Int. J.
Cancer: 108, 613– 619 (2004)
© 2003 Wiley-Liss, Inc.
MENSTRUAL AND REPRODUCTIVE FACTORS AND ENDOMETRIAL CANCER
RISK: RESULTS FROM A POPULATION-BASED CASE-CONTROL STUDY IN
URBAN SHANGHAI
Wang-Hong XU1, Yong-Bing XIANG1, Zhi-Xian RUAN1, Wei ZHENG2, Jia-Rong CHENG1, Qi DAI2, Yu-Tang GAO1 and Xiao-Ou SHU2*
1
Department of Epidemiology, Shanghai Cancer Institute, Shanghai, Peoples Republic of China
2
Department of Medicine, Vanderbilt-Ingram Cancer Center and Vanderbilt Center for Health Services Research,
Vanderbilt University, Nashville, TN, USA
The purpose of our study was to evaluate the association of
menstrual and reproductive factors with the risk of endome-
trial cancer. In a population-based case-control study con-
ducted in urban Shanghai, in-person interviews were com-
pleted for 833 women aged 30 – 69 years and an equal
number of controls frequency-matched to cases by age. All
cases were newly diagnosed with endometrial cancer be-
tween January 1, 1997 and December 31, 2001. The uncon-
ditional logistic regression model was employed to derive the
adjusted odds ratios (ORs) of endometrial cancer and 95%
confidence intervals (CIs) in relation to menstrual and repro-
ductive factors. Earlier menarche age, particularly among
premenopausal women, and later menopausal age were as-
sociated with an elevated risk of endometrial cancer. A clear
dose-response relation between endometrial cancer risk and
years of menstruation was observed (p for trend < 0.01).
Compared to women ever having a pregnancy and women
ever having had a live birth, respectively, nulligravity and
nulliparity were both associated with a more than one-fold
elevated risk of endometrial cancer. Both completed (OR ⴝ
3.02, 95% CI 1.10 – 8.32 for women never having a complete
pregnancy) and incomplete pregnancy (OR ⴝ 0.69, 95%CI
0.55– 0.87) conferred a protective effect against endometrial
cancer, and the protective effect appeared to increase with
total number of pregnancies (p for trend ⴝ 0.01). The effect
of pregnancy on endometrial cancer remained unchanged
with increasing time since the last pregnancy. Stillbirth and
age at first pregnancy was unrelated to endometrial cancer
risk. Our study suggests that prolonged menstruation was
related to an increased risk of endometrial cancer while
pregnancy, including induced abortion, reduced the risk of
endometrial cancer.
© 2003 Wiley-Liss, Inc.
Key words: endometrial cancer; menstruation; pregnancy; abortion;
case-control studies
Chinese women historically have a lower risk of endometrial
cancer compared to their counterparts in the United States and
other western countries. However, the incidence of endometrial
cancer in Shanghai women has substantially increased over the
past 2 decades. The age-adjusted endometrial cancer incidence rate
increased 76% from 2.5/100,000 in 1972–74 to 4.4/100,000 in
1994, becoming 1 of the 10 most common cancers among Shang-
hai women.1 The increase was more pronounced among older
women, with 132.1% and 2.08% for women 55– 64 and 35– 44,
respectively, for the same time period. Menstrual and reproductive
factors, such as age at menarche, age at menopause, nulligravity
and live birth, have been associated with the risk of endometrial
cancer in many previous studies, including a study conducted
among Chinese women.2–5 Prolonged estrogen stimulation without
the protection of progesterone has been suggested as the possible
mechanism for the association of menstrual and reproductive fac-
tors with the risk of endometrial cancer.6 – 8 However, results from
earlier studies were not entirely consistent, particularly regarding
the effect of induced abortion.4,5,9 The high frequency of receiving
hormone replacement therapy and hysterectomy among western
populations makes it difficult to study attribution of menstrual and
reproductive factors on endometrial cancer and may have caused
some of the inconsistency.
Publication of the International Union Against Cancer
The major objective of our study was to test the hypothesis that
prolonged menstruation increases and pregnancy, including in-
duced abortion, reduces the risk of endometrial cancer among
women in Shanghai. The populated-based Shanghai cancer regis-
try, high rate of induced abortion, low rate of hysterectomy and
low frequency of using hormonal replacement therapy among
women in Shanghai provided us a unique opportunity to study the
hypothesis.
MATERIAL AND METHODS
All cases were permanent residents of urban Shanghai between
the ages of 30 and 69 years who were newly diagnosed with
endometrial cancer during the period of January 1997 to December
2001. Through the population-based Shanghai Cancer Registry,
983 eligible endometrial cancer cases were identified, and in-
person interviews were completed for 833 (84.7%) of them.
Among 150 nonparticipants, there were 73 refusals (7.4%), and 36
deaths before interview (3.7%), while 22 could not be located
(2.2%), 10 were absent during the study period (1.0%) and 9 were
excluded for other miscellaneous reasons (0.9%).
Controls were randomly selected from female permanent resi-
dents in the Shanghai urban area and frequency-matched to cancer
cases by age (5-year interval) in a 1:1 ratio. The random selection
was performed at the Shanghai Resident Registry. Women who
had a prior history of endometrial cancer or hysterectomy were
ineligible for the study (5.1%). The number of controls in each
age-specific stratum was determined in advance according to the
age distribution of the incident endometrial cancer cases reported
to the Shanghai Cancer Registry in 1996. In-person interviews
were completed for 833 of the 1,165 eligible controls identified.
The response rate for the controls was 71.5%. The reasons for
nonparticipation were refusal (24.9%) and absence during the
study period (3.6%).
Interviewers were trained nurses. The structured questionnaire
used for the study took, on average, 70 min to complete. It covered
demographic factors, menstrual and reproductive history, hormone
use, usual dietary intake, disease history, tobacco and alcohol use,
weight history and family history of cancer. Date of diagnosis (for
cases) and interview (for controls) were used as the “reference
date” during the interview. All exposure information was collected
up to or before the reference date, often one year before the
Grant sponsor: NCI; Grant number: R01CA92585.
*Correspondence to: Center for Health Services Research, 6009 Medical
Center East, Vanderbilt University, 1215 21st Ave South, Nashville, TN
37232-8300, USA. E-mail: Xiao-Ou.Shu@vanderbilt.edu
Received 19 March 2003; Revised 7 July 2003, 19 August 2003;
Accepted 26 August 2003
DOI 10.1002/ijc.11598
614 XU ET AL.

