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Introduction: Meningiomas frequently occur within the field of neuro-oncology, but it is unclear whether exogenous or imbalanced endogenous hormones are involved in the pathophysiology. A previous case-control study found an almost 20-fold increase in the risk of developing meningioma among users of androgenic anabolic steroids. We, therefore, investigated this hypothesis., Methods: We compared the incidence rate of meningioma in a cohort of males sanctioned for the use of androgenic anabolic steroids with age- and sex-matched controls with an identical enrollment date., Results: We followed 1189 males sanctioned for using androgenic anabolic steroids for a total of 13,305 person-years and found 0 cases of meningioma. The control cohort of 59,450 males was followed for a total of 654,938 person-years, and 16 were diagnosed with meningioma. Thus, the incidence rate ratio was 0 (95% CI: 0-12.8)., Conclusion: We did not find any evidence supporting the hypothesis of an increased risk of meningioma development with the use of androgenic anabolic steroids. Due to the limited sample size, we cannot exclude androgenic anabolic steroids as a potential risk factor for meningioma development, despite the lack of apparent evidence in this study., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To assess the risk of intracranial meningioma associated with the use of selected progestogens., Design: National case-control study., Setting: French National Health Data System (ie, Système National des Données de Santé )., Participants: Of 108 366 women overall, 18 061 women living in France who had intracranial surgery for meningioma between 1 January 2009 and 31 December 2018 (restricted inclusion periods for intrauterine systems) were deemed to be in the case group. Each case was matched to five controls for year of birth and area of residence (90 305 controls)., Main Outcome Measures: Selected progestogens were used: progesterone, hydroxyprogesterone, dydrogesterone, medrogestone, medroxyprogesterone acetate, promegestone, dienogest, and intrauterine levonorgestrel. For each progestogen, use was defined by at least one dispensation within the year before the index date (within three years for 13.5 mg levonorgestrel intrauterine systems and five years for 52 mg). Conditional logistic regression was used to calculate odds ratio for each progestogen meningioma association., Results: Mean age was 57.6 years (standard deviation 12.8). Analyses showed excess risk of meningioma with use of medrogestone (42 exposed cases/18 061 cases (0.2%) v 79 exposed controls/90 305 controls (0.1%), odds ratio 3.49 (95% confidence interval 2.38 to 5.10)), medroxyprogesterone acetate (injectable, 9/18 061 (0.05%) v 11/90 305 (0.01%), 5.55 (2.27 to 13.56)), and promegestone (83/18 061 (0.5%) v 225/90 305 (0.2 %), 2.39 (1.85 to 3.09)). This excess risk was driven by prolonged use (≥one year). Results showed no excess risk of intracranial meningioma for progesterone, dydrogesterone, or levonorgestrel intrauterine systems. No conclusions could be drawn concerning dienogest or hydroxyprogesterone because of the small number of individuals who received these drugs. A highly increased risk of meningioma was observed for cyproterone acetate (891/18 061 (4.9%) v 256/90 305 (0.3%), odds ratio 19.21 (95% confidence interval 16.61 to 22.22)), nomegestrol acetate (925/18 061 (5.1%) v 1121/90 305 (1.2%), 4.93 (4.50 to 5.41)), and chlormadinone acetate (628/18 061 (3.5%) v 946/90 305 (1.0%), 3.87 (3.48 to 4.30)), which were used as positive controls for use., Conclusions: Prolonged use of medrogestone, medroxyprogesterone acetate, and promegestone was found to increase the risk of intracranial meningioma. The increased risk associated with the use of injectable medroxyprogesterone acetate, a widely used contraceptive, and the safety of levonorgestrel intrauterine systems are important new findings., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from French National Health Insurance Fund (Cnam) and the Health Product Epidemiology Scientific Interest Group (ANSM-Cnam EPI-PHARE Scientific Interest Group) for the submitted work, no financial relationships with any organizations that might have an interest in the submitted work in the previous three years, and no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cyproterone acetate (CPA) is a synthetic progesterone derivative introduced in the 1970s and prescribed as antiandrogenic therapy for inoperable prostate cancer, sexual deviations in men, and signs of androgenization in women. In 2020, the CPA summary of product characteristics (SmPC) was revised to include an updated special warning and precaution about (1) the risk of meningioma with increasing cumulative dose and (2) contraindication in patients with meningioma or history of meningioma. A Direct Healthcare Professional Communication (DHPC) was distributed. The European Medicine Agency's Pharmacovigilance Risk Assessment Committee requested that marketing authorization holders in Europe conduct a survey to assess physicians' knowledge of the updated key safety information. The primary objective of this study was to measure physicians' awareness (i.e., did they receive and review the revised SmPC and DHPC) and level of knowledge and understanding of the key safety information pertaining to the restricted use of CPA monotherapy because of the risk of meningioma., Methods: This cross-sectional web-based survey was administered to dermatologists, endocrinologists, gynecologists, urologists, oncologists, psychiatrists, and general practitioners in France, Germany, Poland, Spain, and the Netherlands who had prescribed CPA monotherapy in the previous 12 months to assess awareness of the risk of meningioma associated with CPA monotherapy., Results: Of the 613 physicians who participated, 85% correctly indicated that CPA monotherapy should be prescribed with the lowest effective dose, 75% correctly indicated that the risk of meningioma increases with increasing cumulative CPA monotherapy doses, and 73% correctly indicated that treatment with CPA-containing products must be stopped permanently if a patient is diagnosed with meningioma. Overall, 40% of physicians reported having received the DHPC, and 42% reported having received the revised SmPC., Conclusions: Despite low recall of receipt of the updated SmPC and DHPC, most physicians surveyed are aware of the meningioma risk and actions to mitigate the risk., (© 2024. Bayer AG.)

