Hormonal decline is not a disease. It is a predictable feature of aging. Total testosterone in men decreases approximately 1-2% per year after age 30, and bioavailable testosterone declines even faster as sex hormone-binding globulin (SHBG) rises [1]. DHEA follows a similar trajectory. Thyroid function subtly shifts. Growth hormone secretion falls.
The question is not whether this decline happens — it does, measurably. The question is whether correcting it improves health outcomes, and if so, for whom and how.
Here is what I tell my patients: hormonal optimization is one of the most evidence-supported interventions in longevity medicine, but only when it is done correctly. That means treating documented deficiencies, not chasing supraphysiological levels. It means monitoring carefully. And it means understanding that hormones are part of a system — optimizing one in isolation while ignoring the others rarely produces the results patients expect.
Testosterone
When Replacement Makes Sense
The TRAVERSE trial, published in 2023, was a landmark moment for testosterone replacement therapy (TRT). This large, randomized, placebo-controlled trial in over 5,000 men with hypogonadism demonstrated that testosterone replacement did not increase cardiovascular risk — addressing a concern that had shadowed the field for a decade [2].
The evidence supports testosterone replacement in men with:
- Documented low total testosterone (typically below 300 ng/dL on morning draws) or low free/bioavailable testosterone
- Symptoms consistent with hypogonadism: persistent fatigue, reduced muscle mass, increased body fat, decreased libido, cognitive complaints, depressed mood
- No contraindications (untreated prostate cancer, severe polycythemia, uncontrolled heart failure)
In these patients, the clinical data shows meaningful improvements in body composition, bone density, sexual function, mood, and quality of life [3].
What I Do Differently
Many clinics prescribe testosterone based on a single blood draw. In my practice, I require at least two morning measurements (testosterone is highest in the morning and can vary day to day) along with a comprehensive hormonal panel including free testosterone, SHBG, estradiol, LH, FSH, prolactin, and thyroid function. The pattern matters as much as the absolute numbers.
I also investigate why testosterone is low before simply replacing it. Common and treatable causes include:
- Sleep deprivation (particularly sleep apnea)
- Obesity and insulin resistance
- Chronic stress and elevated cortisol
- Medications (opioids, certain antidepressants)
- Micronutrient deficiencies (zinc, vitamin D, magnesium)
Addressing these root causes sometimes resolves the deficiency without exogenous testosterone. When replacement is indicated, I prefer bioidentical testosterone administered via transdermal gel or injection, titrated to restore levels to the upper-normal physiological range — not to supraphysiological levels.
Monitoring
Testosterone replacement requires ongoing monitoring:
- Hematocrit and hemoglobin (testosterone stimulates erythropoiesis; polycythemia is a real risk)
- Estradiol (aromatization of testosterone can cause elevated estrogen)
- PSA (while TRT does not cause prostate cancer, monitoring is prudent)
- Lipid profile
- Liver and kidney function
- Symptom assessment
DHEA
Dehydroepiandrosterone (DHEA) is the most abundant circulating steroid hormone and serves as a precursor to both testosterone and estrogen. DHEA levels peak in the mid-twenties and decline approximately 2-3% per year thereafter.
The evidence for DHEA supplementation is more modest than for testosterone. Controlled trials have shown benefits for bone density, skin health, sexual function, and mood in some populations, particularly women (covered in the women’s hormone article) and older adults with very low levels [4].
In my practice, I measure DHEA-S levels and consider supplementation (typically 25-50 mg daily for men) when levels are significantly below age-appropriate ranges and symptoms are consistent. I monitor levels and adjust accordingly. DHEA is available without prescription in many countries, but I recommend medical supervision because it can influence multiple downstream hormones.
Thyroid
Thyroid function is frequently undertreated in conventional medicine, particularly subclinical hypothyroidism. Standard screening relies on TSH, which is a reasonable starting point but insufficient for complete assessment.
In my longevity assessments, I evaluate:
- TSH
- Free T4 and Free T3
- Reverse T3
- Thyroid antibodies (anti-TPO, anti-thyroglobulin)
The pattern I see frequently: TSH within the “normal” reference range (which is broad — 0.4 to 4.5 mIU/L in most laboratories) but free T3 in the lower quartile, with symptoms of fatigue, cold intolerance, weight gain, and cognitive sluggishness. Whether treating these patients improves outcomes is debated in endocrinology. In my clinical experience, careful thyroid optimization — targeting a TSH in the lower half of the reference range with adequate free T3 levels — produces meaningful symptomatic improvement in a substantial proportion of patients.
I want to be direct: this is an area where clinical practice and guideline medicine diverge. I document my rationale, monitor closely, and adjust based on both laboratory values and clinical response.
Growth Hormone
Growth hormone (GH) and its mediator IGF-1 decline with age. The temptation to replace GH for anti-aging purposes is understandable given its effects on body composition, skin quality, and energy.
However, the evidence here requires careful interpretation. Exogenous growth hormone at replacement doses has demonstrated improvements in body composition and quality of life in adults with genuine GH deficiency [5]. But GH replacement in aging adults without documented deficiency carries meaningful risks, including insulin resistance, fluid retention, joint pain, and — more concerning — a theoretical increased cancer risk due to IGF-1’s role in cell proliferation.
The animal data is particularly sobering: growth hormone receptor knockout mice (Laron dwarfism model) actually live longer than their wild-type counterparts. High IGF-1 levels are associated with increased cancer risk in epidemiological studies.
My position: I test IGF-1 and consider GH status as part of a comprehensive assessment. I do not routinely prescribe growth hormone for longevity purposes unless there is documented deficiency. For patients interested in supporting their natural GH production, optimizing sleep (GH is secreted primarily during deep sleep), maintaining adequate protein intake, and regular high-intensity exercise are the evidence-based approaches.
The Integrated Approach
Hormones do not function in isolation. Testosterone, thyroid, cortisol, insulin, DHEA, and growth hormone exist in a dynamic equilibrium. Optimizing one while ignoring the others is like tuning a single instrument in an orchestra — technically correct but practically insufficient.
What I have learned over years of practice is that the best outcomes come from addressing the complete hormonal picture in the context of the patient’s metabolic health, sleep quality, stress management, and nutritional status. Hormonal optimization is a powerful tool. It is not the entire toolkit.
References
- Harman SM, et al. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Journal of Clinical Endocrinology & Metabolism. 2001;86(2):724-731.
- Lincoff AM, et al. Cardiovascular Safety of Testosterone-Replacement Therapy. New England Journal of Medicine. 2023;389(2):107-117.
- Snyder PJ, et al. Effects of Testosterone Treatment in Older Men. New England Journal of Medicine. 2016;374(7):611-624.
- Rutkowski K, et al. Dehydroepiandrosterone (DHEA): hypes and hopes. Drugs. 2014;74(11):1195-1207.
- Hoffman AR, et al. Growth hormone (GH) replacement therapy in adult-onset GH deficiency. Endocrine Reviews. 2019;40(3):880-921.
This content is educational and does not constitute medical advice. Hormone therapy requires proper diagnosis, prescription, and medical monitoring.
