Monitoring tests during testosterone enanthate treatment

Laboratory control is what separates the medical use of testosterone from a risky experiment. Most of the unwanted changes against the background of the drug do not give symptoms for a long time, but are clearly visible in the tests. The editors compiled a structured list of indicators recommended by clinical guidelines and explained why each of them is needed and what errors occur in their interpretation.

Why is laboratory control necessary?

Testosterone enanthate affects many systems simultaneously: blood formation, lipid metabolism, liver, prostate, hormonal axis. For each of these systems, there are simple and accessible analyzes that allow you to see changes long before complaints appear. Therefore, the clinical guidelines of the Endocrine Society (2018) and the American Urological Association (2018) pay special attention to monitoring.

Laboratory control has three tasks. The first is to confirm that the therapy is achieving the goal, that is, the testosterone level is in the target range. The second is to detect side effects in time, primarily erythrocytosis. The third is to watch for conditions that may be affected by testosterone, such as benign hyperplasia or prostate cancer.

A basic examination is carried out before the start of therapy. It confirms the diagnosis of hypogonadism and excludes contraindications: high haematocrit, suspected prostate or breast cancer, untreated severe sleep apnoea, uncontrolled heart failure, plans for conception in the near future.

Further, the analyzes are repeated according to the schedule determined by the doctor. The editors emphasize: even a complete list of tests does not make the non-medical use of supraphysiological doses safe. Analyzes only show what is happening, but do not cancel the changes themselves.

Hormonal panel

Total testosterone. The main indicator of the effectiveness of therapy. The diagnosis of hypogonadism is based on at least two morning fasting tests, and against the background of treatment, the doctor assesses whether the level falls into the average normal range. An Endocrine Society position statement (Rosner et al., 2007) recalls the limitations of immunoassays and the advantage of mass spectrometry for precise measurements.

SHBG and free testosterone. Sex hormone-binding globulin determines how much testosterone is bioavailable. With obesity, type 2 diabetes, changes in thyroid or liver function, total testosterone can be misleading. Free testosterone is then calculated, most often by the Vermeulen formula, or measured by the equilibrium dialysis method.

LH and FSH. Before starting therapy, these hormones help distinguish primary hypogonadism (testicular damage, elevated LH and FSH) from secondary (problem in the pituitary or hypothalamus, low or normal LH and FSH). Against the background of exogenous testosterone, they decrease, which is an expected consequence of axis suppression.

Oestradiol and prolactin. Oestradiol is measured in the presence of symptoms: gynaecomastia, edema, changes in libido. For men, it is desirable to use sensitive methods, because conventional immunoassays are inaccurate at low concentrations. Prolactin is included in the initial examination in secondary hypogonadism to rule out prolactinoma.

Blood, lipids and liver

Haematocrit and haemoglobin are the most important indicators of safety. Endocrine Society guidelines recommend measuring haematocrit before treatment, after 3–6 months, and annually thereafter. A baseline level of more than 50% requires caution, and more than 54% on the background of therapy - a review of treatment until the cause is determined.

Lipidogram (total cholesterol, HDL, LDL, triglycerides) makes it possible to assess cardiovascular risk. Injectable testosterone in physiological doses usually does little to change lipids, but at supraphysiological levels, HDL is markedly reduced.

Liver function tests (ALT, AST, gamma-glutamyl transferase, bilirubin) are less critical for injectable testosterone than for oral 17-alpha-alkylated steroids. However, they remain part of the general assessment. It is worth noting that in individuals who train intensely, ALT and AST levels may be elevated due to muscle damage; therefore, they should be interpreted in conjunction with creatine kinase levels.

Glucose, HbA1c, and creatinine levels help assess metabolic status and kidney function. Creatinine levels in individuals with high muscle mass are often above the normal range without signs of kidney disease; therefore, a doctor may also consider cystatin C levels.

Prostate, heart, and other examinations

PSA (prostate-specific antigen) levels are monitored in men for whom prostate cancer screening is recommended based on age and risk factors. Endocrine Society guidelines recommend assessing PSA levels prior to treatment and again 3–12 months after initiation. A significant rise in PSA or abnormal findings during a digital rectal examination warrant a urology consultation.

Blood pressure is not a laboratory test, but it is a mandatory part of monitoring. Home measurements taken under consistent conditions provide significantly more information than isolated readings taken during a clinic visit.

ECG and echocardiography are not part of routine monitoring for replacement therapy, but a physician may order them if cardiovascular disease, symptoms, or signs of hypertrophy are present. In individuals who have used supraphysiological doses for extended periods, echocardiography allows for the assessment of left ventricular structure and function.

Bone densitometry (DXA) may be appropriate for men with osteoporosis or long-standing hypogonadism. Semen analysis is mandatory for those planning to have children; testosterone suppresses spermatogenesis, and this factor must be considered before therapy begins.

• Before therapy: hormone panel, haematocrit, PSA (age-appropriate), lipids, liver function tests, and semen analysis if indicated.
• After 3–6 months: testosterone, haematocrit, PSA, and assessment of symptoms and blood pressure.
• Thereafter: annual monitoring or more frequently at the physician's discretion.

Timing of tests and common errors

For injectable enanthate, the timing of blood sampling is critical. Endocrine Society guidelines recommend measuring testosterone levels at the midpoint of the injection interval. If the test is performed immediately after an injection, the result will show a peak and may appear alarmingly high; if done just before the next injection, it may create a false impression of an insufficient dose.

A second common mistake is comparing results from different laboratories. Reference ranges and measurement methods vary, so it is best to track changes using a single laboratory and a consistent methodology.

A third mistake is ignoring pre-test conditions. Strenuous exercise the day before, dehydration, sleep deprivation, acute illness, or biotin intake can skew results. Adequate hydration is important for haematocrit levels, while avoiding strenuous exercise for 48 hours is necessary for liver function tests.

Finally, lab tests do not replace clinical assessment. A physician correlates the numerical values ​​with symptoms, medical history, and physical examination findings. Attempting to "adjust" oneself to fit reference ranges based on test results without medical supervision is a recipe for error.

Editorial Conclusions

The minimum monitoring panel for testosterone therapy includes total testosterone, haematocrit, PSA (age-dependent), and a lipid profile; SHBG, free testosterone, LH, FSH, oestradiol, and a semen analysis are added as needed.

Haematocrit is the most critical safety indicator: it is the parameter most likely to exceed the normal range and is directly linked to the risk of thrombosis.

With injectable enanthate, results depend significantly on the timing of the blood draw; therefore, tests should be performed midway between injections and at the same laboratory.

To better understand the significance of these figures, please read our materials on the pharmacokinetics of testosterone enanthate, its effects on the cardiovascular system, and the suppression of endogenous testosterone production.

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. Position statement: 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. Pope HG Jr, Wood RI, Rogol A, et al. Adverse health consequences of performance-enhancing drugs: an Endocrine Society scientific statement. Endocr Rev. 2014;35(3):341–375.
6. European Association of Urology. EAU Guidelines on Sexual and Reproductive Health. Arnhem: EAU; актуальна редакція.