Proper follow-up of men receiving testosterone therapy should include:
- Monitoring of testosterone levels.
- Confirmation of symptomatic improvement.
- Checking for any changes in haematocrit, PSA and digital rectal examination.15
Monitoring of serum testosterone levels
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 serum level within the lower third of the normal range. This commonly corresponds to testosterone levels in the range of 15-30 nmol/L.1 However, it should be noted that exact values 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 achieve symptomatic relief.
Monitoring of symptomatic improvement
The primary aim of testosterone therapy is to alleviate symptoms of low testosterone. It is recommended that clinical assessment of symptoms is done by the use of validated questionnaires, such as the Ageing Male Symptoms Scale . The AMS provides a quantitative assessment of the severity of baseline symptoms, and the progressive symptomatic response to testosterone therapy.
It is critical to keep in mind that potential maximal benefits of testosterone therapy may be seen after 12 months.1 For instance, AMS scores may continue to progressively improve for 2 years and erectile function may continue to progressively improve for up to 9 years with uninterrupted testosterone treatment for a long period of time.16 Potential 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.16-19
While symptomatic relief is the primary aim of testosterone therapy, treatment may provide other secondary benefits, such as increased muscle mass and bone mineral density, reduced body fat mass and improved glucose control and lipid profile.16-20 Monitoring and seeing improvements in these objective outcomes during testosterone therapy can help motivate patients to adhere to treatment.
Monitoring of hematocrit
Measure haematocrit levels at 3, 6 and 12 months and then annually after starting testosterone therapy.
Elevated haematocrit, defined as 54% or higher by most guidelines, is the most common side-effect of testosterone therapy and is caused by testosterone-induced erythrocytosis.
The clinical significance of a high haematocrit is unclear, but theoretically it may be associated with increased blood viscosity and thrombosis, although this has not been proven.21 The effect of testosterone therapy on erythropoiesis and haematocrit may become evident after 3 months and reaches a plateau at 9-12 months after start of testosterone therapy.22
Regular therapeutic phlebotomy may help keep haematocrit below 54%. If not, reduced dose frequency of testosterone therapy is recommended. If haematocrit remains 54%, temporary withholding of testosterone therapy may be necessary until haematocrit returns to below 54%.23 Testosterone therapy may then be reintroduced at a decreased dose, or a change of testosterone preparation may be advisable.
Monitoring of PSA and DRE (digital rectal examination)
Assess prostate health by checking PSA level and performing a digital rectal examination before the start of testosterone replacement therapy.
PSA should be measured at 3-6 months, 12 months and then annually thereafter. Men at high risk for prostate cancer may need more in-depth prostate monitoring by a urologist.
For patients who have an elevated PSA at baseline, a second confirmatory PSA measurement is recommended to rule out a spurious elevation. In patients who have two baseline PSA tests that raise suspicion for the presence of prostate cancer, referral to a urologist for a more in-depth prostate examination (which may include reflex testing and/or prostate biopsy) is recommended before initiating testosterone therapy.
Men with very low testosterone levels before start of testosterone therapy are more likely to experience elevation in PSA, albeit within the normal range. When PSA increases, it commonly does so over the first 6-12 months, then no further increases are usually seen with continued testosterone therapy.21
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 may experience alleviation of LUTS with long-term testosterone therapy. However, BPH is a known common side effect of testosterone therapy and renal/urinary disorders are a known uncommon side effect.3,4,24
Monitoring of body weight, waist circumference, lipids and glycemic control
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 signfiicantly (P<0.0001) reduces body weight, waist circumference and HbA1c, and improves the lipid profile vs untreated group.17,25-29 Seeing improvement in these parameters can be a motivating factor for patients to adhere to testosterone therapy.
Monitoring of bone mineral density
In men with low bone mineral density or osteoporosis before initiation of testosterone therapy, it is recommended to repeatedly measure bone mineral density with DEXA (dual energy x-ray absorptiometry) every 1–2 years after start of testosterone therapy.1,2