Testosterone replacement is the best-studied hormone treatment in men, with large randomized trials behind it. Those trials did not test every form, and they did not all measure the same things. This article explains what was tested, how the medicine is monitored, and where fertility fits.
Forms and routes
The large trials used a 1.62% gel applied daily (TRAVERSE) or intramuscular injections (T4DM used 1,000 mg of testosterone undecanoate every 12 weeks for 24 months). Troches, creams and hydrogels deliver the hormone differently, so the trial numbers describe those forms only indirectly.
Oral testosterone undecanoate (Kyzatrex) is a separate product, taken with food and adjusted to blood levels. Its own study is described in our oral testosterone article.
What the trials measured
- Testosterone Trials (2016 to 2017) tested older men with low testosterone on sexual function, physical function, vitality, cognition, anemia, bone and coronary plaque. The authors reported improvements in sexual function, walking and bone density, no gain in vitality or cognition, and an increase in coronary noncalcified plaque volume (Snyder et al., Endocr Rev 2018).
- TRAVERSE tested major cardiac events. Its findings are in our heart article and are not repeated here.
- T4DM tested blood sugar in men with prediabetes who were also in a lifestyle programme (see the benefits above).
Dose and monitoring
The Endocrine Society guideline asks clinicians to check prostate risk before starting and again three to twelve months after starting. A confirmed PSA rise above 1.4 ng/mL in the first year calls for urology review; after the first year, prostate screening follows standard practice (Bhasin et al., JCEM 2018).
Raised hematocrit is a contraindication at baseline. The Testosterone Trials confirmed that testosterone increases the risk of erythrocytosis (a high red-cell count), so hematocrit is measured during treatment. The guideline does not give one hematocrit threshold for every man, so the threshold your clinic uses belongs in your treatment plan.
Estradiol is measured in many clinics because testosterone is converted to estradiol. The guideline does not set an estradiol target in the text we reviewed; our physicians set the target for you.
Fertility, hCG and enclomiphene
Testosterone suppresses the pituitary signals that drive sperm production. In one retrospective series of hypogonadal men on testosterone plus low-dose hCG, semen parameters were maintained during treatment (26 men, mean follow-up 6.2 months; Hsieh et al., J Urol 2013).
Enclomiphene and clomiphene raise the body's own testosterone while keeping sperm production. A 2025 pooled analysis found that these SERMs raised total testosterone by about 274 ng/dL against placebo (see our enclomiphene and clomiphene articles).
A 2026 trial protocol states that randomized evidence that hCG improves sperm availability is still lacking (Chandra et al., Front Reprod Health 2026).
What this does not say
- The trial results describe averages in men who met each study's criteria. They are not predictions for one man, and they do not describe compounded products.
- The blood-sugar result is a prevention outcome in men without a hypogonadism diagnosis. It is not a labelled use.
- The trials ran for one year (Testosterone Trials) to about 33 months (TRAVERSE). Longer outcomes are not established.
How we use this
We start testosterone only after a diagnosis of low testosterone with symptoms, and we check your levels, hematocrit, prostate markers and estradiol as the plan requires. Fertility is discussed before treatment, because it changes which medicines fit.
We do not promise the trial outcomes. We use them to explain what the medicine can and cannot do, and what we will measure along the way.
Explore weight loss treatmentsSources
- 1.Snyder PJ et al. Effects of testosterone treatment in older men (Testosterone Trials). N Engl J Med 2016. NEJM
- 2.Snyder PJ et al. Lessons from the Testosterone Trials. Endocr Rev 2018. Endocrine Reviews
- 3.Roy CN et al. Association of testosterone levels with anemia in older men: a controlled clinical trial. JAMA Intern Med 2017. JAMA Internal Medicine
- 4.Bhasin S et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2018. Endocrine Society
- 5.Wittert G et al. Testosterone treatment to prevent or revert type 2 diabetes in men enrolled in a lifestyle programme (T4DM). Lancet Diabetes Endocrinol 2021. The Lancet Diabetes & Endocrinology
- 6.Long-term outcomes of testosterone treatment in men: a T4DM post-randomisation observational follow-up study. J Clin Endocrinol Metab 2023. Journal of Clinical Endocrinology & Metabolism
- 7.Hsieh TC et al. Concomitant intramuscular human chorionic gonadotropin preserves spermatogenesis in men undergoing testosterone replacement therapy. J Urol 2013. The Journal of Urology
- 8.Chandra V et al. Gonadotropin therapy in idiopathic hypogonadal non-obstructive azoospermia (APHRODITE Groups 3-4): a multicenter randomized controlled trial (protocol). Front Reprod Health 2026. Frontiers in Reproductive Health