Hormone replacement therapy and cardiovascular disease.

Oestrogen alone probably confers a degree of protection against ischaemic heart disease and stroke and is appropriate for women requiring hormone replacement therapy (HRT) who have undergone hysterectomy. However, the cardiovascular effects of the progestogens used with oestrogen in the much larger number of women who have not undergone hysterectomy are unknown. Some widely used progestogens have adverse effects on lipoprotein levels and may raise blood pressure. The antithrombin III level may be involved in determining the response to oestrogen in different settings. The indications for HRT and the effects of different formulations on cardiovascular disease constitute one of the most pressing but complex issues in present-day medical practice. These questions can only be satisfactorily answered by the randomised controlled trials that should have been initiated several years ago and the feasibility of which is only now being investigated.     

Hormone replacement therapy in hypopituitarism

Hypopituitarism is a disease complex characterised by varying pituitary hormonal deficiencies. The causes and manifestations of hypopituitarism are diverse, the most common being the presence of or treatment of a pituitary adenoma. Pressure effects from the tumour itself on normal pituitary tissue, together with the effects of surgical resection, results in variable degrees of hypopituitarism. The latter precipitates end-organ failure leading to a variety of symptoms and signs, which are often nonspecific and vague. The broad aims of managing patients with hypopituitarism are to provide amelioration of the symptomatology associated with the condition, to avoid potentially acute life-threatening complications and to protect against long-term sequelae that may include osteoporosis and cardiovascular disease. This is achieved through lifelong therapeutic replacement of target hormonal deficiencies, such as corticosteroids or sex hormones, or replacement of the pituitary hormones themselves (i.e., growth hormone and vasopressin). Although the general principle of replacing missing hormones seems straightforward, in reality, existing hormonal therapeutic regimes often result in unphysiological replacement. Furthermore, there may be problems associated with their administration and routine monitoring. There is now little doubt that the hypopituitary state is associated with increased cardiovascular mortality. However, the precise underlying mechanisms responsible have not been fully elucidated, but probably include untreated growth hormone deficiency and/or unphysiological replacement of other target hormones. An effective strategy of tailoring hormonal replacement regimes to individual needs remains a challenge but is imperative if the increased morbidity and mortality associated with hypopituitarism is to be addressed.     

激素替代疗法及其安全性

目的：绝经妇女广泛使用激素替代疗法(hormone replacement therapy，HRT)，在学术界始终存在争议，其安全性令人担忧。方法：检索2000年～2002年文献，综述评价。结果：绝经妇女使用激素治疗是必须的，关键是如何安全、合理、规范使用HRT剂量，权衡HRT利与弊。结论：HRT引起绝经妇女的副作用与医生、患者错误地使用有很大关系，HRT防止心血管疾病、预防骨质疏松及对其它器官系统的益处相比，利大于弊。     

Hormone replacement therapy in hypopituitarism

Hypopituitarism is a disease complex characterised by varying pituitary hormonal deficiencies. The causes and manifestations of hypopituitarism are diverse, the most common being the presence of or treatment of a pituitary adenoma. Pressure effects from the tumour itself on normal pituitary tissue, together with the effects of surgical resection, results in variable degrees of hypopituitarism. The latter precipitates end-organ failure leading to a variety of symptoms and signs, which are often nonspecific and vague. The broad aims of managing patients with hypopituitarism are to provide amelioration of the symptomatology associated with the condition, to avoid potentially acute life-threatening complications and to protect against long-term sequelae that may include osteoporosis and cardiovascular disease. This is achieved through lifelong therapeutic replacement of target hormonal deficiencies, such as corticosteroids or sex hormones, or replacement of the pituitary hormones themselves (i.e., growth hormone and vasopressin). Although the general principle of replacing missing hormones seems straightforward, in reality, existing hormonal therapeutic regimes often result in unphysiological replacement. Furthermore, there may be problems associated with their administration and routine monitoring. There is now little doubt that the hypopituitary state is associated with increased cardiovascular mortality. However, the precise underlying mechanisms responsible have not been fully elucidated, but probably include untreated growth hormone deficiency and/or unphysiological replacement of other target hormones. An effective strategy of tailoring hormonal replacement regimes to individual needs remains a challenge but is imperative if the increased morbidity and mortality associated with hypopituitarism is to be addressed.     

