Original article

Role of Reproductive Factors on the Risk of Endometrial Cancer in

Nineveh Province, Iraq: A Case-Control Study
Zahraa Dheyauldin Abdulwahhab1, Humam Ghanim Ibrahim2
1Ministry of Health, Nineveh Health Directorate, Mosul, Iraq, 2Department of Family and Community Medicine, College of Medicine, University of Mosul,
Mosul, Iraq
Correspondence to: Dr. Zahraa Dheyauldin Abdulwahhab, E-mail: zahraa.23hmp27@[Link]

ABSTRACT
Background: Endometrial cancer (EC) is the sixth most common cancer worldwide. This study aimed to evaluate the
associations between reproductive risk factors and EC in Nineveh Province, north Iraq, due to limited research.
Methods: The study was conducted from September 2024 to the end of the year, using a case-control design. It included
100 cases of histologically diagnosed EC from 2022 to 2024 and 200 age-matched controls admitted to hospitals in the same
catchment area for non-neoplastic and non-gynecological conditions. Informed consent was obtained before the
interviews. The association between risk factors and EC development was measured using odds ratios (OR) and 95%
confidence intervals (CI), with P-values ≤ 0.05 considered statistically significant.
Results: The study found that nulliparous women were present in 12/94 (12.77%) cases and 10/194 (5.15%) controls, with a
risk nearly three times significantly higher than that of parous women (OR, 2.69; 95% CI, 1.12–6.48, P = 0.032). The mean
number of children in cases (5.16 ± 2.45) was significantly lower (P = 0.001) than that in controls (6.51 ± 2.66), and the
mean age at first birth was significantly higher in cases (23.13 ± 5.50, P = 0.001). However, there was no significant
difference in the age at menarche and menopause between the cases and controls.
Conclusion: Parity and first-age delivery differed significantly among study participants. However, the age of menarche and
menopause is not associated with increased EC risk.
Keywords:
Endometrial cancer, Reproductive factors, Parity, Age at first birth, Age at menarche, Age at menopause.

INTRODUCTION estrogen exposure may be linked to reproductive

Endometrial cancer, is a type of cancer that affects the characteristics like parity, age at menarche, menopause,
endometrium, which is the lining of the uterus. Cancer of and delivery age.
the endometrium is a common gynecological cancer Numerous studies have found that early menarche 5–
affecting women worldwide,1 particularly those 9
and late menopause 5,9 are risk factors for EC. Women
experiencing menopause, and it is the sixth most common with a menarche age of 17 years or older had a 45% [95%
malignancy in women.2,3 The number of EC cases, CI 0.36–0.83] reduced risk compared to those aged 12
percentage, and crude incidence rate among Iraqi women years or younger. A link existed between lifetime
by primary site and gender in 2023 were 1302, 5.2%, and menstrual years and EC risk, with a 1.9% increase for each
6.07/100,000, respectively.4 additional year. Additionally, individuals with menstrual
The endometrium's structure varies in response to periods lasting until age 55 or beyond have a 5-fold higher
the menstrual cycle, and unopposed estrogen exposure risk of EC [95% CI = 2.48–10.69] compared to those who
increases this risk.5 Individual differences in unopposed went through menopause before the age of 45.9
Endometrial carcinoma is increasingly prevalent in
ARTICLE INFO nulliparous women.2,10,11 Childlessness is associated with
Article History an increased risk of type I and type II EC.10 Hormonal
Received: 01.01.2024 | Accepted: 29.03.2025
Conflict of Interest: The authors declare no conflict of interest. changes during pregnancy may have immunological
Funding: None advantages and influence the incidence of EC,12 reducing
Copyright: © 2025 Abdulwahhab et al. This article is licensed under the the risk of the disease by 10.9% for each additional child.13
Creative Commons Attribution-NonCommercial 4.0 International The risk of developing EC decreases with increasing
License (CC BY-NC 4.0), which permits unrestricted non-commercial
use, sharing, and reproduction in any medium, provided the original age at the time of her first live birth.14,15 A study by
author and source are properly credited. Sugawara et al.,16 found that a woman's risk of developing
Citation: Abdulwahhab ZD, Ibrahim HG. Role of reproductive factors on EC decreased with age at the time of her first live birth.
the risk of endometrial cancer in Nineveh Province, Iraq: A case-control Multivariate hazard ratios were 0.79 for women aged 23-
study. J Fatima Jinnah Med Univ. 2025; 19(1): 00–00.
25 at first birth and 0.53 for those aged 26 and above,
DOI: [Link] respectively, compared to those aged 22 years or less at
first delivery. However, some studies suggest older age at

