19 April 2007
The Medicines and Healthcare products Regulatory Agency (MHRA) is aware of the new data for the safety of hormone replacement therapy (HRT) from the Women’s Health Initiative trial and the Million Women Study. Both these publications will be included in the comprehensive review that was already scheduled by the Commission on Human Medicines’ Expert Advisory Group on Medicines for Women’s Health (MWHEAG) at their meeting in July. After preliminary review of these publications, the MWHEAG concluded that these findings do not require any urgent changes to the current advice or to the timing of the planned July review.
Advice for prescribers and women remains that HRT is an effective therapy for the short-term relief of menopausal symptoms in the majority of women, but that the minimum effective dose should be used for the shortest duration. Because of the associated risks, HRT is not the first treatment of choice for the long-term prevention of osteoporosis in women over the age of 50.
All women who wish to start HRT should discuss the risks and benefits of treatment with their doctor. The decision to start, continue or stop treatment should be made jointly by a woman and her doctor, based on the best advice available and her own personal circumstances. Women on HRT should have regular health check-ups, and the need to continue HRT should be re-assessed at least annually
Any woman on HRT who is concerned should discuss the need to continue treatment with her doctor.
Million Women Study (MWS) and ovarian cancer – Lancet article (19 April, 2007)
The results of this study confirm that the use of oestrogen-only HRT for more than 5 years is associated with an increase in the risk of ovarian cancer. A warning about this risk is already provided in the information for prescribers and women. Use of oestrogen-only HRT for less than 5 years did not appear to increase this risk.
This study has provided new data about the risk of ovarian cancer associated with the use of combined (oestrogen plus progestogen) HRT. This type of HRT was similarly found to be associated with a small increase in the risk of ovarian cancer after 5 or more years of use.
HRT users were more likely to die from ovarian cancer than were never-users. Importantly, past users of HRT were not at an increased risk of developing or dying from ovarian cancer.
Women’s Health Initiative (WHI) trial and cardiovascular disease – JAMA article (4 April, 2007)
HRT has never been authorised for the prevention of heart disease. Product information currently states that there is no evidence of benefit to the heart, and that there is a possible increased risk of cardiovascular disease in the first year of use. However, since much of these data relate to the use of conjugated equine oestrogen plus medroxyprogesterone in 2 large trials, it is uncertain whether these findings also apply to other HRT products.
The latest publication from the WHI trial examined whether the risk of coronary heart disease (CHD) and stroke varies by age or time since menopause, or both. The results of this re-analysis, although inconclusive, suggest that the risk of CHD may increase with time since menopause—with no apparent increase for women closest to the menopause, and with increased risks for women further from the menopause. No women with a reduced risk of CHD were identified, although overall mortality was reduced among women aged 50–59 years.
The risk of stroke did not vary with age or time since menopause, but remained elevated in all women.
Current MHRA/Commission on Human Medicines (CHM) position
In December 2003, the Chairman of CHM (Professor Sir Gordon Duff) wrote to healthcare professionals in the UK to inform them of the findings of a review of the balance of risks and benefits of HRT in its licensed indications, which was initiated in response to growing safety concerns. Prof Duff explained that the WHI and MWS “and previous studies provide good evidence that use of HRT increases the risk of breast cancer, endometrial cancer and ovarian cancer in a duration-dependent manner. There is no evidence for a beneficial effect of HRT on cardiovascular disease – in fact HRT has been shown to increase the risk of myocardial infarction and VTE, especially in the first year of use, and to increase the risk of ischaemic stroke. The risk of most of these conditions increases with age, therefore increasing the overall risks the longer HRT is taken”.
The review also concluded that:
- for the treatment of menopausal symptoms, HRT is beneficial for the majority of women in the short-term;
- when used in the long-term the balance of risks and benefits of HRT is such that it should be restricted to second-line therapy for the prevention of osteoporosis.
The decision to use HRT should take into consideration a woman’s age, history, risk factors and personal preferences, and for all women the minimum effective dose should be used for the shortest duration. Continued use of HRT should be regularly re-assessed (eg, at least annually).
Current advice for women and prescribers
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. For long-term use women should be made aware of the increased incidence of adverse effects.
HRT should not be considered the first treatment choice for the long-term prevention of osteoporosis in women who are over 50 years of age and at an increased risk of fractures. However, HRT remains an option for those who are intolerant of, or do not respond to, other osteoporosis-prevention therapies. In such cases, the individual balance of risks and benefit should be assessed carefully.
In younger women who have experienced a premature menopause (due to ovarian failure, surgery or other causes) HRT may be used for treatment of menopausal symptoms and for prevention of osteoporosis until the age of 50 years. After this age, therapy for prevention of osteoporosis should be reviewed and HRT considered a second choice.