Male Hormones

PHARMACOLOGY
 Androgens
The androgens are a group of steroids that have
anabolic(formation) and/or masculinizing effects in
both males and females.
Testosterone
- Most important androgen in humans
-Is synthesized in the testes (by Leydig cells located in the
interstitial space between the seminiferous tubules)and, in
smaller amounts, in the ovary of the female and by the
adrenal gland in both sexes.
-Other androgens secreted by the testes are 5α-
dihydrotestosterone (DHT), androstenedione, and
dehydroepiandrosterone (DHEA) in small amounts.
Synthetic androgenic steroids are available such as
methyltestosterone
 Actions of androgens

Normal maturation in the male

Sperm production
Increased synthesis of muscle proteins and
hemoglobin
Decreased bone resorption.
Development and maintenance of the male sex
organs.
Anabolic action.
Stimulate erythropoietin production by
kidneyerythropoiesis.
Source and Regulation of Androgen Synthesis

In adult male, testosterone secretion by leyding cell is

regulated by the pituitary gonadotropins :
luteinizing hormone (LH) and follicle-stimulating
hormone (FSH)
LH is the primary hormone that stimulates testosterone
production.
FSH…control spermatogenesis
 Cont…
Release of the pituitary gonadotropins (LH, FSH) is
regulated by gonadotropin-releasing hormone (GnRH)
from the hypothalamus.
 negative feedback system
Increased plasma levels of testosterone inhibit the release
of GnRH, LH, and FSH, thus maintaining testosterone
levels within a relatively finite range.
Fluctuations may occur in the amount of testosterone
produced over a given period, and androgen production
tends to diminish slowly as part of normal aging.
Androgen production, however, does not correspond to a
regular monthly cycle similar to hormonal production in
women.
 Mechanism of action

Androgens enter the target cell and bind to a cytoplasmic

receptor(The activated steroid-receptor complex then
travels to the cell’s nucleus, where it binds to specific
chromatin units. )… The hormone-receptor complex
binds to DNA and stimulates the synthesis of specific
RNAs and proteins.

E.g. Testosterone increases protein synthesis in

skeletal muscle, thus increasing muscle mass in certain
situations, such as at the onset of puberty.
 Physiologic Effects of Androgens

Development of Male Characteristics:

The influence of testosterone on sexual differentiation
begins in utero. In the fetus, the testes produce small
amounts of testosterone that affect the development of
the male reproductive organs.
Androgen production then remains relatively
unimportant until puberty.
At the onset of puberty…significant amounts of
testosterone. ..increased body hair, increased skeletal
muscle mass, voice change, and maturation of the
external genitalia.
 Role in Spermatogenesis

• Sperm production takes place in the testes. Each testis contains

close to 1000 coiled tubles – SEMENIFEROUS TUBULES – that
produce thousands of sperm each second in healthy males.
Testosterone is produced by the Leydig cells located in the
interstitial space between the seminiferous tubules.
LH serves as the primary stimulus to increase androgen production
from Leydig cells. Testosterone enters the tubules to directly
stimulate the production of sperm through an effect on protein
synthesis within the tubule cells.
FSH must also be present in the testes to work synergistically with
testosterone to allow full growth and maturation of developing
sperm.( FSH affects the Sertoli cells that line the seminiferous
tubules and are responsible for the development and maturation of
normal sperm .FSH stimulates the growth and function of Sertoli
cells)
( FSH, for example, increases the expression of a polypeptide
known as androgen-binding protein (ABP).ABP helps
concentrate testosterone within the seminiferous tubules and
helps transport testosterone to the epididymis. FSH may also
affect Leydig cell function indirectly by increasing
the production of other chemical messengers from the Sertoli
cells that enhance differentiation and function of Leydig cells.
FSH acts on the Sertoli cells to stimulate their function and help
testosterone reach target tissues within the seminiferous tissues.
Growth hormone, thyroid hormones, insulin-like growth factor 1,
and prolactin may also affect the functions of Leydig and Sertoli
cells, thereby influencing the production and effects of
testosterone.)
 Androgenic effects
Replacement Therapy

Primary hypogonadism(testicular dysfunction)

Secondry hypogonadism (due to faliure of
hypothalmus/pituitary)

risk of prostate cancer

 Anabolic effects

Used to treat conditions where there is

substantial(large) muscle catabolism and protein loss.
Such conditions include chronic infections, severe
traumas, severe burns, and recovery from extensive
surgeries.
Androgens can also be used to increase lean body mass
in men who are infected with human immunodeficiency
virus (HIV). Men with HIV infection may have muscle
wasting because of low testosterone production
combined with the catabolic effects of this infection and
subsequent anti-HIV therapies
 Delayed Puberty.

In males, androgens may be administered on a

limited basis to accelerate the normal onset of
puberty. These drugs are typically used when
puberty is anticipated to occur spontaneously but at
a relatively late date—that is, when puberty is not
delayed because of some pathologic condition
Endometriosis :Danazol, a mild endrogen, is used in
the treatment of endometerosis and fibrocystic
breast disease. It inhibits release of FSH&LH.

Androgens have been used to treat a limited number of

hormone-sensitive tumors, such as certain cases of
breast cancer in women.
 Anemia.

potent stimulators of erythropoietin synthesis from

the kidneys and other tissue…stimulates production of
red blood cell synthesis in bone marrow.

