Aggressive and malignant pituitary tumours: does the sex matter?

PURPOSE: Aggressive pituitary tumours (APT) and pituitary carcinomas (PC) are rare pituitary neoplasms and occur more frequently in men. Corticotroph and lactotroph tumours represent the most frequent secreting subtypes, showing different sex-related distribution, clinical features, and behaviour compared with benign disease. This review evaluates whether these sex-related differences persist in APT/PC and their clinical and therapeutic implications.

METHODS

A literature review of case reports, series, and clinical studies, published between 2000 and October 2025, reporting sex-related data on corticotroph and lactotroph APT/PC, was conducted. Clinical presentation, pathological features, and outcomes were extracted and analysed by sex.

RESULTS

93 corticotroph APT/PC (38 W, 55 M) and 80 lactotroph APT/PC (29 W, 51 M) were included. Among corticotroph APT/PC, men more commonly had non-functioning lesions (36.5%, vs. 17.6%), showed loss of hormonal secretion (7.7%, n = 4/52), and had invasive disease (100%, vs. 73.3%, p: 0.03). Women more frequently harboured Crooke’s cell tumours (26.3% vs. 5.5%, p: 0.006) and showed complete radiological responses (22.2%, vs. 9.1%). In lactotroph APT/PC, men had giant tumours (27.3%, vs. 5.0%), invasive disease (83.3%, vs. 63.6%), higher prolactin levels, and dopamine agonist resistance. Complete tumour responses to temozolomide occurred exclusively in women (22.7%, n = 5/22, p: 0.02), whereas partial durable responses predominated in men (46.2%, n = 18/39).

CONCLUSION

Male sex is associated with higher prevalence and more aggressive disease, whereas women achieve more profound tumour and hormonal responses. Sex-specific stratification may support personalized management of these rare pituitary tumours.