Meningiomas occur more commonly in females. The coincidence between meningioma and breast cancer and case reports of tumor growth during pregnancy support a hormonal hypothesis. A case control study was conducted to investigate this. Female subjects treated between 1987 and 1992 were identified from 3 hospitals in the Chicago area. Female spouses of male back pain patients were recruited as controls. A self-administered mail questionnaire focused on exogenous, endogenous and other hormonal factors, personal and family medical history as well as radiation exposures. Odds ratios and 95% confidence intervals were estimated using crude, stratified and multivariable logistic models including 219 cases and 260 controls. Participation rates were 86% among cases and 75% among controls. An increased odds ratio (OR) was observed comparing African Americans to Caucasians [OR 5 2.4, 95% confidence interval (CI) 5 1.0-6.1]. A protective effect was observed for pregnancy, which increased with number and age at first pregnancy. The odds ratio for 3 or more pregnancies compared to none was 0.3 (95% CI 5 0.2-0.6). Age at menarche or total period of hormonal activity was not protective. Ever smokers showed a decreased odds ratio for meningioma (OR 5 0.6, 95% CI 5 0.4-0.9). The increased odds ratios with African Americans was retained in post-menopausal women, while the protective odds ratios for pregnancy, smoking and oral contraceptives (OCs) became stronger in pre-menopausal women. The pattern by duration and timing of use does not suggest an etiologic role for OCs or hormone replacement therapy. These data add to the evidence that factors known to influence endogenous hormones (pregnancy and indirectly smoking) may have protective effects for meningiomas primarily in premenopausal women. ' 2006 Wiley-Liss, Inc.Key words: case-control; meningioma; hormonal; reproductive The hypothesis of a hormonal influence on the occurrence of meningiomas was initially put forth because of the female preponderance in rates, the coincidence between meningioma and breast cancer 1 and case reports of tumor growth during pregnancy. 2 These indirect observations, stimulated studies of sex steroid receptors and a number of receptors and growth factors have been identified in tumor tissue. 3 Progesterone receptors predominate, although estrogen receptors may be present. 4 Although the role of these biologic markers in tumor development has not been established, it appears that the evidence for a role in tumor progression is stronger for progesterone receptors than for estrogen receptors. 5-7 A progesterone antagonist, mifepristone (RU-486), has been used therapeutically in an attempt to slow the growth of unresectable meningiomas, 8 but it has slowed the proliferation of meningioma tumor cells in vitro. 9 The role of hormone replacement therapy (HRT) in symptomatic postmenopausal women with previously treated disease or dormant tumors remains controversial. 6 A few small epidemiological studies suggested a potential role for both endogenous and exo...