Is a male patient of reproductive age with normal Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH) levels, but low total testosterone (191 ng/dL), likely experiencing secondary hypogonadism?

Diagnosis: This is NOT Secondary Hypogonadism

With a total testosterone of 191 ng/dL and normal FSH/LH levels, this patient has confirmed biochemical hypogonadism, but the classification as "secondary" is premature and potentially incorrect without measuring free testosterone and SHBG. 1

Why This Diagnosis Requires Further Testing

The critical issue here is that normal gonadotropins (FSH/LH) in the setting of low total testosterone does NOT automatically confirm secondary hypogonadism—this pattern can also occur with:

• Elevated SHBG causing functional hypogonadism: When SHBG is high, it binds most testosterone in an inactive form, creating low total testosterone while free testosterone may be even lower, yet LH/FSH remain inappropriately normal because the hypothalamic-pituitary axis responds to free testosterone, not total testosterone 2, 3
• Primary hypogonadism with compensated LH elevation: In older men or those with chronic illness, LH may appear "normal" (within reference range) but is actually inappropriately low for the degree of testosterone deficiency 4

Required Diagnostic Workup Before Classification

You must obtain these tests before determining the type of hypogonadism: 1

• Free testosterone by equilibrium dialysis: This is the biologically active fraction and is essential when total testosterone is in the low range, as total testosterone alone misses approximately 50% of hypogonadism diagnoses when SHBG is abnormal 5, 2
• SHBG level: Elevated SHBG (>50 nmol/L) can cause symptomatic androgen deficiency even when total testosterone appears borderline-low, and this pattern is particularly common in men over 60 years 3, 2
• Repeat morning testosterone measurements: Diagnosis requires persistent hypogonadism confirmed on at least two separate morning (8-10 AM) measurements due to assay variability and diurnal fluctuation 1

Diagnostic Algorithm for Classification

If Free Testosterone is Also Low (<6.5 ng/dL):

• Measure serum prolactin: Hyperprolactinemia causes secondary hypogonadism and is a reversible cause 1
• Consider pituitary MRI: If prolactin is elevated or if there are other signs of pituitary dysfunction (headaches, visual changes), obtain MRI of the sella turcica 1
• Evaluate for reversible causes: Check thyroid function, iron saturation, assess for sleep disorders, metabolic syndrome, and medications that suppress the hypothalamic-pituitary-gonadal axis 1

If SHBG is Elevated (>50 nmol/L):

• Calculate free testosterone index: Total testosterone/SHBG ratio <0.3 indicates functional hypogonadism despite "normal" gonadotropins 2
• Investigate causes of elevated SHBG: Check thyroid function (hyperthyroidism), liver function tests (chronic liver disease), review medications (anticonvulsants, oral estrogens), and assess for HIV infection 2, 3

Critical Pitfall to Avoid

Never diagnose secondary hypogonadism based solely on "normal" LH/FSH with low total testosterone—this is a common diagnostic error that leads to inappropriate treatment selection. 1, 3

• In men over 60 years, the frequency of normal total testosterone with low free testosterone is 26.3%, and these men have symptomatic hypogonadism that would be missed by screening with total testosterone alone 3
• Total testosterone between 280-350 ng/dL is not sensitive enough to reliably exclude hypogonadism, and total testosterone must exceed 350-400 ng/dL to reliably predict normal free testosterone 5
• At a total testosterone of 191 ng/dL, the sensitivity of total testosterone for detecting low free testosterone is 91%, meaning 9% of men will have normal free testosterone despite this low total testosterone level 5

Treatment Implications of Correct Classification

The distinction between primary and secondary hypogonadism has critical treatment implications: 1

• Secondary hypogonadism with fertility concerns: Gonadotropin therapy (recombinant hCG plus FSH) is mandatory, and testosterone replacement therapy is absolutely contraindicated as it causes azoospermia 1, 6
• Primary hypogonadism: Testosterone replacement therapy is the only option, as the testes cannot respond to gonadotropin stimulation 1
• Functional hypogonadism from elevated SHBG: Treat underlying causes first (hyperthyroidism, liver disease, discontinue SHBG-elevating medications), then consider testosterone replacement if free testosterone remains low 2

Expected Treatment Outcomes

If testosterone replacement therapy is ultimately indicated, set realistic expectations: 1

• Small but significant improvements in sexual function and libido (standardized mean difference 0.35) 1
• Little to no effect on physical functioning, energy, vitality, depressive symptoms, or cognition 1
• Modest quality of life improvements, primarily in sexual function domains 1