And Abuses Of HRT
John STUDD, DSc, MD, FRCOG
Professor of Gynaecology
Until recently it was believed that HRT was an extremely
safe treatment for vasomotor symptoms, osteoporosis, depression
and a major preventative measure for heart disease, colon
cancer, Alzheimer's disease and probably strokes. This has
all been turned upside down by two greatly flawed studies,
The Women's Health Initiative, (WHI) and the Million Women
Study (MWS). These will be discussed.
There is no evidence that oestradiol given in the appropriate
dose in women below the age of 60 is associated with serious
side effects although the addition of continuous progestogen
may be the harmful factor in the causation of cardiovascular
The WHI study studied a single preparation, Prempro (not
available in this country), in the belief that one dose
fits all patients. This is untrue because different women
require different dose via a different route with different
combinations of different hormones for different symptoms
for different symptoms with different surgical status and
for different stages. There was an added fault in that patients
were recruited who were without symptoms - hence none of
them needed this inappropriate therapy anyway.
This lecture will describe the different therapies required
in women after hysterectomy and bilateral salpingo-oophorectomy,
for premature menopause, for the perimenopausal patients
with depression or libido problems, for women in the early
post menopausal state and for older women in the late menopausal
Women with vasomotor symptoms or pelvic atrophy are easily
treated with low dose oestradiol either by the oral route
or by transdermal gel or patch. The treatment can last for
the duration of the symptoms and there is no reason to limit
therapy to 5 or 10 years. In patients with a uterus they
will require endometrial protection with a progestogen which
can be for the orthodox 14 days or continuously or, with
patients with progestogen intolerance for 7 days each month.
Young women with premature ovarian failure need oestrogen
therapy to protect their bones and their cardiovascular
system as well as prevent symptoms until at least the age
of 50 - the time of the normal menopause. If there is a
suggested limit for the duration of HRT then the counting
starts from the age of 50, the age of the normal menopause.
It is important to check the bone density of these patients
before treatment and every 3 years.
After hysterectomy and bilateral salpingo-oophorectomy,
women need oestrogens, sometimes in the higher dose than
for more mild symptoms. If they have lost their ovarian
androgens, they benefit from the addition of testosterone.
These women often suffer symptoms of the female androgen
deficiency syndrome, (FADS) which is loss of energy, loss
of libido and loss of self confidence, depression and headache.
The ideal way to treat these patients is by implantation
of oestradiol 25 mgs and testosterone 75 mgs every 6 months.
Patients with perimenopausal depression which is often linked
with cyclical premenstrual depression are better treated
with transdermal oestrogens in the form of oestradiol patches
100 mcgs or even 200 mcgs. This not only wipes out the cycles
producing the cyclical symptoms of PMS but has a mental
tonic effect for the perimenopausal women. These women of
course require cyclical progestogen tablets but as these
women with hormone responsive depression, (perhaps better
called reproductive depression) are progestogen intolerant,
a Mirena IUS should be considered.
Osteoporosis can usually be prevented by oestradiol therapy
and the bone density can be increased in established osteoporosis
by the use of oestrogens which produce plasma oestradiol
levels of at least 300 pmol/L. This is a most effective
therapy, more effective than bisphosphonates or SERMS but
of course will not correct any deformity that may have occurred
in established osteoporosis.
Many patients have loss of energy and loss of libido and
these respond well to a higher dose of oestradiol with or
without testosterone. Patients should have a clear explanation
of the advantages and the putative dangers of HRT and their
need for HRT assessed every year. The lowest effective dose
should be used for the appropriate symptom or indication
remembering that a higher dose is required for depression
or correction of osteoporosis than for vasomotor symptoms.
There may be an increased risk of breast cancer after 5
or 10 years but these data are disputed and on a practical
level it is very difficult to persuade women who feel well
on HRT to discontinue. Until this issue is clarified, I
believe patients should be advised to have a mammogram every
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