الفهرس 
Historical prospectiveOnly 14 pages are availabe for public view
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Abstract
Aging related health problems, including the gradual decrease in gonadal function in men after middle age, have gained interest in the medical community.
Androgen deficiency in aging male (ADAM) is defined as a clinical and biochemical syndrome associated with advancing age and characterized by typical symptoms and a deficiency in serum testosterone levels.
The most prevalent symptoms of ADAM are reduced sexual desire and sexual activity, erectile dysfunction and often these symptoms are the presenting symptoms. These symptoms have an insidious onset with slow progression and are not manifested in all men.
ADAM has been recently considered one of the many adverse consequences of being overweight and having obesity. On the other hand, low T levels could contribute to the accumulation of excess fat, establishing a vicious cycle. Changes in body composition and in particular an increase in visceral obesity often characterize the condition.
Several questionnaires have been proposed to screen for TD in aging men. These include the Androgen
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Deficiency in Aging Males (ADAM) Questionnaire, the Aging Male Symptoms (AMS) Scale, and the Massachusetts Male Aging Study (MMAS) questionnaire. All these questionnaires have a good sensitivity but in practice, they are not useful in the diagnosis of TD because they have very low specificity. The current data do not conclusively support the use of hypogonadism questionnaires for screening.
NERI Hypogonadism screener showed promising results in discriminating men with low TT from controls; Data on sensitivity and specificity are not complete.
The main diagnostic test is the measurement of serum total testosterone. However T circulates in the blood mainly bound to proteins, especially to SHBG, so assessing free testosterone ”FT” will be helpful in clinical decision-making. Calculated FT (cFT) appears to be a simple and reliable indicator FT as measurement of FT is difficult.
All blood samples should be obtained in a fasting state, between 08:00 am and 12:00 pm (midday), in view of the diurnal rhythm of serum T. if serum T values are so low that T treatment is considered, the measurement has to be repeated a couple of weeks later, together with the assessment of LH and prolactin.
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Levels below 2 ng/mL (7 nmol/L) are in most cases associated with impairment of sexual function and nocturnal erections while the effect of T seems maximum from the level of 3.5 to 4 ng/mL (12 to 16 nmol/L) and above. There seems to be a gray zone, between 2 and 4 ng/mL where other investigations as cFT level below 65 pg/mL (225 pmol/L) can provide supportive evidence.
Only men who are found to have both low T level and relevant symptoms come within the indications of treatment. The purpose of Testosterone treatment is to bring and maintain serum Testosterone levels within the mid-normal physiological range.
Forms of testosterone therapy are variable and can be taken by different routes. The most frequently used preparations are: injectable as testosterone undecanoate, cypionate and enanthate, oral as testosterone undecanoate, buccal tabs and transdermal as testosterone patches (scrotal and non-scrotal) and testosterone gel.
The oral route is the easiest one to replace but almost completely inactivated by its first pass through the liver. The 17α-alkylated derivatives of T (especially methyltestosterone and fluoxymesterone) are more active, but due to their potential hepatotoxicity these formulations
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should no longer be clinically used. The most active and safe oral formulation is T Undecanoate (TU), However, its absorption is variable and highly dependent on the lipid content of fat of the meal and two, or better three doses, have to be taken daily.
Trans-buccal administration provides the absorption of T through the oral mucosa, avoiding liver inactivation, it requires twice a day applications.
Transdermal preparations are available either as skin patches or as gel, topical solution to be applied to the underarm once a day is also available. The patches can be scrotal and non-scrotal. Dose adjustment should be considered since the skin absorption can vary between men, Patient’s compliance with T gel seems much better than with T patches, but the possibility of T transfer from T gel-treated males to women and children requires specific precautions.
Injectable T preparations in oily depot include short and long acting formulations. The short acting T Enanthate and Cypionate must be injected at intervals of 1 to 2 weeks which may induce supra physiological serum peak levels of T after injection, followed by a rapid decline to sub physiological levels. The long acting T
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Undecanoate shows a more favorable kinetics with serum T levels in the mid normal range for about 12 weeks, and requires only four to five injections a year.
Treatment is contra-indicated in men with Clinical evidence of prostate cancer, any prostatic abnormality suspicious for cancer and Breast cancer.
There is no compelling evidence that high baseline endogenous T or T treatment causes prostate cancer. Treatment is contra-indicated in men with clinical evidence of prostate cancer until more evidence on safety is available.
Treatment in men deemed cured from their prostate cancer seems reassuring but the number of reported cases is still small, and the duration of follow-up often short.
Relative contraindications of Treatment include significant erythrocytosis/polycythemia (hematocrit > 52–54%), severe symptoms of Bladder Outlet Obstruction and Severe obstructive sleep apnea.
Monitoring during therapy is very important to detect any early side effect. In men older than 40 years digital rectal examination (DRE) and PSA measurement are mandatory as baseline before therapy, every 3 to 6 months for the first 12 months and yearly thereafter. Trans-rectal
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ultrasound guided biopsies of the prostate are indicated only if DRE is abnormal or PSA rises above 4.0 ng/ml or more than 1.0 ng/ml in the first 6 months of treatment or more than 0.4 ng/ml/year thereafter