However, there is a lot of research in progress to find out more about the effects of testosterone in older men and also whether the use of testosterone replacement therapy would have any benefits. Patients generally see an improvement in their sex drive and self-esteem following testosterone replacement therapy. Symptoms of male hypogonadism, such as lack of sex drive, inadequate erections (erectile dysfunction) and infertility, can lead to low self-esteem and cause depression. Regular blood tests should be carried out during treatment to check for an increase in red blood cells. It’s treatable with testosterone replacement therapy. It is therefore important that physicians are aware of the major symptoms of the condition and of the treatment options currently available. Its high prevalence in older men, the obese and in men with metabolic syndrome, and type 2 diabetes makes it likely that primary care physicians meet these patients in their clinics every day. There is, however, no established consensus about what constitutes a significant rise in PSA levels or when urological referral should occur for men with normal PSA levels at baseline. There is also the evidence that PSA concentrations are lower in type 2 diabetes patients and related to testosterone concentrations (46,94). In addition, 5 alpha-reductase inhibitors, such as finasteride and dutasteride, reduce prostate volume and PSA levels. For a primary care physician, it might be considered appropriate to refer a patient who requires further testosterone tests to an endocrinologist. Table 8 gives a list of conditions when SHBG levels may be higher or lower than normal. As testosterone is subject to circadian and circannual rhythms it is recommended to draw the blood sample in the morning. Most hospital laboratories can provide total testosterone measurements of good accuracy and reliability. Serum total testosterone is the easiest and most straightforward measurement to take for the first measurement. In our opinion, screening for at-risk patients is therefore worthy of consideration. Screening tools can be helpful in identifying patients with a high probability of having low testosterone. There is a high prevalence of hypogonadism in the middle- and older-aged male population and various prevalence figures have been described in a number of studies. These risks, however, are often exaggerated and should not outweigh the benefits of testosterone treatment. There are a number of formulations available for testosterone therapy including intramuscular injections, transdermal patches, transdermal gels, buccal patches and subcutaneous pellets. 2.6 In men with type 2 diabetes mellitus who have low testosterone concentrations, we recommendagainst testosterone therapy as a means of improving glycemic control. 2.5 We suggest that clinicians consider short-term testosterone therapy in HIV-infected men with low testosterone concentrations and weight loss (when other causes of weight loss have been excluded)to induce and maintain body weight and lean mass gain. Elevated haematocrit values above 54% require action – usually therapy should be stopped until the values decrease to a safe level. Any significant increase in PSA deserves a referral to a urologist and treatment should be discontinued until evaluated. AEs, adverse events; BMD, bone mineral density; DRE, digital rectal examination; PSA, prostate-specific antigen. 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). This is in contrast to what was found in the MMAS study where total testosterone levels were unrelated to all-cause mortality (34,35). In fact, epidemiological analyses have found that HDL levels are positively linked to testosterone levels in middle-aged men. The Massachusetts Male Ageing Study (MMAS) measured a combination of testosterone levels and hypogonadal symptoms and found between 6% and 12% of men had symptomatic androgen deficiency (21). For both men and women, an alternative to testosterone replacement is low-dose clomifene treatment, which can stimulate the body to naturally increase hormone levels while avoiding infertility and other side effects that can result from direct hormone replacement therapy. The free androgen index, essentially a calculation based on total testosterone and sex hormone-binding globulin levels, is the worst predictor of free testosterone levels and should not be used. The standard range given is based on widely varying ages and, given that testosterone levels naturally decrease as humans age, age-group specific averages should be taken into consideration when discussing treatment between doctor and patient. As a result of the concerns about prostate cancer it is important to monitor PSA levels and perform a DRE regularly during the course of treatment. Studies with hypogonadal men have demonstrated that once testosterone levels are restored to a stable normal range, there is an improvement in libido, sexual function, mood and energy levels relatively early in the course of treatment (78,84–86). When looking at the treatment options, it is important to keep in mind that the goal of testosterone replacement therapy is to increase blood testosterone concentrations to the normal (eugonadal) range and to match the most appropriate treatment to the individual patient. Elevated LH and FSH levels suggest primary hypogonadism, whereas low or low-normal LH and FSH levels suggest secondary hypogonadism. The Endocrine Society recommends that the diagnosis of testosterone be made in men who have both consistent signs and symptoms and low total testosterone levels. A negative view of testosterone’s impact on cardiovascular disease comes from the observation that high-density lipoprotein (HDL) cholesterol levels decrease in patients on oral testosterone therapy, or when taken in supraphysiological doses by athletes (29,30). It should be noted that low testosterone can be caused by a combination of both primary and secondary hypogonadism (also called mixed hypogonadism) that reflects defects in the hypothalamus and/or the pituitary as well as the testes.
