Androgen and

Antiandrogen
Prof. DR. dr. Hadyanto Lim, M.Kes, SpFK, FESC,
FIBA
Dept. of Pharmacology, Faculty of Medicine,
Methodist University of Indonesia

Hypothalamic-Pituitary-Gonadal Axis

Androgen
antagonist

Antiandroge
n
Estrogen
antagoni
st

Gonadotroph
in receptor
agonists

Androgen
Androgen are produced by the testis,
ovary, and adrenal gland.
Testosterone is the most important
androgen in males. It stimulates
virilization and is an important
spermatogenic hormone.
In both sexes, androgens stimulate
body hair growth, positive nitrogen
balance, bone growth, muscle
development, and erythropoiesis.

Clinical Use of Androgen

Replacement therapy in men
whose production of testosterone
is impaired.
Testosterone synthesis inhibitors
and antiandrogens are used to
limit the effects of androgens in
patients with androgendependent disorders, such as
prostatic cancer, histutism, and

Testosterone Synthesis
Testosterone, a 19-carbon
steroid hormone, is synthesized
from cholesterol in the Leydig
cells of the testis.
The principal regulator of the
testosterone synthesis and
secretion is luteinizing hormone
(LH), which is produced by the
anterior pituitary gland.

Pathways of
Testosterone
Synthesis in the
Leydig Cell

Testosterone Synthesis
Testosterone synthesis begins during the
first trimester of pregnancy.
The human fetal testis is stimulated by
human gonadotrophin (hCG) of placental
region to produce the testosterone
required fro male sexual differentiation.
In the 2 nd trimester, as in the adult, the
principal stimulus to the fetal
gonadotroph, is gonadotrophin-releasing
hormone (GnRH).

Hormonal
Control of
Testicular
Function

Testosterone Synthesis
GnRH and sex steroid production decline
late in fetal life.
At puberty, gonadotrophin secretion
increases and reawakens the Leydig cell
to produce testosterone.
Normal woman produce approximately
0.25 mg/day of testosterone, compared
with the 5 to 7 mg/day for adult men.

Metabolism of
Testosterone

Androgen Action
Binding of circulating testosterone
- serum glycoprotein of hepatic origin, sex
hormone
binding globulin (SHBG).
- albumin
- unbound (1-3%)
Bound and unbound testosterone can enter
target tissues (50%).
Once testosterone enters the target cells,
it may be converted to other compounds or
interact directly with Androgen Receptors .

Androgen Action at Target Cell

Mechanism of Testosterone Action and Its

Major Functions

Pharmacokinetic Parameters
Androgen in Clinical Use

Antiandrogen Therapies
Used to treat prostatic disease in men.
Non steroidal androgen antagonists
(flutamide, nilutamide) are selective for
testosterone receptors and are devoid of
effects on other steroid receptors. Their use
leads to increased LH secretion and
testosterone synthesis.
Spironolactone, the mineralocortocoid
antagonist, is also an androgen agonist, is
used for female hirsutism.

Antiandrogen Therapies
Finasteride, a 5-reductase inhibitor, is
moderately effective in improving the
symptoms of prostatic hypertrophy,
and male pattern baldness.

Antiandrog
en Therapy