Hypogonadism Done by Kulanthaivel Shanmugaraj,141B Crimean Federal University, Simferopol, Russia

1. Hypogonadism
Done by
Kulanthaivel Shanmugaraj,141B
Crimean Federal University, Simferopol, Russia
Presented to
Assoc. Prof. Divinskaya Valentina Alexandrovna,
Ph. D. in Medicine

4. Definition
• Hypogonadism in men is a clinical
syndrome that results from failure of the
testis to produce physiological levels of
testosterone (androgen deficiency) and
the normal number of spermatozoa due to
disruption of one or more levels of the
hypothalamic-pituitary-gonadal (HPG) axis.

5. • A decrease in either of the two major
functions of the testes: – sperm production
And / or – testosterone production

7. Primary Hypogonadism
• 1. Klinefelter Syndrome .
• 2. XX Male (Sex Reversal)
• 3. Noonan Syndrome (Male Turner Syndrome)
• 4. Myotonic Dystrophy
• 5. Congenital Anorchia (Vanishing Testis Syndrome)
• 6. Sertoli-Cell-Only Syndrome
• 7. Acquired Germinal Cell Aplasia
• 8. Orchitis
• 9. Others : CRF, Cirrhosis, HIV, Drugs, XRT

8. Primary Hypogonadism
• Klinefelter Syndrome
• 46 XXY, 46 XY/XXY, 48 XXXY 1 in 500 men
Eunuchoid lower segment, Taller than Average,
Gynecomastia , Gynecoid Features, Very Small
Testis, Normal to Low Testosterone, FSH
increase >LH, Modest Elevation of Estradiol,
Severe Oligospermia to Azospermia Associated
Conditions: COPD, Cancer of Breast, Germ Cell
Tumors, Autoimmune Diseases, Diabetes
Mellitus, Osteopenia, Mitral Valve Prolapse,
Mental Slowness, Antisocial Behavior

10. Primary Hypogonadism
• XX Male (Sex Reversal) Translocation of
the SRY gene, Shorter than Average,
Normal Intelligence, Gynecomastia, Small
Testis, Azospermia
• Noonan Syndrome (Male Turner
Syndrome) 46 XY, Short Stature, Webbed
Neck, Shield Chest, Small Testis, Impaired
Spermatogenesis, May Have Low
Testosterone Associated Conditions:
Mental Retardation, Pulmonary Stenosis,
Hypertrophic Cardiomyopathy,

11. Myotonic Dystrophy
• Autosomal Dominant Inability to Relax
Striated Muscle, Frontal Balding, Ptosis ,
Cataracts , Atrophy of Facial Muscles ,
Distal Muscle Wasting, Testicular Atrophy
after Puberty Associated Conditions:
Cardiomyopathy , Type II Diabetes
Mellitus, Mental Retardation, Decreased
Myotonin (transfers phosphate to ATP)

12. Congenital Anorchcia (Vanishing
Testis Syndrome)
• 46XY, No Discernable Testicular Tissue in
Most, Bilateral Testicular Torsion in Utero?
HCG Stimulation—Detect Testicular
Remnants

13. Sertoli-Cell-Only Syndrome
• 46XY, Germinal Cell Aplasia, FSH>LH
Testosterone Normal Sertoli Cells
Vacuolated—Functional Abnormality

14. • Acquired Germinal Cell Aplasia Chemotherapy,
Radiation, Environmental Toxins
(Dibromodichloralpropane)
• Orchitis Post-Pubertal Mumps: 40% have
Orchitis, 40% with Orchitis have Varying
Degrees of Testicular Atrophy, Sperm Count
Lower in Most with Atrophy but True Impaired
Fertility in 15% Autoimmune Orchitis: Type I and
II endocrine deficiency
• Others : Cirrhosis, Chronic Renal Failure, Long-
Term Glucocorticoid Therapy

16. Secondary Hypogonadism
• congenital : 1. Isolated hypogonadotropic
hypogonadism 2. Kallman’s syndrome 3.
LH orFSH mutations 4. Leptin or leptin
receptor mutations 5. Gonadotrope
receptor mutations 6. Hypopituitarism 7.
CAH

17. Kallmann's syndrome
• Genetics: Sporadic, Dominant, Recessive, X-
linked Etiology: Absent neural cell adhesion
molecule (anosmin) in 10-14%, KAL Gene Point
Mutation Hypogonadotropic hypogonadism
Anosmia or hyponosmia Somatic abnormality
– cleft lip, cleft palate, short metacarpal bone,
pes carvus , renal agenesis, urogenital tract
defect Neurological abnormality –
Uncoordinated eye movement, spatial attention,
mental retard, sensoryneural deafness, seizure,
cerebellar ataxia, red green color blinness
Prevalence: one in 10,000

