HRT is effective at relieving menopausal symptoms, and many women can stop taking HRT within a few years without recurrence of these symptoms. Previously, it was believed that long-term HRT use, although increasing the risk of breast cancer and thrombo-embolic disease, reduced osteoporosis, bowel cancer, cardiovascular events, Alzheimer's dementia, and possibly stroke.

A report in July 2002 revealed that a large Women's Health Initiative (WHI) trial to evaluate combined oestrogen and progestogen therapy in postmenopausal women had been stopped early because there was compelling evidence that health risks exceeded health benefits. The report highlighted a 26% increased risk of breast cancer in women taking HRT. In response to this, the Australian Drug Evaluation Committee (ADEC) established an Expert Committee to examine the JAMA article and provide advice on the significance of the study outcomes in the Australian context, the necessary and appropriate action required of the Therapeutic Goods Administration (TGA), and the information that should be provided to Australian health professionals and consumers.

The ADEC report noted that the WHI trial was designed to investigate the efficacy and safety of long-term combined HRT in preventing diseases such as coronary heart disease and hip fracture in postmenopausal women. It was not designed to study the effects of HRT being used to treat menopausal symptoms or established osteoporosis so the mean age of women in the study was 63 years, with two-thirds being over 60. This, and the apparently high frequency of cardiac risk factors in the group (one-third being overweight and one-third obese, 50% being previous or current cigarette smokers, one-third having received treatment for high blood pressure, and over 10% having raised cholesterol requiring medication), may have led to a higher risk of cardiovascular events in the study. However, this must be set against a likely underestimate of the excess risk as a result of treatment dropout and crossover.

There was no difference in overall mortality between the HRT and control groups for the duration of the study (mean, 5.2 years). The absolute increase in disease risk for an individual woman shown in the study was small: among 10 000 women in the age group studied and with their characteristics taking combination HRT for a year, there would be seven more cases of coronary heart disease (37 v 30), eight more cases of invasive breast cancer (38 v 30), eight more cases of stroke (29 v 21), and eight more cases of pulmonary embolism (15 v 7), but six fewer bowel cancers (10 v 16) and five fewer hip fractures (10 v 15), than among women not using HRT. Over the five years of the trial, there would be one extra case of an adverse event per 100 women taking the combined HRT continuously. The Expert Committee noted the increase in harm reported was smaller in the first two to three years after starting HRT than it was after three or more years of combined HRT use.

The conclusions of the Expert Committee of the Australian Drug Evaluation Committee were:

The previously anticipated health benefits from prolonged combined HRT use - reduced heart disease and strokes - were not borne out in the WHI study. However, the absolute risks associated with HRT are small. Women who are currently taking combined HRT, and their doctors, should consider these new findings carefully in the light of their reasons for starting and continuing HRT before deciding whether to continue or stop. In women with osteoporosis, the benefit of a reduced fracture rate with long-term combined HRT must now be balanced against the increased risks of breast cancer, stroke, heart disease and thrombo-embolism. The relative efficacy and safety of HRT must be considered against that of other interventions, such as dietary intake and supplementation of calcium and vitamin D, exercise, or taking other medications for osteoporosis such as bisphosphonates or selective oestrogen-receptor modulators.

Article #8022

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