Testosterone, DHEA, and the Hormonal Decline Nobody Prepares Men For
Dr. RP, MD — Board-Certified, Emergency Medicine & Critical Care Medicine — Founder, Analog Precision Medicine
I still ski whenever I can get to the mountains — not as often as when I lived in Park City and had the Wasatch Range close enough that a powder morning was an actual option on a weekday, but the trips still happen. What I've noticed over the years is that skiing has become a useful personal diagnostic. How my legs feel on day three, how quickly I recover, whether my reaction time in variable snow feels dialed or slightly behind — these are the kinds of inputs that tell me something about where my physical condition actually is, rather than where I'd like to think it is.
I mention this not because I'm particularly focused on self-quantification, but because it illustrates something relevant: the physiological changes that accumulate through a man's forties happen gradually enough that year-over-year they're essentially invisible, but decade-over-decade they're substantial. Testosterone decline is part of that picture — not in the oversimplified “low T” marketing framing, but in the genuine clinical sense that testosterone is a central regulator of muscle, bone, metabolism, libido, mood, and recovery, and that its gradual decline deserves a serious conversation rather than either dismissal or reflexive prescription.
The Biology of the Decline
Testosterone production is regulated by the hypothalamic-pituitary-gonadal (HPG) axis. The hypothalamus drives pulsatile GnRH release; the pituitary responds with LH; LH stimulates testicular Leydig cells to produce testosterone, which feeds back to suppress the axis. It's a well-tuned system in young adulthood that becomes progressively less efficient with age — through reduced Leydig cell number and function, less regular LH pulsatility, and diminished axis sensitivity.
The result is a gradual decline in testosterone averaging roughly 1–2% per year from peak levels, beginning in the early to mid-thirties. By the sixth decade, average total testosterone is typically 30–40% lower than peak. SHBG also increases with age, binding more testosterone and reducing the bioavailable fraction — meaning total testosterone measurements alone can systematically understate the degree of functionally relevant decline.
The Diagnosis: What the Guidelines Actually Say
The clinical challenge with testosterone deficiency is that its symptoms — fatigue, reduced libido, decreased muscle mass, increased body fat, low mood, diminished exercise tolerance — overlap heavily with thyroid disease, sleep apnea, depression, metabolic syndrome, and a dozen other conditions. Symptom overlap alone doesn't make the diagnosis.
Both the American Urological Association and the Endocrine Society are explicit: the diagnosis requires both consistently low testosterone biochemically (total testosterone below 300 ng/dL on two separate morning measurements) and symptoms attributable to that deficiency, with other causes appropriately evaluated (AUA Guideline, 2018; Bhasin et al., JCEM, 2018).[1,2] Neither a low number in isolation nor symptoms without confirmed biochemical deficiency is sufficient for treatment.
“Applying pharmaceutical intervention to every number in the lower half of the reference range is not precision medicine — it's what you get when the incentive is to prescribe rather than to diagnose.”
The range from 300–400 ng/dL is where most clinical nuance lives. A man in this range with significant symptoms and no alternative explanation may benefit from treatment. A man in this range who feels excellent generally doesn't. Applying pharmaceutical intervention to every number in the lower half of the reference range is not precision medicine — it's what you get when the incentive is to prescribe rather than to diagnose.
What Treatment Evidence Shows
For men with genuine, documented testosterone deficiency, the evidence for treatment benefit is reasonable across several domains:
Sexual function and libido is the most consistently documented benefit. The Testosterone Trials (TTrials) — seven coordinated, placebo-controlled trials in hypogonadal men over 65 — demonstrated statistically significant improvement in sexual activity and libido compared to placebo (Snyder et al., N Engl J Med, 2016).[3]
Body composition. Testosterone therapy consistently produces modest increases in lean mass and reductions in fat mass in deficient men. Effects on muscle strength are more meaningful when combined with resistance training. Testosterone therapy alone, without the exercise stimulus, produces smaller gains.
Bone density. The TTrials showed significant bone density improvements at the spine and hip. A subsequent analysis found reduced fracture rates in treated men.
Mood. Modest, statistically significant improvement in mood parameters was seen in the TTrials — but no improvement in clinical depression, and no significant reduction in fatigue. These are real effects, but small in magnitude.
