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.