Several international medical societies have issued recommendations on the diagnosis, treatment and monitoring of men with hypogonadism, also known as testosterone deficiency:
Guidelines mandate that the diagnosis of hypogonadism is made based on typical symptoms and/or signs combined with a low testosterone level. While there is no universal diagnostic threshold for what should be counted as a low testosterone level, several guidelines recommend <12.1 nmol/L (<350 ng/dL) as a landmark. Because of inter-individual differences in androgen receptor sensitivity, some men can suffer from hypogonadism symptoms/signs despite having “normal” testosterone level. In these patients, a therapeutic trial of testosterone therapy for 12 months may be recommended. Due to less sensitive androgen receptors, these patients may require higher on-treatment testosterone levels in order to achieve symptomatic relief and metabolic benefits.
The aim of testosterone therapy is to restore testosterone levels to a point that results in resolution of symptoms; hence, symptom resolution is a critical indicator of testosterone therapy efficacy.4,12-14 While there is no single optimal target serum testosterone level, clinical guidelines recommend a therapeutic target in the mid to upper part of the reference range.1 The absolute values corresponding to the mid to upper part of the reference range vary among assays and laboratories, but an approximation is 15-30 nmol/L or 433-865 ng/dL.1 Failure to improve clinical symptoms within a reasonable period of time should result in re-evaluation of testosterone therapy with regard to dosage, compliance and achieved testosterone level.13 For more information, see “Testosterone Therapy Practical Advice”
For men with hypogonadism who do not have any contraindications, after initiation of testosterone therapy it is recommended to evaluate patients at 3, 6 and 12 months, and then annually thereafter.
Measure testosterone levels at 3, 6 and 12 months and then annually after starting testosterone therapy. The dose of testosterone therapy should be adjusted to achieve a total testosterone level in the mid to upper normal range. This commonly corresponds to testosterone levels in the range of 15-30 nmol/L or 433-865 ng/dL.6 However, it should be noted that exact values for mid to upper normal range can vary greatly between testosterone lab assays. Due to inter-individual differences in androgen receptor sensitivity, some men may need to reach higher physiological testosterone levels in order to achieve symptomatic relief.
It is critical to keep in mind that maximal benefits of testosterone therapy are seen after 12 months.1 For instance, AMS scores can continue to progressively improve for 2 years and erectile function can continue to progressively improve for up to 9 years with uninterrupted testosterone therapy.15 Maximal improvements in obesity parameters (BMI and waist circumference), glycemic control, lipid profile and bone mineral density also take many years of uninterrupted testosterone therapy to be achieved.15-18 Failure to achieve symptomatic relief in a patient can be an indication that the patient has less sensitive androgen receptors, and may hence require higher testosterone levels to achieve health benefits. These patients may need a larger dose of testosterone therapy and higher target testosterone levels in the high end of the normal range. The vast majority of men who receive effective long-term testosterone therapy will experience symptomatic relief. While symptomatic relief is the primary aim of testosterone therapy, effective treatment will provide a wide range of benefits, such as increased muscle mass and bone mineral density, reduced body fat mass and improved glucose control and lipid profile.15-19 Monitoring and seeing improvements in these objective outcomes during testosterone therapy can help motivate patients to adhere to treatment.
Regular therapeutic phlebotomy may help keep hematocrit below 54%. If not, reduced dose of testosterone therapy is recommended. If hematocrit remains 54%, temporary withholding of testosterone therapy may be necessary until hematocrit returns to below 54%. Testosterone therapy may then be reintroduced at a decreased dose, or a change of testosterone preparation may be advisable. It should be pointed out that the risk of hematocrit elevation is much lower with Nebido® (long-acting testosterone undecanoate injections) than other testosterone preparations. For more information, see our detailed report “Hematocrit elevation following testosterone therapy – does it increase risk of blood clots?”
PSA increases greater than 1.4 ng/mL during any 1-year period after initiation of testosterone therapy or a PSA velocity greater than 0.4 ng/mL per year during sequential PSA measurements over more than 2 years warrant a urologic evaluation and more intensive surveillance for prostate cancer thereafter.1 Men with BPH can be prescribed testosterone therapy; these men can actually experience alleviation of LUTS with long-term testosterone therapy.3,22,23
Monitoring of body weight, waist circumference, lipids and glycemia is not required for safety follow-up, but is useful for monitoring the efficacy of testosterone treatment.1,2 Several long-term “real life” studies in men with overweight and obesity have shown that testosterone therapy significantly reduces body weight, waist circumference and HbA1c, and improves the lipid profile.17,24-28 Seeing improvement in these parameters can be a motivating factor for patients to adhere to testosterone therapy.