Testosterone propionate: understanding laboratory monitoring

Most of the risks of testosterone—from increased hematocrit to lipid changes—are asymptomatic, so testing remains the important part of clinical risk assessment. Testosterone propionate with its short ester also has a special complication: the results are highly dependent on the time of blood sampling. The editors explain what indicators are monitored by doctors, why each of them is needed and how to avoid errors in interpretation.

Why is laboratory control necessary?

Testosterone affects hematopoiesis, lipid metabolism, the hormonal axis, the prostate and the cardiovascular system. Changes in these systems usually develop gradually and are not felt until they become significant. Laboratory tests allow you to see the problem at an early stage, when it is still easy to fix.

In medical practice, control of testosterone therapy is clearly regulated. Clinical guidelines from the Endocrine Society (2018) and the American Urological Association (2018) specify which indicators to check before starting treatment, at what time after starting, and how often thereafter. The goal is to maintain testosterone in the average physiological range and to notice side effects in time.

Basic tests before the start of any therapy have diagnostic value. They confirm that testosterone deficiency really exists, reveal its cause and contraindications. For example, a high hematocrit or elevated PSA may be a reason to delay treatment until further examination.

It is important to understand that tests are not a "permission" for independent use. They should be interpreted by a doctor who sees the general clinical picture, knows the history and can prescribe additional examinations. Independent reading of numbers without context often leads to wrong conclusions.

Hormonal panel

Total testosterone is the primary measure by which deficiency is assessed and diagnosed, and therapy is monitored. To diagnose hypogonadism, the test is taken in the morning on an empty stomach, at least twice. During treatment, the goal is the middle range of the normal range for healthy young men, not the maximum possible values.

SHBG and free testosterone. Sex hormone-binding globulin determines the balance between bound and free testosterone. In obesity, type 2 diabetes, or hypothyroidism, SHBG is often reduced, and in aging or liver disease, it is increased. Free testosterone is usually calculated using the Vermeulen formula, because direct immunological methods, according to the Endocrine Society (Rosner et al., 2007), are not reliable enough.

Estradiol reflects the aromatization of testosterone. It is monitored especially when breast tenderness, fluid retention or mood swings occur. For men, it is desirable to choose laboratories with sensitive methods, optimally — liquid chromatography with mass spectrometry.

LH and FSH show the state of the hypothalamic-pituitary axis. Before treatment, they help distinguish primary hypogonadism from secondary. Against the background of exogenous testosterone, they naturally decrease, and after its withdrawal, their dynamics allow us to assess recovery. According to indications, prolactin and thyroid-stimulating hormone are also checked.

Blood, lipids and heart

A complete blood count with hematocrit is an important monitoring measure. Testosterone stimulates erythrocyte production in a dose-dependent manner (Coviello et al., 2008). The 2018 Endocrine Society guideline treats baseline hematocrit above 48% (above 50% at high altitude) as a relative contraindication. During treatment, a value above 54% requires stopping testosterone and clinical evaluation. Check at baseline, after 3–6 months and then annually.

Lipidogram includes total cholesterol, HDL, LDL and triglycerides. Androgens lower HDL, especially in high doses, so the dynamics of this indicator is an important marker of cardiovascular risk. The analysis is taken on an empty stomach, in a stable condition, without acute diseases.

Glucose and glycated hemoglobin help assess carbohydrate metabolism. The effect of testosterone on glycemia is ambiguous: in deficient men, replacement therapy may improve insulin sensitivity, but at supraphysiological levels and in combination with other substances, the picture may be different.

Outside the laboratory, you should not forget about blood pressure, and according to indications - about ECG and echocardiography. A study by Baggish et al. (2017) showed that long-term use of anabolic steroids is associated with a decrease in left ventricular function that cannot be detected without instrumental examination.

