Prolactinoma course and management in transgender women: case report and systematic review

Prolactinomas are the most common functioning pituitary neuroendocrine tumors (PitNETs). In transgender women, gender-affirming hormone therapy (GAHT) usually combines high doses of estrogen and anti-androgen therapy, both of which can elevate serum prolactin levels. Whether GAHT influences tumor behavior in patients with pre-existing prolactinomas remains unclear.

Case report illustrating the clinical challenges in managing a prolactinoma in the context of GAHT initiation, combined with a systematic review of all published cases and available guidelines of GAHT in the prolactinoma context.

A 22-year-old female (46,XY; assigned male at birth) with untreated gender dysphoria and hypogonadism was diagnosed with a macroprolactinoma (39.9 mm; serum prolactin 285 × upper limit of normal (ULN)). Cabergoline therapy reduced prolactin levels to 27.3 × ULN within one year. Pituitary apoplexy with acute visual field and acuity deterioration required emergency transsphenoidal debulking. Two months postoperatively, prolactin levels were 8.6 × ULN with total hypopituitarism and small irresectable remnants. Initiation of estrogen therapy led to unexpected biochemical (128.4 × ULN) and radiological progression despite cabergoline reintroduction and dose escalation, necessitating estrogen withdrawal to stabilize the disease. Subsequent radiotherapy allowed safe estrogen reintroduction. To date, 24 prolactinomas in transgender women (including this case) have been reported, most diagnosed after GAHT initiation and lacking baseline prolactin data. Current clinical guidelines provide no specific recommendations for pituitary tumors in this population.

GAHT initiation might induce rapid progression and concomitant dopamine-agonist resistance in residual macroprolactinoma. Individualized, multidisciplinary management is needed. Development of dedicated clinical guidelines is essential to combine tumor control with gender-affirming care.