18. • Isolated Gonadotrophin Deficiency No Somatic
Abnormalities, No Anosmia, Abnormal GnRH
Receptor in a Few
• Selective Gonadotrophin Deficiency Isolated LH
Deficiency (Pasqualini syndrome): “Fertile” Eunuch,
Absence Virilization with Spermatogenesis Isolated
FSH Deficiency: Somewhat Small Testis,
Oligospermia to Azospermia, Normal Virilization
• Congenital adrenal hypoplasia with
hypogonadotropic hypogonadism : X-chromosomal
recessive disease, in the majority of patients caused
by mutations in the DAX1 gene. (prevalence 1 in
12,500 individuals)

20. Secondary Hypogonadism
• acquired : 1. Hyperprolactinemia 2. GnRH
analog therapy 3. Glucocorticoid therapy 4.
Critical or Chronic illness 5. Diabetes
mellitus 6. Opiates 7. Pituitary mass
lesions 8. Infiltrative diseases 9. Sellar
surgery or radiation 10.hemochromatosis

21. Hyperprolactinemia (HP)
• caused by prolactin-secreting pituitary adenomas or drug-
induced ; additional causes may be chronic renal failure or
hypothyroidism A literature review encompassing more than
300 hyperprolactinemic men found sexual dysfunctions in 88%,
The most typical pattern associated ED with a reduced sexual
desire. HPRL impairs the pulsatile LH release, which results
in a decrease of serum testosterone secretion.
• It is generally believed that this hypogonadism is the main
cause of ED. In fact, it may not explain every case. Serum
testosterone is in the normal range in nearly half of the ED
patients with marked HPRL. In addition, serum sex
hormonebinding globulin is low in hyperprolactinemic
males,and there are also testosterone-independent
mechanisms, probably mainly set at the level of the brain's
neurotransmittor systems or deacrease in DHT production

22. • MALE HYPOGONADISM DUE TO
DEFECTS OF ANDROGEN TARGET
ORGANS

23. Androgen insensitivity synd.
• The effects that androgens have on the human body
virilization, masculinization, anabolism, etc. are the result
of androgens bound to androgen receptors, the
androgen receptor mediates the effects of androgens in
the human body.
• AIS can result if even one of the steps involved in
androgenization is significantly disrupted, as each step is
required in order for androgens to successfully activate
the AR and regulate gene expression
• Clinical findings indicative of AIS can be
CAIS ,PAIS ,MAIS Laboratory findings include a
46,XY karyotype and normal or elevated postpubertal
testosterone , LH , and estradiol levels.

24. Late onset hypogonadim

25. • A clinical and biochemical syndrome
associated with advancing age and
characterized by typical symptoms and a
deficiency in serum testosterone levels. It
may result in significant detriment in the
quality of life and adversely affect the
function of multiple organ systems. The
key words in this definition are deficiency
in androgen levels , aging, detriment in the
quality of life and multiple organ
dysfunction.

26. • Other terms: Male Menopause Male
Climacteric andropause Androgen Decline
in the Ageing Male (ADAM) partial ADAM
Ageing Male Syndrome (AMS)

27. Pathophysiology of LOH
• Hypothalamus & aging
• 1-number of GnRH secreting neurons
decreases 2-decrease in the release of
neuropeptide Y(an excitatory peptidergic
signal to GnRH secreting neurons) 3-beta
receptors become less functional in aged
men 4-hypothalamic norepinephrine content
decrease with aging 5-diminished GnRH
impulse strength is the proximate cause of
the relative hypogonadism of old age.

28. Pituitary & aging
• 1-GnRH- receptor-activated voltage-
dependent Ca2+ channels are less able to
mobilize the Ca2+ needed for LH release 2-
stess increase cytokines, (IL-1 alpha), which
activate the corticotropicadrenal axis and
impair gonadotropin secretion 3-IL-1 alpha
reduces both the frequency and amplitude of
LH secretion through the intermediary
arginine vasopressin (AVP) 4-the stress-
related inhibition of pituitary LH secretion is
more prominent in aged compared to young
men.

29. • Testes & aging
• 1-age-associated decrement in testicular
steroidogenesis 2-with aging, mean serum
testosterone concentrations decrease and
circadian rhythmicity is lost

31. clinical presentation
• The clinical presentation depends on :
(1) age at onset of androgen deficiency,
(2) duration of androgen deficiency, (3) the
profoundness of the deficiency (4) genetic
factors controlling androgen receptor
responsiveness reflecting androgen
receptor polymorphism and mutations.

