Hormone Health Series: Testosterone & Men’s Hormone Therapy
This article is the third in our Hormone Health series. It focuses on the science, safety, and personalized treatment of testosterone decline in men.
Quick Takeaway
Testosterone naturally declines about 1% per year after age 30, a gradual process often called andropause.
Low testosterone can impact muscle, mood, metabolism, and libido — but similar symptoms can come from stress, poor sleep, thyroid issues, or lifestyle factors.
The TRAVERSE Trial (NEJM, 2023) provides the strongest evidence to date that, in appropriately selected men and over ~3 years, supervised TRT did not increase major adverse cardiovascular events (heart attack or stroke) or prostate cancer. ¹
Restoring physiologic testosterone (not boosting beyond normal) can improve libido, mood, muscle mass, bone density, insulin sensitivity, and overall quality of life in symptomatic aging men. ³ ⁷ ⁸
Estrogen matters for men — it supports bone, brain, and vascular health. Both high and low levels can cause problems. ¹²
Fertility-preserving options like enclomiphene or hCG have roles but limitations. ⁸
Ongoing monitoring and lifestyle optimization are essential for safe, effective therapy. ⁴
Performance Enhancement vs. Therapeutic Use
There’s a crucial distinction between medical testosterone therapy and anabolic steroid misuse — and it sets the foundation for understanding this topic.
Therapeutic TRT aims to restore testosterone to a healthy physiologic range in men with symptoms of deficiency or age-related decline. It’s not about chasing performance, but about restoring balance — supporting mood, libido, muscle, metabolism, and long-term vitality.
Anabolic or performance use, in contrast, involves supraphysiologic, non-medical dosing for rapid gains in muscle or endurance. These regimens can suppress natural hormone production and increase risks for infertility, cardiovascular strain, liver stress, and psychological instability. ⁹ ¹⁰
When used responsibly and monitored appropriately, restoring physiologic testosterone can help maintain:
Healthy muscle and bone mass ³ ¹⁴
Stable mood, focus, and motivation ³ ⁸
Improved insulin sensitivity and metabolic control ⁷
Cognitive clarity and long-term cardiovascular health ¹ ¹¹
This isn’t about “boosting testosterone” — it’s about preserving health and function through evidence-based medicine and appropriate follow-up.
Why This Matters
Testosterone therapy has surged in popularity, with “Low T” clinics advertising quick fixes. Yet hormones are rarely simple.
Many men with fatigue, weight gain, or low motivation assume testosterone is the solution, but these same symptoms can stem from sleep apnea, thyroid imbalance, depression, or metabolic issues.
At the same time, decades of conflicting data have created confusion and hesitation, especially regarding prostate cancer and cardiovascular safety.
Modern research and guidelines now give us clarity: testosterone therapy, when done correctly, is safe, effective, and often life-improving for the right candidates. ¹
Core Science Explained Simply
What Is Andropause?
Andropause describes the gradual, individualized decline in testosterone that occurs with aging — roughly 1% per year after 30, and about 2% per year for free testosterone. ¹⁵
Unlike menopause, it’s not a hormonal “off switch.” Some men experience symptoms; others remain stable. This decline involves changes in the hypothalamic-pituitary-gonadal (HPG) axis, which regulates testosterone production.
What Testosterone Does
Testosterone plays vital roles throughout the body. Optimal levels help maintain:
Muscle and strength, preserving metabolism and mobility. ³
Fat distribution and insulin sensitivity, reducing metabolic syndrome risk. ⁷
Mood, focus, and cognition, influencing energy and emotional stability. ³ ⁸
Bone health, lowering fracture risk. ¹⁴
Inflammation control — low testosterone is linked to higher CRP and IL-6 (markers of inflammation), and normalization may improve inflammatory balance. ²
Recognizing Symptoms — and Why Testing Matters
Typical low-testosterone symptoms include:
Low libido or erectile changes ⁸
Fatigue, decreased motivation, or mood changes ³
Increased abdominal fat or reduced muscle mass
Cognitive “fog” or lower focus
Fewer morning erections
However, these symptoms are not exclusive to testosterone deficiency. Sleep disorders, stress, thyroid dysfunction, poor nutrition, and certain medications (SSRIs, opioids, glucocorticoids) can produce similar effects.
