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Margaret Wierman, MD and Andrew Buelt, DO

  • ‘Low T’ by itself is not an indication for testosterone supplementation.

    Pearls:

    • Diagnosing hypogonadism requires a testosterone level below the normal range PLUS associated signs and symptoms.

    • Symptoms of hypogonadism include sexual dysfunction, erectile dysfunction, decreased libido, fatigue, and decreased muscle mass.

    • Hypogonadism can be a primary disorder (due to testicular malfunction) or a secondary one (due to a hypothalamic or pituitary cause).

    • Potential causes of acquired hypogonadism and/or low testosterone levels are opiate use, sleep apnea, and marijuana.

    • Laboratory studies to consider in a patient with suspected hypogonadism are a testosterone level, FSH, LH, and a prolactin level.

    • For patients with low testosterone levels, the LH and FSH can help determine if the cause is central (FSH and LH low or low-normal) or due to a testicular disorder (FSH and LH high or high-normal).

    • Hypogonadism is a complex of signs and symptoms which are associated with a testosterone level below the normal range.  Symptoms can be both specific and nonspecific.

      • Specific symptoms include sexual dysfunction, erectile dysfunction, and decreased libido.

      • Nonspecific symptoms are fatigue, decreased muscle mass, and loss of body hair.

      • The diagnosis of hypogonadism requires at least two testosterone levels below the normal range plus associated signs and symptoms.

    • Hypogonadism is a disorder of one of the three parts of  the testosterone axis:  the hypothalamus (the brain GnRH pulse generator), the pituitary (which releases FSH and LH; LH in turn triggers testicular testosterone production) , or the testes.  A problem with any of these three can result in low testosterone levels.

      • Primary hypogonadism is  due to testicular disorders.  Testicular damage can occur in utero or postnatally.

        • Mumps orchitis, undescended testes, genetic disorders (such as Klinefelter syndrome), testicular trauma, and radiation therapy can all lead to low testosterone levels.

        • Acquired primary hypogonadism can be due to drugs or medications.

          • Opiates are known to cause reduced testosterone levels.  A dose of 40-45 mg of methadone or morphine equivalent will result in the testosterone level falling below 200.

          • Marijuana can cause hypogonadism.

      • Secondary hypogonadism is due to either malfunction of the hypothalamus or the pituitary.

        • Idiopathic hypogonadotropic hypogonadism is a deficiency of GnRH.  It is rare, affecting 1:5000 men, and manifests as a failure to undergo puberty in a male.

        • Tumors of the hypothalamus or abnormal development of the hypothalamus (Kallmann syndrome).

        • Tumors of the pituitary, such as craniopharyngiomas, prolactinomas, and Rathke cleft cysts.

        • Tumors which secrete LH and FSH that are biologically inactive, therefore reducing testosterone production.  This is also called a non-functioning gonadotropin tumor.

        • Glucocorticoids, especially in the injectable form, can suppress testosterone production.

        • Supplements and even protein powders can be contaminated with prohormones, such as DHEA, which converts into weak androgens.  The androgens suppresses the GnRH pulse generator so that testosterone drops either temporarily or permanently.

        • Obstructive sleep apnea can cause low testosterone levels.  When the tongue falls back at night, the oxygen level drops.  This causes an increase in cortisol levels which contributes to  insulin resistance, weight gain and hypertension.  The GnRH pulse generator gets slightly depressed, ultimately leading to low testosterone levels.

    • When evaluating a patient with hypogonadism, it is important to take a careful history.

      • Understanding the timing and onset of puberty is helpful, to make sure that it went normally.

      • Determine when the signs and symptoms of hypogonadism began.

      • Distinguish between decreased libido due to hypogonadism and erectile dysfunction.

        • Erectile dysfunction has 5 major causes:

          • Vascular — predicted by hypertension or hyperlipidemia.

          • Neurologic — may be due to alcohol, diabetes, spinal cord injury.

          • Hormonal

          • Psychogenic — due to stress or performance anxiety.

          • Iatrogenic — often due to medications.

        • Testosterone does not benefit most men with erectile dysfunction unless they also have a low testosterone.

    • Which laboratory studies should be ordered on a patient with suspected hypogonadism?  How frequently should they be repeated?

      • Primary care doctors who suspect hypogonadism should order a total testosterone level.  Optimally, the blood should be drawn in the morning, since levels naturally decline as the day goes on.  Additional labs to consider are an LH, FSH, prolactin level and, if symptoms suggest it, thyroid function tests.

      • The current assays for measuring testosterone levels are done on a platform, although some labs are now using mass spectrometry.

      • Many insurance companies and the current guidelines from the endocrine society recommend two testosterone levels.

      • The more commonly used platform assays detect testosterone in the range of 240-800 ng/dL (8.3-27.7 nmol/L)  and have a poor sensitivity and specificity, especially in the lower range.

      • The range for testosterone levels is wide because when measuring total testosterone, we are measuring free testosterone as well as the proteins with which it circulates, namely sex  hormone binding globulin (SHBG).

        • Young men make lots of SHBG, so their total testosterone level will be higher within the normal range.

        • As men age, their SHBG decreases as a result of age and insulin resistance.  This is reflected in a lower total testosterone level (but still within the normal range).

        • The available assays unfortunately do not detect only free testosterone.

    • When a patient’s testosterone level is low, how do you interpret lab test results to try to identify the cause of hypogonadism?

      • If the LH and FSH are normal or low, that suggests a central or secondary cause of hypogonadism, a problem originating from the hypothalamus or the pituitary gland.

      • If the FSH and/or LH are high or high-normal, the cause is more likely a primary testicular defect.   As the testes fail, FSH goes up first, followed by a rise in LH.

      • If the patient’s testosterone level is very low, such as 100 or 150 (3.5-5.2 nmol/L), and the LH and FSH are undetectable, the patient may be taking an anabolic steroid.