HYPOGONADISM (MALE HORMONE DEFICIENCY)
The absence of genital development in boys due to male genital hormone deficiency is called
Symptoms & features
Causes of Hypogonadism
Investigations & Diagnosis
Response of treatment
Side effects of treatment
What is Hypogonadism: When male hormone testosterone and
other hormones are low leading to absence of normal genital
development in the boy is called male hormone deficiency i.e.
Hypogonadism. Thus hypogonadism is called when gonad i.e. testis is
functioning less than normal or not functioning et all, leading to
deficiency of male genital hormone which includes testosterone & few
others & sometimes even absent sperm production.
Symptoms & features
of male hormone deficiency are absent genital
development or underdeveloped genital organ development like
small genitals (genitalia) like small pennis, under developed
testis, shrunken scrotum.
Decreased development of secondary genital characters like
less beard & moustache, less body hair, soft skiin as found in
girls, soft voice like females, less muscular development i.e. less
manly body, decreased confidence on himself so that patient may feel
less confidence on himself so that patient may feel less confident &
even sometimes nervousness in talking to others. Sometimes even
breast may enlarge due to less concentration of testosterone. Then
body energy becomes less so that patient feel tired all the time.
Decreased testosterone & other male hormone like DHEAS lead to
decreased genitaldesire, less hardness of pennis i.e.dysfunction &
other genital disorders. This also leads to less development of
sperms leading to decreased sperm count & motility & even absent
sperm. Due to less muscular development & less beard & moustache
they look younger then their age & less mature look so that in
workplace & among friends they are always treated like young so that
they perform less well in career. There memory also may be less.
Sometimes all above disorders can lead to severe anxiety & even
frank depression may occur.
Sometimes they may have less aggressive behavior, feminine nature,
poor in study, poor memory, poor performance in office or business,
less confidence on his capabilities, less sperm (oligospermia, Nil
sperms), thin semen, female like voice can occur. Patient may have
one or more of the above mentioned features. Thus symptoms of
hypogonadism are absence of development of male like features.
Causes of male hypogonadism
(Inadequate genital development)
Hypothalamic - pituitary deficiency: Idiopathic GnRH deficiency,
Kallman syndrome, Prader-Willi syndrome, Laurence-Moon-Biedl
syndrome , Hypothalmic deficiency, pituitary hypoplasia, Trauma,
post surgical, postiradiation, Tumour (Adenoma, craniopharyngioma,
other), Vascular (pituitary infraction, carotid aneurysm),
Infiltrative (Sarcoidosis, histiocytosis, tuberculosis, fugal
infection, hemochromatosis)Autoimmune hypophysitis, Drugs
(drug-induced hyperprolactinemia, genital steroids use) Untreated
endocrinopathies, Glucorticoid excess, Hypopituitarism,Isolated
gonadotropin deficiency (non acquired) : Pituitary ,
HypothalamicAssociated with multiple pituitary hormone deficiencies
: Idiopathic pan hypo pituitarism (hypothalamic defects), Pituitary
dysgenesis, Space-occupying lesions (craniopharyngiomas, Rathke
pouch cycts, hypothalamic tumors, pituitary adenomas), Following
surgery, Following cranial irradiation, Following CNS chemotherapy,
Following inflammation, Infiltrative or destructive processes
(autoimmune, hemosiderosis), Associated with syndromes involving
hypthalamic function, Laurence-Moon-Beidl sundrome Prader-Willi
syndrome , Frohlich syndrome
Genetic Mutuations : KALI (kakallmann), Gonadotropin-releasing
hormone receptor (GnRHR), FSH3 isolalated FSH deficiency, PROP1
(pituitary deficiency), Hgenital1 (septo-optic dysplasia), DAX1
Isolated gonadotropic deficiency with or without anosmia, Fertile
eunuch syndrone, Idiopathic hypopituitarism, CNS disorders : tumors,
infections, pituitary agenesis or hypoplasia, hydrocephalus,
Septooptic dysplasia, CNS radiation for leukemia or brain tumor,
Prader-Willi and Laurence-Moon-Biedly Syndrome, Thalassemia major
Hypergonadotropic hypogonadism :
Klinefelter syndrome, Noonan syndrome,
Infections: Viral orchitis, Mumps Orchitis, Leprotic Orchits
Drug Induced: Cytotxic drugs, Testicular irradiation. ),
Drugs (cytotoxic drungs, ketoconazole, cimetidine, spironolactone)
Developmental: Testicular disorders (primary leydig cell
Chromosomal Disorder: (Klinefelter syndrome and variants, XX
male gonadal dysgenesis),
Defects in androgen biosynthesis
Toxins (alcohol, opiates, fungicides, insecticides, heavy
metals, cotton seed oilSystemic illness (uremia, liver failure),
End-organ resistance (impaired androgen action)
Androgen Receptor defects,
Postreceptor transduction abnormalities,
5 alpha-Reductase deficiency.
Constitutional delayed growth and puberty.
Investigation & Diagnosis :
Following tests are required to reach the correct diagnosis of cause
Complete male hormone profile: This profile includes all the
male hormone tests which affects testicular development, growth &
other genital organ development as well as genital functions.