A proper diagnosis requires both symptoms and consistently low morning testosterone on at least two occasions, interpreted in clinical context. ⁴
Beyond the Number: The Clinical Context
We treat the patient and the symptoms, not a single lab number in isolation.
A man whose total testosterone is 450 ng/dL is technically “in range,” but if he has profound fatigue, weight gain, and low libido, he may be clinically deficient for his unique physiology.
Conversely, a man with 350 ng/dL who is fit and asymptomatic may not need therapy.
In practice, decisions integrate symptoms plus repeat morning total testosterone, ideally with LH/FSH and SHBG to interpret free T and distinguish primary vs secondary hypogonadism. ⁴
What We Know vs. What We Don’t Fully Know
What We Know
TRAVERSE (NEJM 2023): >5,000 men followed ~3 years; no increase in heart attack, stroke, or prostate cancer with supervised TRT in appropriately selected men. ¹
Benefits: TRT improves lean body mass, libido, bone density, and mood in men with confirmed deficiency. ³ ⁸
Guidelines: AUA (2024) and Endocrine Society (2018) recommend TRT for symptomatic men with confirmed low morning testosterone. ⁴ ⁵
Estrogen is essential: Derived from testosterone via aromatase; critical for bone, brain, and vascular health in men. ¹²
What We Don’t Fully Know
Outcomes beyond 10 years of therapy.
Benefits in men with borderline levels but no clear symptoms.
Estradiol balance matters: There is no universally accepted “ideal” T:E ratio for men in current guidelines. At ZinovyMed, we generally interpret testosterone-to-estradiol ratios in the 3–5% range as a practical clinical reference point, aiming to support bone and brain health while minimizing aromatization-related side effects. This range is always individualized and interpreted in the context of symptoms and lab trends. ¹²
Long-term safety of fertility-preserving agents like enclomiphene or hCG.
The Role of Estrogen in Men
Estradiol plays an underappreciated role in men’s health.
Healthy estrogen levels support:
Bone strength and density
Sexual function and libido
Mood and cognition
Cardiovascular elasticity ⁹
The balance: Too much estrogen (from obesity or excess aromatase activity) can cause gynecomastia and water retention. Too little estrogen (from over-suppression) can lead to fatigue, low libido, joint pain, and bone loss. The goal is balance, not suppression.
Therapeutic Options
Goal: From a strict research stand point the recommendation seems to be to restore levels to a normal physiologic range (≈400–700 ng/dL). ⁴
Many practices, ZinovyMed included, sometimes aim for about 600-1000 ng/dl for a more longevity benefit. This is always tailored to the individual based on many unique factors.
1. Testosterone Replacement Therapy (TRT)
Injectables (cypionate, enanthate): reliable and cost-effective; may cause peaks/troughs.
Topical gels/patches: convenient; risk of transfer to partners/children.
Pellets: long-acting; brief in-office insertion every 3–6 months.
Oral undecanoate: lymphatic absorption; variable consistency and a blood-pressure warning—monitor BP periodically.
2. Fertility & TRT: Considerations for Younger Men
For men prioritizing future fatherhood, standard TRT is often avoided due to its contraceptive effect. We prioritize fertility preservation first. ¹⁵
Enclomiphene: a selective estrogen receptor modulator (SERM) that stimulates LH/FSH to boost endogenous testosterone. Regulatory note: enclomiphene is not FDA-approved for treating male hypogonadism; use is off-label in the U.S. ⁸
hCG therapy: mimics LH, stimulating natural testosterone and supporting spermatogenesis; can be used alone or alongside low-dose TRT.
Potential Side Effects & Safety Monitoring
TRT is safe for appropriately diagnosed men under medical supervision, but monitoring remains vital. ⁴
Common, manageable effects
Erythrocytosis (high hematocrit): thickens blood and can raise the risk of blood clots; monitor CBC every 3–6 months. Manage with dose/frequency adjustments; therapeutic phlebotomy if needed. ⁴
Acne or oily skin: more likely in acne-prone men.
Fluid retention: typically mild and dose-dependent.
Mood changes: linked to hormonal peaks/troughs; improve with dose/formulation adjustments.