interview date. Data collected on reproductive history included
outcome and duration of each pregnancy. Menopause was defined
as cease of menstrual period, excluding those caused by pregnancy
and nursing, for at least 12 months before the reference date. The
median interval between diagnosis and interview (25th, 75th per-
centile) for cases was 5 months (3 months, 8 months). Years of
menstruation were age at reference date minus age at menarche for
premenopausal women, and age at menopause minus age at men-
arche for postmenopausal women. Each participant was also mea-
sured for current weight, circumferences of the waist and hip and
sitting and standing heights. All interviews were tape-recorded and
were reviewed by the field supervisor and quality control staff to
monitor the quality of interview data. Additional data quality
procedures included range and logic check and double entry.
Odds ratios (ORs) were used to measure the association of
endometrial cancer risk with menstrual and reproductive charac-
teristics. The unconditional logistic regression model was em-
ployed in the analysis to obtain maximum likelihood estimates of
the ORs and their 95% confidence intervals (CIs) with an adjust-
ment for potential confounders.10 Collinearity between variables
was checked before they were included in the regression model.
Categorical variables were treated as dummy variables in the
model. Tests for trend were performed by entering the categorical
variables as continuous parameters in the models.
RESULTS
Cases and controls were well matched on age distribution (Table
I). The mean age was 55.2 years for cases and 55.1 years for
controls. There were no major case-control differences with re-
spect to marital status, per capita income one year before interview
or in 1978 and total energy intake. Compared to controls, cases
were more likely to be better educated (p ⫽ 0.05), have a higher
body mass index (BMI) (p ⬍ 0.01) and waist-to-hip ratio (WHR)
(p ⬍ 0.01), more likely to have a family history of cancer among
first-degree relatives (p ⬍ 0.01), less likely to be a drinker (p ⬍
0.01) and less likely to have used oral contraceptives (p ⬍ 0.01).
All subsequent analyses included these variables and age as po-
tential confounders.
Table II presents ORs and 95% CIs for menstrual characteristics
in association with endometrial cancer risk. There was an inverse
association between age at menarche and endometrial cancer risk

