vs. -5.7 +/- 1.4 microm; p < 0.01), while women on HRT displayed preservation of bone balance (2.4 +/- 2.4 microm vs. 2.5 +/- 2.5 microm; NS). No significant differences in wall thickness between the two groups were demonstrable, but the untreated women developed a pronounced increase in erosion depth over 2 years (46.9 +/- 1.8 microm vs. 52.0 +/- 1.9 microm; p < 0.05), while the HRT group revealed no change (47.8 +/- 2.7 microm vs. 44.6 +/- 1.7 microm; NS). Furthermore, the placebo group displayed an increased osteoclastic erosion depth (17.8 +/- 1.6 microm vs. 25.0 +/- 1.7 microm; p < 0.001), compared with unchanged values in the HRT group (20.0 +/- 1.6 microm vs. 16.9 +/- 1.4 microm/day; NS). While the placebo group revealed a slight increase in volume referent resorption rate (35 +/- 8% vs. 38 +/- 8%; NS) the HRT group revealed a pronounced decrease (46 +/- 8% vs. 28 +/- 5%; p < 0.05). No significant changes in marrow star volume (an index of trabecular perforations) were demonstrable in either group. Our results demonstrate that bone remodeling in early postmenopausal women is characterized by progressive osteoclastic hyperactivity, which is reduced by cyclic HRT. This reduction of resorptive activity at the BMU level after HRT seems to precede the reduction in activation frequency demonstrated in previous studies on older postmenopausal women.     

Hormone replacement therapy (HRT) and anaesthesia

Br J Anaesth 2001; 86: 709–16     

Hormone replacement therapy, body mass index and asthma in perimenopausal women: a cross sectional survey

BACKGROUND: Hormone replacement therapy (HRT) and obesity both appear to increase the risk of asthma. A study was undertaken to investigate the association of HRT with asthma and hay fever in a population of perimenopausal women, focusing on a possible interaction with body mass index (BMI). METHODS: A postal questionnaire was sent to population based samples in Denmark, Estonia, Iceland, Norway, and Sweden in 1999-2001, and 8588 women aged 25-54 years responded (77%). Pregnant women, women using oral contraceptives, and women <46 years were excluded. Analyses included 2206 women aged 46-54 years of which 884 were menopausal and 540 used HRT. Stratified analyses by BMI in tertiles were performed. RESULTS: HRT was associated with an increased risk for asthma (OR 1.57 (95% CI 1.07 to 2.30)), wheeze (OR 1.60 (95% CI 1.22 to 2.10)), and hay fever (OR 1.48 (95% CI 1.15 to 1.90)). The associations with asthma and wheeze were significantly stronger among women with BMI in the lower tertile (asthma OR 2.41 (95% CI 1.21 to 4.77); wheeze OR 2.04 (95% CI 1.23 to 3.36)) than in heavier women (asthma: p(interaction) = 0.030; wheeze: p(interaction) = 0.042). Increasing BMI was associated with more asthma (OR 1.08 (95% CI 1.05 to 1.12) per kg/m2). This effect was only found in women not taking HRT (OR 1.10 (95% CI 1.05 to 1.14) per kg/m2); no such association was detected in HRT users (OR 1.00 (95% CI 0.92 to 1.08) per kg/m2) (p(interaction) = 0.046). Menopause was not significantly associated with asthma, wheeze, or hay fever. CONCLUSIONS: In perimenopausal women there is an interaction between HRT and BMI in the effects on asthma. Lean women who were HRT users had as high a risk for asthma as overweight women not taking HRT. It is suggested that HRT and overweight increase the risk of asthma through partly common pathways.