How should a patient with low testosterone and normal sex‑hormone‑binding globulin (SHBG), luteinizing hormone (LH), prolactin, and follicle‑stimulating hormone (FSH) be evaluated and managed?

Low Testosterone with Normal SHBG, LH, Prolactin, and FSH

This presentation suggests secondary (central) hypogonadism with inappropriately normal gonadotropins—the LH and FSH should be elevated in response to low testosterone but are not, indicating hypothalamic-pituitary dysfunction despite appearing "normal" on paper. 1

Understanding the Paradox

When testosterone is low but LH and FSH are normal (not elevated), this represents secondary hypogonadism—the pituitary is failing to appropriately respond to low testosterone signals. In true primary testicular failure, LH and FSH would be elevated. Normal gonadotropins in the setting of low testosterone indicate the feedback loop is broken at the hypothalamic-pituitary level. 1

Diagnostic Confirmation

Before proceeding, confirm the diagnosis meets AUA criteria:

• Two separate early morning (7-10 AM) fasting total testosterone measurements both <300 ng/dL 1
• Use the same laboratory and methodology for both measurements
• Document specific hypogonadal symptoms: reduced libido, erectile dysfunction, fatigue, reduced energy/endurance, decreased work performance, poor concentration, impaired memory, depression, or irritability 1
• Perform targeted physical examination for: decreased body hair in androgen-dependent areas, gynecomastia, small/soft testes, increased waist circumference/BMI 1

Since SHBG is normal, calculated free testosterone is reliable and should also be assessed—this is particularly important as it confirms true androgen deficiency rather than binding protein abnormalities. 2, 3

Identifying the Underlying Cause

With normal LH, FSH, and prolactin, systematically evaluate for reversible causes of secondary hypogonadism:

Most Common Reversible Causes:

• Obesity (BMI ≥30): Prevalence of hypogonadism 2-8% in obese men 2
• Medications: Opioids, corticosteroids, checkpoint inhibitors, medications causing hyperprolactinemia 2, 4
• Severe acute or chronic illness 2
• Obstructive sleep apnea (particularly if severe and untreated) 5

Less Common but Important Causes:

• Prior head/neck radiation or severe head trauma 2
• Pituitary dysfunction: Even with normal prolactin, consider pituitary imaging if no reversible cause identified 4
• Thyroid dysfunction: Check TSH—both hypo- and hyperthyroidism can suppress the gonadal axis 4, 6
• Chronic conditions: Diabetes, HIV, chronic narcotic use, chronic corticosteroid use 1

Management Algorithm

Step 1: Address Reversible Causes First

If BMI ≥30: Weight loss is first-line therapy, NOT testosterone 2

• Weight loss ≥5% significantly increases testosterone levels
• Associated with improved physical function, libido, and erectile function
• Defer testosterone therapy until weight loss attempted

If on causative medications:

• Discontinue or substitute opioids, corticosteroids, or other offending agents when medically feasible
• Reassess testosterone 3-6 months after medication changes

If severe untreated sleep apnea:

• Initiate CPAP therapy before considering testosterone
• Untreated severe OSA is a contraindication to testosterone therapy 5

Step 2: Consider Testosterone Therapy

Testosterone therapy is indicated when: 1, 5

• Permanent secondary hypogonadism confirmed (post-radiation, severe head trauma, irreversible pituitary dysfunction)
• Unable to discontinue causative medications
• Failed weight loss attempts in obesity-induced hypogonadism (though this remains controversial)
• Symptomatic with confirmed biochemical hypogonadism after addressing reversible causes

Absolute contraindications to testosterone therapy: 5

• Breast or prostate cancer
• PSA >4 ng/mL or PSA >3 ng/mL with high prostate cancer risk
• Elevated hematocrit/erythrocytosis
• Severe untreated obstructive sleep apnea
• Uncontrolled heart failure
• MI or stroke within last 6 months
• Thrombophilia
• Planning fertility in near term (testosterone suppresses spermatogenesis)

Critical Pitfalls to Avoid

1. Do not assume "normal" LH/FSH means normal pituitary function—in the context of low testosterone, these should be elevated. Normal = inappropriately low = secondary hypogonadism 1, 2

2. Do not start testosterone in obese men without attempting weight loss first—this is the most common reversible cause and testosterone may worsen metabolic parameters 2

3. Do not overlook medication-induced hypogonadism—opioids and corticosteroids are frequently missed culprits 2, 4

4. Do not skip pituitary imaging if no reversible cause identified—even with normal prolactin, structural pituitary lesions can present this way 4

5. Do not prescribe testosterone to men desiring fertility—it will suppress spermatogenesis. Consider selective estrogen receptor modulators (clomiphene) or hCG instead if fertility preservation needed 1, 5

When Testosterone Therapy is Initiated

Target mid-normal testosterone range (450-600 ng/dL) with monitoring plan including: 5

• Testosterone levels at 3-6 months, then annually
• Hematocrit monitoring (risk of erythrocytosis)
• PSA and digital rectal exam in men >50 years
• Symptom assessment and treatment adherence