TABLE I – COMPARISON OF CASES AND CONTROLS ON DEMOGRAPHICS AND SELECTED ENDOMETRIAL

CANCER RISK FACTORS1
Cases Controls
(n ⫽ 833) (n ⫽ 833) p-value
No. % No. %

Age (mean ⫾ SD) 55.2 ⫾ 8.70 55.1 ⫾ 8.56 0.83

Per capita income in last year
(yuan)
ⱕ4166.7 231 27.8 240 28.8
4166.8⬃5833.3 68 8.2 75 9.0
5833.4⬃7500.0 204 24.5 193 23.2
7500.1⬃8750.0 151 18.1 160 19.2
⬎8750.0 178 21.4 164 19.7 0.80
Per capita income in 1978 (yuan)
ⱕ187.5 156 18.8 194 23.5
187.6⬃250.0 211 25.4 205 24.8
250.1⬃312.5 129 15.6 128 15.5
312.6⬃416.7 169 20.4 158 19.1
⬎416.7 164 19.8 142 17.2 0.19
Education
ⱕElementary 201 24.1 232 27.9
Middle & high 506 60.7 504 60.5
Prof. & College 126 15.1 97 11.6 0.05
Material Status
Unmarried 14 1.7 11 1.3
Married or cohabit 724 86.9 730 87.6
Seperation/divorce/bereft of 95 11.4 92 11.0 0.81
spouse
Oral contraceptive use
Ever 148 17.8 207 24.9
Never 685 82.2 626 75.2 ⬍0.01
Cancer among first degree
relatives
No 535 64.8 605 73.1
Yes 290 35.2 223 26.9 ⬍0.01
Body Mass Index (by quartile)
ⱕ21.411 123 14.9 209 25.2
21.412⬃23.681 166 20.1 208 25.0
23.682⬃26.271 217 26.3 206 24.8
⬎26.271 320 38.7 208 25.0 ⬍0.01
Waist-to-Hip Ratio (by quartile)
ⱕ0.782 106 12.8 207 24.9
0.783⬃0.816 162 19.5 209 25.1
0.817⬃0.855 239 28.8 207 24.9
⬎0.855 323 38.9 209 25.1 ⬍0.01
Regular alcohol drinking
Ever 20 2.4 42 5.0
Never 813 97.6 791 95.0 ⬍0.01
Total energy intake (Kcal, Mean 2213.1 ⫾ 492.4 2201.9 ⫾ 512.5 0.66
⫾ SD)
1
Subjects with missing values were excluded from the analysis.
 MENSTRUAL, REPRODUCTIVE FACTORS AND EC RISK 615
TABLE II – ODDS RATIOS (ORS) OF ENDOMETRIAL CANCER ASSOCIATED WITH MENSTRUAL CHARACTERISTICS1

Cases Controls OR1 (95% CI) OR2 (95% CI)

Age at menarche (years)

