Hormone Health & Longevity: Why Hormones Matter for Both Women and Men

Written By Sam Hetz

Hormones play a central role in how we age — influencing metabolism, cognition, bone health, mood, and cardiovascular risk. In both women and men, hormonal balance is not just about symptom relief — it’s a foundational element of longevity medicine. At LifespanMD, we integrate hormone care — including hormone replacement therapy (HRT) for women and testosterone replacement therapy (TRT) for men — into a broader framework of metabolic optimization, fitness, and preventative diagnostics.

Women’s Hormone Therapy: Evidence and Longevity

Mortality & Longevity Signals

Large-scale studies have shown that postmenopausal hormone therapy can reduce overall mortality and chronic disease risk when started near the onset of menopause:

  • A 2020 meta-analysis found that estrogen therapy was associated with a 20–50% lower all-cause mortality in users versus non-users【1】.

  • Combined HRT (estrogen + progestin) was linked to a 9% reduction in all-cause mortality in a UK cohort【2】.

  • Women using HRT showed slower biological (epigenetic) aging, suggesting a potential impact on longevity【3】.

These benefits appear greatest when therapy is initiated earlier in the menopausal transition — supporting what researchers call the “timing hypothesis.”

Timing & Cardiovascular Protection

The ELITE trial demonstrated that estrogen therapy begun within 6 years of menopause helped maintain healthier blood vessel function compared to starting more than 10 years after menopause【4】. Similarly, the American Heart Association (2023) concluded that menopausal hormone therapy can be beneficial for symptomatic women under 60, provided cardiovascular risks are assessed and managed【5】.

Molecular & Antioxidant Mechanisms

Beyond symptom relief, estrogens influence cellular health and longevity pathways. Studies show estrogen replacement upregulates antioxidant genes and supports mitochondrial function, helping reduce oxidative stress and vascular aging【6】.

Risks & Caveats

While benefits are clear for many women, hormone therapy is not without some risk:

  • The Women’s Health Initiative (WHI) trial found increased risks of breast cancer, stroke, and venous thromboembolism (VTE) with certain formulations, especially in women starting HRT late after menopause【7】.

  • The EVTET trial found increased recurrence of VTE among women with prior thrombosis using oral estrogen + progestin【8】.

  • A large international meta-analysis confirmed that combined estrogen–progestin therapy very modestly increases breast cancer risk, emphasizing the need for individualized care【9】.

At LifespanMD, we mitigate these risks by using transdermal routes, lower doses, and bioidentical formulations when appropriate — always guided by individualized risk assessment.

Men’s Hormonal Health & Testosterone Therapy (TRT)

Low Testosterone and Healthspan

For men, testosterone levels gradually decline beginning in their 30s — a process sometimes called andropause. Low testosterone is linked to decreased muscle mass, fatigue, low mood, and metabolic dysfunction.

Population data show that men with lower endogenous testosterone have higher risks of all-cause and cardiovascular mortality【10】. This association suggests testosterone may act as a biomarker of vitality — and potentially a modifiable one.

Clinical Evidence for TRT

Randomized controlled trials and meta-analyses provide support for carefully monitored testosterone therapy in men with confirmed hypogonadism:

  • The Testosterone Trials (NEJM 2016) found that TRT improved sexual function, mood, and bone density compared with placebo【11】.

  • A 2023 review in Drugs & Aging summarized that TRT can safely improve energy, muscle strength, and quality of life in selected older men when monitored appropriately【12】.

  • A meta-analysis in Int. J. Mol. Sci. (2023) reported improvements in waist circumference and triglycerides, indicating potential metabolic benefits【13】.

  • The TRAVERSE trial (NEJM 2023) showed TRT was non-inferior to placebo for major adverse cardiovascular events, supporting its cardiovascular safety when prescribed responsibly【14】.

Risks and Monitoring

While most recent data suggest TRT is safe in properly selected patients, potential concerns include elevated hematocrit, reduced HDL, and prostate monitoring requirements. A meta-analysis of randomized trials found no overall increase in cardiovascular events but emphasized the importance of ongoing evaluation【15】.

