HORMONE REPLACEMENT THERAPY .2. A PHARMACOECONOMIC APPRAISAL OF ITS ROLE IN THE PREVENTION OF POSTMENOPAUSAL OSTEOPOROSIS AND ISCHEMIC-HEART-DISEASE

The reduction in estrogen production that occurs at menopause is assoc iated with several long term sequelae. There is an accelerated decreas e in bone mineral density leading to an increased risk of osteoporotic fracture. Furthermore, changes in plasma lipid profiles and other car diovascular parameters increase the risk of cardiovascular and cerebro vascular pathology. These effects are additional to the menopausal sym ptoms experienced by many women. The effectiveness of estrogen-based h ormone replacement therapy (HRT) is well established in preventing bon e mineral loss and also in ameliorating menopausal symptoms, with the addition of progestogen maintaining or possibly enhancing the bone-con serving effects. However, prolonged therapy appears to be necessary to conserve bone mineral density and prevent osteoporotic fracture, part icularly in women aged greater-than-or-equal-to 75 years, and complian ce with long term therapy is likely to be poor Estrogen favourably alt ers plasma lipid profiles, improves coronary bloodflow and inhibits th e central distribution of body fat. Effects on haemostatic mechanisms and coronary vasomotor response to acetylcholine have also been sugges ted as mechanisms for the beneficial effects of estrogen on ischaemic heart disease. The effects of concomitant progestogens on plasma lipid s are variable, and may depend on the type, dosage regimen and duratio n of therapy. Pharmacoeconomic analyses of HRT have used a variety of risk assumptions. Relative risk rates of osteoporotic fracture and mor tality 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 end ometrial cancer is 4.0 to 8.0 in women with intact uteri receiving pro longed unopposed estrogen therapy. HRT that includes progestogens is a ssumed 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 f or hip fracture of 0.95 to 0.36 have been assigned, depending on assum ptions of disability. Cost-benefit, cost-effectiveness and cost-utilit y studies evaluating HRT in the prevention of osteoporotic fracture ha ve differed widely in methodology, making comparison of results diffic ult. HRT appears to be most economically useful in the prevention of f racture if used in women who have undergone hysterectomy, in women wit h high risk of osteoporotic fracture or ischaemic heart disease, and/o r in women with menopausal symptoms. Long term therapy (greater-than-o r-equal-to 10 years) is usually more cost-effective than short term (5 years) treatment. In a hypothetical model, screening with bone minera l absorptiometry and HRT for women in the high-risk group (bone minera l density <0.9 g/cm2) cost $US11700 per year of life saved (YLS), comp ared with $US68900 per YLS for universal treatment for 15 years. The c ost effectiveness of HRT is substantially improved when adjusted for q uality of life, and cost per quality-adjusted life year (QALY) is simi lar to the cost/QALY estimated for other health interventions common i n 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. Notwithsta nding this, HRT is medically and economically beneficial in women with severe menopausal symptoms and in women with high risk of osteoporoti c fracture, with its cardioprotective abilities adding a significant f urther benefit central to its cost effectiveness.