32. Fetal development
• Depending on when hypogonadism
develops, and how much testosterone is
present, a child who is genetically male
may be born with: Female
genitalsAmbiguous genitals — genitals
that are neither clearly male nor clearly
female Underdeveloped male genital

33. Puberty
• Decreased development of muscle
mass Lack of deepening of the voice
Impaired growth of body hair Impaired
growth of the penis and testicles
Excessive growth of the arms and legs in
relation to the trunk of the body
Development of breast tissue
(gynecomastia)

34. • AFTER PUBERTY : LOH

35. BARRIERS TO RECOGNITION
OF TD
• Nonspecificity of signs and symptoms
Lack of consensus on the definition of
TD Lack of confidence in diagnostic
tests Nonuse of screeners
Perception that TD is difficult to manage

36. • Studies suggest that hypogonadism in
adult men is often underdiagnosed and
under treated. This may be because the
symptoms are easily attributed to aging or
other medical causes, or ignored by
patients and physicians. In fact, only about
5% of hypogonadal men receive
testosterone replacement.

37. Group A: Symptoms and signs suggestive of
androgen deficiency in men:
• incomplete sexual development, eunuchoidism,
aspermia 2. Reduced sexual desire (libido) and
activity 3. Decreased spontaneous erections 4.
Breast discomfort, gynecomastia 5. Loss of body
(axillar and pubic) hair, reduced shaving 6. Very
small or shrinking testis (especially 5ml) 7.
Inability to father children, low or zero sperm
counts 8. Height loss, low-trauma fracture, low
bone mineral density 9. Reduced muscle mass
and strength 10. Hot flushes, sweats

38. Group B: Symptoms and signs associated with androgen
deficiency that are less specific than those in group A
• Decreased energy, motivation, initiative,
aggressiveness, self confidence 2. Feeling
sad or blue, depressed mood, dysthymia 3.
Poor concentration and memory 4. Sleep
disturbance, increased sleepiness 5. Mild
anemia (normochromic, normocytic) 6.
Increased body fat, body mass index 7.
Diminished physical or work performance

39. Sexual
• Reduced libido ED Decreased
spontaneous erection Reduced intensity of
orgasm Oligo- or azoospermia Very small
or shrinking testes Hot flushes, sweats
Breast discomfort, gynecomastia Loss of
pubic and axillary hair

40. Psychological
• Depressed mood Diminished energy,
vitality, or well-being Poor concentration
and memory Sleep disturbanc

41. Physiologic
• Fatigue Increased body fat Decreased
muscle mass and strength Osteoporosis
or low bone mineral density Anemia

43. Testosterone Therapy
We recommend 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.
J Clin Endocrinol Metab, June 2010, 95(6):2536–2559

44. We suggest that when clinicians prescribe
testosterone
therapy, the therapeutic target should be to raise
serum
testosterone levels into a range that is mid-normal
for
healthy, young men.
In men receiving testosterone enanthate or
cypionate,
serum testosterone levels vary during the dosing
interval;
We suggest aiming for testosterone levels between
Testosterone Therapy
J Clin Endocrinol Metab, June 2010, 95(6):2536–2559

49. Monitoring men receiving testosterone
therapy
Evaluate the patient 3 to 6 months after treatment initiation and
then annually to assess whether symptoms have responded to
treatment and whether the patient is suffering from any adverse
effects.
Monitor testosterone level 3 to 6 months after initiation of
testosterone therapy:
Therapy should aim to raise serum testosterone level into the mid-
normal range.
Injectable testosterone enanthate or cypionate: measure serum
testosterone level midway between injections. If testosterone
is 700 ng/dl (24.5 nmol/liter) or 400 ng/dl (14.1 nmol/liter),
adjust dose or frequency.
Transdermal patches: assess testosterone level 3–12 h after
application of the patch; adjust dose to achieve testosterone level in
the mid-normal range.
J Clin Endocrinol Metab, June 2010, 95(6):2536–2559

50. Monitoring men receiving testosterone
therapy
Buccal testosterone bioadhesive tablet: assess level immediately
before or after application of fresh system.
Transdermal gels: assess testosterone level any time after patient has
been on treatment for at least 1 wk; adjust dose to achieve serum
testosterone level in the mid-normal range.
Testosterone pellets: measure testosterone levels at the end of the
dosing interval. Adjust the number of pellets and/or the dosing
interval to achieve serum testosterone levels in the normal range.
Oral testosterone undecanoatea: monitor serum testosterone level 3
to 5 h after ingestion.
Injectable testosterone undecanoate: measure serum testosterone
level just prior to each subsequent injection and adjust the dosing
interval to maintain serum testosterone in mid-normal range.
J Clin Endocrinol Metab, June 2010, 95(6):2536–2559

51. Check hematocrit at baseline, at 3 to 6 months,
and then annually. If hematocrit is 54%, stop
therapy until hematocrit decreases to a safe level;
evaluate the patient for hypoxia and sleep apnea;
reinitiate therapy with a reduced dose.
Measure bone mineral density of lumbar spine
and/or femoral neck after 1–2 yr of testosterone
therapy in hypogonadal men with osteoporosis or
low trauma fracture, consistent with regional
standard of care.
Monitoring men receiving testosterone
therapy
J Clin Endocrinol Metab, June 2010, 95(6):2536–2559