A Textbook of Clinical Pharmacology and Therapeutics

MALEREPRODUCTIVEENDOCRINOLOGY 313

infusion using an infusion pump to induce or augment labour,
usually in conjunction with rupture of membranes. Uterine
activity must be monitored carefully and hyperstimulation
avoided. Large doses of oxytocincan cause excessive fluid
retention. Oxytocinshould not be started within six hours of
administration of vaginal prostaglandins.
A combination formulation of ergometrineandoxytocin
(syntometrine) is used for bleeding due to incomplete abortion
and in the routine management of the third stage of labour.
This is administered by intramuscular injection with the deliv-
ery of the anterior shoulder. A useful alternative in severe
postpartum haemorrhage in patients with an atonic uterus
unresponsive to ergometrineandoxytociniscarboprost.

OXYTOCIN

Oxytocinproduces contractions of the smooth muscle of the
fundus of the pregnant uterus at term, and of the mammary
gland ducts. It is released from the pituitary by suckling and
also by emotional stimuli. Any role in the initiation of labour
is not established. There is no known disease state of over- or
under-production of oxytocin. Synthetic oxytocinis effective
when administered by any parenteral route, and is usually
given as a constant-rate intravenous infusion to initiate or
augment labour, often following artificial rupture of the mem-
branes. A low dose is used to initiate treatment titrated
upwards if necessary.
The side effects of oxytocininclude uterine spasm, tetanic
contractions, water intoxication and hyponatraemia, and uter-
ine hyperstimulation.

ERGOMETRINE

Ergometrine(an alkaloid derived from ergot, a fungus that
infects rye) is a powerful oxytocic. The uterus is sensitive at all
times, but especially so in late pregnancy. It is given intramuscu-
larly, or intravenously in emergency. Oxytocinproduces slow
contractions with full relaxations between, whilst ergometrine
produces faster contractions superimposed on a tonic persistent
contraction (it is for this reason that ergometrineis unsuitable
for induction of labour). If given intramuscularly, oxytocinacts
within one to two minutes, although the contraction is brief, but
ergometrinetakes five minutes to act.
Ergometrinecan cause hypertension, particularly in pre-
eclamptic patients, in whom it should be used with care, if at all.

PROSTAGLANDINS

Prostaglandins are naturally occurring lipid-derived medi-
ators. Prostaglandins are involved in a wide range of physio-
logical and pathological processes, including inflammation
(see Chapter 26) and haemostasis and thrombosis (see
Chapter 30). Prostaglandin E 2 has a potent contractile action
on the human uterus, and also softens and ripens the cervix. In
addition, it has many other actions, including inhibition of
acid secretion by the stomach, increased mucus secretion
within the gastro-intestinal tract, contraction of gastro-intestinal
smooth muscle, relaxation of vascular smooth muscle and
increase in body temperature.

Specialized uses of prostaglandins in the perinatal period

include the use of prostaglandin E 1 (alprostadil) in neonates

with congenital heart defects that are ‘ductus-dependent’. It

preserves the patency of the ductus arteriosus until surgical cor-

rection is feasible. Conversely, in infants with inappropriately

patent ductus arteriosus, indometacingiven intravenously can

cause closure of the ductus by inhibiting the endogenous

biosynthesis of prostaglandins involved in the preservation of

ductal patency.

MALE REPRODUCTIVE ENDOCRINOLOGY

INTRODUCTION

The principal hormone of the testis is testosterone, which is

secreted by the interstitial (Leydig) cells. Testosterone circu-

lates in the blood, bound to a plasma globulin. The plasma

concentration is variable, but should exceed 10 nmol/L in

adult males. Cells in target tissues convert testosterone

into the more active androgen dihydrotestosterone by a 5-α-

reductase enzyme. Both testosterone and dihydrotestosterone

are inactivated in the liver. Androgens have a wide range of

activities, the most important of which include actions on:

• development of male secondary sex characteristics
  (including male distribution of body hair, breaking of the
  voice, enlargement of the penis, sebum secretion and
  male-pattern balding);


• protein anabolic effects influencing growth, maturation of
  bone and muscle development;


• spermatogenesis and seminal fluid formation.
  Testicular function is controlled by the anterior pituitary.


• Follicle-stimulating hormone acts on the seminiferous
  tubules and promotes spermatogenesis.


• Luteinizing hormone stimulates testosterone production.
  The release of FSH and LH by the pituitary is in turn mediated
  by the hypothalamus via gonadotrophin-releasing hormone.

ANDROGENS AND ANABOLIC STEROIDS

Uses

Many cases of impotence are psychogenic in origin and treat-

ment with androgens is inappropriate. In impotent patients

with low concentrations of circulating testosterone, replace-

ment therapy improves secondary sex characteristics and may

restore erectile function and libido, but it does not restore fer-

tility. (Treatment of patients with hypogonadism secondary to

hypothalamic or pituitary dysfunction who wish to become

fertile includes gonadotrophins or pulsatile gonadotrophin-

releasing hormone.) Replacement therapy is most reliably

achieved by intramuscular injection of testosterone esters in

oil, of which various preparations are available. They should

usually be given at two- to three-week intervals to control