Background: Use of estrogen-containing menopausal hormone therapy has been shown to influence the risk of central nervous system (CNS) tumors. However, it is unknown how the progestin-component affects the risk and whether continuous versus cyclic treatment regimens influence the risk differently., Methods and Findings: Nested case-control studies within a nationwide cohort of Danish women followed for 19 years from 2000 to 2018. The cohort comprised 789,901 women aged 50 to 60 years during follow-up, without prior CNS tumor diagnosis, cancer, or contraindication for treatment with menopausal hormone therapy. Information on cumulative exposure to female hormonal drugs was based on filled prescriptions. Statistical analysis included educational level, use of antihistamines, and use of anti-asthma drugs as covariates. During follow-up, 1,595 women were diagnosed with meningioma and 1,167 with glioma. The median (first-third quartile) follow-up time of individuals in the full cohort was 10.8 years (5.0 years to 17.5 years). Compared to never-use, exposure to estrogen-progestin or progestin-only were both associated with increased risk of meningioma, hazard ratio (HR) 1.21; (95% confidence interval (CI) [1.06, 1.37] p = 0.005) and HR 1.28; (95% CI [1.05, 1.54] p = 0.012), respectively. Corresponding HRs for glioma were HR 1.00; (95% CI [0.86, 1.16] p = 0.982) and HR 1.20; (95% CI [0.95, 1.51] p = 0.117). Continuous estrogen-progestin exhibited higher HR of meningioma 1.34; (95% CI [1.08, 1.66] p = 0.008) than cyclic treatment 1.13; (95% CI [0.94, 1.34] p = 0.185). Previous use of estrogen-progestin 5 to 10 years prior to diagnosis yielded the strongest association with meningioma, HR 1.26; (95% CI [1.01, 1.57] p = 0.044), whereas current/recent use of progestin-only yielded the highest HRs for both meningioma 1.64; (95% CI [0.90, 2.98] p = 0.104) and glioma 1.83; (95% CI [0.98, 3.41] p = 0.057). Being an observational study, residual confounding could occur., Conclusions: Use of continuous, but not cyclic estrogen-progestin was associated with increased meningioma risk. There was no evidence of increased glioma risk with estrogen-progestin use. Use of progestin-only was associated with increased risk of meningioma and potentially glioma. Further studies are warranted to evaluate our findings and investigate the influence of long-term progestin-only regimens on CNS tumor risk., Competing Interests: LSM reports receiving grants from Health Insurance ”Denmark”, The Danish Cancer Society’s Scientific Committee, and Novo Nordisk for research unrelated to the present study. LSM reports being Vice Chair of Danish Society for PharmacoEpidemiology (DSFE) and representative for Nordic PharmacoEpidemiological Network (NorPen). CTP reports receiving grants from Bayer and Novo Nordisk for research unrelated to the present study. NP, AM, and SF declare no competing interests., (Copyright: © 2023 Pourhadi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The risks of meningioma associated with the use of cyproterone acetate at high doses (25 to 100 mg/day) have been known since 2007. Recently, two additional molecules have been incriminated: nomegestrol acetate and chlormadinone acetate. The higher the cumulative dose and the longer the treatment duration, the bigger the risk of meningioma (12-fold after 5 years of treatment for nomegestrol acetate, and 7-fold after 3.5 years of treatment for chlormadinone acetate). Nevertheless, these medications have many indications that demonstrate their importance in the daily practice of the general practitioner, of the gynecologist and of the reproductive endocrinologist. Therefore, caution is required when introducing a powerful progestin that is incriminated in the long term at high doses. If the benefit/risk balance favours the initiation of progestin therapy, it is recommended to use the minimal effective dose and to limit the duration of use. Clinical and brain imaging monitoring should also be performed. Finally, if a meningioma develops on progestin, it is recommended that any medication containing a progesterone agonist be suspended.

Background and Purpose: It is currently unknown whether vaginal oestradiol is associated with development of meningioma and glioma. The aim of this study was to examine associations between cumulative use and treatment intensity of vaginally administered oestradiol tablets and incidence of meningioma and glioma in a nationwide, population-based study., Methods: We conducted a nested case-control study within a nationwide cohort of Danish women followed from 2000 to 2018. The cohort consisted of 590,676 women aged 50-60 years at study start, without prior cancer diagnosis or use of systemic hormone therapy. Information on cumulative dose, duration, and intensity of vaginal oestradiol tablet use was assessed from filled prescriptions. Conditional logistic regression provided adjusted hazard ratios (HRs) for the association between vaginal oestradiol use and diagnosis of meningioma or glioma., Results: We identified 1108 women with meningioma and 835 with glioma. Of these, 19.8% and 14.0% used vaginal oestradiol tablets, respectively. The HRs in those with ever-use of vaginal oestradiol tablets was 1.14 (95% confidence interval [CI] 0.97-1.34) for meningioma and 0.90 (95% CI 0.73-1.11) for glioma. The corresponding HRs for new users exclusively were 1.18 (95% CI 0.99-1.40) for meningioma and 0.89 (95% CI 0.71-1.13) for glioma. Intensity of vaginal oestradiol tablet use according to duration and user status yielded slightly elevated HRs for meningioma without an apparent dose-response pattern, while the HRs for glioma were generally below unity. Among new users, the HR with high intensity of current or recent vaginal oestradiol tablet use for 2+ years was 1.66 (95% CI 1.09-2.55) for meningioma and 0.77 (95% CI 0.41-1.44) for glioma., Conclusion: Use of vaginal oestradiol tablets was associated with a slightly increased incidence of meningioma but not of glioma. Owing to the observational nature of the study, residual bias cannot be ruled out., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Cyproterone acetate (CPA) is known to induce meningioma, and recently, nomegestrol acetate (NMA) and chlormadinone acetate (CMA) were also involved. Progestagen-induced meningioma management starts with progestogen discontinuation and is either interventional (surgery and/or radiotherapy) or conservative (clinical and MRI radiological follow-up). We performed a retrospective volumetric radiological outcomSe study of progestogen-induced meningiomas diagnosed in our hospital. We analysed progestogen-related meningiomas diagnosed until 30 June 2021, with at least one diagnostic and one follow-up MRI results. Meningioma volumes were centrally retrospectively measured using a T1-weighted 3D millimeter sequence with gadolinium injection on a postprocessing console. We analysed 98 meningiomas of 38 females and one transgender (male-to-female), of which 25 (64.1%) had taken CPA, seven (17.9%) NMA, three (7.7%) CMA, and four (10.2%) several progestogens. Eleven patients (24 meningiomas) underwent interventional management, seven patients had meningiomas followed by conservative or interventional management, and 21 patients (51 meningiomas) had only conservative management. Of these 21 patients, 17 had discontinued their progestogen less than 6 months before, of which 14 (82.3%) had decreased or stable meningioma(s) during a 24-month median follow-up (3 to 75) period. Overall, four of the 39 patients experienced meningioma progression (three during conservative treatment and one after surgery), including two patients who had continued NMA or CMA treatment several years after diagnosis. Our study confirms a generally favourable outcome of progestogen-related meningioma after conservative treatment, especially for CPA. It also underlines the need for progestogen discontinuation at meningioma diagnosis., (© 2023 Société Française de Pharmacologie et de Thérapeutique.)

Introduction: No formal indication currently exists for seizure prophylaxis in neurosurgical oncology patients. Neither have specific recommendations been made on the use of antiepileptic drugs (AED) in seizure-free patients with meningiomas scheduled for surgery. AEDs are generally prescribed on a discretionary basis, taking into consideration a range of clinical and radiological risk factors. We present a systematic review and meta-analysis exploring the effectiveness of antiepileptic prophylaxis in patients with meningioma and no history of seizures., Methods: We performed a systematic review of the PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Embase, and clinicaltrials.gov databases. Of a total of 4368 studies initially identified, 12 were selected for extraction of data and qualitative analysis. Based on the clinical data presented, we were only able to include 6 studies in the meta-analysis. We performed heterogeneity studies, calculated a combined odds ratio, evaluated publication bias, and conducted a sensitivity analysis., Results: AED prophylaxis in patients with meningioma and no history of seizures did not significantly reduce the incidence of post-operative seizures in comparison to controls (Mantel-Haenszel combined odds ratio, random effects model: 1.26 [95% confidence interval, 0.60-2.78]; 2041 patients). However, we are unable to establish a robust recommendation against this treatment due to the lack of prospective studies, the presence of selection bias in the studies reviewed, the likelihood of underestimation of seizure frequency during follow-up, and the strong influence of one study on the overall effect., Conclusions: Despite the limitations of this review, the results of the meta-analysis do not support the routine use of seizure prophylaxis in patients with meningioma and no history of seizures., (Copyright © 2022. Published by Elsevier España, S.L.U.)