[Link]
Abdulwahhab et al 13

first childbirth increases the risk of EC,17 while others find (such as age at menarche and menopause, parity, and age
no association between the maternal age at first birth.18 at first childbirth) were included in the questionnaire and
The present study aimed to identify the reproductive considered as independent variables. BMI was
risk factors associated with EC in Nineveh Province over determined using the formula: [weight (kg) / height (m)]2.
the past three years, as no previous research has been The questionnaire was translated from English to Arabic
conducted in this area. to make data collection easier.
Sampling technique and sample size determination: In
SUBJECTS AND METHODS the current study, cases and controls were individually
Study Design: The methodology employed in the current matched based on age (± 5 years) and were selected using
study was a retrospective case-control design to achieve convenience sampling. The formula for unmatched case-
the objectives delineated in this research. To explore the control studies was used to estimate the sample size,
potential association between exposure to a specific providing a conservative approximation, as there was no
reproductive risk factor and the occurrence of EC, a group prior information on the percentage of discordant pairs
of women diagnosed with EC (cases) was compared to a (i.e., pairs where the exposure status differed between
group of women without such a diagnosis (controls). The the matched case and control):
ratios of cases and controls exposed to specific risk n = ((Z1–α/2 + Z1–β) ².(P0 (1 – P0)+P1 (1 – P1)/(P1 – P0)²)
variables to those who were not exposed were then Z1–α/2 = 1.96: standard normal deviate for 95% confidence
carefully analyzed. level,
Study setting: The current study was conducted from Z1–β = 0.84: standard normal deviate for 80% power,
September 2024 to the end of that year at the Oncology P1: The estimated proportion of exposure among the
and Nuclear Medicine Hospital, its departments (Ibn-Sinna cases (based on previous studies)
Teaching Hospital and Medical Research and Care Center), P0: The estimated proportion of exposure among the
and Al-Salam Teaching Hospital in Nineveh Province, controls (based on previous studies)
northern Iraq. n = ((1.96 + 0.84)².(0.20(1 – 0.20) + 0.20)+0.38(1 –
Recruitment criteria: The cases included adult women 0.38)/(0.38 – 0.20)²)
diagnosed histologically with EC irrespective of clinical n= ~ 96
staging or metastasis, who attended the Oncology and The predicted minimum sample size was 192 (96
Nuclear Medicine Hospital and its departments from 2022 cases and 96 controls). To increase statistical power and
to 2024. The controls included adult women visiting account for probable data loss, researchers used a 1:2
hospitals in the same catchment area for non-neoplastic matching ratio, resulting in a final sample size of 100 cases
and non-gynecological issues. These women do not exhibit and 200 age-matched control subjects.
suspicious symptoms, such as irregular vaginal bleeding, Statistical Analysis: Data coding, tabulation, and analysis
discharge, or pelvic pain, and have no prior malignancies were performed using Microsoft Excel 2013, Med-Calc,
anywhere in the body. Patients with secondary EC were and SPSS statistical software. Descriptive statistics
excluded. Furthermore, women with suspected EC included mean ± standard deviation (SD) for measurable
symptoms and a personal history of any other malignancy variables and frequencies and percentages for categorical
were excluded from the control group. Overall, those who variables.
did not agree to participate were excluded from the An independent t-test of the two means was used to
study. compare the quantitative parameters. Chi-square test was
Data collection: The cases were identified and selected used to compare categorical variables. OR and 95% CI
from the medical records of the Oncology and Nuclear were used to measure the association between the risk
Medicine Hospital and its departments. The information factors and the development of EC. P-values ≤ 0.05 were
gathered from medical records included age, height and considered statistically significant throughout the data
weight, phone number, and year of diagnosis. They were analysis.
then contacted via phone, and informed consent was Ethical Considerations: The Scientific and Ethical Research
obtained. Those who provided consent were interviewed Committee/Nineveh Health Directorate approved this
over the phone to answer other required questions of the study on September 16, 2024 (Research ID: 2024144). The
predefined structured questionnaire. Responses to the study procedures followed the ethical criteria outlined in
questionnaire were used to collect data regarding the Declaration of Helsinki.
controls during direct interviews with them.
Demographic parameters (such as age, educational
level, occupation, ethnicity, marital status, body mass
index (BMI), and smoking status) and reproductive history

[Link] J Fatima Jinnah Med Univ 2024; 19 (1): 12-17

14 Reproductive Factors and Risk of Endometrial Cancer

Table 1: Distribution of study subjects according to socio-demographic variables.