ⱕ12 109 77 1.00 1.002
13 167 147 0.80 (0.56–1.16) 0.79 (0.54–1.15)
14 167 152 0.78 (0.54–1.12) 0.81 (0.55–1.18)
15 166 177 0.66 (0.46–0.95) 0.76 (0.52–1.12)
16 128 141 0.64 (0.44–0.94) 0.75 (0.51–1.13)
ⱖ17 94 137 0.49 (0.33–0.72) 0.55 (0.36–0.83)
⬍0.01 0.02
Menstrual status
Premenopause 330 294 1.00 1.003
Natural menopause 491 534 0.62 (0.46–0.84) 0.61 (0.45–0.84)
Induced menopause 12 5 1.84 (0.64–5.34) 1.68 (0.56–5.07)
Age at menopause (among women with natural menopause)
⬍45 31 66 1.00 1.003
45⬃49 192 247 1.65 (1.03–2.63) 1.67 (1.03–2.70)
50⬃54 220 204 2.27 (1.42–3.63) 2.38 (1.46–3.87)
ⱖ55 48 17 5.80 (2.86–11.75) 5.15 (2.48–10.69)
⬍0.01 ⬍0.01
Years of menstruation
⬍30 123 173 1.00 1.002
30⬃ 286 337 1.34 (1.00–1.81) 1.30 (0.95–1.78)
35⬃ 327 270 1.99 (1.46–2.72) 1.93 (1.38–2.70)
40⬃ 95 51 3.21 (2.06–5.02) 2.71 (1.67–4.40)
⬍0.01 ⬍0.01
Length of menstrual cycle
26⬃30 553 540 1.00 1.004
⬍26 128 149 0.84 (0.64–1.09) 0.90 (0.68–1.19)
⬎30 152 144 1.03 (0.80–1.33) 1.00 (0.76–1.31)
Regularity of menstrual cycle
Always regular 770 793 1.00 1.004
Always irregular 40 26 1.58 (0.86–2.62) 1.37 (0.80–2.35)
Sometimes irregular 22 14 1.62 (0.82–3.19) 1.61 (0.80–3.26)
Days of monthly menstrual bleeding
5⬃7 571 509 1.00 1.004
⬍5 207 289 0.64 (0.52–0.79) 0.60 (0.48–0.75)
⬎7 44 27 1.45 (0.89–2.38) 1.62 (0.96–2.75)
1
OR1, Adjusted for age; OR2, Adjusted for age, education, oral contraceptives use, alcohol drinking, any cancer history among first degree
relatives, body mass index, ever having had a live birth and ever having had an induce abortion.–2Additionally adjusted for menstrual
status.–3Additinally adjusted for age at menarcheal.–4Additionally adjusted for menstrual status, age at menarcheal.

