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CSM advice
The Committee on Safety of Medicines says that in
healthy women without symptoms, the risk:benefit of HRT is generally
unfavourable,
as is first-line HRT use for osteoporosis prevention. However,
it maintains that the risk benefit of HRT is favourable for the
treatment of menopausal symptoms at the “minimum effective
dose for the shortest duration”. |
More confusion over hormone replacement therapy is likely to arise after
experts criticised a major study which found no benefits for HRT in preventing
cardiovascular disease.
The US Women’s Health Initiative was originally designed to test
observed evidence that HRT could improve cardiovascular and other risks
in postmenopausal women. However, the trial was stopped early — in
July 2002 — because of increases in stroke and cardiovascular disease
found among
participants.
Study design flawed
Latest results from WHI address questions on dementia
More negative and neutral findings from the
WHI have just been released. Unopposed oestrogen slightly increased
the risk of developing
dementia and failed to prevent cognitive decline. This arm of the
trial (the memory study) involved almost 3,000 postmenopausal women
aged 65–79 years. The WHI had already reported similar results
with oestrogen plus medroxyprogesterone.
Additional results from the memory study indicate that oestrogen
HRT has an adverse effect on overall cognition as measured by recall,
verbal fluency, reasoning and other factors. Again, a commentator
suggests that the trialists may have intervened too late and looked
for dementia too early at around age 75 years (JAMA 2004;291:2959). |
Now scientists led by Frederick Naftolin, Yale University, New Haven,
Connecticut, propose that the study was flawed. Their criticisms relate
to the study population — over 16,000 generally healthy postmenopausal
women aged 50–79 years.
They say that the cardiovascular benefits of HRT affect women whose
oestrogen levels have just started to fall, ie, those entering the
menopause. They
suggest that most of the participants in the WHI trial were studied years
after the menopause when damage had already been done and could not be
reversed by oestrogen (Fertility and Sterility 2004;81:1498).
The critics say that the WHI recruited only 574 women aged 50–54
years, who had symptoms of recent oestrogen deficiency. This made the
study underpowered to detect a clinical change in their cardiovascular
events. They call for new trials to determine cardioprotection of HRT
during menopausal
transition.
The trial in question used oestrogen plus medroxyprogesterone. The authors
say that their criticisms also apply to unopposed oestrogen given to
women with hysterectomy, in light of other WHI results published earlier
this year. This arm of the study was also stopped early, in May.
British Menopause Society spokesman John Stevenson thinks that dose may
have affected the study findings. He commented that older women were
known to be more sensitive to the effects of oestrogen and required lower
doses than younger women. However, Dr Stevenson, who is consultant metabolic
physician, Royal Brompton Hospital, London, does not believe that the
WHI findings should have an impact on prescribing. “Prevention
of cardiovascular and other disease is not currently a licensed indication
for HRT,” he comments.
He advises doctors to carry on using the treatment for the relief of
menopausal symptoms and for cost-effective prevention of
osteoporosis.
Nuttan Tanna, who runs a menopause and osteoporosis medication management
clinic at Northwick Park Hospital, Middlesex, is pleased that criticisms
have raised awareness of “unanswered questions” from the
WHI study.
She says that menopausal women suffering from vasomotor symptoms and
for whom individual risk-benefit ratios favoured HRT use had stopped
treatment due to adverse media publicity on HRT as a result of recent
trials, namely the WHI and the UK million women study. (The million women
study found a doubling of breast cancer risk with combined HRT but was widely accepted to be flawed [PJ,
16 August 2003, p199].)
“What is important is that the scientific community realises the
need for further research on HRT, especially for any cardiovascular protection
and also to answer questions on optimal duration of HRT use,” she
comments.
She explains that the trial used a global weighted safety index to assess
response. “Perhaps this wasn’t set at the right level,” Dr
Tanna says, adding that certain subgroups may have shown different outcomes.
Dr Tanna and other pharmacists all over the UK are facing patients with
questions about the efficacy of HRT. According to Dr Tanna, the four
groups of women who should still consider HRT are as follows:
· Women who have gone through an early menopause should consider HRT
to the age of 50 years to prevent osteoporosis
· Women going through the menopause with vasomotor symptoms affecting
quality of life
· Women at increased risk for osteoporosis (HRT may be the optimal treatment
choice during the early menopause stage, with other options such as SERMs
[selective estrogen receptor modulators] and bisphosphonates held in
reserve for later use)
· Postmenopausal women with osteoporosis who are having difficulty in
taking other treatments (specialist opinion should be sought in complex
cases)
Individualised risk-benefit evaluation
Dr Tanna says that each woman going through the menopause needs to
have an individualised risk-benefit evaluation to help her make an informed
decision on whether to take HRT or not.
The risk of breast cancer with long-term HRT use needs to be considered
in context. She adds that women choosing HRT should be reviewed regularly,
especially in view of changes in evidence.
Parts of the WHI study are ongoing. A dietary arm is looking at the
impact of low fat, high fibre food and an observational group aims
to detect
the effect of lifestyle factors such as alcohol intake, smoking and
exercise on disease.
Dr Tanna says that a healthy lifestyle is integral to holistic menopause
and osteoporosis patient management, in addition to prescribed treatment.
All health professionals, including pharmacists, have a role in improving
public health. For well-being during the menopause women need a healthy
balanced diet, smoking cessation advice, reduced alcohol intake, stress
relief and regular exercise, she adds.
In the light of this confusion, whether or not a woman opts for HRT
will, therefore, remain a highly personal decision for the forseeable
future.
Pharmacists can help ensure that a woman makes that decision only when
she really understands what the evidence is.
Article, p59 (PDF 60K) |
The
Pharmaceutical Journal