The accepted medical indications for hormone replacement therapy (HRT) are for the short-term treatment of hot flushes and vaginal dryness, and for women who have established osteoporosis. hormone replacement therapy is no longer recommended as a long-term preventative treatment for heart disease and osteoporosis in healthy women since the release of two studies in July 2002 showing more harm than good from ‘continuous’ oestrogen and progestogen, and an increased risk of ovarian cancer among long-term use of oestrogen replacement. A hoped-for benefit in reducing risk of Alzheimer’s disease or improving cognitive function has also not eventuated, and preventative hormone replacement therapy for these disorders is similarly not recommended.
The Women’s Health Initiative study (WHI) was a long-term study designed to evaluate risks and benefits of hormone replacement therapy when taken by post-menopausal women to prevent coronary heart disease, hip fracture and other conditions. The study did not set out to investigate the effects of hormone replacement therapy being used in peri-menopause and recently menopausal women to treat symptoms experienced at the time of menopause. As a result, two-thirds of the women were over 60 and many were overweight. Fifty per cent were previous or current cigarette smokers when they entered the study, and about 30 per cent had received treatment for high blood pressure. More than 10 per cent had raised cholesterol levels and were being treated with medication.
The biggest increase in disease risk seen amongst the women taking hormone replacement therapy was in the cardiovascular system. For every 100 000 women taking continuous hormone replacement therapy for one year, there were seven more cases of heart disease, eight more cases of stroke and eight more cases of pulmonary embolus or deep venous thrombosis (DVT) than in women not on this medication. The age and health profile of the women on the trial means that these statistics probably cannot be extrapolated to the entire Hormone Replacement Therapy-taking community. The other risk seen with hormone replacement therapy was an increase in invasive breast cancer, with eight more cases per 100 000 women taking hormone replacement therapy over those not taking Hormone Replacement Therapy. On the positive side, there were five fewer cases of hip fracture and six fewer cases of bowel cancer, but when the overall risk of disease outweighed the observed benefits, the trial was stopped early, just over five years after it was started.
Since the release of the WHI study findings there has been considerable confusion amongst women over what these findings mean for them. The use of hormone replacement therapy for an individual needs to be assessed in the light of their particular background risk of developing either heart disease, breast cancer or osteoporosis, all of which increase with age. The physical, inherited and other characteristics that increase an individual’s risk of developing these conditions are summarised in Table ‘Factors associated with increased risk of breast cancer’ and Table ‘Factors associated with increased risk of cardiovascular disease’.
Since the risk of breast cancer increases with both age and duration of use, younger women (50 and under) who take hormone replacement therapy for less than five years have a relatively low increase in breast cancer risk above women not taking Hormone Replacement Therapy. As a woman ages, however, this risk changes, and women over 55 who have no compelling reason to be on hormone replacement therapy should cease medication. The picture with cardiovascular risk is somewhat different because risks of heart attack, emboli and stroke increase soon after commencing hormone replacement therapy (HRT), and in the WHI study, this risk remained higher for the duration of the trial.
Table Factors associated with increased breast cancer risk
• Never having been pregnant and not having breastfed (or pregnancy and breastfeeding later in life)
• Family history of breast cancer
• hormone replacement therapy for more than five years
• Increased breast density on mammogram before starting Hormone Replacement Therapy
Table Factors associated with increased risk of cardiovascular disease
• Cigarette smoking
• Elevated triglycerides, total cholesterol and low HDL cholesterol
• Poor physical fitness
• Inadequate diet, including a low omega-3 fatty acid intake
• Hormonal medication including hormone replacement therapy and the Pill, especially when taken by women over 35