Objective: Numerous studies have confirmed a strong association between progestins and meningiomas and the regression and/or stabilization of meningiomas after discontinuation of treatment. Osteomeningiomas represent a small subgroup of meningiomas that appear to be more common among progestin-related meningiomas. However, the specificity of the behavior of this subset of meningiomas after discontinuation of progestin has not yet been assessed., Methods: Thirty-six patients (mean age 49.5 years) who presented with at least one progestin-related osteomeningioma (48 tumors total) were identified from a prospectively collected database of patients and had been referred to our department for meningioma and had documented use of cyproterone acetate, nomegestrol acetate, and/or chlormadinone acetate. Hormonal treatment was stopped at the time of diagnosis for all the patients, and the clinical and radiological evolution of this subgroup of tumors was evaluated., Results: For half of the 36 patients, treatment was prescribed for signs of hyperandrogenism, such as hirsutism, alopecia, or acne. Most lesions were spheno-orbital (35.4%) or frontal (31.2%). Although the tissular part of the meningioma shrank in 77.1% of cases, the osseous part exhibited discordant behavior with 81.3% showing volume progression. The combination of estrogens, as well as the prolonged duration of progestin treatment, seems to increase the risk of progression of the osseous part after treatment discontinuation (p = 0.02 and p = 0.028, respectively). No patient required surgical treatment at diagnosis or during the study., Conclusions: These results show that while the soft intracranial part of progestin-related osteomeningioma tumor is the most likely to regress after treatment discontinuation, the bony part is more likely to increase in volume. These findings suggest the need for careful follow-up of these patients, especially those with tumors near the optical apparatus.

Purpose: To report the results of systematic meningioma screening program implemented by French authorities in patients exposed to progestin therapies (cyproterone (CPA), nomegestrol (NA), and chlormadinone (CMA) acetate)., Methods: We conducted a prospective monocentric study on patients who, between September 2018 and April 2021, underwent standardized MRI (injection of gadolinium, then a T2 axial FLAIR and a 3D-T1 gradient-echo sequence) for meningioma screening., Results: Of the 210 included patients, 15 (7.1%) had at least one meningioma; seven (7/15, 47%) had multiple meningiomas. Meningiomas were more frequent in older patients and after exposure to CPA (13/103, 13%) compared to NA (1/22, 4%) or CMA (1/85, 1%; P = 0.005). After CPA exposure, meningiomas were associated with longer treatment duration (median = 20 vs 7 years, P = 0.001) and higher cumulative dose (median = 91 g vs. 62 g, P = 0.014). Similarly, their multiplicity was associated with higher dose of CPA (median = 244 g vs 61 g, P = 0.027). Most meningiomas were ≤ 1 cm 3 (44/58, 76%) and were convexity meningiomas (36/58, 62%). At diagnosis, patients were non-symptomatic, and all were managed conservatively. Among 14 patients with meningioma who stopped progestin exposure, meningioma burden decreased in 11 (79%) cases with no case of progression during MR follow-up., Conclusion: Systematic MR screening in progestin-exposed patients uncovers small and multiple meningiomas, which can be managed conservatively, decreasing in size after progestin discontinuation. The high rate of meningiomas after CPA exposure reinforces the need for systematic screening. For NA and CMA, further studies are needed to identify patients most likely to benefit from screening., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Purpose: A dose-dependent association between the use of cyproterone acetate (CPA) and intracranial meningioma has been identified but data for other potent progestogens are scarce. The association was assessed between intracranial meningioma surgery and exposure to three potent progestogens: CPA (≥25 mg/day), nomegestrol acetate (NOMAC) (3.75-5 mg/day) and chlormadinone acetate (CMA) (2-10 mg/day)., Methods: In this nationwide population-based case-control study, cases underwent surgery for intracranial meningioma in France from 2009 to 2018. They were matched to five control subjects for sex, year of birth and area of residence. Progestogen exposure was defined as progestogen use within the year before surgery for cases or the same date for their controls., Results: In total, 25,216 cases were included (75% women, median age 58 years). Progestogen exposure was noted for 9.9% of cases (2497/25,216) and 1.9% (2382/126,080) of controls, with an odds ratio (OR) of 6.7 (95% confidence interval [CI] 6.3-7.1). The OR was 1.2 (1.0-1.4) for short-term use (<1 year) and 9.5 (8.8-10.2) for prolonged use. A strong association was identified for prolonged use of CPA (OR = 22.7, 95% CI 19.5-26.4), NOMAC (OR = 6.5, 95% CI 5.8-7.2) and CMA (OR = 4.7, 95% CI 4.5-5.3). Progestogen exposure increased the risk of meningioma for all histological grades and anatomical sites, particularly for the anterior and middle skull base: OR = 35.7 (95% CI 26.5-48.2) and 23.9 (95% CI 17.8-32.2) for CPA. The estimated number of attributable cases was 2124 (95% CI 2028-2220) (212/year)., Conclusion: A strong association between prolonged exposure to potent progestogens and surgery for meningioma was observed. The risk increased from CMA to NOMAC to CPA. Individuals should be informed of this risk., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Meningiomas are the most common tumors of the central nervous system. Most meningiomas are benign and occur mainly in middle-aged women. Only a few cases of meningiomas in identical twins have been reported. Cyproterone acetate (Androcur® Bayer Healthcare SAS) (CPA) is an antiandrogenic progestin used to treat female hirsutism in some countries including France. We report a case of identical twin sisters who developed multiple, atypically located meningiomas in the setting of long-term CPA use. Eighteen-month follow-up showed spontaneous decrease of meningiomas after cessation of CPA. This case illustrates CPA's ability to induce development of atypically located meningiomas that differ even between identical twins, confirms benefit of surgical abstention, and raises questions regarding security of use of CPA., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: Meningioma is the most common primary intracranial tumor. Previous studies have shown the possible association between hormonal contraceptive use and meningioma location. Therefore, this study aimed to analyze the association between the history of hormonal contraceptive use and the location of meningioma in the Indonesian population., Methods: In total, 99 histologically confirmed female meningioma patients admitted to Dr. Sardjito General Hospital Yogyakarta, Indonesia, were included in this study. Data on hormonal contraception and other variables were collected from medical records. Meningioma locations were determined from brain Magnetic Resonance Imaging (MRI) or Computerized Tomography (CT) scan before surgery., Results: Seventy-two (72.7%) patients had a history of hormonal contraceptive use. The subjects consist of 83 (83.8%) WHO grade I and 16 (16.2%) WHO grade II and III tumors. A total of 57 (57.6%) tumors were located in the spheno-orbital region. We found a significant association between hormonal contraceptive use and meningioma location in the spheno-orbital region (Odds ratio (OR) 2.573, p=0.038). This resulted in the patients in the hormonal contraception group having more visual impairment (p=0.044)., Conclusion: The use of hormonal contraception is associated with the location of meningioma in the spheno-orbital region.

