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P A R T 7
Drugs acting on the reproductive system
metabolism. They are excreted in the urine. Oestrogens
cross the placenta and enter breast milk.
Contraindications and cautions
Oestrogens are contraindicated in the presence of
any known allergies to oestrogens and in people
with idiopathic vaginal bleeding, breast cancer, any
oestrogen-dependent cancer or with a history of
thromboembolic disorders, including cerebrovascu-
lar accident. Heavy smokers are at
increased risk of
thrombus and embolus development
.
Oestrogens are contraindicated during pregnancy
due to the risk of serious fetal defects
and should be
avoided during breastfeeding
because of possible effects
on the neonate.
Oestrogens should be used cautiously
in people with metabolic bone disease
because of the
bone-conserving effect of oestrogen, which could exacer
bate the disease
; with renal insufficiency,
which could
interfere with the renal excretion of the drug and increase
the risk for potential adverse effects on fluid and electro-
lyte balance
; and with hepatic impairment,
which could
alter the metabolism of the drug and increase the risk
for the adverse effects, including those on the liver and
gastrointestinal tract.
Adverse effects
Many of the most common adverse effects associated
with oestrogens involve the genitourinary (GU) tract.
They include breakthrough bleeding, menstrual irregu
larities, dysmenorrhoea, amenorrhoea and changes in
libido. Other effects can result from the systemic effects
of oestrogens, including fluid retention, electrolyte dis-
turbances, headache, dizziness, mental changes, weight
changes and oedema. GI effects are also fairly common
and include nausea, vomiting, abdominal cramps and
bloating and colitis. Potentially serious GI effects,
including acute pancreatitis, cholestatic jaundice and
hepatic adenoma, have been reported with the use of
oestrogens.
Clinically important drug–drug interactions
If oestrogens are given in combination with drugs that
enhance their hepatic metabolism (e.g. barbiturates,
rifampicin, tetracyclines, phenytoin), serum oestrogen
levels may decrease. Whenever a drug is added to or
removed from a drug regimen that contains oestrogens,
the health professional should evaluate that drug for
possible interactions and consult with the prescriber
for appropriate dose adjustments.
Oestrogens have been associated with increased
therapeutic and toxic effects of corticosteroids, so people
taking both drugs should be monitored very closely.
Smoking while taking oestrogens should be strongly
discouraged because the combination with nicotine
increases the risk for development of thrombi and
emboli.
Grapefruit juice can inhibit the metabolism of
oestradiols, leading to increased serum levels. People
should be discouraged from drinking large quantities of
grapefruit juice if they are taking oestrogens. St John’s
wort can affect the metabolism of oestrogens and can
make oestrogen-containing contraceptives less effective.
This combination should be discouraged. Other herbal
and alternative therapies used for menopausal symptoms
may interact with oestrogens.
Progestogens
Progestogens are used as contraceptives, most effectively
in combination with oestrogens (Box 40.3 lists availa-
ble contraceptives). They are used to treat primary and
secondary amenorrhoea and functional uterine bleeding
and as part of fertility programs. Like the oestrogens,
some progestogens are useful in treating specific cancers
with specific receptor-site sensitivity (see Chapter 14).
See Table 40.1 for usual indications for each type of
progestogen.
The progestogens transform the proliferative endo-
metrium into a secretory endometrium, inhibit the
secretion of FSH and LH, prevent follicle maturation
and ovulation, inhibit uterine contractions and may
have some anabolic and oestrogenic effects. When they
are used as contraceptives, the exact mechanism of
action is not known, but it is thought that circulating
progestogens and oestrogens “trick” the hypothalamus
and pituitary, and prevent the release of gonadotropin-
releasing hormone (GnRH), FSH and LH, thus prevent-
ing follicle development and ovulation. The low levels
of these hormones do not produce a lush endometrium
that is receptive to implantation, and if ovulation and
fertilisation were to occur, the chances of implantation
would be remote.
Pharmacokinetics
The progestogens are well absorbed, undergo hepatic
metabolism and are excreted in the urine. They are
known to cross the placenta and to enter breast milk.
Like oestrogens, progestogens are available in several
forms. Etonogestrel, in addition to being available as
a vaginal ring,
NuvaRing,
is available as a subdermal
implant that may be left in place for up to 3 years
and then must be removed. Another implant could
be placed at that time. Levonorgestrel is available in
combination-form oral contraceptives or as an intrauter-
ine device. It is also used for emergency contraception as
the “morning after” pill (
Levonelle, Postinor
).
