314 REPRODUCTIVE ENDOCRINOLOGY
symptoms. Alternatively, testosterone undecanoateormes-
terolonecan be taken by mouth; these drugs are formulated in
oil, favouring lymphatic absorption from the gastro-intestinal
tract.
Delayed puberty due to gonadal deficiency (primary or
secondary) or severe constitutional delay can be treated by
testosterone esters or gonadotrophins. Care is needed because
premature fusion of epiphyses may occur, resulting in short
stature and such treatment is best supervised by specialist
clinics.
Occasional patients with disseminated breast cancer derive
considerable symptomatic benefit from androgen treatment.
Anabolic steroids (e.g. nandrolone,stanozolol,danazol)
have proportionately greater anabolic and less virilizing
effects than other androgens. They have generally been disap-
pointing in therapeutics and have been widely abused by ath-
letes and body builders. Their legitimate uses are few, but
include the treatment of some aplastic anaemias, the vascular
manifestations of Behçet’s disease and the prophylaxis of
recurrent attacks of hereditary angioneurotic oedema.
Mechanism of action
Testosterone and dihydrotestosterone interact with intracellular
receptors in responsive cells, leading to new protein synthesis.
Adverse effects
Virilization in women and increased libido in men are pre-
dictable effects. In women, acne, growth of facial hair and deep-
ening of the voice are common undesirable features produced
by androgens. Other masculinizing effects and menstrual irregu-
larities can also develop. In the male, excessive masculinization
can result in frequent erections or priapism and aggressive
behaviour. Children may undergo premature fusion of epiphy-
ses. Other adverse effects include jaundice, particularly of the
cholestatic type, and because of this complication methyl-
testosteroneis no longer prescribed. Azospermia occurs due to
inhibition of gonadotrophin secretion. In patients treated for
malignant disease with androgens, hypercalcaemia (which may
be severe) is produced by an unknown mechanism. Oral testos-
teronepreparations in oil cause various gastro-intestinal symp-
toms including anorexia, vomiting, flatus, diarrhoea and oily
stools.
Pharmacokinetics
Although testosterone is readily absorbed following oral
administration, considerable presystemic metabolism occurs
in the liver. It can be administered sublingually, although this
route is seldom used. Testosterone in oil is well absorbed from
intramuscular injection sites, but is also rapidly metabolized.
Esters of testosterone are much less polar and are more slowly
released from oily depot injections and are used for their pro-
longed effect. Inactivation of testosterone takes place in the liver.
The chief metabolites are androsterone and etiocholanolone,
which are mainly excreted in the urine. About 6% of adminis-
tered testosterone appears in the faeces having undergone
enterohepatic circulation.
ANTI-ANDROGENSCYPROTERONE
Uses
Cyproterone acetateis used in men with inoperable prostatic
carcinoma, before initiating treatment with gonadotrophin-
releasing hormone analogues to prevent the flare of disease
activity induced by the initial increase in sex hormone release.
It has also been used to reduce sexual drive in cases of sexual
deviation and in children with precocious puberty. In women,
it has been used to treat hyperandrogenic effects (often seen in
polycystic ovary disease), including acne, hirsutism and male-
pattern baldness. The potentially adverse effects of cypro-
teroneon HDL and LDL caution against long-term use, and
the risk–benefit ratio should be considered carefully before
embarking on treatment for relatively minor indications.Mechanism of action
Cyproteroneacts by competing with testosterone for its high-
affinity receptors, thereby inhibiting prostatic growth, spermato-
genesis and masculinization. It also has strong progestational
activity and a very weak glucocorticoid effect.Adverse effects
Side effects include gynaecomastia in approximately 20% of
patients (occasionally with benign nodules and galactor-
rhoea), inhibition of spermatogenesis (which usually returns
to normal six months after cessation of treatment) and tired-
ness and lassitude (which can be so marked as to make driv-
ing dangerous).DUTASTERIDE AND FINASTERIDE
Use
Dutasterideandfinasterideinhibit 5α-reductase and reduce
prostate size with improvement in urinary flow rate and
symptoms of obstruction. They are useful alternatives to
alpha blockers (e.g. doxazosin) for benign prostatic hypertro-
phy, particularly in men with a significantly enlarged prostate.
Prostate-specific antigen should be measured as treatment
must not delay the diagnosis of prostate cancer.
Adverse effects include impotence, decreased libido, ejacu-
lation disorders, breast tenderness and enlargement. Women
of child-bearing potential should avoid handling crushed or
broken tablets of finasterideor leaking capsules of dutasteride.
A low strength of finasterideis licensed for treating male-
pattern baldness in men.DRUGS THAT AFFECT MALE SEXUAL
PERFORMANCEThe complex interplay between physiological and psychological
factors that determines sexual desire and performance makes it
difficult to assess the influence of drugs on sexual function. In
randomized placebo-controlled blinded studies, a small but