The influence of exposure to hormonal treatments, particularly cyproterone acetate (CPA), has been posited to contribute to the growth of meningiomas. Given the widespread use of CPA, this systematic review and meta-analysis attempted to assess real-world evidence of the association between CPA and the occurrence of intracranial meningiomas. Systematic searches of Ovid MEDLINE, Embase and Cochrane Controlled Register of Controlled Trials, were performed from database inception to 18th December 2021. Four retrospective observational studies reporting 8,132,348 patients were included in the meta-analysis. There was a total of 165,988 subjects with usage of CPA. The age of patients at meningioma diagnosis was generally above 45 years in all studies. The dosage of CPA taken by the exposed group (n = 165,988) was specified in three of the four included studies. All studies that analyzed high versus low dose CPA found a significant association between high dose CPA usage and increased risk of meningioma. When high and low dose patients were grouped together, there was no statistically significant increase in risk of meningioma associated with use of CPA (RR = 3.78 [95% CI 0.31-46.39], p = 0.190). Usage of CPA is associated with increased risk of meningioma at high doses but not when low doses are also included. Routine screening and meningioma surveillance by brain MRI offered to patients prescribed with CPA is likely a reasonable clinical consideration if given at high doses for long periods of time. Our findings highlight the need for further research on this topic., (© 2022. The Author(s).)

Introduction: Growing evidence recommends antifibrinolytic agent tranexamic acid (TXA) to reduce blood loss and transfusions rate in various surgical settings. However, postoperative seizure, as one of the major adverse effects of TXA infusion, has been a concern that restricts its utility in neurosurgery., Methods and Analysis: This is a randomised, placebo-controlled, non-inferiority trial. Patients with supratentorial meningiomas and deemed suitable for surgical resection will be recruited in the trial. Patients will be randomised to receive either a single administration of 20 mg/kg TXA or a placebo of the same volume with a 1:1 allocation ratio after anaesthesia induction. The primary endpoint is the cumulative incidence of early postoperative seizures within 7 days after craniotomy. Secondary outcomes include the incidence of non-seizure complications, changes of haemoglobin level from baseline, intraoperative blood loss, erythrocyte transfusion volume, Karnofsky Performance Status, all-cause mortality, and length of stay, and total hospitalisation cost., Ethics and Dissemination: This trial is registered at ClinicalTrial.gov and approved by the Chinese Ethics Committee of Registering Clinical Trials (ChiECRCT20200224). The findings will be disseminated in peer-reviewed journals and presented at national or international conferences relevant to subject fields., Trial Registration Number: NCT04595786., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Meningiomas are common intracranial tumors with a female predominance. Their etiology is still poorly documented. The role of sexual hormones has long been evoked, and data have been conflicting across studies. However, a dose-dependent relationship between the incidence and growth of meningiomas and hormonal treatment with the progestin cyproterone acetate (CPA) has recently been established. CPA-associated meningiomas seem to be mainly located in the anterior and middle skull base, are more likely to be multiple, may harbor P1K3CA mutations in up to one-third of cases, and are more common with a longer duration of treatment. A similar but lower risk of meningiomas has been recently reported with the use of chlormadinone acetate and nomegestrol acetate as progestin treatments. Concerning hormonal replacement therapy (HRT) in menopausal patients, evidence from epidemiological studies seem to favor an increased risk of meningiomas in treated patients although a recent study failed to show an increased growth of meningiomas in HRT treated vs nontreated patients. Until larger studies are available, it seems wise to recommend avoiding HRT in patients with meningiomas. Evidence from published data does not seem to support an increased risk of meningiomas with oral contraceptive oral contraceptive (OR) use. Data are too scarce to conclude on fertility treatments. Based on studies demonstrating the expression of hormonal receptors in meningiomas, therapies targeting these receptors have been tried but have failed to show an overall favorable clinical outcome in meningioma treatment., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The long-term use of cyproterone acetate (CPA) is associated with an increased risk of developing intracranial meningiomas. CPA discontinuation most often induces a stabilization or regression of the tumor. The underlying biological mechanisms as well as the reasons why some meningiomas still grow after CPA discontinuation remain unknown. We reported a series of patients presenting CPA-induced meningiomatosis with opposed tumor evolutions following CPA discontinuation, highlighting the underlying histological and genetic features., Methods: Patients presenting several meningiomas with opposite tumor evolution (coexistence of growing and shrinking tumors) following CPA discontinuation were identified. Clinical and radiological data were reviewed. A retrospective volumetric analysis of the meningiomas was performed. All the growing meningiomas were operated. Each operated tumor was characterized by histological and genetic analyses., Results: Four women with multiple meningiomas and opposite tumor volume evolutions after CPA discontinuation were identified. Histopathological analysis characterized the convexity and tentorial tumors which continued to grow after CPA discontinuation as fibroblastic meningiomas. The decreasing skull base tumor was characterized as a fibroblastic meningioma with increased fibrosis and a widespread collagen formation. The two growing skull base meningiomas were identified as meningothelial and transitional meningiomas. The molecular characterization found two NF2 mutations among the growing meningiomas and a PIK3CA mutation in the skull base tumor which decreased., Conclusion: To our knowledge, this is the first report describing an atypical tumor evolution of CPA-associated meningiomas after CPA discontinuation. The underlying biological mechanisms explaining this observation and especially the close relationship between mutational landscapes and embryologic origins of the meninges in CPA-related meningiomas as well as their clonal origin require further research., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Objective: The aim of this study was to describe progestin-associated meningiomas' characteristics, outcome and management., Material and Methods: We included 53 patients operated on and/or followed in the department for meningioma with progestin intake longer than one year and with recent drug discontinuation., Results: Cyproterone acetate (CPA), nomegestrol acetate (NomA), and chlormadinone acetate (ChlA) were involved in most cases. Mean duration of progestin drugs intake was 17.5 years. Tumors were multiple in 66% of cases and were located in the anterior and the medial skull base in 71% of cases. Transitional subtype represented 16/25 tumors; 19 meningiomas were WHO grade I and 6 were grade II. The rate of transitional subtype and skull base location was significantly higher compared to matched operated meningioma general population. No difference was observed given WHO classification. But Ki67 proliferation index tends to be lower and 5/6 of the WHO grade II meningiomas were classified as WHO grade II because of brain invasion. Strong progesterone receptors expression was observed in most cases. After progestin discontinuation, a spontaneous visual recovery was observed in 6/10 patients. Under CPA (n=24) and ChlA/NomA (n=11), tumor volume decreased in 71% and 18% of patients, was stabilized in 25% and 64% of patients, and increased in 4% and 18% of patients, respectively. Volume outcome was related to meningioma location., Conclusions: Outcome at progestins discontinuation is favorable but different comparing CPA versus ChlA-NomA and comparing tumor location. Long-term follow-up is required. In most cases, simple observation is recommended and surgery should be avoided., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Introduction: The relationship between meningioma and progestins has not been elucidated. Meningioma regression after acetate cyproterone (CA) withdrawal has been reported. Our purpose was to evaluate the meningioma evolution after withdrawal of progestins in patients who underwent long-term exposure to CA, nomegestrol acetate (NA), chlormadinone acetate (ChlA)., Methods: Our study retrospectively included 69 patients with intracranial meningioma and exposed to one of these 3 progestins between December 2006 and March 2019. In each patient, clinico-radiological (MRI) follow-up was performed every 6 months after diagnosis and treatment withdrawal recommendation. Statistical analyses were applied to compare tumor location and respect of prescription rules between the 3 groups., Results: The mean hormonal exposure was 16 years in CA group (n = 46), 16 years in NA group (n = 12) and 9.7 years in ChlA group (n = 11). A higher rate of "out of label" use was observed in the CA group (p = 0.003). Multiple meningiomas were demonstrated in more than 60% of cases in each group. Anterior skull base location was noted in 60.5% of cases in CA group, 25% of cases in NA group and 36.7% of cases in ChlA group (p = 0.05). Incomplete tumor regression was recorded in 11 cases of CA group and in 2 cases of ChlA group., Conclusion: In CA group, our results suggest a strong relationship between this treatment and development of intracranial meningioma. In presence of voluminous asymptomatic meningioma, treatment can be delayed due to the potential regression after withdrawal. On the contrary in NA and ChlA groups, further studies are needed., (Copyright © 2021 Elsevier B.V. All rights reserved.)