(p for trend ⫽ 0.02). Compared to women with menarchal age 12
or less, women with menarchal age 17 or more had a 45% (95% CI
0.36 – 0.83) lower risk of endometrial cancer. Cases were more
likely than controls to be premenopausal (OR ⫽ 0.61, 95% CI
0.45– 0.84). Older age at menopause was associated with an ele-
vated risk of endometrial cancer (p for trend ⬍ 0.001). Compared
to subjects whose menopause occurred before age 45, those whose
menstrual periods continued until age 55 or later had a 5-fold (95%
CI 2.48 –10.69) increased risk of endometrial cancer. The risk of
endometrial cancer increased with years of menstruation (p for
trend ⬍ 0.01). Compared to women whose days of monthly
menstrual bleeding was 5–7 days, women whose monthly bleeding
was less than 5 days had a lower risk of endometrial risk (OR ⫽
0.60, 95% CI 0.48 – 0.75). Length and regularity of menstrual
cycle was unrelated to the risk of the disease.
Nulligravity was associated with a significantly elevated risk of
endometrial cancer (OR ⫽ 1.82, 95% CI 1.16 –2.85) (Table III).
Exclusion of unmarried women (14 cases and 11 controls) did not
change the association. Among subjects who were involuntarily
infertile (i.e., tried to become pregnant for 2 or more years without
success), 17 cases and 7 controls reported to have a physician
diagnosed fertility problem. The protective effect of pregnancy on
the risk of endometrial cancer increased with the increasing num-
ber of pregnancies (p for trend ⫽ 0.01). Although women whose
latest pregnancy ended with a miscarriage had a marginally ele-
vated risk (OR ⫽ 2.27, 95% CI ⫽ 0.97–5.25), ever having had a
miscarriage did not appear to be related to the risk of endometrial
cancer (OR ⫽ 1.03, 95% CI ⫽ 0.67–1.58). Induced abortion only
before first birth was rare (19 cases and 15 control) in the study
population and was not related to the risk of the disease. Age at last
pregnancy was not significantly associated with the risk of endo-
metrial cancer (data not shown). Neither the number of live births
nor the number of induced abortions conferred additional protec-
tion from endometrial cancer. The protective effort of pregnancy
on endometrial cancer remained little changed for more than 30
years after the last pregnancy among all gravid women and women
who had no induced abortion after their last birth. Excluding
women who had ever used hormone replacement therapy (HRT)
did not change the associations (data not shown).
Additional analyses stratified by menopausal status were con-
ducted and presented in Table IV. Later age at menarche was
associated with a markedly decreased risk of endometrial cancer
among premenopausal women (p for trend ⫽ 0.01) but the reduc-
tion in risk was much smaller among postmenopausal women.
However, test for multiplicative interaction was not significant.
Similarly, prolonged menstruation was associated with a slightly
higher risk of endometrial cancer among premenopausal women
than that of postmenopausal women, although test for interaction
was not significant and the linear trend between years of menstru-
ation and endometrial cancer risk was only observed for postmeno-
pausal women. Ever having a pregnancy or a live birth appears to
have a slightly stronger protective effect on postmenopausal en-
dometrial cancer, while the effect of induced abortion was slightly
more protective among premenopausal women. Again, the inter-
action did not reach statistical significance.
Among gravid women, a lower proportion of cases than controls
had ever used oral contraceptives (OR ⫽ 0.64, 95% CI 0.50 –
0.84). It was uncommon to use noncontraceptive hormones among
Shanghai women and there were no case-control differences with
 TABLE III – ODDS RATIOS (ORS) OF ENDOMETRIAL CANCER ASSOCIATED WITH REPRODUCTIVE CHARACTERISTICS1

Cases Controls OR1 (95% CI) OR2 (95% CI)

