How to optimize male hormones according to science

Male hormonal optimization goes well beyond testosterone levels. Dr. Kyle Gillette, a specialist in hormonal medicine, spoke with Andrew Huberman about the pillars of a healthy hormonal environment across the full lifespan: from adolescence through the forties and beyond. The key is not to intervene pharmacologically from the start, but to build a solid foundation before taking that step.

Blood work: what to measure and how often

The starting point is a basic hormonal panel. Gillette recommends measuring total testosterone alongside SHBG (sex hormone-binding globulin), or directly measuring free testosterone, since SHBG determines what fraction of testosterone is available to act on tissues. A review with your physician every six months is sufficient in the absence of acute symptoms.

The core pillars: diet, exercise, and sleep

Nutrition plays a fundamental role in hormone production. During development (adolescence and the twenties), eliminating entire food groups can reduce free androgens. Dairy products contribute to elevated IGF-1, an important growth factor for bone, muscle, and secondary sexual development. Prebiotic fiber establishes the gut microbiome that will accompany the individual for decades.

For exercise, vigorous training three to four times per week for no more than one hour per session is the protocol most favorable to the hormonal profile. Caloric restriction in people without excess body fat reduces testosterone: it lowers available precursors, increases catabolism, reduces GH and IGF-1 signaling, and raises SHBG.

Evidence-based supplements

Gillette reviews several supplements with a scientific basis for those seeking to optimize their hormones without resorting to replacement therapy:

Creatine. Slightly increases total testosterone and promotes the conversion of testosterone to dihydrotestosterone (DHT). It does not raise androgens to supraphysiological levels; it brings the individual closer to their natural potential. Its association with hair loss is not well supported by current evidence.

Betaine. Useful for people who respond poorly to creatine; helps with amino acid synthesis and homocysteine processing. Can be taken at 1-3 g/day.

L-carnitine. Increases androgen receptor density in cells, improving sensitivity to testosterone even without altering its circulating levels. Oral bioavailability is low (approximately 10%), so doses of 1-5 g/day are needed orally.

Tongkat ali (Eurycoma longifolia). Activates several enzymes in the steroidogenesis cascade and raises LH, total and free testosterone, and reduces SHBG in people with elevated SHBG. Standard dose: 300-1,200 mg/day standardized to eurycomanones.

Fadogia agrestis. Stimulates LH release from the pituitary. The safe human-equivalent dose is 300 mg/day, taken on alternating days or three times per week.

Vitamin D3. Acts as a steroid hormone and optimizes testosterone production when deficiency is corrected.

Boron. At 5-12 mg/day, acutely reduces SHBG, releasing more free testosterone.

Testosterone therapy: when and how

TRT only makes sense when levels are clearly below normal range and the patient experiences specific symptoms: reduced libido, poor recovery, or loss of motivation. In young men with in-range levels (300-900 ng/dL), the benefit-to-risk ratio rarely justifies exogenous treatment.

The standard starting protocol is 100-120 mg of testosterone cypionate or enanthate per week, divided into two or three injections. Single bi-weekly doses are less favorable due to the hormonal fluctuations they generate. Follow-up should monitor acne, hair loss, mood changes, blood count, lipid panel, fertility, and cardiovascular markers.

Alcohol and aromatase

Alcohol increases aromatase, the enzyme that converts testosterone to estradiol, in a dose-dependent manner. Gillette recommends limiting consumption to no more than three to four standard drinks every two weeks. Alcohol is also GABAergic and reduces LH and FSH release, directly impacting testosterone production.

Low-dose tadalafil

Tadalafil at 2.5-5 mg/day (not for erectile dysfunction, but for prostate health and blood flow) has an additional benefit: it increases androgen receptor density similarly to L-carnitine. It may also reduce nocturia, improving sleep quality and, secondarily, hormonal optimization.

Conclusion

Optimizing male hormones starts by building a solid foundation: good sleep, regular training, varied nutrition, and stress management. Supplements like creatine, tongkat ali, or L-carnitine can add a marginal benefit without suppressing endogenous production. Testosterone therapy is a powerful tool but requires clinical indication, rigorous monitoring, and a physician who understands all the systems that interact with the hormone.