We present a 69-year-old transgender woman who underwent gender-affirming surgery in 1998 and gender-affirming hormone therapy (cyproterone acetate (CPA) and estradiol) since this time. Following an MRI scan to investigate tremor in 2013, an incidental left anterior clinoid and right petrous meningioma were identified. Subtotal surgical resection was achieved for the anterior clinoid meningioma (WHO grade 1, meningothelial subtype). At follow-up in 2016, an olfactory groove meningioma and left greater wing of sphenoid meningioma were identified. By 2017, both tumours, along with the petrous meningioma, demonstrated significant growth. In 2018, clinical decline was evident and MRI demonstrated further tumour growth. Surgery was scheduled and the olfactory groove meningioma was completely resected (WHO grade 2, chordoid subtype). Hormones were stopped, after which regression of the petrous meningioma was observed. This case demonstrates an association between high-dose CPA and estradiol and the development, growth and regression of meningiomas in a transgender woman., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The etiology of the central nervous system (CNS) tumors remains largely unknown. The role of pesticide exposure has been suggested by several epidemiological studies, but with no definitive conclusion., Objective: To analyze associations between occupational pesticide exposure and primary CNS tumors in adults in the CERENAT study., Methods: CERENAT is a multicenter case-control study conducted in France in 2004-2006. Data about occupational pesticide uses-in and outside agriculture-were collected during detailed face-to-face interviews and reviewed by experts for consistency and exposure assignment. Odds ratios (ORs) and 95% confidence intervals (95% CI) were estimated with conditional logistic regression., Results: A total of 596 cases (273 gliomas, 218 meningiomas, 105 others) and 1 192 age- and sex-matched controls selected in the general population were analyzed. Direct and indirect exposures to pesticides in agriculture were respectively assigned to 125 (7.0%) and 629 (35.2%) individuals and exposure outside agriculture to 146 (8.2%) individuals. For overall agricultural exposure, we observed no increase in risk for all brain tumors (OR 1.04, 0.69-1.57) and a slight increase for gliomas (OR 1.37, 0.79-2.39). Risks for gliomas were higher when considering agricultural exposure for more than 10 years (OR 2.22, 0.94-5.24) and significantly trebled in open field agriculture (OR 3.58, 1.20-10.70). Increases in risk were also observed in non-agricultural exposures, especially in green space workers who were directly exposed (OR 1.89, 0.82-4.39), and these were statistically significant for those exposed for over 10 years (OR 2.84, 1.15-6.99)., Discussion: These data support some previous findings regarding the potential role of occupational exposures to pesticides in CNS tumors, both inside and outside agriculture.

Purpose: The improving knowledge of interactions between meningiomas and progestin refines the management of this specific condition. We assessed the changes over time of the management of progestin-associated meningiomas., Methods: We retrospectively studied consecutive adult patients who had at least one meningioma in the context of progestin intake (October 1995-October 2018) in a tertiary adult Neurosurgical Center., Results: 71 adult women with 125 progestin-associated meningiomas were included. The number of progestin-associated meningioma patients increased over time (0.5/year before 2008, 22.0/year after 2017). Progestin treatment was an approved indication in 27.0%. A mean of 1.7 ± 1.2 meningiomas were discovered per patient (median 1, range 1-6). Surgery was performed on 36 (28.8%) meningiomas and the histopathologic grading was WHO grade 1 in 61.1% and grade 2 in 38.9%. The conservative management of meningiomas increased over time (33.3% before 2008, 64.3% after 2017) and progestin treatment withdrawal increased over time (16.7% before 2008, 95.2% after 2017). Treatment withdrawal varied depending on the progestin derivative used (88.9% with cyproterone acetate, 84.6% with chlormadinone acetate, 28.6% with nomegestrol acetate, 66.7% with progestin derivative combination). The main reason for therapeutic management of meningiomas was the presence of clinical signs. Among the 54 meningiomas managed conservatively for which the progestin had been discontinued, MRI follow-up demonstrated a regression in 29.6%, a stability in 68.5%, and an ongoing growth in 1.9% of cases., Conclusions: Conservative management, including progestin treatment discontinuation, has grown over time with promising results in terms of efficacy and safety.

