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Low testosterone in men

Male hypogonadism is the failure of the testes to produce adequate amounts of testosterone. This has become a common clinical finding, particularly in the older population. This is probably because of an increased awareness and detection of the problem by physicians rather than a true increase in the prevalence.

The finding of a low blood testosterone needs to be confirmed by an endocrinologist prior to beginning treatment. It is important to determine whether the causes because of the pituitary disorder or because of a testicular disorder.

The Hypothalamic pituitary gonadal axis

Testosterone is produced under the control of luteinizing hormone and sperm control is under the control of follicle-stimulating hormone. These are abbreviated LH and FSH. Testosterone is been produced by the leydig cells and result in a negative feedback inhibition of LH and FSH secretion. Testosterone and estradiol are both pituitary regulators of LH secretion.

Followup on a low testosterone

If a low testosterone is found to be low it is important to determine if it was done at the appropriate time. Serum testosterone levels follow a diurnal rhythm. In younger men, values near 8 AM average 30% higher than the lowest level later on in the day. This diurnal rhythm is lost in older men. The timing of this variation may be different and night shift workers. Another factor affecting testosterone levels is the patient's health status at the time. If the patient has had an acute illness such as pneumonia or infection, testosterone values may decrease considerably.

If an 8 AM testosterone is low, it is appropriate to check another testosterone on the subsequent day along with LH and FSH levels. Of total circulating testosterone: 60% is bound to sex hormone binding globulin (SHBG) and 38% to albumin and only 2% of it is 'free'. All of these fractions can be measured to assess for testosterone deficiency. Free testosterone is the biologic active hormone and is considered to be a better representation of true testosterone status. There are situations in which the total testosterone level is low but free testosterone levels are normal. This can happen when there is an altered SHBG or albumin level in the body. A reduction in the SHBG can happen in obesity, type II diabetes mellitus, malnutrition, liver disease, cirrhosis, acromegaly and hypothyroidism. Sex hormone binding globulin can also be low in patients that take steroids, progestins, or thos who have kidney disease. Regardless of the type of measurement chosen, all testosterone levels should be interpreted with caution if they're not measured at a reliable reference laboratory. Interested patient's can see a list of these locations on the US Centers for Disease Control and prevention- Hormone standardization program website

Clinical features of low testosterone

A history of erectile dysfunction, decreased libido, and fatigue can be seen in in men with low testosterone. It should be noted that the symptoms are very vague and can be seen by patient's with either low testosterone or with many other medical conditions. The physical findings such as muscle weakness and reduce body hair are also seen and low testosterone patients but also in other medical conditions as well. Patients with Kallmans' Syndrome and Kleinfelter's syndrome will have a distinctive appearances.

Primary versus secondary

A history of testicular trauma, chemotherapy, and mumps orchitis may suggest that there is a problem with the testicles. Darkening of her skin, breast milk production, changes in the visual fields, and headaches may direct a physician toward a pituitary problem. Once the low testosterone value has been confirmed then LH and FSH values help direct further evaluation. Semen analysis is usually reserved for patient's that need help with fertility. Thyroid levels and iron levels need to be evaluated for other causes of low testosterone.

Primary hypogonadism
Causes of primary hypogonadism include Klinefelter's syndrome-which is the most common cause, toxin exposure, chemotherapy, congenital defects, orchitis, testicular trauma, hemachromatosis, medications that inhibit androgen synthesis such as ketoconazole, and an increase in a temperature of a testicular environment due to varicoceles

Secondary hypogonadism
There are several causes of secondary hypogonadism which include the following: 
Congenital disorders 
such as Kallman's syndrome, e.g. NRH receptor mutations and genetic mutations associated with pituitary hormone deficiencies
Acquired disorders that suppress gonadotropins
Drugs such as steroids and narcotics and Lupron, obesity related conditions such as type II diabetes and sleep apnea. Also aging especially in men over the age of 60 shows that there may be a loss of circadian rhythm. Hemochromatosis is an iron overload syndrome that can result and low testosterone levels because of iron deposition and hypothalamus pituitary or testes. Hyperprolactinemia is another cause of low testosterone. This can be caused by several other medications. Estrogen excess. Anabolic steroid use, anorexia nervosa, acute illness, HIV, alcohol abuse, severe hypothyroidism
Acquired disorders that damage gonadotropins
This list include pituitary masses or cysts, lymphocytic hypothesize, Langerhans cell histiocytosis, hemachromatosis, sarcoidosis, trauma, radiation exposure, surgery

MRI in evaluating secondary hypogonadism
There is a very low yield on MRI evaluation in older men with secondary hypogonadism. There is little data regarding the appropriate criteria for performing the study. However, patients who have multiple pituitary abnormalities should undergo MRI for evaluation. The endocrine society recommends that MRI be performed to exclude a pituitary mass that the patient has severe secondary hypogonadism especially if the testosterone is less than 150, panhypopituitarism, persistent hyperprolactinemia, or symptoms of tumor mass effect such as headache

Treating the underlying cause only if one can be found
During the evaluation of low testosterone there may be a diagnosis of a clear cause for the condition that we can treat. Such conditions include prolactin elevation or sleep apnea. In these cases treatment should be directed at the underlying cause. Most commonly treating obesity improves testosterone levels. If the prolactin is elevated than the use of a dopamine agonist may be indicated. If there are other hormone deficiencies they should be treated as well. It is important to note that treatment with testosterone can reduce the patient's fertility because it will reduce the amount of semen production.
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