614
P A R T 7
Drugs acting on the reproductive system
O
estrogen receptor modulators
Two available oestrogen receptor modulators are ralox-
ifene (
Evista
) and toremifene (
Fareston
). The long-term
effects of these two drugs are not yet known.
Therapeutic actions and indications
Oestrogen receptor modulators are not hormones but
affect specific oestrogen receptor sites, stimulating some
and blocking others. They were developed to produce
some of the positive effects of oestrogen replacement
while limiting the adverse effects. See Table 40.1 for
usual indications for these drugs. Toremifene is dis-
cussed in greater detail in Chapter 14, which discusses
antineoplastic agents.
Pharmacokinetics
Administered orally, raloxifene is well absorbed from the
GI tract and is metabolised in the liver. Excretion occurs
through the faeces. It is known to cross the placenta and
enter into breast milk.
Contraindications and cautions
Raloxifene is contraindicated in the presence of any
known allergy to raloxifene
to avoid hypersensitiv-
ity reactions
and during pregnancy and breastfeeding
because of potential effects on the fetus or neonate.
Caution should be used in people with a history of
venous thrombosis or smoking
because of an increased
risk of blood clot formation if smoking and oestrogen
are combined.
Adverse effects
Raloxifene has been associated with GI upset, nausea
and vomiting. Changes in fluid balance may also cause
headache, dizziness, visual changes and mental changes.
Hot flushes, skin rash, oedema and vaginal bleeding
may occur secondary to specific oestrogen receptor
stimulation. Venous thromboembolism is a potentially
dangerous side effect that has been reported.
Clinically important drug–drug interactions
Cholestyramine reduces the absorption of ralox-
ifene. Highly protein-bound drugs, such as diazepam
(
Valium
), ibuprofen (
Brufen
), indomethacin (
Indocin
)
and naproxen (
Naprosyn
), may interfere with binding
sites. Warfarin taken with raloxifene may decrease the
prothrombin time (PT); people using this combination
must be monitored closely.
Prototype summary: Oestradiol
Indications:
Palliation of moderate to severe
vasomotor symptoms associated with menopause;
prevention of postmenopausal osteoporosis;
treatment of female hypogonadism, female
castration, female ovarian failure; palliation of
inoperable and progressing breast cancer and
inoperable prostatic cancer.
Actions:
The most potent endogenous female sex
hormone, responsible for oestrogen effects on the
body.
Pharmacokinetics:
Route Onset
Peak
Duration
PO Slow
Days
Unknown
Topical preparations are not generally absorbed
systemically.
T
1/2
:
Not known; with hepatic metabolism and
excretion in the urine.
Adverse effects:
Corneal changes, photosensitivity,
peripheral oedema, chloasma, hepatic adenoma,
nausea, vomiting, abdominal cramps, bloating,
breakthrough bleeding, change in menstrual flow,
dysmenorrhoea, premenstrual-like syndrome.
Prototype summary: Norethisterone
Indications:
Treatment of amenorrhoea, abnormal
uterine bleeding due to hormonal imbalance;
treatment of endometriosis; component of some
hormonal contraceptives.
Actions:
Progesterone derivative that transforms
the proliferative endometrium into a secretory
endometrium; inhibits the secretion of pituitary FSH
and LH, which prevents ovulation; inhibits uterine
contractions.
Pharmacokinetics:
Route Onset
Peak
Duration
PO Varies
Unknown Unknown
T
1/2
:
Unknown, with hepatic metabolism and
excretion in the faeces and urine.
Adverse effects:
Venous thromboembolism, loss
of vision, diplopia, migraine headache, rash,
acne, chloasma, alopecia, breakthrough bleeding,
spotting, amenorrhoea, fluid retention, oedema,
increase in weight.