Objective: Glioma and meningioma are the most common primary brain tumors in adults. Epidemiologic studies of the relationship between female hormone exposure and exogenous hormone use and the risk of meningioma and glioma in females have yielded inconsistent results., Methods: Two investigators comprehensively searched 3 electronic databases, including PubMed, Embase, and Cochrane Library. A total of 11 case-control studies were enrolled for meta-analysis. Dose-response meta-analyses were conducted., Results: Compared with the non-oral contraceptives (OCs) female users, the female OC users might have reduced risk of glioma (risk ratio [RR], 0.87; 95% confidence interval [CI], 0.77-0.97; I 2  = 42.6%). However, there was no obvious evidence of an association between OC use and the risk of meningioma in females (RR, 0.99; 95% CI, 0.87-1.13; I 2  = 42.7%). Using OCs for >10 years in females may significantly decrease the risk of glioma to 30% (RR, 0.7; 95% CI, 0.6-0.81; I 2  = 0%). The dose-response meta-analyses indicated that the risk of glioma in females significantly decreased when the duration of oral OC use was >7.5 years., Conclusions: OC use may not increase the risks of glioma and meningioma in females. Instead, the long-term use of OCs may significantly decrease the risk of glioma, and the benefits are even more pronounced when the time window is >7.5 years. Nonetheless, the pooled results in this study suggest that OC use may not increase the risk of meningioma. Therefore, our conclusion should be validated and supplemented in future larger studies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Context: Growth hormone (GH) deficiency is a common late effect of cranial irradiation. However, concerns have been raised that GH treatment might lead to an increased risk of a second neoplasm (SN)., Objective: To study the impact of GH treatment on the risk of SN in a French cohort of survivors of childhood cancer (CCS) treated before 1986., Design and Setting: Cohort study and nested case-control study., Participants: Of the 2852 survivors, with a median follow-up of 26 years, 196 had received GH therapy (median delay from cancer diagnosis: 5.5 years)., Main Outcome Measures: Occurrence of SN., Results: In total, 374 survivors developed a SN, including 40 who had received GH therapy. In a multivariate analysis, GH treatment did not increase the risk of secondary non-meningioma brain tumors (RR: 0.6, 95% CI: 0.2-1.5, P = 0.3), secondary non-brain cancer (RR: 0.7, 95% CI: 0.4-1.2, P = 0.2), or meningioma (RR: 1.9, 95% CI: 0.9-4, P = 0.09). Nevertheless, we observed a slight non-significant increase in the risk of meningioma with GH duration: 1.6-fold (95% CI: 1.2-3.0) after an exposure of less than 4 years vs 2.3-fold (95% CI: 0.9-5.6) after a longer exposure (P for trend = 0.07) confirmed by the results of a case-control study., Conclusion: This study confirms the overall safety of GH use in survivors of childhood cancer, which does not increase the risk of a SN. The slight excess in the risk of meningioma in patients with long-term GH treatment is non-significant and could be due to difficulties in adjustment on cranial radiation volume/dose and/or undiagnosed meningioma predisposing conditions.

Objective: To analyze the relationship between environmental lead exposure and various types of brain tumors., Methods: Search databases PubMed, Web of Science, Embase and Chinese National Knowledge Infrastructure (CNKI) as of July 1, 2019. Stata 15.0 software was used for analysis., Results: In the case control, lead exposure was associated with gliomas and meningiomas 0.82 (95 % CI: 0.69, 0.95) and 1.06 (95 % CI: 0.65, 1.46). In the cohort study, lead exposure was associated with brain cancer and meningiomas 1.07 (95 % CI: 0.95, 1.19) and 1.06 (95 % CI: 0.94, 1.17). The risk of childhood brain tumors associated with parental lead exposure was 1.17 (95 % CI: 0.99, 1.34)., Conclusions: Lead may be a risk factor for meningiomas and brain cancers. However, the glioma results suggest that lead may be a protective factor, which needs to be further studied., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

The administration of cyproterone acetate (CPA) and estradiol is a common regimen used by male-to-female transsexuals (transwoman) to adjust their body to their gender identity. Major adverse events are uncommon in these subjects in spite of long-term, high dose cross-sex steroid treatments. We describe the occurrence of a meningioma in a transwoman treated with estrogens and CPA over a period of nine years. The meningioma was revealed during a magnetic resonance imaging (MRI) scan performed as follow-up of a previous surgery for ganglioglioma. CPA intake was discontinued and tumor resection was performed. Histological diagnosis confirmed a strong progesterone receptor-positive and slight estrogen positive meningioma. After surgery, the patient continued her treatment with leuprorelina acetate and estradiol. At one-year follow-up, the MRI scan reveals no recurrence of the tumor. This is the ninth case in literature of a meningioma in a transwoman treated with estrogens and CPA, confirming a possible association between female sex steroids and meningioma. Although there is no still strong evidence of an association between meningioma and CPA, this report may suggest use of alternative treatment for transwomen. This report highlights the importance to record all the cases of meningiomas in high dose CPA-users, in order to improve data.

The hormonally active nature of intracranial meningioma has prompted research examining the risk of tumorigenesis in patients using hormonal contraception. Studies exploring estrogen-only and estrogen/progesterone combination contraceptives have failed to demonstrate a consistent increased risk of meningioma. By contrast, the few trials examining progesterone-only contraceptives have shown higher odds ratios for risk of meningioma. With progesterone-only contraception on the rise, the risk of tumor recurrence with these specific medications warrants closer study. We sought to determine whether progesterone-only contraception increases recurrence rate and decreases progression-free survival in pre-menopausal women with surgically resected WHO Grade I meningioma. Comparative analysis of 67 pre-menopausal women taking hormone-based contraceptives (progesterone-only medication, n = 21; estrogen-only or estrogen/progesterone combination medication, n = 46) who underwent surgical resection of WHO Grade I intracranial meningioma was performed. Differences in demographics, degree of resection, adjuvant therapy and time to recurrence were compared between the two groups. Compared to patients taking combination or estrogen-only contraception, those taking progesterone-only contraception demonstrated a greater recurrence rate (33.3 vs. 19.6%) with a reduced time to recurrence (18 vs. 32 months, p = 0.038) despite a significantly shorter follow-up (p = 0.014). There were no significant demographic or treatment related differences. The results from this study suggest that exogenous progesterone-only medications may represent a specific contraceptive subgroup that should be avoided in patients with meningioma.