Fertility suppression: common with exogenous testosterone; recovery may take months post-therapy. ¹⁵
Gynecomastia: from excess aromatization; often resolves with dose balance.
PSA rise: small increases may occur; TRAVERSE found no increase in prostate cancer incidence with supervised TRT over the trial period. ¹ ⁶
Monitoring includes
Baseline, 3–6 months, then annually once stable: ⁴
Total & free testosterone
Estradiol
CBC / hematocrit (consider holding/adjusting if ≥54%)
PSA (prostate screening is PSA-based with shared decision-making) ⁵
Lipids
Liver enzymes
Prolactin (if persistent low libido or pituitary concerns)
Blood pressure (especially with oral testosterone undecanoate)
When to avoid or defer TRT (snapshot)
Active prostate or breast cancer
Hematocrit ≥54% (until addressed)
Uncontrolled heart failure or severe untreated sleep apnea
Desire for near-term fertility (standard TRT suppresses sperm production; consider enclomiphene/hCG strategies instead) ⁴ ⁵ ¹⁵
Lifestyle & Preventive Care
Hormone therapy works best when paired with healthy routines — lifestyle optimization is never optional.
Strength training: builds muscle and supports endogenous testosterone.
Sleep: 7–8 hours nightly; even short deprivation can lower testosterone 10–15%.
Balanced diet: prioritize protein, omega-3 fats, zinc, vitamin D, magnesium.
Healthy weight: less visceral fat → lower aromatase activity.
Stress management & limit alcohol: chronic inflammation disrupts the HPG axis.
Reduce environmental toxins: limit plastics, BPA, and phthalates.
📌 Bottom Line
When prescribed and monitored appropriately, testosterone therapy can safely improve strength, energy, mood, and overall vitality. ¹³
It’s not about chasing youth — it’s about restoring healthy physiology to support longevity, cognition, metabolism, and quality of life.
Personalized dosing, consistent monitoring, and a strong lifestyle foundation ensure safe, meaningful results. ⁴
References
Bhattacharya RK et al. Cardiovascular Safety of Testosterone-Replacement Therapy. N Engl J Med. 2023;388(19):1807–1819. (TRAVERSE Trial)
Traish AM. The Anti-Inflammatory Effects of Testosterone. J Clin Med. 2021;10(2):347.
Snyder PJ et al. Effects of Testosterone Treatment in Older Men. N Engl J Med. 2016;374(7):611–624.
Bhasin S et al. Testosterone Therapy in Men With Hypogonadism: Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018;103(5):1715–1744.
Mulhall JP et al. AUA Guideline: Testosterone Deficiency. Updated 2024.
Morgentaler A, Traish AM. TRT and Prostate Cancer: The Downfall of a Paradigm? Eur Urol. 2021;79(4):447–456.
Grossmann M. Testosterone and Glucose Metabolism in Men. Endocr Rev. 2019;40(2):372–421.
Kaminetsky JC et al. Enclomiphene in Secondary Hypogonadism. J Sex Med. 2022;19(9):1445–1453.
Baggish AL et al. Cardiac Toxicity in Long-term Anabolic Steroid Users. Circulation. 2017;135:1991–2002.
Pope HG et al. Adverse Health Effects of Anabolic Steroids. N Engl J Med. 2014;370(1):23–31.
Yeap BB et al. Testosterone Therapy in Men: Consensus Statement. Lancet Diabetes Endocrinol. 2022;10(5):355–368.
Dhindsa S et al. T/E Ratio & Aging Biomarkers (context on E2 relevance). J Clin Endocrinol Metab. 2019;104(11):4980–4992.
Hackett G. Testosterone for the Aging Male: Evidence & Practice. Aging Male. 2021;24(1):1–13.
Kelly DM, Jones TH. Testosterone: A Metabolic Hormone in Health and Disease. Trends Endocrinol Metab. 2013;24(5):233–243.
Wu FCW et al. Identification of Late-Onset Hypogonadism. N Engl J Med. 2010;363(2):123–135.
⚠️ Medical Disclaimer
This blog is for educational purposes only and is not a substitute for professional medical advice. Always consult your physician before starting or changing any medical treatment.
