Clinical vignette: A 29-year-old woman is referred for management of infertility. After menarche at age 12, menses occurred irregularly for a year and then became regular. She initiated use of oral contraceptive pills at the age of 18, then stopped at age 27 to try to conceive. Evaluation revealed hyperprolactinemia with serum prolactin of 90 ng/ml; pituitary MRI showed a 6-mm microadenoma. Other pituitary function tested was normal. Therapy was initiated with bromocriptine, but it was poorly tolerated, with fatigue, nausea, and lightheadedness to the point of syncopal events during her work as a hairdresser. Treatment was changed to cabergoline, with similar difficulties. Prolactin levels declined to the 30s–40s, but she was never able to tolerate the medication sufficiently to attain normal prolactin levels, and menses were sporadic and infrequent, with only 2–3 occurring per year. She and her husband had not conceived despite regular unprotected intercourse. She asks whether other medical treatment options might be available for her infertility.
Ursula B. Kaiser
Model of mechanisms of hyperprolactinemia-induced hypogonadism.
Increased serum prolactin (PRL) levels result in decreased kisspeptin expression in Kiss1 neurons in both the hypothalamic arcuate (ARC) and anteroventral periventricular (AVPV) nuclei, mediated by prolactin receptors (PRLR) expressed on both populations of Kiss1 neurons. Suppression of kisspeptin, in turn, reduces GnRH release and results in loss of the ovulatory GnRH surge. This leads to reduced pituitary gonadotropin (LH and FSH) secretion and loss of ovarian stimulation, which results in hypogonadism, infertility, and amenorrhea. Prolactin may also have direct effects on GnRH neurons and/or pituitary gonadotropes, or on other GnRH afferent neurons.