HE incidence of meningioma is consistently noted to be higher among women. 6,22 This finding coupled with the biological evidence documenting sex hor- mone receptors in many of these tumors has suggested a possible role for sex hormones in the growth and develop- ment of these tumors. 13 Empirical support for this hypothe- sis arises primarily from studies in which the incidence of meningioma occurring after breast cancer was higher than what would be expected by chance alone, 17,34 and from an- ecdotal observations of exacerbations of these tumors dur- ing pregnancy 11,25,31 and menses, 4 and after the insertion of subcutaneous hormonal contraceptive implants. 26 The role of sex steroid medications remains controversial because other studies have found many hormone receptors to be nonfunctional 24,35 and the occurrence of breast cancer to be simply coincidental. 19 In this study we evaluated the role of exogenous and en- dogenous sex steroid hormones on the subsequent develop- ment of intracranial and spinal meningiomas. More specif- ically, we prospectively evaluated patient age at menarche, parity, age at first full-term pregnancy, and BMI as endoge- nous risk factors, and PMH use and OC use as exogenous risk factors in the ongoing NHS. Clinical Material and Methods Nurses’ Health Study Cohort In 1976, 121,700 registered nurses between 30 and 55 years of age who were living in 11 US states enrolled in the NHS cohort. All participants were women who completed baseline questionnaires regarding risk factors for cancer, cardiovascular disease, and a variety of other health condi- tions. Since enrollment, these women have been followed up by means of biennial mailed questionnaires, updating exposure information and onset of newly diagnosed dis- ease. The follow-up rate for the NHS was greater than 90% as of 1996. 37 Ascertainment of Exposure Information Exposure information related to endogenous sex steroid hormones was ascertained at baseline and at the time of each biennial follow-up questionnaire. The nurses’ ages at menarche were reported on the 1976 questionnaire; we ex- J Neurosurg 99:848–853, 2003 848 Sex steroid hormone exposures and risk for meningioma BALRAJ S. JHAWAR, M.D., SC.D., CHARLIE S. FUCHS, M.D., GRAHAM A. COLDITZ, M.D., DR.P.H., AND MEIR J. STAMPFER, M.D., DR.P.H. Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School; Dana Farber Cancer Institute; and Department of Epidemiology, Harvard School of Public Health, Harvard University, Boston, Massachusetts Object. The goal of this study was to investigate the risk of meningioma in relation to exogenous and endogenous sex hormones. Methods. The study participants were female registered nurses from 11 US states who were between 30 and 55 years of age when they enrolled in the Nurses’ Health Study cohort. These women completed biennial questionnaires between 1976 and 1996. All participants were free from cancer and other major medical illness at the onset of the study. The prima- ry endpoint was meningioma as self-reported in biennial and supplemental questionnaires. During 1,213,522 person-years of follow-up review, 125 cases of meningioma were confirmed. After adjusting for age and body mass index (BMI), compared with postmenopausal women who had never used postmenopausal hormones, the relative risk (RR) for premenopausal women was 2.48 (95% confidence interval [CI] 1.29–4.77; p = 0.01) and the RR for postmenopausal women who received hormone therapy was 1.86 (95% CI 1.07–3.24; p = 0.03). The authors found no ex- cess risk associated with past hormone use. In models that additionally controlled for hormone use and menopausal status, the authors found that, compared with women whose menarche occurred before they were 12 years of age, the RR for women whose menarche occurred at ages 12 through 14 years was 1.29 (95% CI 0.86–1.92; p = 0.21) and the RR for wom- en whose menarche occurred after age 14 years was 1.97 (95% CI 1.06–3.66; p = 0.03). The authors also observed a ten- dency, albeit nonsignificant, for increased risk of meningioma in parous as opposed to nulliparous women (multivariate RR = 2.39, 95% CI 0.76–7.53; p = 0.14). A trend toward an increasing risk of meningioma with increasing BMI was also noted (p for trend = 0.06). No association was found for past or current use of oral contraceptives. Conclusions. The risk for meningiomas was increased among women exposed to either endogenous or exogenous sex hormones. An unexpected relationship with increasing age at menarche was also noted; this remains unexplained. KEY WORDS • patient cohort • estrogen • meningioma • progesterone • prospective study • sex steroid • brain tumor T J. Neurosurg. / Volume 99 / November, 2003 Abbreviations used in this paper: BMI = body mass index; CI = confidence interval; NHS = Nurses’ Health Study; OC = oral contra- ceptive; PMH = postmenopausal hormone; RR = relative risk.