A Textbook of Clinical Pharmacology and Therapeutics

312 REPRODUCTIVE ENDOCRINOLOGY

Oestrogens used in HRT include conjugated oestrogens,
mestranol,estradiol,estriolandoestropipate. Progester-ones
used in HRT include medroxyprogesterone, norgestrel,
norethisterone,levonorgestrelanddydrogesterone.Tibolone
has oestrogenic, progestogenic and weak androgenic activity.

occasionally nausea, vomiting, depression, insomnia, breast

tenderness, headache, intermenstrual spotting, menorrhagia,

endometriosis, convulsions, weight gain, rashes, dizziness

and hair loss.

GONADOTROPHINS

Follicle-stimulating hormone (FSH) and luteinizing hormone

(LH) together, or follicle-stimulating hormone alone, and

chorionic gonadotrophin, are used in the treatment of infertil-

ity in women with proven hypopituitarism or who have not

responded to clomifene, or in superovulation treatment for

assisted conception, for example in vitro fertilization (IVF).

DRUGS FOR SUPPRESSION OF LACTATION

Bromocriptineis a dopamine agonist and inhibits the release

of prolactin by the pituitary. It is used for the treatment of

galactorrhoea and cyclical benign breast disease, as well as the

treatment of prolactinomas.

Cabergoline has actions and uses similar to those of

bromocriptine, but its duration of action is longer. It has a dif-

ferent side-effect profile from bromocriptineand patients

who may not tolerate the latter may be able to tolerate caber-

golineand vice versa.

Althoughbromocriptineandcabergolineare licensed to

suppress lactation, they are not recommended for routine sup-

pression or for the relief of symptoms of postpartum pain and

breast engorgement that can be adequately treated with sim-

ple analgesics and support.

PROSTAGLANDINS AND OXYTOCIC DRUGS

Prostaglandins and oxytocics are used to induce abortion, or

induce or augment labour, and to minimize blood loss from

the placental site. The commonly used drugs include oxy-

tocin, ergometrineand the prostaglandins. All work by

inducing uterine contractions with varying degrees of pain

according to the strength of the contractions induced.

Synthetic prostaglandin E 2 (dinoprostone) is used for the

induction of late (second-trimester) therapeutic abortion,

because the uterus is sensitive to its actions at this stage,

whereas oxytocin only reliably causes uterine contraction later

in pregnancy.

Dinoprostoneis preferred to oxytocinfor the induction of

labour in women with intact membranes regardless of parity

or cervical favourability. Both are equally effective in inducing

labour in women with ruptured membranes. However, oxy-

tocinis preferred for this, because it lacks the many side

effects of prostaglandin E 2 that relate to its actions on extra-

uterine tissues. These include nausea, vomiting, diarrhoea,

flushing, headache, hypotension and fever.

Dinoprostoneis available as vaginal tablets, pessaries and

vaginal gels. Oxytocinis administered by slow intravenous

Key points

HRT is much less used now because of worries about

increased cardiovascular events and hormone-sensitive

cancers (especially breast). Absolute contraindications:

• pregnancy;


• oestrogen-dependent cancers;


• active thrombo-embolic disease;


• liver disease;


• undiagnosed vaginal bleeding;


• breast-feeding.

REPRODUCTIVE HORMONE ANTAGONISTS

Uses

There are a number of agents now available that are used in
early and advanced breast cancer due to their antagonistic or
inhibitory effect on oestrogen, breast cancer commonly being
an oestrogen-sensitive tumour.
Oestrogen receptor antagonists include tamoxifenwhich
is licensed for breast cancer and anovulatory infertility, ful-
vestrantwhich is licensed for the treatment of oestrogen
receptor-positive metastatic or locally advanced breast cancer
in post-menopausal women, and toremifene which is
licensed for hormone-dependent metastatic breast cancer in
post-menopausal women.
The aromatase inhibitors block the conversion of androgens
to oestrogens in the peripheral tissues. They do not inhibit
ovarian oestrogen synthesis and are not suitable for use in pre-
menopausal women who will continue to secrete ovarian
oestrogens. Currently licensed agents include anastrozole,
letrozoleandexemestane.
The gonadorelin analogue goserelinis licensed for the
management of advanced breast cancer in premenopausal
women. It acts by initially stimulating and then depressing
luteinizing hormone released by the pituitary, which in turn
reduces oestrogen production.
Clomifeneandtamoxifenare used in the treatment of
female infertility due to oligomenorrhoea or secondary amen-
orrhoea (for example, that associated with polycystic ovarian
disease). Both drugs can induce gonadotrophin release by
occupying oestrogen receptors in the hypothalamus, thereby
interfering with feedback mechanisms. As an adjunct, chori-
onic gonadotrophin is sometimes used.
Clomifeneis used primarily for anovulatory infertility.
Patients should be warned about the risks of multiple births. It
is contraindicated in those with liver disease, ovarian cysts,
hormone-dependent tumours and abnormal uterine bleeding
of undetermined cause.
Side effects of clomifeneinclude visual disturbances, ovar-
ian hyperstimulation, hot flushes, abdominal discomfort,