Cases, Controls
Parameters
No. (%) No. (%)
Age (years) [Mean ± SD] 59.00 ± 11.00 58.86 ± 10.68
BMI (Kg/m²) [Mean ± SD] 33.39 ± 7.13 30.56 ± 6.67
Occupation
Housewife 86 (86.0) 191 (95.5)
Currently employee 3 (3.0) 5 (2.5)
Previously employee 11 (11.0) 4 (2.0)
Education
Illiterate 33 (33.0) 106 (53.0)
Primary schools 38 (38.0) 67 (33.50)
Secondary schools 25 (25.0) 24 (12.0)
University+ 4 (4.0) 3 (1.5)
Ethnicity
Arab 82 (82.0) 174 (87.0)
Kurd 3 (3.0) 10 (5.0)
Turkmen 7 (7.0) 9 (4.5)
Shabak 8 (8.0) 7 (3.5)
Marital status
Married 54 (54.0) 117 (58.5)
Single 6 (6.0) 6 (3.00)
Widow 35 (35.0) 72 (36.0)
Divorced 5 (5.0) 5 (2.5)
Active smoking
Current 2 (2.0) 13 (6.5)
Former 8 (8.0) 18 (9.0)
Non-smoker 90 (90.0) 169 (84.5)
Passive smoking
Yes 64 (64.0) 128 (64.0)
No 36 (36.0) 72 (36.0)

RESULTS between reproductive factors and risk of EC in the study

Table 1 illustrates the study sample's socio-demographic groups. The ages at menarche and menopause were
characteristics. There were no age differences between similar between the patients and their relatives. Women
the cases and controls, reflecting successful age-individual experiencing menarche at younger ages (<12 years) had a
matching. The mean BMI was (33.39 ± 7.13) for cases and slightly statistically insignificant higher risk compared to
(30.56 ± 6.67) for controls. Regarding women's education, those who had menarche between 12-15 years of age
71 (71%) cases and 173 (86.5%) controls were illiterate or (OR, 1.19; CI, 0.50–2.84). Menarche after 15 years of age
had only primary school education, whereas 29 (29%) was associated with a reduced risk of EC (OR, 0.66; CI,
cases and 27 (13.5%) controls had secondary and higher 0.21–2.12). The risk was approximately 1.5 times higher
education, respectively. among women who had menopause at late ages (≥55
Housewives represented 86% (86/100) of cases years) than among women who had menopause at less
and 95.5% (191/200) of controls, whereas currently and than 55 years, with statistically insignificant differences
previously employees constituted 14% (14/100) of cases among the study sample. Nulliparous women were
and 4.5% (9/200) of controls, respectively. Regarding present in 12/94 (12.77%) cases and 10/194 (5.15%)
marital status, 54 (54%) cases and 117 (58.5%) controls controls, with a risk nearly three times significantly higher
were married, six (6%) cases and six (3%) controls were than that of parous women (OR, 2.69; 95% CI, 1.12–6.48).
single, and 40 (40%) cases and 77 (38.5%) controls were Compared to 25.26% (49/194) of the controls, 37.23%
widowed or divorced at the time of the interview. (35/94) of the cases in the study group had fewer than
Arabs represented 82% (82/100) of the cases and five live births. There were statistically significant
87% (174/200) of the controls, whereas 18% (18/100) of differences in the number of children between women
the cases and 13% (26/200) of the controls were from with EC and the controls (p = 0.001). Compared to
other ethnic groups. Ninety percent (90/100) of the mothers with five or more children, women with a history
patients were non-smokers compared to 84.5% (169/200) of nulliparity and parity of fewer than five children had an
of the controls. The passive smoking percentage was EC risk that was approximately three and two times
equal in both groups. Table 2 shows the relationship greater (OR, 3.45; 95% CI, 1.40–8.50; OR, 2.05; 95% CI,

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16 Reproductive Factors and Risk of Endometrial Cancer

1.19–3.54), respectively. The patients' mean age at first was an insignificant difference among the sampled group
birth was significantly higher (23.13 ± 5.60) than that of for the precise age of thirty, above and below.
the controls (20.53 ± 5.16) (p= 0.001). Nonetheless, there

