FEMALEREPRODUCTIVEENDOCRINOLOGY 311Treatment with depot progestogeninjections should not be
undertaken without full counselling of the patient.
symptoms require systemic therapy and this usually needs to
be given for at least one year. In women with an intact uterus,
progestogenneeds to be added. Women undergoing an early
natural or surgical menopause, i.e. before the age of 45 years,
have a high risk of osteoporosis and have been shown to
benefit from hormone replacement therapy (HRT) given until
at least the age of 50 years.
There is a small increased risk of breast cancer associated
with the duration of HRT. The risk of breast cancer with com-
bined HRT does not appear to start to increase until four years
after commencing HRT.
HRT users have a slightly increased risk of stroke and pos-
sibly also of myocardial infarction. A woman’s baseline risk
of stroke increases with age and using HRT further increases
this risk.
Taking HRT increases the risk of venous thrombo-embolism
(VTE) particularly in the first year of use, although the single
biggest risk factor for a future episode is a personal history of
VTE. The number of cases of VTE per 1000 non-HRT users over
five years is three, compared to seven in those using combined
HRT over five years in the 50–59 age group and the same fig-
ures are 8 and 17, respectively for the 60–69 year age group.
In women with a uterus, oestrogenis given daily with
additionalprogestogenfor the last 12–14 days of each 28-day
cycle. Oestrogen is subject to first-pass metabolism via the oral
route. Subcutaneous and transdermal routes of administra-
tion are available and may be suitable for certain women.
Subcutaneous implants can cause rebound vasomotor symp-
toms, as abnormally high plasma concentrations may occur.
Hormone replacement therapy does not provide contra-
ception and a woman is considered potentially fertile for two
years after her last menstrual period if she is under 50 years of
age, and for one year if she is over 50 years.
Women under 50 years without any of the risk factors for
venous or arterial disease may use a low-oestrogen combined
oral contraceptive pill to gain both relief of menopausal symp-
toms and contraception.Contraindications
Pregnancy, oestrogen-dependent cancers, active thrombo-
embolic disease, liver disease, undiagnosed vaginal bleeding
and breast-feeding.
The relative contraindications include migraine, history of
breast nodules and fibrocystic disease, pre-existing uterine
fibroids, endometriosis, risk factors for thrombo-embolic
disease.
Although caution is recommended in certain other condi-
tions, such as hypertension, cardiac or renal disease, diabetes,
asthma, epilepsy, melanoma, otosclerosis and multiple scler-
osis, there is unsatisfactory evidence to support this, and
many women with these conditions may benefit from HRT.Side effects of HRT
These include nausea and vomiting, weight changes, breast
enlargement and tenderness, premenstrual-like syndrome, fluid
retention, changes in liver function, depression and headache,
altered blood lipids, venous thrombo-embolism.Key points
Progestogen-only contraceptive – absolute
contraindications- pregnancy;
- undiagnosed vaginal bleeding;
- severe arterial disease;
- liver adenoma;
- porphyria.
Adverse effects
The main problems are irregular menstrual bleeding (which
can be heavy, but usually settles down after a few cycles), occa-
sionally breast tenderness and uncommonly nausea, headache,
appetite disturbance, weight changes and altered libido.
Contraindications
These include pregnancy, undiagnosed vaginal bleeding,
severe arterial disease, liver adenoma and porphyria.
ANTI-PROGESTOGENS
Mifepristoneis a competitive antagonist of progesterone. It is
used as a medical alternative to surgical termination of early
pregnancy (currently up to 63 days’ gestation, although it is
also effective during the second trimester). A single oral dose
ofmifepristoneis followed by gemeprost(a prostaglandin
that ripens and softens the cervix), as a vaginal pessary unless
abortion is already complete. Gemeprostcan cause hypoten-
sion, so the blood pressure must be monitored for six hours
after the drug has been administered. The patient is followed
up at 8–12 days and surgical termination is essential if com-
plete abortion has not occurred. Contraindications include
ectopic pregnancy.
HORMONE REPLACEMENT THERAPYUses and risk–benefit profile
Small doses of oestrogenhave been shown to alleviate the
vasomotor symptoms of the menopause, such as flushing, as
well as menopausal vaginitis caused by oestrogen deficiency.
There is now reliable evidence that giving doses of oestrogen
for several years, starting at around the time of the menopause,
reduces the degree of post-menopausal osteoporosis, but
increases the risk of VTE and stroke. There is an increased risk
of endometrial carcinoma after several years of use which can
be countered by progestogen. In the main, the minimum effect-
ive dose should be used for the shortest duration.
For vaginal atrophy, oestrogencan be given as a local top-
ical preparation for a few weeks at a time, repeated as neces-
sary. However, the periods of treatment need to be limited, as
again there is a risk of endometrial carcinoma. Vasomotor