The Sertoli cells of the testes, in addition to stimulating spermatogenesis, also secrete the glycoprotein hormone inhibin, which provides negative feedback to the pituitary, inhibiting the secretion of FSH (11). For this reason, free and albumin-bound testosterones together are termed bioavailable testosterone (BAT). Testosterone binds strongly to SHBG, and it is therefore largely the free and albumin-bound testosterone that is available for biological action (10). FSH, follicle-stimulating hormone; GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone LH acts on the interstitial Leydig cells of the testes, stimulating them to produce testosterone, whereas FSH stimulates spermatogenesis and Sertoli cell function (6,7). Testosterone injections have been available for at least 50 years and are usually the cheapest choice for treatment. Unless fertility is an issue, it is usually not necessary to measure FSH and determining LH levels alone is sufficient. It is important that physicians use reliable laboratories and that they are aware of their reference ranges for testosterone. As testosterone is subject to circadian and circannual rhythms it is recommended to draw the blood sample in the morning. When LH and FSH treatment is ineffective, pulsatile gonadotropin-releasing hormone replacement therapy might be more effective although less readily available. Replacing testosterone to physiologic levels is not thought to cause new prostate cancer or accelerate growth or spread of localized prostate cancer (2). However, a large multi-institutional trial demonstrated that testosterone replacement therapy was non-inferior to placebo with regard to the risk of major adverse cardiac events (1). If no abnormalities are identified, the diagnosis is acquired idiopathic secondary hypogonadism. TRT is thought to have a minimal effect on serum prostate-specific antigen (PSA) levels in men with benign prostatic hyperplasia and in men with treated prostate cancer. Adults with established testosterone deficiency may benefit from replacement therapy. However, if subsequent fertility is not a concern, TRT alone may be used to treat secondary hypogonadism. To help determine the cause of confirmed secondary hypogonadism, testing should include serum prolactin level (to screen for pituitary adenoma) and transferrin saturation (to screen for hemochromatosis). To confirm secondary hypogonadism in adolescents, the GnRH stimulation test may be considered. Free testosterone levels can be calculated based on SHBG, albumin, and testosterone values; there are calculators available online. Concerns that TRT increases risk of cardiovascular events have been raised in some studies. It is reasonable to convert older adolescents totestosterone gel preparations at adult dosages when their IM dosage has reached the equivalent of 100 to 200 mg every 2 weeks. It is reasonable to convert older adolescents to deficiency receive long-acting testosterone enanthate or testosterone cypionate at a dose that is increased gradually over 18 to 24 months, every 1 to 2 weeks. Older adolescents withtestosterone deficiency receive long-acting testosterone enanthate or testosterone cypionate at a dose that is increased gradually over 18 to 24 months, every 1 to 2 weeks. These are efficacious in establishing eugonadal testosterone levels in the blood and relieving symptoms. Is this because low testosterone causes cardiovascular disease, or because cardiovascular disease and its risk factors suppress testosterone? Men with low testosterone and established coronary artery disease have twice the risk of earlier death compared to eugonadal men with the same diagnosis. So for men with significant symptoms and confirmed low testosterone, the conversation about whether to combine lifestyle changes with treatment is a legitimate clinical one. The data from the Massachusetts Male Aging Study showed that comorbidity and obesity significantly decreased testosterone levels, independent of age. Sufficient testosterone levels help maintain health and well-being in adult males. Low testosterone levels increase fat mass and decrease lean muscle, resulting in increased adipose tissue (52). Low testosterone levels are correlated with insulin resistance in both epidemiological and interventional studies, and this may be attributable to the effect of testosterone on adiposity. Another intriguing observation is that prostate-specific antigen (PSA), a marker for prostate cancer, is significantly lower in type 2 diabetics and this is related to their lower plasma testosterone concentrations (46). The first attempt to measure free testosterone and to establish hypogonadism as a feature of male type 2 diabetes was made by Dhindsa et al. in 2004 (40). A recent study (2009) from Italy demonstrates that testosterone treatment in elderly patients with chronic heart failure improves insulin sensitivity and various cardiorespiratory and muscular outcomes (37). If levels do not increase, true hypogonadism is likely. If the test for free and weakly bound testosterone is available, levels are measured. If 2 semen analyses show abnormalities (oligozoospermia or azoospermia), then hormonal evaluation should be performed to exclude hypogonadism as a potential contributor. Total (and, when possible, free) serum testosterone, serum FSH, and serum LH levels are measured simultaneously. LOH is real, common in men with metabolic risk factors, and routinely missed. That distinction determines the entire treatment approach. But the pattern, particularly when sexual symptoms anchor the picture, is something a doctor should be asking about in any man with relevant comorbidities or complaints. None of these symptoms in isolation confirms LOH.
