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Sex-Related Difference in the Growth of Prolactinomas: A Clinical and Proliferation Marker Study¹

Department of Internal Medicine and Endocrinology, University Hospital UCL of Mont-Godinne (E.D., J.D.), 5530 Yvoir, Belgium; Laboratoire d’Histologie-Embryologie and INSERM U-369 (J.Tr.), Faculté de Médecine Lyon-RTH Laënnec, 69372 Lyon Cedex 08, France; the Department of Endocrinology and Nutrition, UCL Saint-Luc (D.M.), 1200 Brussels, Belgium; Clinique Endocrinologique de l’Université Claude Bernard, Hôpital de l’Antiquaille (J.T.), 69321 Lyon Cedex 05, France

Address all correspondence and requests for reprints to: Dr. E. Delgrange, Internal Medicine and Endocrinology, University Hospital UCL of Mont-Godinne, 5530 Yvoir, Belgium.

Prolactinomas in women commonly present as small intrasellar tumors, but are usually much larger in men. This discrepancy has generally been attributed to differences in the delay before diagnosis. However, studies comparing clinical and pathological correlates of growth of these tumors in both sexes are lacking. We conducted a retrospective study comparing 45 men and 51 women bearing prolactinoma to determine whether the predominance of large tumors in men was due to a delay in diagnosis or, rather, to a fundamental sex-related difference in tumor growth.

Basal PRL levels (mean ± SEM, 2789 ± 573 ng/mL) and mean tumor diameter (26 ± 2 mm) were significantly higher in men than in women (292 ± 74 ng/mL and 10 ± 1 mm, respectively; P < 0.001), but were not correlated to the age at diagnosis or the duration of symptoms. Giant tumors (n = 8) occurred in males only. The frequencies of bromocriptine-resistant tumors (30 vs.5%; P < 0.01) and invasive macroadenomas (52 vs.27%; P < 0.001) were significantly greater in men than those in women. Lastly, macroprolactinomas in males exhibited higher indexes of proliferating cells by Ki-67 immunoreactivity (2.6 ± 1.1% of positive nuclei) than did similar tumors in female patients (0.4 ± 0.2%; P = 0.08).

We conclude that the predominance of large prolactinomas in men is due to a high frequency of rapidly growing tumors, which are often invasive and frequently bromocriptine resistant.

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