Hormone replacement therapy and stroke

Stroke is the third most common cause of death in women and a major cause of disability. Stroke occurs in older age in women compared with men. High premenopausal estrogen concentrations in women are thought to be protective against stroke and cardiovascular disease. Estrogens are essential for normal reproductive function and they exert complex and diverse non reproductive actions on multiple tissues such as neuroprotective effects, vasodilatation, improved vascular reactivity, antithrombotic effects and lipid lowering effects. After menopause estrogen concentrations are depleted and in the past estrogen replacement therapy was considered as a potential protective agent against both cardiovascular disease and stroke. Although the use of hormone therapy was originally associated with a reduction in the risk of heart disease by about 50% in observational studies, the results regarding stroke have been less clear. In order to investigate the effect of hormone therapy on stroke risk, randomized controlled trials of cardio-and/or cerebrovascular-disease prevention in women with established heart disease have been designed. The Heart Estrogen-Progestin Replacement Study included stroke as secondary outcome. This study did not show any differences in myocardial infarction (MI) or coronary death (HR 0.99; 95%CI 0.80-1.22) and in stroke rate. In another study, the Women Estrogen Stroke Trial, 17 beta estradiol 1 mg/placebo was administered to women with previous ischemic stroke or transient ischaemic attack (TIA) having a mean age 71. No differences in stroke rate (RR 1.1; 95% CI 0.8-1.4) and in mortality rate (RR 1.2; 95% CI 0.8-1.8) were found, while a trend showing an increased rate of fatal strokes (RR 2.9; 95% CI 0.9-9.0) and for more severe non-fatal strokes (% patients with final National Institutes of Health Stroke Scale (NIHSS) 0-1: 19 % vs. 33%; p = 0.12) was observed. The Women's Health Initiative, a primary prevention study, where conjugated equine estrogen (CEE) plus medroxyprogesterone acetate/placebo was utilized, was stopped because of an excess in breast cancer and increased stroke rates (RR 1.4; 95% CI 1.1-1.8). Recently, a meta-analysis including 39,769 women participating in 28 trials has been published. Twelve studies were of secondary prevention and the overall stroke rate was 2%. In the hormone replacement therapy (HRT) arm there was a 29% increased rate of ischemic stroke (Number Needed to Harm, NNH:147). Furthermore, a 56% increased rate of death or dependency after stroke and a tendency of more fatal stroke were observed. Additionally, a higher stroke risk was reported in the first year of treatment. CONCLUSIONS: There seems to be no indication for hormone replacement therapy in the prevention of stroke in women. Further studies are needed to discover why estrogens have different effects on the heart and brain. Conventional risk-factors which could increase the risk of estrogen therapy need to be identified and as well as more restrictive inclusion and exclusion criteria such as coagulation parameters and intimal thickness should be adopted before new randomized trials are started.     

Hormone replacement therapy and other menopause associated conditions.

In Britain a large majority of the women who use Hormone Replacement Therapy (HRT) use it in order to alleviate symptoms thought to relate to the menopause. These include vasomotor instability, 'minor' psychological disturbance and sexual difficulties. Other HRT effects gained by the women include effects on maintenance of collagen, as in the skin, and on oestrogen sensitive tissues related to the lower urinary tract.     

Hormone replacement therapy and health protection

Menopause is potentially a cause of concern and hormone-related diseases. Hormone replacement therapy (HRT) is considered to be an effective treatment strategy to relieve menopausal symptoms and prevent related diseases, however, knowledge on HRT and its benefits and risks is still evolving. For many climacteric women, HRT is the ideal choice to treat symptoms, prevent diseases and improve quality-of-life, while for others it can cause concerns and problems. Thus, the appropriate role of HRT has still to be fully defined. An individualized, patient-tailored approach to HRT, based on the current evidence of risk factors for hormone-related diseases and treatments, is essential to maximize the benefits and minimize the risks.     