Pregnancy
Ever 770 799 1.00 1.00
Never 63 34 1.93 (1.26–2.96) 1.82 (1.16–2.85)
Reasons for nulligravity
Unmarried 14 11 1.00 1.00
Infertile due to a female fertility problem 17 7 1.90 (0.58–6.20) 2.64 (0.70–9.91)
Infertile due to a male fertility problem 13 3 3.45 (0.78–15.29) 4.50 (0.90–22.60)
Others 19 13 1.16 (0.40–3.34) 1.23 (0.38–3.97)
Number of pregnancies (among gravid women)
1 136 106 1.00 1.00
2 197 201 0.76 (0.55–1.05) 0.75 (0.54–1.05)
3 196 207 0.74 (0.54–1.02) 0.66 (0.47–0.94)
4 141 155 0.71 (0.50–1.00) 0.63 (0.43–0.93)
ⱖ5 100 130 0.60 (0.42–0.86) 0.59 (0.39–0.92)
p trend ⬍0.01 0.01
Outcome of most recent pregnancy (among gravid women)
Live birth 398 364 1.00 1.002
Induced abortion 333 415 0.73 (0.60–0.90) 1.11 (0.76–1.62)
Miscarriage 28 9 2.84 (1.32–6.11) 2.27 (0.97–5.35)
Others 11 11 0.91 (0.39–2.13) 0.98 (0.39–2.50)
Years since last pregnancy
⬍20 259 276 1.00 1.002
20⬃ 243 261 1.03 (0.76–1.38) 0.84 (0.60–1.16)
30⬃ 264 258 1.16 (0.77–1.74) 0.98 (0.63–1.54)
p trend 0.47 0.89
Years since last pregnancy (among women who have no induced abortion after their last birth)
⬍20 113 90 1.00 1.002
20⬃ 133 126 0.77 (0.49–1.22) 0.69 (0.41–1.17)
30⬃ 191 168 0.77 (0.41–1.44) 0.86 (0.42–1.75)
0.46 0.77
Stillbirth (among gravid women)
Never 760 782 1.00 1.002
Ever 10 17 0.60 (0.27–1.31) 0.64 (0.27–1.48)
Livebirth (among gravid women)
Ever 754 793 1.00 1.003
Never 16 6 2.86 (1.11–7.36) 3.02 (1.10–8.32)
Number of live births (among parious women)
1 354 355 1.00 1.003
2 203 229 0.80 (0.60–1.05) 0.82 (0.60–1.10)
3 118 108 0.92 (0.63–1.34) 1.00 (0.65–1.53)
ⱖ4 79 101 0.64 (0.42–0.98) 0.73 (0.45–1.18)
p trend 0.09 0.30
Incomplete pregnancy (among gravid women)
Never 304 246 1.00 1.004
Ever 466 553 0.68 (0.55–0.84) 0.69 (0.55–0.87)
Induced only 371 458 0.65 (0.53–0.81) 0.67 (0.53–0.84)
Miscarriage only 66 49 1.09 (0.73–1.63) 1.03 (0.67–1.58)
Both induced and miscarriage 29 46 0.51 (0.31–0.84) 0.53 (0.31–0.89)
Number of induced abortions (among gravid women)
Never 370 295 1.00 1.004
1 239 308 0.62 (0.49–0.78) 0.64 (0.50–0.82)
2 122 154 0.63 (0.47–0.84) 0.63 (0.46–0.85)
ⱖ3 39 42 0.74 (0.46–1.17) 0.84 (0.52–1.38)
Time of the induced abortion (among gravid women)
Never 370 295 1.00 1.005
Only before first birth 19 15 1.00 (0.50–2.03) 1.02 (0.47–2.21)
Only after last birth 290 365 0.63 (0.51–0.79) 0.68 (0.52–0.88)
Both before and after first birth 9 19 0.38 (0.18–0.85) 0.44 (0.18–1.05)
Others 82 105 0.62 (0.45–0.86) 0.62 (0.41–0.94)
Oral contraceptive use (among gravid women)
Never 625 593 1.00 1.006
Ever 145 206 0.67 (0.52–0.85) 0.64 (0.50–0.84)
Duration of oral contraceptive use (months)
Never 625 593 1.00 1.006
ⱕ24 97 111 0.81 (0.61–1.09) 0.80 (0.58–1.10)
⬎24 45 94 0.46 (0.31–0.67) 0.44 (0.29–0.65)
p trend ⬍0.01 ⬍0.01
Contraceptive injection use (among gravid women)
Never 751 776 1.00 1.002
Ever 19 23 0.86 (0.46–1.59) 1.04 (0.54–1.98)
HRT use
Never 798 800 1.00 1.002
Ever 35 33 1.06 (0.65–1.73) 1.06 (0.63–1.78)
1
OR1, Adjusted for age; OR2, Adjusted for age, education, oral contraceptives use, years of menstruation, menstrual status any cancer history
among first degree relatives, body mass index and alcohol drinking.–2Additionally adjusted for ever having had a live birth, ever having had an
induce abortion, number of pregnancy.–3Additionally adjusted for number of incomplete pregnancy.–4Additionally adjusted for number of
complete pregnancy.–5Additionally adjusted for ever having had a live birth, number of pregnancy.–6Conditions in footnote 2 plus excluding
oral contraceptives use
 MENSTRUAL, REPRODUCTIVE FACTORS AND EC RISK 617
TABLE IV – ODDS RATIOS (ORS) OF ENDOMETRIAL CANCER ASSOCIATED WITH MENSTRUAL AND REPRODUCTIVE FACTORS
BY MENOPAUSAL STATUS1
Premenopause Postmenopause p value for test of
Cases/controls OR (95% CI) Cases/controls OR (95% CI) heterogeneity

