Risks of HRT

Venous thromboembolism (blood clots)
From the Womens Health Initiative (WHI) trial, venous thromboembolism (blood clots) occurred in 1.7 per 1000 women aged over the age of 50, not taking HRT. This risk  doubled in those taking HRT to 3.4 per /1000,. This risk is still small and reassuringly, for women aged 50-59 who were of normal weight, the chances of a blood clot occuring in the HRT group was the same as in those on placebo (not HRT). The greatest risk of a blood clot occurring is within the first year of HRT use and is more likely to happen in women who have other risk factors, including previous or family history of blood clot, obesity, immobility or underlying blood clotting problem. It is possible that transdermal estrogen (patch or gel) and lower doses of oral estrogen may not carry the same risk.

Breast Cancer
Long term HRT use (more than 5 years after the age of 50) is thought to result in a small increased risk of breast cancer. From both the WHI trial and Million Women study, estrogen only HRT carries less of a  risk than estrogen combined with progestogen. The WHI trial demonstrated no increased risk with estrogen only taken for up to 7 years, and  in fact reassuringly  demonstrated a decrease. In women taking combined HRT  an extra 3-4 cases of breast cancer /1000 women  were seen after 5 years of use from aged 50. However the increased risk in the combined HRT group in fact only occurred in the women who had taken HRT before the trial and then taken it for the duration of the trial, suggesting that more than 5years of combined HRT is needed before there may be any increase. Further, 5 years after stopping HRT, the risk returns to normal. It is possible that women who develop breast cancer while taking HRT may actually have a lower risk of dying from the disease than those who develop breast cancer when not taking HRT. To keep this concern about breast cancer in perspective, it should be noted that, postmenopausal obesity or 2 units of alcohol per day cause a greater risk of breast cancer than 5 years of HRT use!.

Ovarian cancer
The WHI trial showed no increased risk of ovarian cancer with HRT, but the Million Women study recently reported an increased risk of 20% in users of HRT for 5 years. In fact the actual risk was said to be 1 extra case per 2,500 women using HRT for 5 years. Even if conclusions can be drawn from this controversial study, the risk is small and it is unlikely that this information should significantly influence use of HRT.

Stroke
Both estrogen only and combined HRT were associated with a small increased risk of stroke in the WHI trial- in women aged 50 to 59 not taking HRT, stroke occurred in 3 per 1000 women over 5 years with 5 years of HRT use  associated with 1 additional case. A more recent study reported from Sweden of almost 17,000 women aged 45 to 73 years, showed no significant association between HRT use and risk of stroke. Of the HRT users who did have a stroke, the risk was associated with advancing age, smoking, obesity and hypertension. Therefore in the absence of other risk factors, the risk of stroke from HRT is extremely small and in fact there is some evidence that lower doses of estrogen than were used in the WHI trial can reduce the risk of stroke compared with women not on HRT.

Risk or benefit?

Heart disease
For many years, HRT was thought to reduce the risk of coronary artery disease. However, the WHI trial has shown early, small increased risks in cardiovascular events, but this increase was only significant in the women who were 20 or more years post menopause, (ie 70+). Reassuringly women who were less than 10 years postmenopausal when starting HRT, showed no increased risk. The results may actually show that HRT reduces the risk of a cardiovascular event in this group of women.

The results also suggest that the dose, type, route and timing of HRT have different effects on the cardiovascular system. If HRT is started early in the menopause when there is no or minimal coronary disease there is unlikely to be any harmful effects whereas once disease of the arteries has developed, commencing HRT may cause further damage.

In summary therefore it is therefore very unlikely that HRT used for women in the early menopause for control of menopausal symptoms will be harmful for the heart and may still yet be shown to be beneficial if started early enough.

Alzheimer’s disease
Some studies show a reduction in risk in HRT users but the WHI showed an increased risk only in older women. Recent analysis from the Women’s Health Initiative Memory Study in fact showed for women who took HRT before the age of 65, there was a reduced risk of all-cause dementia of 46% and a reduced risk of Alzheimer’s disease of 64%.

A major difference between trials such as the WHI trial and the observational studies of the 1980’s and 1990’s   which have often shown a reduced risk of both heart disease and dementia with HRT, is that in the WHI trial, women commenced HRT many years after the menopause, (on average, the women were 12 years post menopause with the age range being 50 to 79 years and only 10% were in the early menopausal years), whereas in observational studies, HRT has generally been commenced early in the menopausal years to control menopausal symptoms. It has been proposed that there is a “window of opportunity” whereby, if HRT is commenced early enough, it may be beneficial not only for control of symptoms and prevention of osteoporosis, but also for prevention of heart disease and dementia. This debate continues!

Benefits of HRT
The main reason for using HRT continues to be for control of menopausal symptoms These symptoms are likely to affect about 70% of menopausal women and for many, no other currently available products, either prescribed or “over the counter” will be as effective as HRT.
HRT is beneficial for preventing osteoporosis by its effect on bone resorption, bowel calcium absorption and renal calcium re-absorption. Although it is not currently recommended as first line treatment of osteoporosis, it still has an important role for women with premature menopause and those with risk factors for osteoporosis who also have menopausal symptoms.
It seems likely that when used within the first 10 years of the menopause, HRT is beneficial for the heart but currently it should not be used with this as the main indication; further trial results are awaited.
Other possible benefits include reduced risk of colon cancer, improved dentition, improved skin healing and reduced wrinkles, reduced macular degeneration and reduced cataract formation but these are all controversial.

The benefits and risks of HRT are influenced by age, duration of therapy, medical history, family history and severity of symptoms. These factors vary between women, and even for each woman will change with time and with development of other medical problems. Treatment has to be individualised and has to be reviewed annually.
Generally, for women with menopause age of less than 50 years, the benefits of HRT for both symptom control and long term health, far outweigh the risks. For women aged between 50 and 60 years who have menopausal symptoms, the benefits of HRT outweigh the risks. For women aged 60 to 70 years, the benefits roughly equal risks and management should be individualised, and for women aged more than 70 years, the risks are likely to outweigh the benefits. However, even with the older women, if symptoms are significant and unresponsive to other therapies, HRT can still be considered as long as an informed choice is made.

Overall, HRT still has an important role in menopause management and when used appropriately and reviewed, the benefits outweigh the risks for by far the majority of users.