Table 2: The relationship between reproductive factors and endometrial cancer in the study sampled groups.
Cases Controls
Reproductive factors OR 95% CI p-value
No. (%) No. (%)
Age of menarche in years
12> 9 (9.0) 15 (7.5) 1.19 0.50 ; 2.84 0.660
≥16 4 (4.0) 12 (6.0) 0.66 0.21 ; 2.12 0.592
12-15a 87 (87.0) 173 (86.5) 1.00
Total 100 (100) 200 (100.0)
Mean ± SD 12.89 ± 1.39 12.84 ± 1.29 0.740
Age of menopause in years
≥55 12 (18.46) 21 (13.29) 1.48 0.68 ; 3.21 0.323
55> 53 (81.54) 137 (86.71)
Total 65c (100) 158c (100)
Mean ± SD 49.63 ± 5.03 49.42 ± 4.65 0.776
Parity
Nulliparous 12 (12.77) 10 (5.15) 2.69 1.12 ; 6.48 0.032b
Parous 82 (87.23) 184 (94.85)
No. of live births
0 12 (12.77) 10 (5.15) 3.45 1.40 ; 8.50 0.005b
1-4 35 (37.23) 49 (25.26) 2.05 `1.19 ; 3.54 0.009b
≥5a 47 (50.0) 135 (69.59) 1.00
Total 94d (100) 194d (100)
Mean ± SD 5.16 ± 2.45 6.51 ± 2.66 0.001b
Age at 1st birth in years
≥30 10 (12.1) 13 (7.07) 1.83 0.77 ; 4.36 0.169
30> 72 (87.8) 171 (92.93)
Total 82e (100) 184e (100)
Mean ± SD 23.13 ± 5.60 20.53 ± 5.16 0.001b
a) Reference group, b) Statistically significant, c) Premenopausal participants were excluded, d) Single participants were excluded, e) Single and
nulliparous participants were excluded.

DISCUSSION infertility treatments, which may increase their exposure

Nulliparity, parity of fewer than five children, and age at to medications and elevate the risk of EC.
first delivery were statistically different between the cases Furthermore, the current study found evidence of a
and controls in this study. These findings are consistent strong association between increasing age at first
with some prior studies that compared parous and childbirth and EC risk. This finding aligns with some older
nulliparous women and discovered that parous women studies 17,21 but contrasts with and contradicts the
had a lower risk of EC. A systematic review of high-quality majority of reports indicating that increasing maternal age
articles published from 2000 to April 2024 by Salehiniya et at first birth is either associated with a reduced risk of EC
al.,2 found that nulliparity increased the risk of EC globally. 14,15,22,23
or not associated with any risk at all.5,24
Similarly, in a pooled cohort analysis of 13 prospective Determining the impact of childbearing factors can be
cohort studies conducted between 1963 and 2014 in the challenging due to their various overlapping influences.
Asia Cohort Consortium, Katagiri et al.,5 discovered that The extent to which these components have been
Asian women who had more deliveries were significantly modeled differs across studies.
less likely to develop EC. Conversely, in a study by Cho et Our study did not associate the age of menarche and
al.,19, having multiple births increased the risk of EC. menopause with the risk of EC. This is compatible with the
Nonetheless, some studies have indicated no link Mexican case-control study by Salazar et al.21; however,
between parity and the risk of EC.20 Cultural diversity is several studies have reported considerable associations
considerable in various countries. In Iraq, traditional between the age of menarche and menopause with EC
culture encourages newly married couples to start a risk 2,5,8. An Italian case-control study (454 cases and
family soon after marriage. Couples experiencing 908controls) by Zucchetto et al.,25 found that the risk of
subfertility are urged to address infertility issues EC increased with increasing years of menstruation. This
promptly. Consequently, they often undergo multiple disparity is hard to explain. The discrepancy may be due

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Abdulwahhab et al 17

to genetic factors interfering with menarche age or Author Contribution

Zahraa Dheyauldin Abdulwahhab: Conception and design, acquisition of
different categories of menarche age. Asian research has
data, analysis and interpretation of data, drafting the article, critical
employed a different menarche age group, with the revision for important intellectual content, proofreading, final approval.
lowest and highest groups being 13 or younger and 17 or
older, respectively. Humam Ghanim Ibrahim: Conception and design, analysis and
In comparison, European and US studies used the interpretation of data, critical revision for important intellectual content,
final approval.
lowest and highest age categories of 11 and 14 or 15
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