Age at menarche (years)2

ⱕ12 54/22 1.00 55/55 1.00
13 64/54 0.45 (0.24–0.87) 103/93 1.07 (0.66–1.76)
14 70/61 0.45 (0.24–0.86) 97/91 1.21 (0.73–1.99)
15 71/74 0.43 (0.23–0.80) 95/103 1.06 (0.64–1.75)
16 50/48 0.47 (0.24–0.91) 78/93 0.97 (0.58–1.62)
ⱖ17 21/33 0.29 (0.13–0.63) 73/104 0.80 (0.47–1.35) p ⫽ 0.24
p trend p ⫽ 0.01 p ⫽ 0.22
Years of menstruation3
⬍30 86/98 1.00 37/75 1.00
30– 117/111 1.23 (0.70–2.17) 169/226 1.47 (0.93–2.33)
35– 98/77 1.39 (0.64–3.00) 229/193 2.47 (1.56–3.92)
40– 29/6 5.12 (1.29–20.44) 66/45 2.65 (1.48–4.76) p ⫽ 0.52
0.15 ⬍0.01
Pregnancy
Ever 303/279 1.00 467/520 1.00
Never 27/15 1.63 (0.81–3.29) 36/19 2.25 (1.25–4.05) p ⫽ 0.58
Livebirth (among gravid women)c
Never 9/4 1.00 7/2 1.00
Ever 294/275 0.55 (0.15–2.02) 460/518 0.21 (0.04–1.16) p ⫽ 0.34
Number of livebirth (among parous women)4
1 247/235 1.00 107/120 1.00
2 38/37 0.73 (0.42–1.29) 165/192 0.93 (0.64–1.35)
3 9/3 1.06 (0.25–4.51) 111/106 1.08 (0.68–1.74)
ⱖ4 77/100 0.79 (0.46–1.34) p ⫽ 0.41
p ⫽ 0.41 p ⫽ 0.51
5
Induced abortion (among gravid women)
Never 126/85 1.00 244/210 1.00
Ever 177/194 0.60 (0.42–0.86) 223/310 0.69 (0.53–0.91) p ⫽ 0.75
Number of induced abortion (among gravid women)5
Never 126/85 1.00 244/210 1.00
1 114/117 0.66 (0.44–0.99) 125/191 0.63 (0.46–0.85)
2 46/59 0.46 (0.28–0.77) 76/95 0.75 (0.51–1.10)
ⱖ3 17/18 0.64 (0.31–1.37) 22/24 1.06 (0.55–2.08) p ⫽ 0.35
p ⬍ 0.01 p ⫽ 0.18
6
Oral contraceptive use (among gravid women)
Never 253/234 1.00 372/359 1.00
Ever 50/45 0.89 (0.55–1.45) 95/161 0.57 (0.42–0.78) p ⫽ 0.14
Duration of oral contraceptive use (months) (among gravid women)6
Never 253/234 1.00 372/359 1.00
ⱕ24 28/25 0.93 (0.51–1.72) 52/58 0.87 (0.57–1.35)
⬎24 21/20 0.81 (0.41–1.62) 41/102 0.39 (0.26–0.59)
p trend 0.54 ⬍0.01 p ⫽ 0.09
1 2
Adjusted for age, education, any cancer history among first degree relatives, body mass index, alcohol drinking.– Additionally adjusted for
oral contraceptives use, ever had a live birth and an induced abortion, and for postmenopausal women, menopausal age.–3Additionally adjusted
for oral contraceptives use, ever had a live birth and an induced abortion.–4Additionally adjusted for oral contraceptives use, years of
menstruation, number of induced abortion.–5Additional adjusted for oral contraceptives use, years of menstruation, number of livebirth.–
6
Additionally adjusted for years of menstruation, ever had a live birth and an induced abortion, number of pregnancies.

