The risk/benefit balance of HRT varies between women, and for each individual woman, from year to year, depending on presence or not of symptoms, other medical history and the number of years that HRT has been taken.
Generally, if you become menopausal early (before age 45) or prematurely, POI, (before age 40), the benefits of taking HRT up to at least age 50 far outweigh the risks. If you are under 60 and having menopausal symptoms, or have risk for osteoporosis, the benefits also outweigh the risks.
There are no arbitrary limits as to how long HRT can be taken, it is up to each woman to balance the risks against the benefits for her, at each annual review.
Some women may not need HRT at all, or may take it for a few years only, while others continue to take HRT for many years since it continues to provide significant benefits for them.
Every woman should be supported to make an informed choice about their use of HRT and for how long they take it.
Currently the evidence we have is:
Proven benefits of for all women HRT: (see the BMS HRT guide)
- It is the most effective treatment for the relief of menopausal symptoms
- Improved bone mineral density with reduced fracture risk while it is being taken
Additional potential benefits of HRT:
- Reduced risk of coronary heart disease when oestrogen is started early (within 10 years of menopause)
- Reduced risk of Alzheimers disease when oestrogen started early (more research is needed to confirm this)
- Reduced risk colorectal cancer
- Reduced risk Type 2 DM (diabetes mellitus)
Risks of HRT:
For the majority of women who use HRT under the age of 60, and for many beyond that age, the benefits of HRT outweigh any risks.
Risks associated with HRT include association with increased risks of breast cancer (with long duration HRT), blood clot and, if HRT is started many years after the menopause, possibly cardiovascular disease.
Cardiovascular disease:
- Studies show that when initiated below age 60 years or within 10 years of onset of menopause HRT reduces atherosclerosis progression and coronary events.
- This article from the BMS about HRT after myocardial infarction may be of interest in women with cardiovascular disease.
- Taking an oral tablet of oestrogen is associated with a small increase in risk of stroke. The risk of stroke in women under 60 years is very low, so the increased risk is small (1 extra woman per 1000 using HRT).
Blood clot / venous thromboembolism
- Taking an oral tablet of oestrogen causes a small increase in risk of blood clot.
- If there is a past or family history of blood clot or an inherited thrombophilia, appropriate investigations may be needed before prescribing HRT
- For some women, who are at risk of blood clot, including those with a body mass index above 30, the pros and cons of use of HRT should be discussed, and if using HRT, taking it as a transdermal oestrogen like a gel, spray or patch with a progestogen with low clot risk should be considered, since there is strong evidence that transdermal estrogen does not increase risk of blood clot in healthy women using moderate doses of oestrogen.
Type 2 Diabetes
- There is no increased risk of developing type 2 diabetes with any type of HRT.
Breast cancer
- The risk of breast cancer for women around menopausal age varies, and is affected by her family history and her lifestyle risk factors (weight, alcohol intake, smoking and exercise). Any woman in the UK has a 1 in 7 chance of developing breast cancer over the course of her lifetime, this is also known as the ‘baseline’ risk.
How does HRT affect risk? Evidence from studies varies.
NICE guidance states that:
- HRT with oestrogen alone is associated with little or no increase in the risk of breast cancer.
- HRT with oestrogen and progestogen can be associated with an increase in the risk of breast cancer; however, any increase in the risk of breast cancer is related to the length of time HRT is taken for, and it reduces after stopping HRT.
This is a summary of current evidence, if you would like more detail:
- Current opinion is that HRT taken for less than 5 years does not significantly increase the risk of breast cancer.
- Studies have shown that after 5 years of HRT use, there is an association with a small increased risk, but once HRT has been stopped, the risk returns back to baseline.
- It seems likely that different types of HRT are associated with different risk: oestrogen appears to increase the risk very little, while there appears to be a small increased risk of cancer promotion with long term use of oestrogen combined with progestogen (combined HRT).
- The progesterone component of HRT that is considered the most ‘breast-friendly’ according to the evidence, is micronised progesterone.
- Lifestyle factors play a role in cancer risk, this link takes you to a chart which is very helpful to show the comparison of lifestyle risk factors vs taking HRT
- If HRT is started at a young age because of premature ovarian insufficiency, POI, then the use of HRT up to the age of 50 is unlikely to 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.
