Review Article

Age at Menopause and Risk of Developing Endometrial Cancer: A Meta-Analysis

Table 1

Characteristics of the included studies for age at menopause with risk of the endometrial cancer among postmenopausal women.

AuthorCountry (year)Age range or mean ageStudy design (years of follow up)Age at menopauseCase (control or person-year)ParticipantsRR(95%CI)Adjustment for covariatesMenopausal type and definition of postmenopausal statusSource of case information

Kvale G [26]Norway
(1988)
27-69Cohort
(20)
≤4516 620791 Age, residential type, parity NACases were identified by records from the Cancer Registry of Norway
46-479 NA
48-4920
50-5121
52-5315
≥54152.55(1.25-5.20)

Shu XO [27]China
(1991)
18-74
56.0/56.4
Case-control≤4529 (44) 4041 Age, number of pregnancies, weightCases were identified by records from the Cancer Registry of Shanghai
(1988-1990)
46-4825 (50)1.00(0.50-2.00)
49-5067 (56)2.30(1.20-4.40)
≥5173 (60)1.90(1.00-3.60)

Brinton LA [28]America
(1992)
20-74
59.2/58.0
Case-control<4539 (28) 5041Age, education, parity, recent weight, OC use, menopausal estrogen useCases were identified by medical records
45-4989 (69)0.88(0.50-1.70)
50-54133 (83)0.99(0.50-1.80)
≥5536 (27)0.77(0.40-1.70)

Hirose K [29]Japan
(1999)
30-80
56.6/48.5
Case-control≤4712 (1408) 78491 Age, BMI NACases were identified by medical records
48-5236 (4738)0.88(0.45-1.69)
≥5324 (1631)1.50(0.75-3.03)

Olson JE [30]America
(1999)
55-69Cohort
(10)
<4541 (30853) 248481 Age NACases were identified by records from the State Health Registry of Iowa
45-4961 (56522)0.80(0.60-1.20)
50-54148 (106394)1.10(0.80-1.50)
>5582 (30987)2.00(1.40-2.90)

Salazar-Martinez E [31]Mexico
(1999)
57.1/54.6
Case-control≤407 (32) 3561Age, anovulatory index, smoking, diabetes mellitus, hypertension, physical activity, BMICases were from the gynecological oncology service and identified by biopsy-positive result.
41-4513 (61)1.10(0.34-3.70)
46-5016 (88)1.00(0.34-3.30)
≥5122 (117)1.20(0.42-3.60)

Xu WH [32]
China
(2004)
30-69
55.2/55.1
Case-control<4531 (66) 10251Age, education, OC use, alcohol drinking, any cancer history among first degree relatives, BMI, ever having had a live birth and ever having had an induce abortion, age at menarche
Women were considered postmenopausal when they reported not having had any menses over the past 12 months
Cases were identified by records from the Cancer Registry of Shanghai (1997-2001)
45-49192 (247)1.67(1.03-2.70)
50-54220 (204)2.38(1.46-3.87)
≥5548 (17)5.15(2.48-10.69)

Trentham-Dietz A [33]America
(2006)
40-79
62.9/63.3
Case-control<50177 (716) 24641 Age
Cases were identified by records from Wisconsin Cancer Reporting System
50-55239 (866)1.20(0.96-1.50)
>55134 (332)1.69(1.30-2.21)

Wernli KJ [34]China
(2006)
NACohort
(9)
<454 (62227) 2674001 Age, parity
Women were considered postmenopausal when they reported not having had any menses over the past 6 months.
Cases were identified by medical record
45-4936 (310089)2.09(0.56-7.75)
50-5481 (394730)3.73(1.03-13.47)
≥5519 (38686)9.09(2.78-29.69)

Setiawan VW [35]America
(2007)
45-75
61.6
Cohort
(7.3)
<45 NA 469331Age, BMI, age at menarche, parity, OC use, smoking, diabetes, hypertension, family
History of endometrial cancer, race

Cases were identified by records from Hawaii Tumor Registry
45-491.27(0.88-1.84)
50-541.67(1.16-2.41)
≥551.79(1.15-2.78)

