Changes in practice since the publication in 2007 of further results from the Women's Health Initiative and the Million Women Study

Abstract

For menopause specialists around the world, 2002 was a watershed. Before this they were confident about prescribing hormone therapy for the relief of climacteric symptoms for women in their late 40s and 50s. A number of practitioners were looking to the possible long-term benefits of hormone replacement therapy (HRT) and prescribing it to women in their 60s and beyond. This set the scene for large trials to be set up in the 1990s, looking at the long-term risks and benefits of hormone treatments. The Women’s Health Initiative (WHI) reported for the combined estrogen and progestogen arm in 20021 and the estrogen-only arm in 2004.2 The Million Women Study (MWS) reported in 2003.3 Almost overnight, HRT went from being considered a safe, useful cure for climacteric symptoms to being regarded a risky treatment, to be used only in the most severe cases. When the initial WHI study (combined estrogen/ progestogen vs placebo) reported,1 the popular press picked up on the fact that the study had been stopped prematurely owing to the increased risk of breast cancer. However, for interested doctors this was not surprising, given the previously published evidence.4 They were more concerned about the increased risk of coronary heart disease reported in the study. While the second WHI study (estrogen only)2 and recent reanalysis by age and time since menopause5 have reassured the medical profession about the likely absence of risk of coronary heart disease among women close to the menopause, patients still worry about the risks of cancer, particularly breast cancer. The MWS suggested the risks of breast cancer and hormone therapy were even greater than the WHI had indicated.3 All HRT regimens (estrogen only, combined sequential and continuous combined) were associated with an increased risk. While the overall risks and benefits are not much different to those perceived before 2002, the studies have still had a large effect on the way we treat symptoms now. Confidence in prescribing has been destabilized by the mixed messages. Publications from the WHI5 and the MWS6 in 2007 have provided more analysis of risks and benefits. A subgroup analysis for the WHI suggested a nonsignificant reduction in the risk of coronary heart disease in women aged 50–59 years in the estrogen-only trial; in the combined trial this reduction was seen in women who started HRT within 10 years of the menopause, adding to the theory of a ‘therapeutic window of opportunity’. The latest from the MWS suggests that prolonged use of HRT increases the risk of ovarian cancer by 20%,7 a worrying headline. Little wonder the patient is confused: one week she is being told that HRT is safer than we thought and the next that the risk of ovarian cancer is increased. However, the attributable risk is very low, with only four extra cases per 10,000 HRT users over five years. This is less than the risk from obesity, lack of exercise, nulliparity or smoking. Much of the change in prescribing has been influenced by regulatory and advisory bodies. Regulatory bodies such as the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK have provided advice for prescribing doctors.8 The latest advice confirms that ‘For the majority of women who typically use HRT for the short-term treatment of symptoms of the menopause, the benefits of treatment are considered to outweigh the risks’. Specialist menopause societies around the world, such as the International Menopause Society (IMS), the European Menopause and Andropause Society (EMAS), the North American Menopause Society (NAMS) and the British Menopause Society (BMS), have regularly published and updated their advice to prescribers. Many have provided timely advice and press releases for each newly published article to try to put the new evidence into context and avoid the more extreme reporting.