- This link can help you understand risk and benefit further, you can individualise it by adjusting the bars on the left: Wellsprings
- This pictogram of risk of HRT and lifestyle is helpful
- The studies to consider, if you would like more detailed information are NICE guidance, which was based upon a review of studies meeting grade criteria, (the largest RCT, randomised control study, in this group being the Women’s health Initiative study, the WHI study); a meta-analysis of all available epidemiologic evidence on the association between HRT use and breast cancer risk was published in the Lancet in August 2019 and the E3N observational studies.
- WHI study: This study suggested that if 1000 women used HRT for 5 years, there would be 4 extra cases of breast cancer with combined HRT use, and 4 fewer cases with oestrogen-only use, on a baseline risk of 15 cases per 1000 women over 5 years. Women who had not used HRT prior to the study showed no increase in breast cancer with combined HRT for 5 years, but a higher risk than never users with over 5 years of treatment.
- The Lancet meta-analysis stated that: for women of average weight, 5 years of HRT use starting at age 50 years would increase their 20-year risk of breast cancer (between the ages of 50 and 69 years) by approximately:
- 1 in every 50 users of oestrogen plus daily progestogen.
- 1 in every 70 users of oestrogen plus intermittent progestogen.
- 1 in every 200 users of oestrogen-only regimens.
- E3N observational studies which found no increased risk of breast cancer over five years with the use of oestradiol and micronised progesterone.
- There is still no evidence of any increase in dying from breast cancer, in women taking HRT.
Ovarian cancer
- There continues to be uncertainty about the possibility of increased risk of ovarian cancer with use of HRT. With 5 years of HRT use, there could be 1 additional ovarian cancer per 1000 users and 1 additional death per 1700 women who use HRT.
Dementia
- More studies are needed in this area. Current evidence suggests that HRT is unlikely to increase the risk of dementia or to have a detrimental effect on cognitive function in women initiating HRT before the age of 65.
Endometrial cancer
- Oestrogen only therapy given to women with a uterus (womb) increases the risk of endometrial hyperplasia (thickening of the lining of the uterus) and eventually endometrial cancer.
- Daily oestrogen combined with progestogen given usually for 14 days per month, giving a monthly bleed is called sequential sHRT. Taking progestogen cyclically in sHRT reduces the risk of endometrial cancer but does not eliminate it. If you are taking sequential combined HRT at the age of 45 or above, within 5 years of taking it this way we would change the way you take HRT to a continuous combined ccHRT. This means you would take you progestogen daily, not cyclically. If you have a 52mg LNG IUD like a Mirena this is like continuous combined HRT. Sequential combined HRT, given for more than 5 years, does increase the risk of endometrial cancer by a small amount. No increased risk appears to apply to oestrogen combined with daily progestogen (continuous combined or period-free HRT).
- It is important to report any unscheduled bleeding on HRT to your Dr.
- It is important that your oestrogen and progestogen dose is balanced, you Dr will look at your risk factors for endometrial cancer and your dose of oestrogen in your HRT when deciding what dose of progestogen to prescribe.
- It is important to take your progestogen as prescribed.
There are medical conditions which can be affected by hormonal change and HRT such as migraine, epilepsy and thyroid disease. Please discuss this with your Dr when you are considering HRT so the safest and correct preparation is prescribed to you.
If you have any questions about benefit and risk please talk with us.
Dr Carys Sonnenberg Rowena Health – this information is provided to you, to the best of our knowledge using links to trusted sources to help you understand the current evidence. There is of course a great deal of information, and risk and benefit of any medication is individual to you, and must be discussed with your prescribing Dr, who has responsibility for your care and knows your medical history. For our patients we will individualise the advice given – July 2024
Other websites to refer to:
Women’s health concern fact sheets
British Menopause Society tools for clinicians – at Rowena Health we support GP’s in their learning, this link takes you to articles which will support the education of your GP
International Menopause Society advice for women
Dr Carys Sonnenberg ,written for patients at Rowena Health Menopause Clinic July 2024. This information should be discussed with your prescribing doctor to take into account your individual medical history and should only be regarded as guidance for discussion.
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