Should Testosterone Be Optimized in Men with a Normal HPG Axis?

No—testosterone therapy is absolutely contraindicated in eugonadal men, even when nonspecific symptoms are present. The 2025 European Association of Urology guidelines issue a strong recommendation against testosterone therapy in eugonadal men, explicitly stating it should not be used for weight loss, cardiometabolic improvement, cognition, vitality, or physical strength. 1

Diagnostic Confirmation Required Before Any Consideration

Before concluding the axis is "good," you must confirm eugonadal status with rigorous biochemical testing:

Two separate fasting morning total testosterone measurements (8–10 AM) both ≥300 ng/dL are required to exclude hypogonadism; single measurements are insufficient due to diurnal variation and assay variability. 1, 2
Measure LH and FSH after any low testosterone result to distinguish primary (elevated gonadotropins) from secondary (low/normal gonadotropins) hypogonadism—this distinction is mandatory because it directs therapy and fertility counseling. 1, 2
If total testosterone is borderline (231–346 ng/dL) or the patient is obese, measure free testosterone by equilibrium dialysis (gold standard) or calculate the free androgen index (total testosterone ÷ SHBG × 100); an FAI <30 indicates true hypogonadism despite borderline total testosterone. 1, 2

Why Testosterone Is Contraindicated in Eugonadal Men

Lack of Efficacy for Nonspecific Symptoms

Even in confirmed biochemical hypogonadism, testosterone produces:

Small but significant improvement only in sexual function and libido (standardized mean difference ≈0.35)—the sole evidence-based indication. 1, 2
Little to no clinically meaningful effect on energy, vitality, physical functioning, depressive symptoms, or cognition; effect sizes are negligible (e.g., fatigue improvement SMD 0.17, depression improvement SMD −0.19, both below clinical significance thresholds). 1, 2
No benefit for muscle building, athletic performance, or body composition in eugonadal men. 2

In eugonadal men, these minimal benefits disappear entirely. Symptoms such as fatigue, low energy, mood changes, and "brain fog" show minimal correlation with serum testosterone levels and do not improve reliably even when hypogonadism is confirmed. 2

Serious Harms Without Benefit

Testosterone therapy in eugonadal men exposes patients to:

Erythrocytosis in 15–44% of users (higher with injectable formulations), increasing blood viscosity and thrombotic risk, particularly in older adults or those with cardiovascular disease. 1, 2
Permanent infertility: Exogenous testosterone suppresses LH and FSH through negative feedback, causing azoospermia that can take months to years to recover—or may never recover. 1, 2, 3, 4
Cardiovascular risks: Although the 2023 TRAVERSE trial showed no significant increase in major adverse cardiac events in hypogonadal men with pre-existing cardiovascular risk, this safety profile does not extend to eugonadal men, where the risk-benefit ratio is entirely unfavorable. 2
Prostate concerns: Active or treated male breast cancer is an absolute contraindication; PSA monitoring is mandatory in men >40 years, with urologic referral required if PSA rises >1.0 ng/mL within 6 months or >0.4 ng/mL per year thereafter. 1, 2

The Pseudo-Hypogonadism of Obesity and Metabolic Dysfunction

Many men with "low-normal" testosterone have functional hypogonadism driven by reversible conditions—not pathological hypogonadism requiring lifelong replacement:

Obesity causes increased aromatization of testosterone to estradiol in adipose tissue, creating estradiol-mediated negative feedback that suppresses pituitary LH secretion; this reduces total testosterone while the HPG axis remains intact. 1, 5
Reduced SHBG in obesity lowers total testosterone disproportionately, but free testosterone (the biologically active fraction) often remains normal—this is pseudo-hypogonadism, not true androgen deficiency. 5, 6
Metabolic syndrome, type 2 diabetes, obstructive sleep apnea, depression, chronic opioid use, and glucocorticoid therapy all transiently suppress the HPG axis without causing organic hypogonadism. 1, 5, 7, 6

First-line management is correction of the underlying condition, not testosterone:

Weight loss through hypocaloric diets (500–750 kcal/day deficit) and structured exercise (≥150 min/week moderate-intensity aerobic activity plus resistance training 2–3 times/week) can reverse obesity-associated secondary hypogonadism by improving testosterone levels and normalizing gonadotropins; a 5–10% weight loss significantly increases endogenous testosterone production. 1, 2, 5
Optimize diabetes control with intensified therapy (e.g., GLP-1 receptor agonists or SGLT2 inhibitors, which provide cardiovascular benefits). 2
Treat obstructive sleep apnea, thyroid dysfunction, and depression; rationalize concomitant drug regimens (e.g., discontinue or substitute SHBG-elevating medications such as anticonvulsants or estrogens when feasible). 1, 2, 5, 6

