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Cancer Epidemiology
The International Journal of Cancer Epidemiology, Detection, and Prevention
journal homepage: www.cancerepidemiology.net
Spanish Centre for Pharmacoepidemiologic Research (CEIFE), C/Almirante 28, 28, 28004 Madrid, Spain
Global Epidemiology, Bayer HealthCare Pharmaceuticals, Berlin, Germany
c
Department of Public Health and Caring Science, Uppsala University, Sweden
b
A R T I C L E I N F O
A B S T R A C T
Article history:
Received 22 December 2010
Received in revised form 25 July 2011
Accepted 17 August 2011
Available online 22 September 2011
Background: The aetiology of meningiomas is largely unknown although hormones have been suggested
to play a role. Methods: A cohort study was performed to evaluate hormone-related factors associated
with meningioma. Patients (1289 years) with a rst diagnosis of meningioma (January 1996June
2008) were identied from The Health Improvement Network UK primary care database and age- and
sex-matched to controls (n = 10 000) from the same cohort. Odds ratios (ORs) were calculated following
a nested case control analysis using unconditional logistic regression. Results: In total, 745 patients with
meningioma were identied from a study population of 2 171 287. No signicantly increased risk of
meningioma was found among female users of oral contraceptives (OR: 1.15; CI: 0.671.98), hormone
replacement therapy (OR: 0.99; CI: 0.731.35) or low-dose cyproterone acetate (CPA; OR: 1.51; CI: 0.33
6.86) compared with non-users. There was a signicantly increased risk of meningioma among male
users of androgen analogues (OR: 19.09; CI: 2.81129.74) and among users of high-dose CPA (OR: 6.30;
CI: 1.3728.94) compared with non-users, however there were only three cases currently using these
drugs. No signicant association was found between meningioma and prostate, breast, or genital
cancers. Conclusions: Our results do not support a role for exogenous hormone use by females in
meningioma development. The risk in males was only observed with high-dose, short-term (<1 year)
therapy. Impact: While hormonal cancers and therapies are not associated with meningioma in females,
the risk in males requires further investigation.
2011 Elsevier Ltd. All rights reserved.
Keywords:
Meningioma
Nested casecontrol
Exogenous hormones
Cancer
Oral contraceptives
Hormonal replacement therapy
Cyproterone
1. Introduction
Meningiomas are typically benign tumours arising from the
meningothelial cells of the arachnoid membrane covering the
brain and spinal cord. The majority of meningiomas (around 90%)
are intracranial [1,2], and they account for approximately 20% of all
intracranial tumours [3,4]. Because the majority of meningiomas
progress slowly [5], most remain asymptomatic and are discovered
only at autopsy or during neuroimaging studies [6]. A metaanalysis of studies reporting incidental ndings from neuroimaging suggested that 0.3% of the general population has unknown
meningioma [7], and this is likely to increase with age; the
prevalence of previously unknown meningioma was 3% in a study
of women aged 75 years [8]. When symptoms arise from a
meningioma they are usually the result of raised intracranial
pressure and vary according to the size and location of the tumour.
Such symptoms include headache, vomiting, hemiparesis, seizures,
changes in personality and mood, and problems with speech, sight,
coordination, and memory [911]. Meningiomas are primarily
* Corresponding author. Tel.: +34 91 531 62 42; fax: +34 91 531 28 71.
E-mail address: luciaceife@telefonica.net (L. Cea-Soriano).
1877-7821/$ see front matter 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.canep.2011.08.003
Study population
2171287 patients
14059934 person-years
Questionnaire returned
500 cases
Cases (validated)
453
No questionnaire returned
21 cases
Manual review of
returned questionnaires
and documents
Non-cases (validated)
47
199
Cases (ascertained)
292
Non-cases (ascertained)
6
200
201
Table 1
Baseline characteristics of individuals in the casecontrol study, contact with the healthcare system, and the presence of meningioma.
Sex
Male
Female
Age (years)
1339
4049
5059
6069
7079
8089
Index date (calendar year)
19961999
20002002
20032005
20062008
PCP visits
04
59
1019
20
Referrals
0
14
510
>10
Hospitalisations
0
1
2
Characteristics
Male patients
Female patients
2653 (26.5)
7347 (73.5)
196 (26.3)
549 (73.7)
NA
NA
NA
NA
862
1200
2043
2270
2454
1171
(8.6)
(12.0)
(20.4)
(22.7)
(24.5)
(11.7)
57
89
152
170
184
93
(7.7)
(11.9)
(20.4)
(22.8)
(24.7)
(12.5)
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
NA
1326
2183
3314
3177
(13.3)
(21.8)
(33.1)
(31.8)
99
164
247
235
(13.3)
(22.0)
(33.2)
(31.5)
NA
NA
NA
NA
NA
NA
3970
2772
2367
891
(39.7)
(27.7)
(23.7)
(8.9)
138
183
277
147
(18.5)
(24.6)
(37.2)
(19.7)
1.00
2.36 (1.523.67)
4.79 (3.117.38)
6.27 (3.7810.37)
1.00
2.02 (1.542.65)
3.80 (2.934.93)
5.97 (4.408.09)
4945
3871
909
275
(49.5)
(38.7)
(9.1)
(2.8)
148
368
150
79
(19.9)
(49.4)
(20.1)
(10.6)
1.00
3.01 (1.984.58)
5.85 (3.4110.03)
11.57 (5.9622.45)
1.00
2.59 (2.033.30)
3.94 (2.885.39)
6.29 (4.179.49)
1.00
1.52 (0.942.46)
1.80 (1.043.10)
1.00
1.36 (1.011.83)
1.59 (1.082.35)
9085 (90.9)
618 (6.2)
297 (3.0)
610 (81.9)
81 (10.9)
54 (7.2)
a
Adjusted for sex, age, calendar year, and the number of PCP visits.