TABLE V – ODDS RATIOS OF ENDOMETRIAL CANCER ASSOCIATED WITH LIVE BIRTH AND INDUCED ABORTION1
Number of live births
p value for test of
1 2–3 ⬎3 heterogeneity
Cases/controls OR (95% CI) Cases/controls OR (95% CI) Cases/controls OR (95% CI)

No. of induced 0 165/123 1.00 137/110 0.73 (0.50–1.06) 55/59 0.57 (0.35–0.96)
abortion
1 121/149 0.56 (0.40–0.78) 100/128 0.44 (0.30–0.64) 16/30 0.36 (0.18–0.75)
ⱖ2 68/83 0.52 (0.35–0.77) 84/99 0.48 (0.32–0.70) 8/12 0.49 (0.18–1.32) p ⫽ 0.35
1
Adjusted for age, education, menopausal status, years of menstruation, any cancer history among first degree relatives, body mass index,
alcohol drinking, and oral contraceptive use.

respect to HRT use and injectable contraceptive use (Table III).
Further stratified analysis by menstrual status showed that the
difference and the trend of decreasing ORs with increasing dura-
tion of oral contraceptive use were observed only among post-
menopausal women (Tables III and IV).
Finally, we ran a stratified analysis of number of induced abor-
tions by number of live births (Table V). The inverse association
of endometrial cancer with induced abortion appeared to be weak-
ened among women with 3 or more live births. Similarly, the
protective effect of live birth was also less apparent among women
618 XU ET AL.
with 2 or more induced abortions. However, test for multiplicative
interaction was not significant.
DISCUSSION
Similar to many studies conducted in western countries,2,4,5,11 this
population-based case-control study of endometrial cancer, conducted
in a low risk population, found that prolonged menstruation, nulli-
gravity and nulliparity were related to an increased risk of endometrial
cancer. Pregnancy, regardless of whether it was a complete pregnancy
or induced abortion, was related to a reduced risk of endometrial
cancer, and the protective effect lasted for more than 30 years after the
last pregnancy. We also found that the effect of menstrual factors
appeared to be more pronounced among premenopausal women,
while the reproductive factors appear to be slightly more strongly
linked to postmenopausal endometrial cancer. An interesting finding
of the study was the demonstration that induced abortion was asso-
ciated with a decreased risk of endometrial cancer.
Endometrium undergoes a cyclic change from proliferative to
secretory phase and then to menstruation phase among menstru-
ating women under the influence of the rise and fall of estrogen
and progesterone levels. Excessive proliferation or inadequate
shedding caused by prolonged estrogen stimulation, particularly
unopposed by progesterone, has been long suggested as one of the
major mechanisms of endometrial cancer development. In addition
to contributing to the years of menstruation, early menarche and
later menopause have been both linked to anovulatory cycles.12,13
It has also been suggested that level of androstenedione, a precur-
sor of estradiol, increased with anovulation at menopause. Our
present study, like many previous studies,2– 4 found that earlier age
at menarche and later age at menopause are the major risk factors
of endometrial cancer. The stronger association between years of
menstruation and endometrial cancer among premenopausal
women was similar to the report by La Vecchia et al.14 and may be
the result of exposure to estrogen at an earlier age. The latter is
supported by a stronger association between earlier menarche with
premenopausal endometrial cancer found in our study.
Several decades ago it was observed that nulliparous women in
England and Wales had higher deaths rates from endometrial
cancer than parous women.15 U.S. investigators also reported
higher incidence of the disease in single than in married women.16
Case-control and cohort studies have consistently shown that nul-
liparity is associated with a 2- to 3-fold increased risk of endome-
trial cancer.3,17 In agreement with these studies, we found more
than a 2-fold of risk among nulliparous women. In addition, we
found that the risk of endometrial cancer decreased with increased
number of pregnancies, and the effect was unaffected by preg-
nancy outcome.
Several studies showed that age at last live birth might decrease
the risk of the cancer.5,18 –20 Kvale et al.21 hypothesized that the
protective effect of late delivery age may relate to the mechanical
exfoliation of the endometrium at each delivery, by which epithe-
lial cells in early and later stages of malignant transformation
might be removed. However, we found age at last pregnancy was
not significantly associated with the risk of endometrial cancer
after adjustment, suggesting uncontrolled confounding factors
might have accounted for findings from the earlier report. In
contrast, we found that years since last pregnancy was unrelated to
risk of endometrial cancer, suggesting a sustained protective effect
of pregnancy on endometrial cancer.
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