Should a 39-year-old man with irritability, anxiety, depression, insomnia, low estradiol and labs showing total testosterone 469 ng/dL, SHBG 27 nmol/L, LH 3.7 IU/L, and FSH 3.1 IU/L receive testosterone therapy?

Testosterone Therapy is NOT Indicated for This Patient

This 39-year-old man with a total testosterone of 469 ng/dL does not meet diagnostic criteria for hypogonadism and should not receive testosterone therapy. His testosterone level is well within the normal range, and treatment should instead focus on addressing his psychiatric symptoms and potential underlying metabolic or lifestyle factors 1.

Why Testosterone Therapy Should Not Be Initiated

Testosterone Levels Are Normal

• Total testosterone of 469 ng/dL is clearly above the diagnostic threshold for hypogonadism, which requires levels consistently below 320 ng/dL (11.1 nmol/L) according to major guidelines 1.
• The calculated free testosterone with SHBG of 27 nmol/L would also be in the normal range, as this SHBG level is not elevated 1.
• FDA labeling explicitly restricts testosterone products to men with low testosterone due to known pathological causes (primary or secondary hypogonadism from testicular, pituitary, or hypothalamic disorders), not for men with normal levels 2.

LH and FSH Are Normal

• LH of 3.7 IU/L and FSH of 3.1 IU/L are within normal range, indicating intact hypothalamic-pituitary-gonadal axis function 1.
• These values exclude both primary hypogonadism (which would show elevated LH/FSH) and secondary hypogonadism (which would show inappropriately low LH/FSH with low testosterone) 1.

Psychiatric Symptoms Require Alternative Management

• The American College of Physicians explicitly recommends against initiating testosterone therapy to improve energy, vitality, or cognition in men with age-related low testosterone 1.
• While depression and anxiety can co-occur with hypogonadism, this patient does not have biochemical hypogonadism 3, 4, 5.
• The psychiatric symptoms (irritability, anxiety, depression, insomnia) should be evaluated and treated independently through psychiatric consultation, not with testosterone 1.

What Should Be Done Instead

Address Underlying Functional Causes

• Screen for and treat metabolic conditions: obesity, metabolic syndrome, and type 2 diabetes are strongly associated with functional hypogonadism and can lower testosterone levels 1.
• Evaluate for medications or substances that interfere with testosterone production or the HPG axis 1.
• Weight loss through low-calorie diets can reverse obesity-associated secondary hypogonadism and improve testosterone levels naturally 1.

Optimize Lifestyle Factors

• Physical inactivity is commonly associated with borderline testosterone levels and should be addressed 5.
• Assess for sleep disorders, particularly obstructive sleep apnea, which can affect both testosterone levels and mood 1.
• Smoking cessation and alcohol moderation should be recommended 1.

Treat Psychiatric Symptoms Directly

• The high prevalence of depression in men with borderline testosterone (56% in one study) suggests these symptoms may be independent of testosterone status 5.
• Consider SSRI therapy or other appropriate psychiatric interventions for the depression, anxiety, and insomnia 3.
• Men already on SSRIs may experience improvement in depressive symptoms, but this does not apply to men with normal testosterone levels 3.

Investigate Low Estradiol

• Low estradiol in a man with normal testosterone is unusual and warrants further investigation 1.
• Consider aromatase deficiency or other causes of impaired testosterone-to-estradiol conversion.
• This may contribute to mood symptoms and bone health concerns independently of testosterone status.

Critical Pitfalls to Avoid

• Do not prescribe testosterone based solely on nonspecific symptoms when testosterone levels are normal 1.
• Testosterone therapy in men with normal levels can suppress the HPG axis, reduce fertility, and cause adverse effects without proven benefit 1.
• The 2025 European Association of Urology guidelines emphasize that diagnosis of late-onset hypogonadism requires both persistent specific symptoms AND confirmed testosterone deficiency through repeated morning measurements 1.
• Avoid testosterone testing during acute illness, as this can artificially lower results 1.