Laboratory Tests Altered in Secondary Hypogonadism
In secondary hypogonadism, testosterone levels are low while LH and FSH levels are either low or inappropriately normal (low-normal range), distinguishing it from primary hypogonadism where gonadotropins are elevated. 1
Key Laboratory Findings
Testosterone Levels
- Morning total testosterone is below 300 ng/dL (measured between 8-10 AM on two separate occasions to confirm persistent hypogonadism) 1, 2
- Free testosterone levels are also subnormal, which can be measured by equilibrium dialysis or calculated using total testosterone, sex hormone-binding globulin (SHBG), and albumin concentrations 1, 2
Gonadotropin Levels (The Critical Distinguishing Feature)
- LH levels are normal, low-normal, or frankly reduced (not elevated as in primary hypogonadism) 1, 3
- FSH levels are normal, low-normal, or frankly reduced (not elevated as in primary hypogonadism) 1, 3
- The hallmark is that gonadotropin levels are inappropriately low for the degree of testosterone deficiency, representing a failure of the hypothalamic-pituitary axis to mount an appropriate compensatory response 1, 3
Sperm Parameters
- Sperm counts are subnormal in secondary hypogonadism 1
- This contrasts with primary hypogonadism where elevated gonadotropins attempt (unsuccessfully) to stimulate testicular function 1
Diagnostic Algorithm
Step 1: Measure morning total testosterone on two separate occasions between 8-10 AM 1, 2
Step 2: If testosterone is confirmed low (<300 ng/dL), measure serum LH and FSH to distinguish primary from secondary hypogonadism 1, 2
Step 3: Interpret the pattern:
- Primary hypogonadism: Low testosterone + elevated LH/FSH (testicular failure with intact pituitary response) 1
- Secondary hypogonadism: Low testosterone + low or low-normal LH/FSH (hypothalamic-pituitary dysfunction) 1, 3
Step 4: In borderline cases, measure free testosterone by equilibrium dialysis and SHBG levels to confirm true hypogonadism 1, 2
Clinical Significance of This Distinction
The differentiation between primary and secondary hypogonadism has critical treatment implications because secondary hypogonadism patients can potentially achieve both fertility restoration and normal testosterone levels with gonadotropin therapy (hCG plus FSH), whereas primary hypogonadism patients can only receive testosterone replacement therapy, which permanently suppresses fertility by inhibiting the HPG axis 1, 2
Common Pitfall to Avoid
Never attempt to diagnose the type of hypogonadism based on gonadotropin levels while a patient is already on testosterone therapy, as exogenous testosterone will suppress LH and FSH regardless of whether the underlying condition is primary or secondary hypogonadism 2. The patient must undergo a washout period of 2-4 weeks to allow recovery of the hypothalamic-pituitary-gonadal axis before accurate diagnostic testing can be performed 2.