Objectives: In absence of clear evidence regarding possible effects of occupational chemical exposures on brain tumour aetiology, it is worthwhile to explore the hypothesis that such exposures might act on brain tumour risk in interaction with occupational exposure to extremely low frequency magnetic fields (ELF)., Methods: INTEROCC is a seven-country (Australia, Canada, France, Germany, Israel, New Zealand and UK), population-based, case-control study, based on the larger INTERPHONE study. Incident cases of primary glioma and meningioma were ascertained from 2000 to 2004. Job titles were coded into standard international occupational classifications and estimates of ELF and chemical exposures were assigned based on job-exposure matrices. Dichotomous indicators of cumulative ELF (≥50th vs <50th percentile, 1-4 year exposure time window) and chemical exposures (ever vs never, 5-year lag) were created. Interaction was assessed on both the additive and multiplicative scales., Results: A total of 1939 glioma cases, 1822 meningioma cases and 5404 controls were included in the analysis, using conditional logistic regression. There was no clear evidence for interactions between ELF and any of the chemical exposures assessed for either glioma or meningioma risk. For glioma, subjects in the low ELF/metal exposed group had a lower risk than would be predicted from marginal effects. Results were similar according to different exposure time windows, to cut-points of exposure or in exposed-only analyses., Conclusions: There was no clear evidence for interactions between occupational ELF and chemical exposures in relation to glioma or meningioma risk observed. Further research with more refined estimates of occupational exposures is recommended., Competing Interests: Competing interests: MCT reports personal fees from ICF Incorporated, outside this work. DK reports to serving as Chief Risk Scientist and CEO at Risk Sciences International(http://www.risksciences), a Canadian company established in 2006 in partnership with the University of Ottawa conducting work in risk assessment, management and communication of health and environmental risks and their broader impacts on both public and private interests. He also holds an Industrial Research Chair in Risk Science under a peer-reviewed university–industry partnership programme administered by the Natural Sciences and Engineering Research Council of Canada., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: The relationship between long-term intake of progestin and meningioma growth is now well-known and has become a model of hormone-driven meningioma growth. Conversely, it has been demonstrated that cessation of treatment often leads to tumor regression. Consequently, watchful observation has become the strategy of choice in the case of multiple meningiomas in asymptomatic patients undergoing progestin treatment., Case Description: In 2 patients with large tumors (>60 cm 3 ) scheduled for surgery, conservative management with cessation of progestin treatment produced a dramatic reduction of meningioma size from 64 to 11 cm 3 (-83%) and 68 to 13 cm 3 (-81%), respectively, during a 1-year period. This shrinkage was associated with spontaneous devascularization of the meningiomas as observed on T2-weighted images., Conclusions: This observation adds new insights into the role of progesterone in meningioma tumorigenesis and could lead to future discoveries on the molecular relationships between meningioma tumorigenesis, progesterone dependence, and tumor vascularization., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Sex hormones have been proposed as a possible risk factor for the development and growth of meningiomas. Hormonal therapy plays a fundamental role in the treatment of male-to-female transgenders and needs to be continued after sex reassignment surgery. Usually, this treatment leads to no adverse events; however, its impact on hormone-related tumours such as meningiomas has not yet been investigated thoroughly. We searched our cohort of 2810 male-to-female transgender persons, who have been treated between 1975 and 2010, for patients with meningiomas. Additionally, we conducted a literature search in PubMed and EMBASE. We found three patients who developed a meningioma in male-to-female transgenders in addition to five other who have been described in the literature. These findings support the role of female sex hormones in the development and growth of meningiomas. This might be an underrepresentation, because there is no standard protocol for screening for meningiomas in this population and meningiomas can remain asymptomatic for several years. We observed regression of multiple meningiomas in one of these three cases after discontinuation of hormonal treatment. The decision to stop or continue cross-sex hormone therapy in these particular patients should be carefully reconsidered individually., (© 2016 Blackwell Verlag GmbH.)

There is evidence to support a link between treatment with high-dose cyproterone acetate and the development of meningioma. This report describes a case where an elderly man with intellectual disability who was treated with cyproterone for problematic sexual behavior developed a meningioma. The case was the subject of a residential medication management review provided under the auspices of a program funded by the Commonwealth Government of Australia. A discussion of clinical and ethical implications of the case is provided.

Background: There is conflicting evidence regarding the associations between cigarette smoking and glioma or meningioma. Our purpose is to provide further evidence on these possible associations., Methods: We conducted a set of case-control studies in three Canadian cities, Montreal, Ottawa and Vancouver. The study included 166 subjects with glioma, 93 subjects with meningioma, and 648 population-based controls. A lifetime history of cigarette smoking was collected and various smoking indices were computed. Multivariable logistic regression was used to estimate odds ratios (ORs) between smoking and each of the two types of brain tumours., Results: Adjusted ORs between smoking and each type of brain tumour were not significantly elevated for all smokers combined or for smokers with over 15 pack-years ((packs / day) x years) accumulated. We tested for interactions between smoking and several sociodemographic variables; the interaction between smoking and education on glioma risk was significant, with smoking showing an elevated OR among subjects with lower education and an OR below unity among subjects with higher education., Conclusion: Except for an unexplained and possibly artefactual excess risk in one population subgroup, we found little or no evidence of an association between smoking and either glioma or meningioma.

Objective: To examine associations between occupational exposure to selected organic solvents and meningioma., Methodology: A multicentre case-control study conducted in seven countries, including 1906 cases and 5565 controls. Occupational exposure to selected classes of organic solvents (aliphatic and alicyclic hydrocarbons, aromatic hydrocarbons, chlorinated hydrocarbons and 'other' organic solvents) or seven specific solvents (benzene, toluene, trichloroethylene, perchloroethylene, 1,1,1-trichloroethylene, methylene chloride and gasoline) was assessed using lifetime occupational histories and a modified version of the FINJEM job-exposure matrix (INTEROCC-JEM). Study participants were classified as 'exposed' when they had worked in an occupation for at least 1 year, with a 5-year lag, in which the estimated prevalence of exposure was 25% or greater in the INTEROCC-JEM. Associations between meningioma and each of the solvent exposures were estimated using conditional logistic regression, adjusting for potential confounders., Results: A total of 6.5% of study participants were ever exposed to 'any' solvent, with a somewhat greater proportion of controls (7%) ever exposed compared with cases (5%), but only one case was ever exposed to any chlorinated hydrocarbon (1,1,1-trichloroethane). No association was observed between any of the organic solvents and meningioma, in either men or women, and no dose-response relationships were observed in internal analyses using either exposure duration or cumulative exposure., Discussion: We found no evidence that occupational exposure to these organic solvents is associated with meningioma.

The authors describe a male patient who developed a large intracranial meningioma during the hormone therapy for pre-existing prostate cancer. A 70-year-old man received a brain check-up, and no intracranial abnormality was detected. Five months later, prostate cancer was diagnosed, and he underwent prostatectomy. Leuprorelin acetate, a luteinizing hormone-releasing hormone (LH-RH) agonist, was subsequently administered to the patient once a month for 3 years. After that he presented with a large parasagittal mass, which was excised. The tumor was histologically diagnosed as meningothelial meningioma, and LH-RH receptors were verified immunohistochemically in the cytoplasm of the tumor cells. Leuprorelin acetate may accelerate the rapid growth of meningioma in this patient.

Purpose: The aetiology of primary brain tumours is largely unknown; the role of non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin use and glioma risk has been inconclusive, but few population-based studies with reliable prescribing data have been conducted, and the association with meningioma risk has yet to be assessed., Methods: The UK Clinical Practice Research Datalink was used to assess the association between aspirin and non-aspirin NSAID use and primary brain tumour risk using a nested case-control study design. Conditional logistic regression analysis was performed on 5,052 brain tumour patients aged 16 years and over, diagnosed between 1987 and 2009 and 42,678 controls matched on year of birth, gender and general practice, adjusting for history of allergy and hormone replacement therapy use in the glioma and meningioma models, respectively., Results: In conditional logistic regression analysis, excluding drug use in the year preceding the index date, there was no association with non-aspirin NSAID use (OR 0.96, 95 % CI 0.81-1.13) or glioma risk comparing the highest category of daily defined dose to non-users; however, non-aspirin NSAID use was positively associated with meningioma risk (OR 1.35, 95 % CI 1.06-1.71). No association was seen with high- or low-dose aspirin use irrespective of histology., Conclusions: This large nested case-control study finds no association between aspirin or non-aspirin NSAID use and risk of glioma but a slight increased risk with non-aspirin NSAIDs and meningioma.

