FSH and LH Testing Prior to Testosterone Therapy
FSH and LH testing is essential to distinguish primary (testicular) hypogonadism from secondary (hypothalamic-pituitary) hypogonadism, which fundamentally determines whether the patient has a potentially treatable pituitary disorder requiring further investigation versus primary testicular failure. 1
Purpose of FSH and LH Testing
Differentiating Primary vs Secondary Hypogonadism
Measure serum LH and FSH after confirming low testosterone on two separate morning measurements to classify the type of hypogonadism. 1, 2
In primary (testicular) hypogonadism, FSH and LH levels are elevated above the normal range because the pituitary attempts to compensate for testicular failure through increased gonadotropin secretion. 3
In secondary (hypogonadotropic) hypogonadism, FSH and LH levels are low or inappropriately normal despite low testosterone, indicating hypothalamic-pituitary dysfunction rather than testicular failure. 1, 3
Clinical Significance of the Distinction
The pattern of gonadotropins determines whether additional pituitary evaluation is needed - elevated gonadotropins suggest primary testicular pathology (Klinefelter syndrome, chemotherapy damage, orchitis), while low/normal gonadotropins with low testosterone mandate investigation for pituitary or hypothalamic disease. 1
Secondary hypogonadism with low/normal LH and FSH requires evaluation for reversible causes including hyperprolactinemia, hemochromatosis, medications, and structural pituitary lesions before initiating testosterone therapy. 1
When Pituitary MRI is Necessary
Indications for Pituitary Imaging
Order pituitary MRI when testosterone is low with concomitantly low or inappropriately normal LH/FSH levels (secondary hypogonadism), regardless of prolactin levels, to exclude non-secreting pituitary adenomas and other structural lesions. 1, 2
Pituitary MRI is particularly indicated when prolactin is elevated in addition to low gonadotropins, as this raises concern for prolactinomas or other pituitary tumors causing mass effect on normal pituitary tissue. 1, 2
Consider MRI of the sella turcica as part of the comprehensive evaluation for hypothalamic-pituitary dysfunction when secondary hypogonadism is confirmed, even if initial prolactin and iron studies are normal. 1
Additional Workup for Secondary Hypogonadism
Measure serum prolactin levels in all patients with low testosterone combined with low/normal LH and FSH to screen for hyperprolactinemia, which could indicate pituitary adenomas. 2
Check iron saturation to exclude hemochromatosis as a reversible cause of secondary hypogonadism when gonadotropins are inappropriately low. 1
Perform comprehensive pituitary function testing to assess other pituitary hormone axes (thyroid, adrenal, growth hormone) when secondary hypogonadism is identified, as pituitary lesions often affect multiple hormone systems. 1
Fertility Considerations
Measure FSH if the patient has any interest in preserving fertility, as elevated FSH levels may indicate impaired spermatogenesis and primary testicular failure. 2
Counsel patients that testosterone therapy suppresses FSH through negative feedback, which will further impair spermatogenesis and potentially cause infertility during treatment. 2
Consider semen analysis if FSH is elevated, as this provides direct assessment of reproductive potential before initiating testosterone replacement. 2
Common Pitfalls
Do not initiate testosterone therapy in patients with secondary hypogonadism without completing the pituitary workup, as underlying pituitary tumors or other treatable causes may be missed. 1
Recognize that "inappropriately normal" gonadotropins in the setting of low testosterone indicate secondary hypogonadism - the LH and FSH should be elevated if the pituitary-hypothalamic axis is functioning properly. 1, 3
Pituitary incidentalomas are common, so not all pituitary findings on MRI are clinically significant; correlation with hormonal patterns and clinical presentation is essential. 4
Patients with microprolactinomas typically present with sexual dysfunction symptoms, while macroprolactinomas present with mass effect symptoms (headaches, visual field defects), which should guide clinical suspicion. 4