Testosterone therapy is less effective than diet and lifestyle intervention to rectify the reversible conditions responsible for nonspecific symptoms and associated reduced serum testosterone in men with obesity. 5 Unwarranted off-label testosterone treatment leads to adverse effects such as infertility, elevated hematocrit requiring venesection, a prothrombotic state, and testosterone dependence. 5

Age-Related Decline Is Not a Disease

Age-related decline in testosterone is not considered a disease requiring treatment. The FDA mandates that testosterone products be labeled for use only in men with low testosterone due to known medical causes, not for age-related decline. 2
Approximately 20–30% of men over 60 have testosterone levels in the low-normal range, which does not automatically justify therapy. 1, 2
Safety and efficacy of testosterone in "age-related hypogonadism" (late-onset hypogonadism) have not been established. 8

Diagnostic Algorithm to Confirm Eugonadal Status

Obtain two fasting morning total testosterone measurements (8–10 AM) on separate days. 1, 2
- If both <300 ng/dL, proceed to measure LH, FSH, and prolactin. 1, 2
- If both ≥300 ng/dL, the patient is eugonadal—testosterone therapy is contraindicated. 1, 2
If values are 231–346 ng/dL (gray zone), measure free testosterone by equilibrium dialysis and SHBG; calculate FAI (total testosterone ÷ SHBG × 100). 1, 2
- If FAI <30, functional hypogonadism due to elevated SHBG may be present. 2
- If FAI ≥30, the patient is eugonadal. 2
For obese patients or borderline values, always assess free testosterone and SHBG to differentiate true from functional hypogonadism. 1, 2, 5
If LH/FSH are low or low-normal with low testosterone, screen for reversible causes:
- Measure prolactin (if >1.5× ULN, obtain pituitary MRI). 1, 2
- Check TSH, fasting glucose/HbA1c, lipid profile. 1, 2
- Assess for obesity (BMI, waist circumference), metabolic syndrome, sleep apnea, chronic illness, medications (opioids, glucocorticoids). 1, 2, 5, 6
If testosterone <150 ng/dL with LH/FSH <1.5 IU/L, obtain pituitary MRI immediately (even without hyperprolactinemia) to exclude non-functioning adenomas. 2

Common Pitfalls to Avoid

Do not diagnose hypogonadism on a single testosterone measurement or on symptoms alone; two morning values <300 ng/dL plus specific sexual symptoms (diminished libido, erectile dysfunction) are required. 1, 2
Do not prescribe testosterone for weight loss, energy enhancement, mood improvement, or athletic performance—these are not evidence-based indications. 1, 2, 5
Do not omit LH/FSH testing after confirming low testosterone; the primary vs. secondary distinction directs treatment and fertility counseling. 1, 2
Do not ignore reversible causes (obesity, metabolic syndrome, sleep apnea, medications) before considering testosterone. 1, 2, 5, 6
Approximately 20–30% of men receiving testosterone do not meet diagnostic criteria for hypogonadism, representing inappropriate off-label use. 2, 7

When Testosterone Is Indicated (For Contrast)

Testosterone therapy is appropriate only when:

Two morning testosterone measurements are both <300 ng/dL. 1, 2
Specific sexual symptoms are present (diminished libido, erectile dysfunction)—the only symptoms with proven responsiveness. 1, 2
The patient does not desire fertility (testosterone causes prolonged azoospermia). 1, 2
Reversible causes have been addressed (obesity, metabolic syndrome, medications, sleep apnea). 1, 2, 5, 6
Contraindications are absent (hematocrit >54%, active breast or prostate cancer, untreated severe obstructive sleep apnea). 1, 2

Expected outcomes with appropriate use:

Small but significant improvement in sexual function and libido (SMD ≈0.35). 1, 2
Modest quality-of-life improvements confined to sexual domains. 1, 2
Little to no benefit for energy, physical function, mood, or cognition. 1, 2

Bottom Line

Testosterone "optimization" in eugonadal men is medically inappropriate, lacks evidence for benefit, and exposes patients to serious harms including infertility, erythrocytosis, and cardiovascular risk. 1, 2, 5 The 2025 European Association of Urology guidelines issue a strong recommendation against this practice. 1 Address reversible causes (obesity, metabolic syndrome, sleep apnea, medications) through lifestyle modification and treatment of underlying conditions—this is more effective than testosterone and avoids harm. 1, 2, 5, 6

Should testosterone be optimized in an asymptomatic adult male with a normal hypothalamic‑pituitary‑gonadal axis?

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