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ABSENT GENITAL DEVELOPMENT
(Delayed Puberty)
 

Absence of Genital development occurs due to male hormone deficiency, which can occur due to many of the below mentioned causes.


What is Normal Genital Development
Symptoms & features
Causes of Absent genital development 
Investigations & Diagnosis
Treatment
Response of treatment
Side effects of treatment


What is Normal genital Development :Normally  in boys the genital development stars at the age of thirteen to fourteen years. The absent genital development occurs due to male hormone deficiency. The sign & symptoms of testosterone & other male hormone deficiency are as follows:

Symptoms & features: These includes absent genital development or underdeveloped genital organ development like small genitals (genitalia) like small pennis, under developed testis, shrunken scrotum.  Symptoms and signs of male hormone deficiency are less beard & moustache, poor development of body muscles, small pennis, under developed scrotum & testis, 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.

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 genital desire, less hardness of pennis i.e. dysfunction & other 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.

Causes of male absent or Inadequate Genital development:

Hypogonadotropic states

Hypothalamic pituita ovary deficiency: Idiopathic GnRH deficiency, Kallman syndrome, Prader-Willi syndrome, Laurence-Moon-Biedl syndrome, Hypothalamic deficiency, pituitary hypoplasia, Trauma, post surgical, postiradiation, Tumour (Adenoma, craniopharyngioma, other), Vascular (pituitary infraction, carotid aneurysm), Infiltrative (Sarcoidosis, histiocytosis, hemochromatosis) Autoimmune hypophysitis, Drugs (drug-induced hyperprolactinemia, genital steroids use) 
Untreated endocrinopathies, Glucorticoid excess, Hypopituitarism, Isolated gonadotropin deficiency (non acquired): Pituitary, Hypothalamic Associated with multiple pituitary hormone deficiencies: Idiopathic pan hypo pituitarism (hypothalamic defects), Pituitary dysgenesis, Space-occupying lesions (craniopharyngioma, Rathke pouch cysts, hypothalamic tumors, pituitary adenomas), , Laurence-Moon-Beidl syndrome Prader-Willi syndrome , Frohlich syndrome Hypergonadotropic hypogonadism : Klinefelter syndrome,  Noonan syndrome,  Viral orchitis, Cytotxic drugs, Testicular irradiation.

Testicular disorders (primary leydig cell dysfunction), Chromosomal (Klinefelter syndrome and variants, XX male gonadal dysgenesis), Defects in androgen biosynthesis, Orchitis (mumps, HIV, other viral, ) Myotonia dystrophica, Toxins (alcohol, opiates, fungicides, insecticides, heavy metals, cotton seed oil), Drugs (cytotoxic drugs, ketoconazole, cimetidine, spironolactone)

Systemic illness (uremia, liver failure), End-organ resistance (impaired androgen action)
Androgen Receptor defects
5 alpha-Reductase deficiency.
Constitutional delayed growth puberty


Investigation & Diagnosis: For diagnosis of cause of investigation following tests are required. These tests includes:

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.
Thyroid test,
Semen analysis
SHBG
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 hypogonadism.  
Capacity of generation of active testosterone i.e. DHT is tested. This DHT generation test is abnormal in some cases of hypogonadism

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 pituitary disorder.  
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 tests.

Treatment: Treatment of absence of genital development includes cure of primary cause. Treatment may be given in the following form:

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 administration are: 

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 tongue for few minutes. It has no side effect and it is very 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 days. 

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 is found.

4) Growth Factor, Mineral & Micronutrient Therapy 


NOTE: 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 required.

 

Side Effects: It has no side effects if given in proper disease and in patients when it is really indicated.

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