Follicle-Stimulating Hormone (FSH)

FSH is a heterodimeric glycoprotein: a common alpha subunit, shared with LH, TSH and hCG, non-covalently paired with a hormone-specific beta subunit that determines receptor specificity. Neither subunit is active alone. Attached N-linked glycans ending in sialic acid slow renal clearance, which is why FSH persists in circulation for hours while LH is cleared in tens of minutes. Its receptor is a G protein-coupled receptor on granulosa and Sertoli cells, where cyclic AMP signalling induces aromatase in the ovary and supports the germ-cell environment and inhibin B production in the testis.

Recombinant follitropin alfa and beta, expressed in Chinese hamster ovary cells, largely replaced menotropins purified from postmenopausal urine and are approved for assisted reproduction and hypogonadotropic hypogonadism. Diagnostically, FSH rises whenever gonadal feedback fails: the characteristically high FSH after menopause is the clearest example, and in a man a raised FSH alongside a low testosterone points to the testis rather than the pituitary. Day-3 FSH was for years the standard ovarian reserve marker, though anti-Mullerian hormone and antral follicle count have largely displaced it.

Because inhibin B rather than sex steroid is the main brake on FSH, it can move independently of LH, and that divergence is informative. FSH is also far less pulsatile than LH, so a single measurement is more interpretable and carries diagnostic weight that a single LH does not.

The mistake to avoid is expecting FSH to track testosterone. It reports on the seminiferous tubule compartment, not the Leydig cell, so it can be raised in a man whose testosterone is normal, signalling impaired spermatogenesis on its own. The converse traps people too: a normal FSH does not exclude infertility, since obstructive azoospermia leaves the hormonal axis intact and the panel normal.