Testosterone therapy is, for most men who start it, indefinite. Endogenous production is suppressed within weeks and may not fully recover. That makes the decision to initiate a genuinely consequential one, and it deserves more structure than 'his level was low and he wanted to feel better.' This Part is the checkpoint between diagnosis and prescription.
Correct These First
| Contributor | What to do | What to expect |
|---|---|---|
| Obesity, particularly visceral adiposity | Structured weight management; consider anti-obesity pharmacotherapy where indicated | Meaningful weight loss raises total and free testosterone; effect scales with the magnitude of loss |
| Untreated obstructive sleep apnea | Sleep study and treatment | Improves fatigue and libido directly; axis suppression may partially reverse |
| Chronic opioid therapy | Taper, rotate, or reduce dose in collaboration with the prescriber | Opioid-induced androgen deficiency is often substantially reversible on dose reduction |
| Glucocorticoids | Use the lowest effective dose; reassess after taper | Suppression is dose-dependent and often reversible |
| Poorly controlled type 2 diabetes and metabolic syndrome | Optimize glycemic control and lifestyle | Improvement in insulin sensitivity raises SHBG and often testosterone |
| Heavy alcohol use | Reduction and assessment for use disorder | Direct gonadal and hepatic effects improve with reduction |
| Hyperprolactinemia | Identify cause; treat the prolactinoma or offending medication | Treating the cause frequently restores the axis without testosterone |
| Iron overload / hemochromatosis | Ferritin and transferrin saturation; treat the underlying disorder | Early treatment may preserve pituitary function |
Weight loss and OSA treatment effects on testosterone are supported by consistent observational data and several intervention trials; opioid effects are supported by cohort and interventional evidence.
Contraindications
Do not initiate
- Active breast cancer.
- Active or untreated prostate cancer, outside of specialist-directed management.
- Desire for fertility in the near term (see the fertility branch below).
- Hematocrit above roughly 54 percent prior to treatment, until evaluated and corrected.
- Untreated severe obstructive sleep apnea.
- Uncontrolled or severe heart failure.
- Myocardial infarction or stroke within the preceding three to six months.
- Uncontrolled or poorly controlled severe lower urinary tract symptoms with a high IPSS score.
- Thrombophilia or unprovoked venous thromboembolism, pending hematology input.
Evaluate before initiating
- Palpable prostate nodule or induration, or a PSA above the age-appropriate threshold — urology evaluation first.
- Elevated baseline hematocrit between roughly 50 and 54 percent — identify the cause, consider a non-injectable formulation with lower erythrocytosis risk.
- History of venous thromboembolism.
- Planned pregnancy in the next one to two years.
The Fertility Branch Point
Every man of reproductive age must be asked directly: do you want to father children, now or in the future? If the answer is yes or uncertain, exogenous testosterone is generally the wrong first choice. Suppression of intratesticular testosterone reduces sperm production, and azoospermia occurs in a substantial proportion of men on therapy. Recovery after discontinuation is usual but takes months to years and is not universal.
- 1Does he want children now or in the future?
- 2Yes or uncertain → do not start testosterone monotherapy
- 3Consider referral to reproductive urology
- 4Options include hCG, SERM therapy (off-label), aromatase inhibition where appropriate
- 5Sperm cryopreservation before any androgen exposure
- 6No, and family complete → testosterone therapy is reasonable, still counsel and document
Human chorionic gonadotropin acts at the LH receptor and therefore maintains intratesticular testosterone and Leydig cell function, which is the mechanistic basis for its use in men who want to preserve fertility. Selective estrogen receptor modulators such as clomiphene citrate raise endogenous LH and FSH by blocking central estrogen negative feedback; this use is off-label in the United States and should be framed that way with patients. Aromatase inhibitors have a narrower role and should generally be specialist-directed. These are not interchangeable with testosterone replacement and are best co-managed with reproductive urology.
hCG and SERM effects on gonadotropins and semen parameters are supported by consistent observational series and smaller trials; large outcome RCTs are lacking, and several uses are off-label.
Documenting the Decision
- Two confirmatory early-morning fasting testosterone values with dates and the assay used.
- LH and FSH with classification of primary versus secondary.
- Reversible contributors identified and what was done about each.
- Symptoms being targeted, stated in the patient's words, and the specific outcome you will reassess.
- Fertility intent, explicitly asked and documented.
- Baseline hematocrit, PSA where age-appropriate, and prostate examination findings.
- Risks discussed: erythrocytosis, infertility, acne, gynecomastia, sleep apnea worsening, cardiovascular counseling per current labeling, and the indefinite nature of therapy.
- Alternatives discussed, including no treatment and treatment of the reversible contributors alone.
- The patient's stated preference and the agreed monitoring plan.
The hematocrit you noticed before you started
A 58-year-old man with confirmed testosterone deficiency (two morning values of 220 and 240 ng/dL, LH 3.1 IU/L) requests treatment for low libido and fatigue. Baseline labs show hematocrit 52.5 percent and hemoglobin 17.6 g/dL. He is a former smoker with a 30-pack-year history, BMI 31, and reports loud snoring. PSA is 1.2 ng/mL and the prostate examination is normal.
How should you proceed?