- Risks of HRT
Risks associated with HRT include increased risks of breast cancer (with long duration HRT), blood clot and possibly cardiovascular disease. For many women, the benefits outweigh the risks, but for some, alternative treatments for either symptom control or osteoporosis prevention/treatment may be recommended.
- Breast Cancer
Current opinion is that HRT taken for less than 5 years does not significantly increase the risk of breast cancer but studies have shown that after 5 years of use, there is an association with a small increased risk.
Figures produced by Collaberative Group [Ref 1] on Hormonal Factors in Breast Cancer (1997)
Years of HRT No. of cases of breast cancer / 1000 women aged 50-70 No. of extra cases / 1000 women 0 45 0 More than 5 47 2 More than 10 51 6 More than 15 57 12
It is becoming more likely that different types of HRT are associated with different risk. Several studies, including the recently published Million Women study [Ref 9] have shown that estrogen combined with progestogen may have greater risk than estrogen alone but whether giving progestogen cyclically or continuously affects risk is uncertain. It is still recommended to give progestogen along with estrogen if the uterus is intact to reduce the known risk of endometrial cancer (cancer of the lining of the womb), but it is not usually necessary to give progestogen after a hysterectomy.
The Women's Health Initiative trial initially reported an increased risk of breast cancer for those on combined HRT (estrogen plus progestogen), HRT accounting for an extra 3 to 4 cases of breast cancer per 1,000 women taking combined HRT for 5 years after the age of 50. Those taking estrogen only HRT had no increased risk compared to women taking placebo (an inactive tablet). However, final analysis of the information showed that even for those women taking combined HRT, the increased risk only applied to women who had taken HRT for more than 5 years before the trial as well as during the 5 years of the trial, so was only associated with very long duration of use of HRT.
Source of data Extra cases/1,000 women for 5 years HRT Collaborative group 1997 + 2 Million Women study - estrogen only +1.5 Million Women study - estrogen + progestogen +6 Women’s Health Initiative trial - estrogen only 0 Women’s Health Initiative trial - estrogen + progestogen +4 but only in women who had taken HRT for more than 5 years before the trial
If HRT is commenced at a young age because of premature menopause, e.g. after hysterectomy, then the use of HRT up to the age of 50 does not increase breast cancer risk any more than in women who continue to have periods up to the age of 50. Additional risk from HRT only applies if it is then taken for more than 5 years after 50.
After 5 years from stopping HRT, the breast cancer risk returns to baseline. Comparing other known risk factors for breast cancer with HRT risk can be helpful in putting risk into perspective:
- more than 2-3 units of alcohol per day increases risk by 1.5x,
- postmenopausal obesity by 1.6x,
- late first pregnancy ( more than age 30) by 1.9x
- more than 5 years of HRT by 1.35x.
- for a downloadable diagram showing the relative risks of breast cancer with HRT, alcohol and obesity -
Interactive version with weblinks: PDF (677kb)
Print only version: PDF (634kb)
- Clotting Problems - Venous thromboembolism (VTE)
- HRT has been shown to cause a small increase in risk of blood clot [Ref 2] (e.g. deep vein thrombosis) from a baseline risk of 1 in 10,000 women per year. From the WHI trial, venous thrombosis occurred in 1.7 per 1,000 women aged more than 50, not taking HRT and this was doubled in those taking HRT but the risk was still small. When age groups and weight were examined further, women of normal weight aged 50 – 59 taking HRT had a similar risk to those taking placebo (inactive tablet). The greatest risk is within the 1st year of use and is most relevant to women who have other risk factors. If there is a past or family history of blood clot, appropriate investigations may be carried out and fully discussed. For some who are particularly at risk of blood clot, it may be advisable to avoid using HRT or, if there are very good reasons for using HRT, a non-oral preparation should be considered, since there is some evidence that transdermal estrogen may not confer the same increased risk [ref 22].
- Cardio-vascular disease
- For many years, it was thought, from the results of observational studies, that HRT significantly reduced the risk of heart disease and stroke. However, recent (1998) studies such as HERS [Ref 8] and the WHI study suggested that certain types of HRT may lead to a small increased risk of heart attack and stroke. However, final analysis of the WHI trial showed that there was no increased risk with estrogen only and in fact there was a reduction in heart disease compared to placebo (inactive tablet). For women taking combined HRT, there was an increased risk only in women who were 20 or more years post menopausal, and the increase was in the 1st year of use with no overall increase by the end of the trial. The dose, type and route of HRT used are important in cardiovascular effect, as is the timing of commencement of therapy; more studies recently demonstrating a reduced risk of heart disease in women commencing HRT near the time of the menopause. HRT should not currently be taken for presumed cardiovascular benefit [Ref 4] but HRT used in the early menopausal years for control of menopausal symptoms is very unlikely to be harmful to the heart and may yet prove to be beneficial. It is very likely that there is a “window of opportunity” whereby, if HRT is commenced early, it may be beneficial not only for control of symptoms and prevention of osteoporosis, but also prevention of heart disease but if commenced later when disease of the blood vessels has developed, further damage may occur. HRT should therefore only be taken by women who have, or are at risk of cardiovascular disease, if there are very good indications and after full discussion.
- Endometrial Cancer
Estrogen only therapy given to women with an intact uterus increases the risk of endometrial hyperplasia (thickening of the lining of the uterus) and eventually endometrial cancer. Daily estrogen combined with progestogen given for 10 to 14 days per month (sequential HRT) reduces this risk but does not eliminate it. Sequential HRT given for more than 5 years does increase the risk of endometrial cancer by a small amount but no increased risk appears to apply to estrogen combined with daily progestogen (continuous combined or period-free HRT).
bibliography reference [Ref 3]
- Ovarian Cancer
There continues to be uncertainty about the possibility of increased risk of ovarian cancer with use of HRT. Many studies have given inconclusive results, the Women's Health Initiative trial showed no increase in users of HRT, yet the million Women study suggested an increased risk. This increase was of the order of 1 extra case for every 2,500 women taking HRT for 5 years and so if there is an association, this risk is very small.
See news item here.
Contraindications for HRT.
- Undiagnosed abnormal vaginal bleeding
- Active or recent blood clot or myocardial infarction (heart attack)
- Suspected or active breast or endometrial (womb) cancer
- Active liver disease with abnormal liver function tests
- Porphyria cutanea tarda
See also: Balancing the risks and benefits.
Page last updated: 6 December 2011