Your Case: Secondary (Pituitary-Hypothalamic) Hypogonadism
You cannot determine whether you have secondary hypogonadism while on exogenous testosterone—you must discontinue testosterone and allow a 2–4 week washout period before diagnostic testing can accurately classify your hypogonadism type. 1
Why Your Current Labs Are Uninterpretable
Exogenous testosterone suppresses your hypothalamic-pituitary-gonadal (HPG) axis, making LH and FSH artificially low or low-normal regardless of whether you originally had primary or secondary hypogonadism. 1 The diagnostic algorithm requires measuring gonadotropins (LH/FSH) after confirming low endogenous testosterone on two separate morning measurements (8–10 AM), but this is impossible while you are receiving testosterone replacement because:
- Testosterone therapy immediately suppresses GnRH pulsatility from the hypothalamus 1
- This suppression drives LH and FSH to low or undetectable levels in all men on testosterone, regardless of their underlying diagnosis 1
- Your "normal" LH/FSH while on testosterone simply reflects this expected suppression—it tells you nothing about whether your pituitary would function normally off therapy 1
The critical error is attempting to diagnose the type of hypogonadism based on gonadotropin levels while the patient is on testosterone therapy, as the results will be misleading. 1
The Correct Diagnostic Sequence
Step 1: Discontinue Testosterone and Allow Washout
- Stop all exogenous testosterone for 2–4 weeks to permit recovery of the HPG axis in patients with secondary hypogonadism 1
- Injectable testosterone (cypionate/enanthate) requires the full 2–4 weeks because peak levels occur at days 2–5 and return to baseline by days 13–14 1
- Transdermal preparations clear faster but still require at least 2 weeks 1
Step 2: Confirm Hypogonadism with Repeat Morning Testosterone
- Measure morning total testosterone (8–10 AM) on two separate occasions after the washout period 1, 2
- Hypogonadism is defined as total testosterone <300 ng/dL on both measurements 1, 2
- If your testosterone is ≥300 ng/dL off therapy, you do not have hypogonadism and should not have been started on testosterone 1
Step 3: Measure LH and FSH to Classify Hypogonadism Type
Only after confirming low testosterone can you interpret gonadotropins:
Primary (testicular) hypogonadism: Low testosterone + elevated LH/FSH (>normal range) 1, 3
Secondary (hypothalamic-pituitary) hypogonadism: Low testosterone + low or inappropriately normal LH/FSH 1, 2
Why This Distinction Matters Critically
Fertility Implications
Secondary hypogonadism patients can potentially achieve both fertility restoration and normal testosterone with gonadotropin therapy, whereas primary hypogonadism patients can only receive testosterone therapy, which permanently compromises fertility. 1, 3
- If you have secondary hypogonadism and desire fertility now or in the future, testosterone therapy is absolutely contraindicated 1, 2
- Testosterone causes prolonged and potentially irreversible azoospermia (zero sperm count) 1, 2
- Gonadotropin therapy (hCG 1,500–3,000 units subcutaneously 2–3 times weekly, with or without recombinant FSH 75–150 units 2–3 times weekly) directly stimulates the testes and can restore spermatogenesis in secondary hypogonadism 1, 4
Treatment Selection
- Primary hypogonadism: Testosterone replacement is the only option because the testes cannot respond to gonadotropin stimulation 1, 3
- Secondary hypogonadism: You have a choice between testosterone (if fertility is not desired) or gonadotropin therapy (if fertility preservation is important) 1, 4
Common Causes of Secondary Hypogonadism to Investigate
Once you confirm secondary hypogonadism off testosterone, investigate reversible causes:
- Obesity: Increased aromatization of testosterone to estradiol in adipose tissue causes estradiol-mediated negative feedback suppressing pituitary LH secretion 1, 5
- Medications: Opiates, GnRH agonists/antagonists, glucocorticoids, estrogens, progestogens 1
- Hyperprolactinemia: Measure serum prolactin 1
- Pituitary/hypothalamic lesions: Consider MRI of the sella turcica if no other cause is identified 1
- Systemic diseases: Hemochromatosis (check iron studies), sarcoidosis, histiocytosis X 6
- Chronic illness: Type 2 diabetes, metabolic syndrome, cardiovascular disease, chronic obstructive pulmonary disease 5
Critical Pitfalls to Avoid
- Never assume you have secondary hypogonadism simply because you are on testosterone—up to 25% of men on testosterone therapy may not have met diagnostic criteria for hypogonadism initially 1
- Never attempt to diagnose the type of hypogonadism while on testosterone—the suppressed gonadotropins are an artifact of therapy, not a reflection of your underlying pituitary function 1
- Never restart testosterone if fertility is desired—this will immediately suppress spermatogenesis again and may cause irreversible damage 1, 2
- Do not skip the washout period—insufficient time off testosterone will yield falsely low gonadotropins and misclassify your hypogonadism 1
What You Should Do Next
- Discuss with your physician discontinuing testosterone for 2–4 weeks to allow accurate diagnostic testing 1
- After washout, obtain two morning (8–10 AM) total testosterone measurements on separate days 1, 2
- If both values are <300 ng/dL, measure LH and FSH to classify primary vs. secondary hypogonadism 1, 2
- If you desire fertility now or in the future, explicitly state this to your physician—it changes the entire treatment algorithm 1, 2
- If secondary hypogonadism is confirmed and fertility is a concern, request gonadotropin therapy (hCG ± FSH) instead of restarting testosterone 1, 4