Cardiovascular safety. The TRAVERSE trial — over 5,000 hypogonadal men followed for roughly 3 years — found testosterone non-inferior to placebo for major adverse cardiovascular events (Lincoff et al., N Engl J Med, 2023).[4] This is reassuring against the long-standing concern about cardiovascular harm. The trial did identify higher rates of atrial fibrillation in the testosterone group, a signal worth noting in patients with pre-existing cardiac risk.
DHEA: A Shorter Story
DHEA (dehydroepiandrosterone) is a steroid precursor produced by the adrenal glands, with levels peaking in the mid-twenties and declining by 50–80% by the seventh decade. It can be peripherally converted to testosterone and estrogen in various tissues, and its decline has generated significant commercial interest in supplementation.
The evidence in men is unimpressive. A well-designed 2-year RCT in NEJM found that DHEA supplementation — even at doses that restored levels to those of young adults — had no meaningful effect on body composition, muscle strength, or quality of life in older men (Nair et al., NEJM, 2006).[5] The modest testosterone increases that DHEA produced in men were not large enough to generate the effects seen with direct testosterone replacement.
DHEA has somewhat more plausible benefit in women, where adrenal androgens contribute more significantly to circulating androgen levels. In men, where testicular testosterone production dominates, supplementing the precursor does not meaningfully move the functional endpoint.
The Safety Conversation
Honest prescribing of testosterone requires discussing the risks that warrant monitoring:
Polycythemia is the most consistent and clinically significant safety signal — hematocrit elevations above 54% warrant dose adjustment or hold. Baseline CBC and monitoring at 3–6 months post-initiation is standard.
Atrial fibrillation — the signal from TRAVERSE — is relevant for patients with underlying cardiac risk and warrants discussion.
Fertility. Exogenous testosterone suppresses the HPG axis, reducing LH, FSH, and spermatogenesis. Men who wish to preserve fertility should not receive standard testosterone therapy. hCG or clomiphene are alternatives when indicated.
Prostate. Testosterone is contraindicated in active prostate cancer. PSA monitoring is standard. The concern that testosterone causes prostate cancer has been largely refuted by current evidence, but surveillance monitoring for occult disease progression remains appropriate.
The Complete Evaluation
A single total testosterone drawn at an arbitrary time of day is a poor foundation for clinical decisions. A complete male hormone panel should include total testosterone (morning, two measurements), free testosterone or calculated free testosterone, SHBG, LH and FSH (to distinguish primary from secondary deficiency), estradiol, prolactin (elevated levels are a reversible and treatable cause of secondary hypogonadism), PSA, CBC, and DHEA-S.
This panel answers different questions than a standalone testosterone. Is the deficiency primary (testicular failure — elevated LH) or secondary (central — normal or low LH)? Is elevated SHBG masking adequate free hormone? Is there an occult cause — a prolactinoma, hemochromatosis — that explains the picture and has its own treatment? These distinctions change what you do, and they require the full panel to make.
The right approach is a thorough evaluation followed by clinical judgment — not a number matched to a prescription, and not a dismissal of symptoms because the number falls within a broad reference range. For the patient in his forties or fifties who is noticing real changes in how his body responds and recovers, that judgment is worth the physician's time to make carefully.
References
- 1.Bhasin S et al. Testosterone therapy in men with hypogonadism: Endocrine Society guideline. JCEM. 2018;103(5):1715–1744.
- 2.American Urological Association. Testosterone deficiency guideline. 2018.
- 3.Snyder PJ et al.; TTrials Investigators. Effects of testosterone treatment in older men. N Engl J Med. 2016;374(7):611–624.
- 4.Lincoff AM et al.; TRAVERSE Investigators. Cardiovascular safety of testosterone-replacement therapy. N Engl J Med. 2023;389(2):107–117.
- 5.Nair KS et al. DHEA in elderly women and DHEA or testosterone in elderly men. N Engl J Med. 2006;355(16):1647–1659.
- 6.Buratto J et al. Safety and efficacy of testosterone therapy on musculoskeletal health. Endocr Pract. 2023;29(9):727–734.
Dr. RP, MD is dual board-certified in Emergency Medicine and Critical Care Medicine and is the founder of Analog Precision Medicine, a precision medicine practice in Southern California. This article is for educational purposes only and does not constitute medical advice or establish a physician-patient relationship.
← Back to Blog