A 28-year-old woman presents with galactorrhea, secondary amenorrhea, and a serum prolactin of 180 ng/mL. MRI shows a 6mm pituitary lesion. The mechanism by which a microprolactinoma causes amenorrhea is best explained as:

• A Prolactin directly inhibits FSH and LH secretion from gonadotrophs
• B The tumor compresses the optic chiasm disrupting GnRH release
• C Excess prolactin inhibits hypothalamic GnRH pulsatility by stimulating endogenous opioids and reducing dopaminergic tone ✓
• D Prolactin increases somatostatin tone, which then suppresses GnRH

Explanation

Excess prolactin causes hypogonadotropic hypogonadism primarily by disrupting hypothalamic GnRH pulse generator function. Prolactin increases hypothalamic endogenous opioid (particularly beta-endorphin) activity and reduces dopaminergic (tuberohypophyseal) stimulation of GnRH neurons, suppressing the pulsatile GnRH secretion required for normal FSH and LH release. Without adequate GnRH pulsatility, the pituitary cannot sustain gonadotropin secretion. A 6mm microprolactinoma would not cause optic chiasm compression (that occurs with macroadenomas >10mm). Prolactin does not directly suppress pituitary gonadotrophs; the effect is primarily hypothalamic.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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Written and medically reviewed by the StethoPrep medical team.