IT.12 (YUL) - Male Hypogonadism

Male Hypogonadism and
Testosteron Therapy
• Male hypogonadism
- The body doesn't produce enough
testosterone — the hormone that plays
a key role in masculine growth and
development during puberty — or has
an impaired ability to produce sperm or
both
Development of the male reproductive
system
- Male sexual development starts between the 7th and 12th
week of gestation
- The undifferentiated gonads develop into a fetal testis

through expression of the sex-determining region Y gene
(SRY), a gene complex located on the short arm of the
Y chromosome
- The fetal testis produces two hormones: testosterone

and anti-Müllerian hormone (AMH)
system
Testosterone is needed for the development of the Wolffian ducts,
resulting in formation of the epididymis, vas deferens and
seminal vesicle
AMH activity results in regression of the Müllerian ducts
Under the influence of intratesticular testosterone, the number of

gonocytes per tubule increases threefold during the fetal period
system
Testosterone is needed for development of the prostate, penis and
scrotum
However, in these organs testosterone is converted into the more

potent metabolite dehydrotestosterone (DHT) by the enzyme 5a-
reductase
The enzyme is absent in the testes, which explains why 5a-

reductase inhibitors do not have a marked effect on
spermatogenesis
system
Intratesticular testosterone is needed to maintain the spermatogenic process
and to inhibit germ cell apoptosis
The seminiferous tubules of the testes are exposed to concentrations of

testosterone 25-100 times greater than circulating levels
Suppression of gonadotrophins (e.g. through excessive testosterone

abuse) results in a reduced number of spermatozoa in the ejaculate
and hypospermatogenesis
Complete inhibition of intratesticular testosterone results in full cessation of

meiosis up to the level of spermatids
Hypogonadism
Hypogonadism is defined as “inadequate gonadal

function, as manifested by deficiencies in gametogenesis
and/or the secretion of gonadal hormones”
These abnormalities usually result from disease of the

testes (primary hypogonadism) or disease of the pituitary
or hypothalamus (secondary hypogonadism)
In occasional cases, a defect in the ability to respond to

testosterone is the cause of hypogonadism
Hypergonadotropic Hypogonadism
Patients with hypergonadotropic hypogonadism may

have some or all of the following characteristic findings:
• Increased FSH level
• Increased LH level
• Low testosterone level
• Impaired production of sperm
Hypogonadotropic Hypogonadism
The condition of hypogonadotropic hypogonadism is

generally associated with the following findings:
• Low or low-normal FSH level
• Low or low-normal LH level
• Low testosterone level
• Impaired production of sperm
Primary and Secondary Hypogonadism
Primary hypogonadism differs from secondary hypogonadism in

two ways:
 Primary hypogonadism is more likely to be associated with a

decrease in sperm production than in testosterone production
 As a consequence, the sperm count may be low, and the

serum FSH concentration normal or high, yet the serum
testosterone concentration remains normal
In contrast, in secondary hypogonadism, there is a
proportionate
reduction in testosterone and sperm production
Primary hypogonadism differs from secondary
hypogonadism in two ways:
 Primary hypogonadism is more likely to be associated

with gynecomastia, presumably due to the stimulatory
effect of the supranormal serum FSH and LH
concentrations on testicular aromatase activity. This
results in increased conversion of testosterone to
estradiol
General Manifestations
Symptoms of hypogonadism depend primarily on the age of the male patient

at the time of development of the condition.
AACE Hypogonadism Guidelines, Endocr Pract. 2002;8(No. 6)

Symptoms of hypogonadism depend primarily on the age of the male

patient at the time of development of the condition
When hypogonadism develops before the age of puberty, the

manifestations are those of impaired puberty:
• Small testes, phallus, and prostate
• Scant pubic and axillary hair
• Disproportionately long arms and legs (from delayed epiphyseal
closure)
• Reduced male musculature
• Gynecomastia
• Persistently high-pitched voice
In men in whom androgen deficiency develops after completion of

pubertal maturation, symptoms of androgen deficiency include:
 reduced sexual desire and activity,
 decreased spontaneous erections,
 loss of body hair and reduced frequency of shaving,
 infertility,
 reduced muscle bulk and strength,
 hot flushes and sweats,
height loss due to atraumatic fracture,
 small or shrinking testes,
 breast enlargement or tenderness
Less-specific symptoms include decreased energy, motivation, and
initiative; sad or blue feelings, depressed mood, dysthymia; poor
concentration and memory; sleep disturbance and increased
sleepiness; increased body fat; and diminished physical or work
capacity.
Testosterone therapy
 Testosterone therapy for symptomatic men with classical androgen
deficiency syndromes
 Aimed at inducing and maintaining secondary sex characteristics and at