Liver, kidneys, prostate and fertility

Liver tests (ALT, AST, bilirubin, GGT) are more commonly associated with oral 17-alpha-alkylated steroids, which have known hepatotoxicity. Injectable testosterone propionate places much less stress on the liver, but baseline liver tests are usually part of the standard biochemical workup. It should be remembered that ALT and AST can increase after intense training due to muscle damage.

Creatinine and estimated glomerular filtration rate assess kidney function. In people with a large muscle mass, creatinine can be "physiologically" elevated, so sometimes the doctor additionally prescribes cystatin C for a more accurate assessment.

PSA monitoring depends on age, risk and shared decision-making. The 2018 Endocrine Society guideline discusses monitoring for men aged 55–69 and men aged 40–69 at increased risk who choose it. Assessment occurs before treatment and 3–12 months after starting; relevant rises or abnormalities warrant urological review.

Semen analysis is especially important for men who plan to have children. Exogenous testosterone inhibits spermatogenesis, and only ejaculate analysis allows an objective assessment of the situation. A review by Ohlander et al (2016) highlights that testosterone is a common but underappreciated cause of male infertility.

• Biochemistry: ALT, AST, GGT, bilirubin, creatinine, if necessary, cystatin C.
• Urology unit: PSA (in older men), examination by a urologist as indicated.
• Reproductive unit: semen analysis, LH, FSH, inhibin B according to the doctor's decision.

When to submit tests and typical errors

For testosterone propionate, the time of blood sampling is critical. Due to the short half-life, the level of testosterone one day after the injection and three days later may differ several times. Therefore, the doctor usually asks to inform the exact date and time of the last injection, and to compare the results in dynamics — to donate blood at the same moment of the injection cycle.

Diagnostic tests for testosterone (before treatment) are taken in the morning, approximately from 7 to 11 o'clock, on an empty stomach, because the level of the hormone has a daily rhythm and decreases after eating. Acute diseases, lack of sleep, intense training the day before and alcohol can distort the result, so if in doubt, repeat the analysis.

Dehydration, sauna use or intense training can influence hematocrit and complicate interpretation. Lipid tests should follow the laboratory’s preparation instructions and use comparable conditions. Nonfasting lipid testing is often acceptable; fasting is required for some specific assessments, rather than universally.

Finally, results from different laboratories are not always directly comparable: methods and reference intervals differ. To monitor the dynamics, it is advisable to use the services of one laboratory and save all the results so that the doctor can see the complete picture.

Editorial conclusions

Laboratory control is part of clinical risk assessment, not a guarantee that testosterone use is safe. Key indicators are total testosterone, SHBG, estradiol, hematocrit, lipid profile, PSA in older men, LH and FSH, and for those planning children, sperm count.

For testosterone propionate, it is especially important to consider the time of blood collection relative to the injection: without this information, the numbers are easily misinterpreted.

Tests do not replace a doctor's consultation. Only a specialist can combine laboratory data with symptoms, examination and instrumental examinations and make an informed decision.

The editors recommend also reading "Testosterone propionate and the cardiovascular system: lipids, pressure, hematocrit", "Effect of testosterone propionate on own production of testosterone (HPG axis inhibition)" and "Pharmacokinetics of testosterone propionate".

References

1. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715–1744.
2. Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol. 2018;200(2):423–432.
3. Rosner W, Auchus RJ, Azziz R, et al. Utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. J Clin Endocrinol Metab. 2007;92(2):405–413.
4. Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab. 1999;84(10):3666–3672.
5. Coviello AD, Kaplan B, Lakshman KM, et al. Effects of graded doses of testosterone on erythropoiesis in healthy young and older men. J Clin Endocrinol Metab. 2008;93(3):914–919.
6. Baggish AL, Weiner RB, Kanayama G, et al. Cardiovascular toxicity of illicit anabolic-androgenic steroid use. Circulation. 2017;135(21):1991–2002.
7. Ohlander SJ, Lindgren MC, Lipshultz LI. Testosterone and male infertility. Urol Clin North Am. 2016;43(2):195–202.