CI, condence interval; NA, not applicable; PCP, primary care physician.
duration of less than 1 year (OR: 1.38; 95% CI: 0.772.48) or who
had a treatment duration of greater than 1 year (OR: 0.60; 95% CI:
0.181.98) compared with non-users.
Current users of HRT were not at increased risk of developing
meningioma (OR: 0.99; 95% CI: 0.731.35). Among current users, a
total of 87.3% of controls and 84.5% of cases were aged 50 years or
more; the corresponding OR was 1.10 (95% CI: 0.801.52) when the
Table 2
Risk of developing meningioma in female patients receiving hormonal therapy.
Exposurea
Number (%)
Number (%)
6485
262
100
162
600
(88.3)
(3.6)
(1.4)
(2.2)
(8.2)
482
20
9
11
47
(87.8)
(3.6)
(1.6)
(2.0)
(8.6)
1.00
1.15
1.32
1.01
1.17
(0.671.98)
(0.642.76)
(0.502.03)
(0.811.69)
5706
708
341
62
305
933
(77.7)
(9.6)
(4.6)
(0.8)
(4.2)
(12.7)
408
58
29
3
26
83
(74.3)
(10.6)
(5.3)
(0.5)
(4.7)
(15.1)
1.00
0.99
1.01
0.53
1.08
1.10
(0.731.35)
(0.671.52)
(0.171.73)
(0.701.67)
(0.841.44)
7295
52
17
35
(99.3)
(0.7)
(0.2)
(0.5)
545
4
2
2
(99.3)
(0.7)
(0.4)
(0.4)
1.00
1.03 (0.362.95)
1.51 (0.336.86)
0.78 (0.183.35)
Oral contraceptives
Non-use
Current use
Current use of progesterone
Current use of progesterone and oestrogens
Past use
Hormone replacement therapy
Non-use
Current use
Current use of oestrogens
Current use of steroids (tibolone)
Current use of oestrogens and progesterone
Past use
Cyproterone acetate and oestrogen combination
Non-use
Ever use
Current use
Past use
a
Ever use: any use before the index date; current use: when the most recent prescription lasted until the index date or ended in the year before the index date; past use:
when the most recent prescription ended more than 1 year before the index date.
b
Adjusted for age, index year, and number of primary care physician visits.
c
Excludes cyproterone acetatae in combination with oestrogen.
CI, condence interval.
202
Table 3
Risk of developing meningioma in male patients receiving hormonal therapy.
Exposurea
LHRH agonists
Non-use
Current use
Past use
Antiandrogensc
Non-use
Current use
Past use
Androgen analoguesd
Non-use
Current use
Past use
Cyproterone acetate
Non-use
Ever use
Current use
Past use
Number (%)
Number (%)
2623 (98.9)
26 (1.0)
4 (0.2)
191 (97.4)
4 (2.0)
1 (0.5)
1.00
1.33 (0.453.94)
2.89 (0.3027.64)
2644 (99.7)
7 (0.3)
2 (0.1)
195 (99.5)
1 (0.5)
0
1.00
1.16 (0.149.62)
2642 (99.6)
2 (0.1)
9 (0.3)
192 (98.0)
3 (1.5)
1 (0.5)
2641
12
4
8
192
4
3
1
(99.5)
(0.5)
(0.2)
(0.3)
(98.0)
(2.0)
(1.5)
(0.5)
1.00
19.09 (2.81129.74)
1.25 (0.1510.21)
1.00
3.28 (1.0110.64)
6.30 (1.3728.94)
1.37 (0.1611.42)
a
Ever use: any use before the index date; current use: when the most recent prescription lasted until the index date or ended in the year before the index date; past use:
when the most recent prescription ended more than 1 year before the index date.
b
Adjusted for age, index year, and number of primary care physician visits.
c
Antiandrogens include bicalutamide and utamide.
d
Androgen analogues include testosterone, mesterolone, and uoxymesterone.
CI, condence interval; LHRH, luteinising hormone-releasing hormone.
Table 4
Risk of meningioma associated with hormone-related comorbidities.
Comorbidity
Female patients
Breast cancer
Genital cancer
Male patients
Prostate cancer
Number (%)
Number (%)
n = 7347
252 (3.4)
95 (1.3)
n = 2653
42 (1.6)
n = 549
26 (4.7)
3 (0.6)
n = 196
8 (4.1)
1.26 (0.831.91)
0.38 (0.121.20)
1.84 (0.834.07)
Adjusted for age, index year, and number of primary care physician visits.
CI, condence interval.
Genital cancer includes cancer of the cervix, uterus, endometrium, ovary, fallopian tube vagina, labia, vulva and clitoris.
203
204
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