Purpose: The relationship between hormone replacement therapy (HRT) and the incidence of meningioma in women has been investigated in several epidemiologic studies, but their results were not entirely consistent. Here, we performed a meta-analysis of case-control and cohort studies to analyze this association., Methods: The PubMed database was searched from inception to 30 September 2012 to identify relevant studies that met pre-stated inclusion criteria. We also reviewed reference lists from the retrieved articles. Two researchers evaluated study eligibility and extracted the data independently. Odds ratios (ORs) or relative risks and 95 % confidence intervals (CIs) were extracted and pooled using the fixed-effect or random-effects models., Results: A total of 11 studies (six case-control and five cohort studies) were included in this meta-analysis, involving 1,820,954 participants, of whom 3,249 had meningioma. When compared to never users of HRT, the pooled OR with ever users for meningioma was 1.29 (95 % CI 1.03-1.60). Sensitivity analyses restricted to postmenopausal women yielded similar results (OR: 1.22; 95 % CI 1.02-1.46). Subgroup analyses showed that the pooled ORs were 1.27 (95 % CI 1.08-1.49, p < 0.05) and 1.12 (95 % CI 0.95-1.32) for current and past users of HRT, respectively., Conclusion: Hormone replacement therapy use is associated with an increased risk of meningioma in women, as well as in postmenopausal women. Besides, the significant risk elevation is present in current users but not in past users. Future research should attempt to establish whether this association is causal and to clarify its mechanisms.

Transsexualism is defined as a strong conviction of belonging to the opposite sex in individuals without any physical intersex condition. Cross-sex hormone therapy is an important component of medical treatment of transexuals but it is not exempt from adverse effects. We report a case of a meningioma in a male-to-female transsexual patient treated with estrogens and cyproterone acetate for the past 4 years. He claimed recently severe headache and visual impairment. Blood tests showed normal results. A contrast-enhanced magnetic resonance imaging (MRI) scan revealed a mass in the tuberculum sellae consistent with a meningioma. Treatment was discontinued and tumor resection was performed. Histologic diagnosis confirmed strongly progesterone receptor-positive and estrogen negative meningioma. After surgery, the patient rejected the possibility of continuing with the treatment of estrogens and cyproterone, and so triptorelin (GnRH agonist) was initiated. At 1-year follow-up the patient's symptoms had ameliorated and a MRI scan revealed no recurrence of the tumor. This is the third case reported in the literature of a meningioma after treatment with estrogens and cyproterone acetate. We consider extremely important a long-term follow-up observation of male-to-female transsexual undergoing cross-sex hormone therapy in order to detect as soon as possible the adverse effects that can be derived from this therapy., (Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.)

Objectives: Chlorinated solvents are classified as probable or possible carcinogens. It is unknown whether exposure to these agents increases the risk of malignant or benign brain tumours. Our objective was to evaluate associations of brain tumour risk with occupational exposure to six chlorinated solvents (i.e., dichloromethane, chloroform, carbon tetrachloride, 1,1,1-trichloroethane, trichloroethylene and perchloroethylene)., Methods: 489 glioma cases, 197 meningioma cases and 799 controls were enrolled in a hospital-based case-control study conducted at three U.S.A. hospitals in Arizona, Massachusetts and Pennsylvania. Information about occupational history was obtained through a detailed inperson interview that included job-specific modules of questions such that the interview was tailored to each individual's particular work history. An industrial hygienist assessed potential solvent exposure based on this information and an exhaustive review of the relevant industrial hygiene literature. Unconditional logistic regression models were used to calculate OR and 95% CI for each solvent for ever/never, duration, cumulative, average weekly and highest exposure., Results: Overall, we found no consistent evidence of an increased risk of glioma or meningioma related to occupational exposure to the six chlorinated solvents evaluated. There was some suggestion of an association between carbon tetrachloride and glioma in analyses restricted to exposed subjects, with average weekly exposure above the median associated with increased risk compared with below the median exposure (OR = 7.1, 95% CI 1.1 to 45.2)., Conclusions: We found no consistent evidence for increased brain tumour risk related to chlorinated solvents.

Sexual hormones have been related to the growth of meningiomas, also due to the almost constant expression of hormonal receptors by tumoral cells. A case of a woman with previous history of multiple treatment for infertility, harboring a huge meningioma is here described. The tumor was surgically resected and the immunohistochemical examination revealed a high expression of progesterone receptors on tumoral cells surface. A putative role of past progesterone administration in the growth of meningioma has been hypothesized. Particular caution should be paid whenever adopting sexual hormonal therapy, especially for fertility. A radiological examination (ideally MRI) could be advised before starting therapy, in order to rule out any intracranial meningioma.

The authors conducted a nationwide cohort study to evaluate the association between postmenopausal hormone therapy and meningioma incidence in Finland. All women who had used hormone therapy at least for 6 months at the age of 50 years or older during 1994-2009 were included. Women who had used postmenopausal hormone therapy were identified from the medical reimbursement register of the Social Insurance Institution (131,480 estradiol users and 131,248 estradiol-progestin users), and meningioma cases were identified from the Finnish Cancer Registry. During the average 9 years of follow-up, 289 estradiol users and 196 estradiol-progestin users were diagnosed with meningioma. Ever use of estradiol-only therapy was associated with an increased risk of meningioma (standardized incidence ratio = 1.29, 95% confidence interval: 1.15, 1.44). Among women who had been using estradiol-only therapy for at least 3 years, the incidence of meningioma was 1.40-fold higher (95% confidence interval: 1.18, 1.64; P < 0.001) than in the background population. In contrast, this risk was not increased in users of combination therapy (standardized incidence ratio = 0.93, 95% confidence interval: 0.80, 1.06). There was no difference in risk between continuous and sequential use of hormone therapy. Estradiol-only therapy was accompanied with a slightly increased risk of meningioma.

Aim: Information from the spontaneous reporting system raised the hypothesis of an increased risk of meningioma in patients treated with high doses of cyproterone acetate (CPA). The objective of this study was to test the hypothesis of an increased risk of meningioma among users of high dose CPA as compared with non-users in a medical records computerized database., Methods: A retrospective cohort study was performed in a Spanish primary care database (BIFAP). Meningioma incidence rates were compared in patients exposed to high dose CPA (users) with those non-exposed and with those exposed to low dose CPA. Poisson regression analysis was used to estimate the incidence rate ratios after adjusting for age and gender., Results: Among 2474 users of high dose cyproterone (6663 person-years) four meningioma cases were identified, resulting in an incidence rate (IR) of 60.0 (95% CI 16.4, 153.7) per 100,000 person-years, which was significantly higher than that observed among the non-users (IR 6.6; 95% CI 6.0, 7.3) and among women users of low dose cyproterone (IR 0.0, 95% CI upper limit 5.5). After adjusting for age and gender, patients exposed to high dose CPA showed an increased risk of meningioma of 11.4 (95% CI 4.3, 30.8) as compared with non-users., Conclusions: The results of this study support the hypothesis that the exposure to high dose CPA increases the risk of meningioma., (British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society. No claim to original US government works.)