Hormone Replacement Therapy

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Abstract
The reduction in estrogen production that occurs at menopause is associated with several long term sequelae. There is an accelerated decrease in bone mineral density leading to an increased risk of osteoporotic fracture. Furthermore, changes in plasma lipid profiles and other cardiovascular parameters increase the risk of cardiovascular and cerebrovascular pathology. These effects are additional 10 the menopausal symptoms experienced by many women. The effectiveness of estrogen-based hormone replacement therapy (HRT) is well established in preventing bone mineral loss and also in ameliorating menopausal symptoms, with the addition of progestogen maintaining or possibly enhancing the bone-conserving effects. However, prolonged therapy appears to be necessary to conserve bone mineral density and prevent osteoporotic fracturem particularly in women aged ≥75 years, and compliance with long term therapy is likely to be poor. Estrogen favourably alters plasma lipid profiles, improves coronary blood flow and inhibits the central distribution of body fat. Effects on haemostatic mechanisms and coronary vasomotor response to acetylcholine have also been suggested as mechanisms for the beneficial effects of estrogen all ischaemic heart disease. The effects of concomitant progestogens on plasma lipids are variable, and may depend on the type. dosage regimen and duration of therapy. Pharmacoeconomic analyses of HRT have used a variety of risk assumptions. Relative risk rates of osteoporotic fracture and mortality from myocardial infarction are assumed to reduce to 0.5 after >5 years’ therapy. Long term HRT is associated with a relative risk of approximately 1.3 for breast cancer, whereas the relative risk of endometrial cancer is 4.0 to 8.0 in women with intact uteri receiving prolonged unopposed estrogen therapy. HRT that includes progestogens is assumed to incur no added risk of endometrial cancer, and this treatment is generally recommended for women with intact uteri. Data concerning the effect of HRT on quality of life are limited and utility values for hip fracture of 0.95 to 0.36 have been assigned, depending on assumptions of disability. Cost-benefit, cost-effectiveness and cost-utility studies evaluating HRT in the prevention of osteoporotic fracture have differed widely in methodology, making comparison of results difficult. HRT appears to be most economically useful in the prevention of fracture if used in women who have undergone hysterectomy, in women with high risk of osteoporotic fracture or ischaemic heart disease, and/or in women with menopausal symptoms. Long term therapy (≥10 years) is usually more cost-effective than short term (5 years) treatment. In a hypothetical model, screening with bone mineral absorptiometry and HRT for women in the high-risk group (bone mineral density <0.9 g/cm2) cost $US11 700 per year of life saved (YLS), compared with $US68 900 per YLS for universal treatment for 15 years. The cost effectiveness of HRT is substantially improved when adjusted for quality of life, and cost per quality-adjusted life year (QALY) is similar to the cost/QALY estimated for other health interventions common in the older patient population. The definitive pharmacoeconomic status of HRT is difficult to determine, with numerous variables to consider and further evidence required in many therapeutic aspects. Notwithstanding this, HRT is medically and economically beneficial in women with severe menopausal symptoms and in women with high risk of osteoporotic fracture, with its cardioprotective abilities adding a significant further benefit central to its cost effectiveness. The reduction in estrogen levels associated with menopause is an important contributory factor to bone mineral loss and the development of osteoporosis. Bone mineral density decreases after menopause at a rate of approximately 1 to 3% per year for 10 to 15 years. The major consequence of this bone loss is an increased susceptibility to fracture, most commonly of the vertebrae, hip or wrist. The incidence of fracture is 2- to 3-fold higher in women than in age-matched men. Hip fractures are most common in women aged ≥ 75 years, with 5 to 20% mortality within the first year. Furthermore, up to 50% of women have significant disability following hip fracture. The prevalence of osteoporosis and incidence of osteoporotic fracture arc increasing, partly because of increasing longevity. Caucasian and Asian populations are particularly affected, and other contributing factors include sedentary lifestyle, smoking, alcohol (ethanol) abuse and low dietary calcium intake. In the US, osteoporosis causes more than 1.3 million fractures per year, including 540 000 to 640 000 spine, 200 000 to 250 000 hip and 170 000 to 200 000 wrist fractures. Postmenopausal women also lose the protective influence of estrogen on serum lipid profiles and other cardiovascular parameters, causing increased risk of ischaemic heart disease. By the age of 70 years mortality in women due to cardiovascular disease approaches that in the male population. There are many alternatives available for the treatment and prevention of both menopausal symptoms and osteoporosis. However, estrogen-based hormone replacement therapy (HRT) is the only option that has proven efficacy in both indications, and that has the additional benefit of reducing cardiovascular risk. Biochemical markers of bone turnover decrease during HRT, and bone mineral densitometry indicates prevention of bone loss and, in some cases, a modest increase in bone mineral density. Concomitant progestogens prevent endometrial hyperplasia and do not appear to counteract the beneficial effect of estrogens on plasma lipid profiles if given in low dosages or for long periods. Oral unopposed estrogens decrease plasma levels of total cholesterol and low density lipoprotein (LDL) cholesterol and increase high density lipoprotein (HDL) cholesterol. Smaller improvements in serum lipid...