Nonetheless, androgens may be used as an adjunct to

erythropoietin and other drugs to stimulate red blood
cell production in certain patients with severe anemia.
 Hereditary Angioedema

This hereditary disorder is characterized by a defect in

the control of clotting factors that ultimately leads to
increased vascular permeability.
Loss of vascular fluid from specific capillary beds causes
localized edema in various tissues such as the skin,
upper respiratory tract, and gastrointestinal tract.
Certain androgens act on the liver to restore production
of several clotting factors and to increase production of
a glycoprotein inhibiting the initial stages of the clotting
sequence that leads to increased vascular permeability
TABLE 30-1
 Adverse Effects of Clinical
Androgen Use
In women, androgen administration can produce
hirsutism, hoarseness or deepening of the voice, and
male pattern baldness, Irregular menstrual periods and
acne may also occur in women undergoing androgen
therapy.

In men, these drugs may produce bladder irritation,

spermatogenesis, breast swelling and
soreness(gynecomastia), and stimulation of growth of
prostate.
In children, androgens may cause abnormal sexual
maturation and impairment of normal bone development
due to premature closure of epiphyseal plates.
General effects: Other side effects of longterm, high-
dose androgen use include liver damage and hepatic
carcinoma.
Hypertension may occur because of the salt-retaining
and water-retaining effects of these drugs.
androgens can adversely affect plasma lipids (increased
total cholesterol, decreased levels of high density
lipoproteins HDL).
 Adverse effects

adverse effects are related to the dose and duration

In adults, most of these adverse effects are
reversible, and symptoms will diminish once the
agent is discontinued. A few effects, however—such
as vocal changes in females—may persist even
after the drugs are withdrawn.
Skeletal changes are irreversible, and permanent
growth impairment may occur if these drugs are
used in children.
 Androgen Abuse

Anabolic steroids are used to increase lean body

mass, muscle strength and endurance in atheletes
and body builders.
In some popular publications,
DHEA(dehydroepiandrosterone) used as an
antiaging hormone as well as performance enhancer.

With its ready availability in health food stores, the

drug has been abused.
 Androgen Abuse
Nature of Androgen Abuse
Typically, androgen use is associated with athletes
involved in strength and power activities such as weight
lifting, bodybuilding, shot put, and the like.
There also appears to be a contingent of men, women,
and adolescents who are not athletes, but take anabolic
steroids to increase lean body mass for cosmetic
purposes; that is, these individuals take these drugs to
simply appear more muscular
These agents include testosterone, synthetic analogs of
testosterone, and precursors that are converted to
anabolic substances within the body. .. Deca-Durabolin
In addition, several different androgens are often taken
simultaneously for a combined dose that is 10 to 100
times greater than the therapeutic dose. This “stacking”
of different anabolic steroids often consists of combining
oral and injectable forms of these drugs .
Athletes often self-administer these drugs in cycles that
last between 7 and 14 weeks, and the dosage of each drug
is progressively increased during the cycle.
 How To help control anabolic steroid abuse

drug testing at the time of a specific competition

To prevent detection, an athlete will employ a complex

pattern of high-dosage androgen administration
followed with washout periods…thus allowing the drug
to be eliminated from the body before testing.

NO planned schedules but randomized drug testing

 Effects of Androgens on
Athletic Performance
In general, it appears that athletic men taking androgens
during strength training may experience greater
increments in lean body mass and muscle strength than
athletes training without androgens.
The extent of the increase depends on the dosage and type
of androgens used.
It also remains unclear what magnitude of any strength
gains can be directly attributed to anabolic steroids.
In particular, androgens appear to increase aggressiveness.
 Consequently, strength increments in the athlete taking
androgens may be brought about by the enhanced quality
and quantity of training rather than as a direct effect of
anabolic steroids on muscle protein synthesis.
 Adverse Effects of Androgen Abuse
High doses of androgens can produce liver damage, including
the formation of hepatic tumors
Androgens can also produce detrimental changes in cardiac
structure and function that result in cardiomyopathy,
ischemic heart disease, arrhythmias, and heart
failure.
unfavorable changes in blood lipid profiles, such as decreased
high-density lipoprotein cholesterol levels…atherosclerotic
lesions and subsequent vessel occlusion
Androgens also cause hypertension because of direct effects
on the myocardium and because of the salt- and water-
retaining properties of these drugs.
Problems with glucose metabolism brought about by insulin
Androgens can affect bone metabolism, and avascular
necrosis of the femoral heads has been documented
in a weight lifter using these drugs.
Androgens also accelerate closure of epiphyseal plates
and can lead to impaired skeletal growth in young
children…athletes may begin to self-administer anabolic
steroids at a relatively young age (i.e., prior to age 16).
behavioral changes, including increased aggression,
leading to radical mood swings and violent episodes in
some individuals.
In males, high levels of androgens act as negative
feedback and lead to testicular atrophy and
impaired sperm production(azoospermia)… it
takes 4 months or longer to return to normal
In females, androgens produce certain masculinizing
effects, such as an increase in body hair, a deepening
of the voice, and changes in the external
genitalia(vocal changes in females, may be
permanent).
 Antiandrogens
 Cyproterone
 Flutamide

They are steroid competitively inhibit androgens at their

receptors. (Dihydrotestosterone accelerates the growth and
development of the prostate gland; these antiandrogens may be
helpful in attenuating this effect in conditions such as benign
prostate hypertrophy)

Antiandrogens are drugs that inhibit the synthesis or

effects of endogenous androgen production.

Use in prostate cancer and other conditions aggravated

by excessive androgen production. Male baldness & Female
THANKS