Patients who qualify for TRT should have their serum levels of free and total testosterone, estradiol, hematocrit, and PSA measured before starting TRT. Questionnaires, such as the Androgen Deficiency in the Aging Male (ADAM) questionnaire or the aging male symptoms (AMS) rating, can help evaluate the symptoms of hypogonadism. Dhindsa et al. found that 50% of obese diabetic men above 45 years old have low free testosterone levels (13). Grosman et al. found that hypertension, increased triglycerides and elevated waist circumference have the strongest association with decreased testosterone (12).
The effects of testosterone therapy on cardiovascular health remain unclear. As part of the Choosing Wisely campaign, the American Urological Association says physicians should not prescribe testosterone therapy for men with erectile dysfunction and normal testosterone levels.20 There is some evidence supporting the use of testosterone therapy as second-line therapy in men with low testosterone when phosphodiesterase-5 inhibitors are ineffective.18,19 There is no evidence that testosterone improves erectile function in men with normal testosterone levels. Because of circadian variations in testosterone levels, serum testosterone measurement should occur in the morning, or within two hours of awakening in shift workers (Figure 19 ).
The ratio of estradiol to androgens is the key factor in the development of gynecomastia rather than absolute increases in androgens themselves. Exogenous testosterone is known to cause an imbalance in the hypothalamic-pituitary axis. Case reports regarding testosterone supplementation leading to changes in hair patterns have been documented; however no randomized, placebo-controlled trials exist. While polycythemia may be an adverse side-effect, this is a potential benefit in patients with chronic renal failure and anemia. In patients with end-stage renal disease (ESRD) on dialysis, fluid shifts are less of a concern in patients on TRT since the fluid retention can be handled with dialysis. It has also been shown that TRT may improve hepatic function in patients with end-stage liver disease.
But there aren’t many studies on the long-term effects of TRT (for example, over decades). If you stop taking testosterone, your levels will return to baseline. This is because if your symptoms don’t improve, your testosterone level may not be the cause of your symptom. But it’s important to remember that TRT comes with potential risks and side effects.
The autoinjector is filled with 50, 75 or 100 mg of testosterone in sesame oil and the recommended starting dose is 75 mg every week. The starting dose of testosterone enanthate or cypionate is 200 (or 250) mg intramuscularly every two weeks in adult men. Testosterone enanthate injection was the main testosterone preparation for therapeutic use in hypogonadal men for over 50 years.71 Testosterone enanthate (Delatestryl®) and testosterone cypionate (Depo-Testosterone®) formulated in sesame or cotton seed oil, respectively, have similar pharmacokinetics.
One under-discussed aspect of low testosterone? "We never just give you testosterone and send you on your way," Pemdejian explains. Harvard Health emphasizes that TRT should be tailored to the individual and revisited frequently to minimize risks and optimize outcomes.

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