Zucchetto A [36]Italy
(2009)
18-79
60/61
Case-control<5097 (252) 10771Period of interview, BMI, age at menarche, parity, OC use NACases were identified by medical records.
50-54193 (358)1.57(1.13-2.18)
≥5564 (113)1.76(1.14-2.72)

Dossus L [4]Denmark (2010) NACohort
(8.7)
≤50221 (535097) 3026181Age, BMI, physical activity, alcohol, diabetes, smoking, educationWomen were considered postmenopausal when they reported not having had any menses over the past 12 months, or when they were older than 55 years.Cases were identified by record linkage, health insurance records, cancer and pathology registries and active follow-up of study subjects.
51-52106 (170078)1.32(1.04-1.68)
53-55118 (156492)1.49(1.18-1.89)
>5553 (43212)2.20(1.61-3.01)
Karageorgi S [37]America
(2010)
30-50
41.8
Cohort
(19.3)
<4541 (71578) 1217001Age, parity, age at first birth, age at last birth, OC use, PMH use, BMI, smoking, diabetes, family history of endometrial cancer, age at menarche
Cases were identified by medical records.
45-49141 (310321)0.82(0.57-1.18)
50-54386 (521943)1.22(0.81-1.85)
≥5568 (77867)1.25(0.78-2.01)

Amankwah EK [38]Canada
(2013)
40-79
62.1/62.6
Case-control<50127 (297) 11031Age, residential type, smoking, BMI, hypertensionPostmenopausal status was defined as age ≥60 years, or self-identified as postmenopausal with the last menstrual period ≥12 months, or 50 to 59 years and using menopausal hormones for ≥2 years.Cases were identified by records from Alberta Cancer Registry
50-54176 (348)1.23(0.92-1.64)
≥5558 (97)1.55(1.03-2.33)

Dashti SG [39]America
(2015)
18-86
40
Cohort
(15)
<505 (3357) 11281Country, education, ascertainment, age at menarche, parity, PMH use
Women were considered postmenopausal when they reported not having had any menses over the past 12 months
Cases were identified by records from Colon Cancer Family Registry
≥5014 (4375)1.64(0.53-5.05)

Jung KJ [40]Korea
(2016)
55.6Cohort
(12.1)
≤455 664661Age, smoking, age at menarche, SBP, TC, HDL cholesterol, diabetes, exercise, exogenous hormone use, health insurance premiumWomen were considered postmenopausal when they reported not having had any menses over the past 12 monthsCases were identified by records from National Health Insurance Service in Korea
46-4830.80(0.18-3.57)
49-51122.68(0.82-8.78)
≥52113.06(0.89-10.47)

Yang HP [41]Poland
(2016)
20-74 Case-control<4533 (110)1Age, study site, age at menarche, oral contraceptive use, parity, LOC
Cases were identified by records from Polish Cancer Study
45-49111 (355)1.44(0.83-2.48)
50-54252 (579)2.71(1.38-5.35)
≥55114 (179)3.59(1.62-7.96)

Sponholtz TR [42]America
(2017)
21-69
36.6
Cohort
(18)
<4512 (22960) 475551Age, study peroid, education, marital status, age at menarche, parity, menopausal status, OC use, estrogen-only female menopausal hormone use, estrogen plus progestin female menopausal hormone use, smoking status, BMI, physical activity
Women were considered postmenopausal when they reported not having had any menses over the past 12 months, bilateral oophorectomy, or when they were ≥57 years of age and whose menopausal status was obscured due to hormone use.
Cases were identified by record linkage from state cancer registries
45-4938 (46155)1.45(0.73-2.89)
50-5464 (64053)1.32(0.67-2.56)
≥5528 (19161)1.45(0.70-3.02)

RR, relative risk; CI, confidence interval; NA, not available; BMI, body mass index; OC, oral contraceptive; PMH, postmenopausal hormone use; SBP, systolic blood pressure; TC, total cholesterol; HDL, high density lipoprotein; LOC, lifetime number of ovulatory cycles. ①, among women only with natural menopause; ②, among women with natural menopause and surgical menopause