Hormone replacement therapy aggravates postmenopausal urinary incontinence

(1) In the WHI trials, which involved more than 20 000 women, the frequency of urinary incontinence increased among postmenopausal women taking hormone replacement therapy compared with placebo. Among women who were continent at enrollment, the frequency of stress incontinence at 1 year was 16% with an oestrogen-progestin combination, compared with 9% with placebo (relative risk 1.87, 95% confidence interval: 1.61-2.18). Among women who were already incontinent, the relative risk of aggravation with hormone replacement therapy compared with placebo was about 1.40. (2) The results of another trial involving nearly 3000 women were similar. (3) Other, smaller trials failed to show any positive impact of oestrogen-progestin therapy on urinary incontinence in postmenopausal women. (4) In practice, postmenopausal hormone replacement therapy does not protect against urinary incontinence; on the contrary, it may trigger or worsen urinary incontinence.     

妇科恶性肿瘤的激素补充治疗

性激素补充治疗可以缓解雌激素缺乏的相关症状如潮热、失眠、泌尿生殖系统萎缩等,预防绝经后骨质疏松及冠心病等,目前大部分妇科医师已达成共识,激素补充治疗利大于弊,并建议健康绝经后妇女应用激素补充治疗(hormone replacement therapy,HRT)。随着妇     

女性围绝经期综合征的激素替代治疗

<正>女性更年期是指女性因卵巢功能逐渐衰退、生殖器官开始萎缩而至月经终止的一段时间。由于更年期的定义含糊,1994年世界卫生组织(WHO)提出使用围绝经期一词。围绝经期是指从接近绝经出现与绝经有关的内分泌、生物学和临床特征起至绝经一年内的期间(即绝经过渡期至绝经后一年)。绝经是指月经完全停止一年以上。绝经年龄因人而异,我国城市妇女目前平均绝经年龄为     

Hormone replacement and cancer.

The increasing extended use of noncontraceptive oestrogen by postmenopausal women, intended to prevent other conditions, may at the same time increase their risk of reproductive cancer. The risk of endometrial cancer triples after only a few years of unopposed oestrogen, persists for many years after oestrogen has been discontinued, and appears to be preventable by the addition of a progestin. The effect of replacement hormones on the risk of breast or ovarian cancer is unknown. Most studies suggest a small but significant increased risk of breast cancer after long-term use. Awareness of the known and uncertain cancer risks should be included in decisions to use replacement hormones.     

Hormone replacement therapy: optimising the dose and route of administration

Several new products and regimens for estrogen replacement in the postmenopausal woman have recently been introduced, giving physicians and patients greater choice not only in dose but also in route of administration. Estrogen treatment in the postmenopausal woman has several proven benefits for those who have vasomotor symptoms or problems related to urogenital atrophy. However, the most controversial area is in the long-term preventive benefits of estrogen against the development of osteoporosis and cardiovascular disease, particularly in women older than 60 years. It is in these areas that decisions on the dose and optimal route of administration of estrogen replacement therapy (ERT) must be made. Although adding a progestogen to an ERT regimen is mandatory, particularly in a woman with an intact uterus, discussion now focuses on which progestogen least attenuates the beneficial effects of estrogen. Emerging trends suggest that lower doses of estrogen (i.e. ethinylestradiol 5 microg/day, estradiol 0.25 mg/day or conjugated estrogens [CEE] 0.3 mg/day) continuously combined with lower doses of medroxyprogesterone (MPA) are equally effective at relieving vasomotor symptoms as the most commonly prescribed regimen in the US (CEE 0.625mg/MPA 2.5mg daily), with fewer adverse events, leading to greater patient acceptance and likelihood for continuation of therapy. This is especially important when therapy is initiated at an older age.