At LifespanMD, TRT is not in isolation, but through a combination approach, included:

  • Comprehensive hormone and metabolic testing (testosterone, SHBG, estradiol, LH, insulin, ApoB)

  • VO₂ max and body composition assessment

  • Ongoing cardiovascular and prostate screening

  • Lifestyle and nutritional integration

“Optimizing testosterone isn’t about chasing youth — it’s about restoring function and resilience,” says Dr. Sam Hetz, LifespanMD Founder and Medical Director.

The Longevity Lens

Hormones do not operate in isolation — they interact with every aspect of healthspan.
At LifespanMD, hormonal therapies are integrated with:

  • Metabolic optimization: nutrition, insulin sensitivity, and body composition

  • Cardiovascular prevention: lipid management, ApoB and calcium scoring

  • Cognitive support: sleep, stress management, and recovery

  • Fitness and VO₂ max training: maximizing mitochondrial and cardiorespiratory capacity

By aligning hormonal, metabolic, and behavioral interventions, we help clients age stronger, not slower.

References

  1. Mikkola TS, et al. (2020). Use of menopausal hormone therapy and risk of all-cause mortality: a meta-analysis of observational studies. Am J Med, 133(5), 604–616. https://doi.org/10.1016/j.amjmed.2019.12.030

  2. Vinogradova Y, et al. (2020). Use of hormone replacement therapy and risk of mortality in postmenopausal women: cohort study. BJOG, 127(6), 755–764. https://doi.org/10.1111/1471-0528.17008

  3. Levine ME, et al. (2023). Hormone therapy and epigenetic age acceleration among postmenopausal women. JAMA Netw Open, 6(7), e2320897. https://doi.org/10.1001/jamanetworkopen.2023.20897

  4. Hodis HN, et al. (2016). Vascular effects of early versus late postmenopausal treatment with estradiol. N Engl J Med, 374(13), 1221–1231. https://doi.org/10.1056/NEJMoa1505241

  5. Cho L, et al. (2023). Menopausal hormone therapy and cardiovascular disease: A statement from the American Heart Association. Circulation, 147(15), e670–e689. https://doi.org/10.1161/CIRCULATIONAHA.122.061559

  6. Kantarci K, et al. (2021). Estrogen replacement therapy and upregulation of antioxidant genes in menopause. Front Aging Neurosci, 13, 683979. https://doi.org/10.3389/fnagi.2021.683979

  7. Rossouw JE, et al. (2002). Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA, 288(3), 321–333. https://doi.org/10.1001/jama.288.3.321

  8. Daly E, et al. (2000). Estrogen in Venous Thromboembolism Trial (EVTET): randomized controlled trial of hormone therapy after venous thrombosis. Lancet, 356(9241), 1447–1451. https://doi.org/10.1016/S0140-6736(00)02860-3

  9. Collaborative Group on Hormonal Factors in Breast Cancer. (2019). Type and timing of menopausal hormone therapy and breast cancer risk: meta-analysis of worldwide evidence. Lancet, 394(10204), 1159–1168. https://doi.org/10.1016/S0140-6736(19)31709-X

  10. Yeap BB, et al. (2023). Endogenous testosterone levels and mortality: Analysis from NHANES and longitudinal cohorts. Evol Med Public Health, 11(1), 30–43. https://doi.org/10.1093/emph/eoac028

  11. Snyder PJ, et al. (2016). Effects of testosterone treatment in older men. N Engl J Med, 374(7), 611–624. https://doi.org/10.1056/NEJMoa1506119

  12. Spitzer M, et al. (2023). Testosterone treatment in older men: Present and future. Drugs & Aging, 42(4), 275–287. https://doi.org/10.1007/s40266-025-01209-1

  13. Corona G, et al. (2023). Testosterone therapy and metabolic syndrome: a systematic review and meta-analysis. Int J Mol Sci, 25(22), 12221. https://doi.org/10.3390/ijms252212221

  14. Budoff MJ, et al. (2023). Cardiovascular safety of testosterone replacement therapy in men: the TRAVERSE randomized clinical trial. N Engl J Med, 389(1), 14–25. https://doi.org/10.1056/NEJMoa2301930

  15. Ponce OJ, et al. (2018). The efficacy and adverse events of testosterone replacement therapy in men: A systematic review and meta-analysis of randomized controlled trials. J Clin Endocrinol Metab, 103(5), 1745–1754. https://doi.org/10.1210/jc.2018-00191

Sam Hetz
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