Ultrasound of testis, other tests which may be required depending on
likelihood of the any of above causes.
Tests may show low testosterone. L.H. & F.S.H. may be decreased or
increased may be low. Thyroid test may show low free T3 & free T4 &
TSH may be increased or decreased. Similarly prolactin hormone may
be low or high. In biochemistry tests liver function or kidney
function may be abnormal. But for interpretation of all above tests
one need to be expert of hormone diseases with good experience.
Based on above test result diagnosis of cause of hypogonadism is
made once the cause is found treatment becomes very simple.
Then we do testis functional capacity in this we inject single
injection of gonadotropin as intramuscular injection
then three day later the rise in concentration of serum total
testosterone confirms whether testis has capacity to function
normally or not.
Chromosomal analysis is done to see the genetic structure of
testis, because there are many chromosome disorders lead to
Capacity of generation of active testosterone i.e. DHT is
tested This DHT generation test is abnormal in some cases of
Tests to locate testis as ultrasonography or C.T. Scan abdomen is
needed if testis is not palpable.
Serum inhibin is tested which tells that whether hypogonadism is
temporary or permanent.
Serum Iron, T.I.B.C. & ferritin concentration tested for
hypogonadism due to hemochromatosis.
Combined Pituitary hormone tests is performed when suspecting
Molecular genetic studies done in some special cases.
Serum estrogen increased whenever testicular function decreased.
Serum DHT is low in some conditions when generation of
dihydrotestosterone is decreased.
Assessment of androgen receptor is due when needed, dynamic tests as
HCG test, response to antiestrogen & gonadotropin releasing hormone
Treatment : Treatment of
hypogonadism includes cure of primary cause of hypogonadism.
In case of low L.H. & F.S.H. hormone treatment is given in form of
Gonadotropin releasing hormone, Human chorionic gonadotropin, human
menopausal gonadotropin or purified follicle stimulating when we
start treatment with any of the above mentioned gonadotropins,
enlargement of testis followed by rise in testosterone level occurs.
This lead to development of beard & moustache, normal pennis size,
sperm & semen normalizes & genital dysfunction is cured. Thus almost
all patient are cure in one year time.
Many times hypogonadism is temporary as in constiutional delayed
growth & puberty, in many psychiatric disorders & in protein caloric
malnutrition. In these cases after correct diagnosis we can
permanently cure the hypogonadism in short time. In these patient
with in one-year patient achieves normal development.
When pituitary neoplasia is the cause then surgical treatment is
required. When drugs are the culprit then stopping the offending
drugs, cure the problem.
In some long term treatment with androgen as testosterone is
1) Male Hormone Replacement: Treatment with male hormone
testosterone is available as oral tablets, skiin patch, skiin gels
or injection is given with very good results.
The various preparation of testosterone & route of
a) Oral preparation that is available in capsule form. It need to be
given one to three capsule daily.
These have no side effects.
b) Transdermal Testosterone given as testosterone gel preparations.
It need to be applied any part of skiin once a
day. It is very effective & has no side effects.
c).Transdermal Testosterone scrotal patch are also available which
are very effective even if used in small doses
. It is very effective & has no side effects.
d) Sublingual Testosterone cyclodextrin is now available which is
very fast acting & very effective is fast & better
genital organ secondary genital character
development. It is used as one tablet daily to be kept under the
for few minutes. It has no side
effect and it is very effective.
e) Local application of D.H.T. gel available as Andractim gel
is a new preparation for male hormone replacement.
f) Injection Testosterone esters these includes
Testosterone enanthate & testosterone cypionate given
intramuscular injections every 10 to 14
g) Long acting testosterone as testosterone bucilate given
once in 4 months.
h) Testosterones implants are now available which once injected
remain effective for up to six months.
2) Gonadotropin therapy is also
very effective in testis enlargement. This is available as
injections which has no side effects with very good results. After
start of treatment testis starts enlarging in three months time.
With in one year time testis enlarges to normal size. Its function
also normalizes in most patients. Later testis starts producing
normal level of male hormone testosterone. Once testosterone
production normalizes, enlargement of testis followed by rise in
testosterone level occurs. This lead to development of beard &
moustache, normal pennis size, sperm & semen normalizes & genital
dysfunction if present is cured as erection & genital desire becomes
normal. Physical weakness disappears & mentally becomes more active
& alert. All other symptoms also normalizes. Bone strength recovers.
Testosterone treatment is harmless if given by expert in hormone in
proper doses. Thus almost all patient are cure in one-year time.
2) Gonadotropin Releasing hormone therapy is effective in
many cases of underdeveloped testis even when gonadotropin therapy
has failed in normalizing testicular size & function. It is
effective when in cases of low L.H. & F.S.H..
3) Growth hormone therapy in many cases where somatrop deficiency
4) Growth Factor, Mineral & Micronutrient Therapy
Side Effects: It has no side
effects if given in proper disease and in patient's when it is
really indicated. This it is absolutely safe in young patients below
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