Monograph: |
Conjugated Oestrogens
Conjugated Estrogens.
A mixture of sodium oestrone sulphate and sodium equilin
sulphate, derived wholly or in part from equine urine or syn-
thetically from oestrone and equilin. It contains other oestro-
genic substances of the type excreted by pregnant mares. The
USP substance contains 52.5 to 61.5% of sodium oestrone
sulphate and 22.5 to 30.5% of sodium equilin sulphate: the
total of the two combined should comprise not less than
79.5% of the labelled content of conjugated oestrogens. The
USP also states that it should contain, as sulphate conjugates,
13.5 to 19.5% of 17a-dihydroequilin, 2.5 to 9.5% of 17-alpha
oestradiol, and 0.5 to 4.0% of 17p-dihydroequilin, relative to
the labelled content of conjugated oestrogens.
If it is obtained from natural sources it is a buff-coloured
amorphous powder which is odourless or has a slight charac-
teristic odour: the synthetic form is a' while to light buff-col-
oured crystalline or amorphous powder, odourless or with a
slight odour. Store in airtight containers.
Adverse Effects and Precautions
As for oestrogens in general
Effects on the cardiovascular system: Treatment of men
with a previous myocardial infarction with conjugated oestro-
gens 5 mg daily in the USA Coronary Drug Project was
discontinued because of a higher incidence of subsequent cor-
onary events.' Moreover, treatment with the lower 2.5 mg
dose was later also discontinued because of suggestions of
adverse trends including a greater incidence of venous
thrombo-embolism.' However, observational studies of
menopausal hormone replacement therapy indicate that in
postmenopausal women there is a reduction in risk of coro-
nary heart disease.
Effects on the gallbladder. Analysis of data obtained dur-
ing the Coronary Drug Project indicated a significant increase
in the development of gallbladder disease among men treated
with conjugated oestrogens 2.5 and 5 mg daily, compared
with those treated with placebo.
Effects on the nervous system. Reversible chorea devel-
oped in a 57-year-old woman receiving conjugated oestro-
gens and norgestrel; the woman had a history of migraine
and Sydenham's chorea.
Hypersensitivity. A report of an anaphylactic reaction fol-
lowing the intravenous administration of conjugated oestro-
gens.
Pharmacokinetics
Orally administered conjugated oestrogens are hy-
drolysed by enzymes present in the intestine that re-
move the sulphate group and allow absorption of the
unconjugated oestrogen. Metabolism occurs prima-
rily in the liver: there is some enterohepatic recy-
cling.
Uses and Administration
Conjugated oestrogens have actions and uses similar
to those described for oestradiol.
When used as menopausal hormone replacement
therapy doses of 0.3 to 1.25 mg daily are
given by mouth either cyclically or continuously, in
conjunction with a progestogen either cyclically or
continuously in women with a uterus. Topical vagi-
nal therapy may be used specifically for menopausal
atrophic vaginitis; 0.5 to 2 g of a 0.0625% cream
may be employed daily for 3 weeks of a 4-week cy-
cle. If used long-term in a woman with a uterus, cy-
clical progestogen is required.
Doses of 1.25 mg daily by mouth are used as re-
placement therapy for primary ovarian failure and
doses of 2.5 to 7.5 mg daily administered on a cycli-
cal basis are used for female hypogonadism.
For the palliative treatment of prostatic carcinoma
(p.491), a dose of 1.25 lo 2.5 mg three times daily
has been employed. A dose of 10 mg three limes
daily for at least 3 months has been used for pallia-
tive treatment of breast carcinoma in postmenopau-
sal women.
Abnormal uterine bleeding has been treated acutely
by giving 25 mg of conjugated oestrogens by slow
intravenous injection, repeated if required after 6 to
12 hours; the intramuscular route has also been
used.
Haemorrhagic disorders. Some references lo the use of
high-dose intravenous or oral conjugated oestrogens in the
management of haemorrhagic disorders.
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