improving their sexual function, sense of well-being, and bone mineral
density
 The therapeutic target should be to raise serum

testosterone levels into a range that is mid-normal for
healthy, young men
Testosterone therapy in men with sexual
dysfunction
Testosterone therapy to men with low testosterone levels and

low libido to improve libido and to men with ED who have
low testosterone levels after evaluation of underlying causes
of ED and consideration of established therapies for ED
HIV-infected men with weight loss
We suggest that clinicians consider short-term testosterone

therapy as an adjunctive therapy in HIV-infected men with low
testosterone levels and weight loss to promote weight
maintenance and gains in LBM and muscle strength.
Guidelines for Testosterone Therapy in Androgen-Deficient Men J Clin Endocrinol Metab, June 2010,
95(6):2536–2559
Glucocorticoid-treated men
We suggest that clinicians offer testosterone therapy to

men receiving high doses of glucocorticoids who have low
testosterone levels to promote preservation of LBM and bone
mineral density.
Guidelines for Testosterone Therapy in Androgen-Deficient Men J Clin Endocrinol Metab, June 2010,
95(6):2536–2559
Time course of effects
The time course of the effects of testosterone

replacement is variable.
Increases in fat-free mass, prostate volume,

erythropoiesis, energy, and sexual function occurred
within the first three to six months.
In contrast, the full effect on bone mineral density

(BMD) did not occur until 24 months.
Benefit of TRT
In general, the benefits of TRT are more consistent in men

with very low testosterone concentrations than in those
with concentrations just below the normal range.
Health care professionals should make patients aware of

the possible increased cardiovascular risk when deciding
whether to start or continue a patient on testosterone therapy.
TRT should not be provided to men who have untreated or

metastatic prostate cancer or breast cancer.
Testosterone and Cardiovascular Risk, Endocr Prac. 2015;21(No. 9)
Relative contra-indications include :
untreated severe sleep apnea,
a hematocrit >50%,
severe lower urinary tract symptoms with an International Prostate
Symptom Score above 19,
uncontrolled or poorly controlled heart failure,
 a MI or cerebrovascular accident within the past 6 months,
a personal or family history of a procoagulant state,
or a personal history of thromboembolism
Testosterone and Cardiovascular Risk, Endocr Prac. 2015;21(No. 9)

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Male Hypogonadism and

- The undifferentiated gonads develop into a fetal testis

- The fetal testis produces two hormones: testosterone

AMH activity results in regression of the Müllerian ducts

Under the influence of intratesticular testosterone, the number of

However, in these organs testosterone is converted into the more

The enzyme is absent in the testes, which explains why 5a-

The seminiferous tubules of the testes are exposed to concentrations of

Suppression of gonadotrophins (e.g. through excessive testosterone

Complete inhibition of intratesticular testosterone results in full cessation of

Hypogonadism is defined as “inadequate gonadal

These abnormalities usually result from disease of the

In occasional cases, a defect in the ability to respond to

Patients with hypergonadotropic hypogonadism may

The condition of hypogonadotropic hypogonadism is

Primary hypogonadism differs from secondary hypogonadism in

 Primary hypogonadism is more likely to be associated with a

 As a consequence, the sperm count may be low, and the

 Primary hypogonadism is more likely to be associated

Symptoms of hypogonadism depend primarily on the age of the male patient

AACE Hypogonadism Guidelines, Endocr Pract. 2002;8(No. 6)

Symptoms of hypogonadism depend primarily on the age of the male

When hypogonadism develops before the age of puberty, the

In men in whom androgen deficiency develops after completion of

 Aimed at inducing and maintaining secondary sex characteristics and at

 The therapeutic target should be to raise serum

Testosterone therapy to men with low testosterone levels and

We suggest that clinicians consider short-term testosterone

We suggest that clinicians offer testosterone therapy to

The time course of the effects of testosterone

Increases in fat-free mass, prostate volume,

In contrast, the full effect on bone mineral density

In general, the benefits of TRT are more consistent in men

Health care professionals should make patients aware of

TRT should not be provided to men who have untreated or

Testosterone and Cardiovascular Risk, Endocr Prac. 2015;21(No. 9)

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