PLoS One. reported that grand multiparity (≥ 5 births) reduces the risk of endometrial cancer by 43%.9 Compared to other cases with endometrial cancer, there is lim-ited information about the clinical and pathological findings of grand multiparous patients in literature. It has been known for decades that nulliparity is associated with an increased risk for certain reproductive malignancies, including breast, ovarian and uterine cancers. Rarely, endometrial tissue may spread beyond pelvic organs.With endometriosis, displaced endometrial tissue continues to act as it normally would — it thickens, breaks down and bleeds with each menstrual cycle. Age at last birth in relation to risk of endometrial cancer: pooled analysis in the epidemiology of endometrial cancer consortium. The 95% confidence intervals (95% CIs) for the SIRs were based on the assumption that the number of observed cases represents a Poisson distribution. The SMRs among GM women were 0.73 (95% confidence intervals (CI) 0.66–0.80) for breast cancer, 0.54 (95% CI 0.29–0.79) for endometrial cancer and 0.64 (95% CI 0.49–0.79) for ovarian cancer. 57 Other routes of spread follow lymphatic channels. There is no bias in cohort selection or cancer follow‐up because the national population and cancer registries in Finland are virtually complete 10 and computerised linkage procedures using personal identifiers as the key are very precise.11. Jordan SJ, Na R, Weiderpass E, Adami HO, Anderson KE, van den Brandt PA, Brinton LA, Chen C, Cook LS, Doherty JA, Du M, Friedenreich CM, Gierach GL, Goodman MT, Krogh V, Levi F, Lu L, Miller AB, McCann SE, Moysich KB, Negri E, Olson SH, Petruzella S, Palmer JR, Parazzini F, Pike MC, Prizment AE, Rebbeck TR, Reynolds P, Ricceri F, Risch HA, Rohan TE, Sacerdote C, Schouten LJ, Serraino D, Setiawan VW, Shu XO, Sponholtz TR, Spurdle AB, Stolzenberg-Solomon RZ, Trabert B, Wentzensen N, Wilkens LR, Wise LA, Yu H, La Vecchia C, De Vivo I, Xu W, Zeleniuch-Jacquotte A, Webb PM. Parity and risk of death from gallbladder cancer among a cohort of premenopausal parous women in Taiwan. However, other definitions are also used. We investigated the significance of parity, age at first birth, intensity between births, length of time from the first to the last birth and length of delivery‐free premenopausal period in a cohort of grand multiparous (GM) women, i.e., women with at least 5 births. Epub 2012 Jul 23. MAIN OUTCOME MEASURE(S): The effect of multiparity on PD. Screening and Prevention . Long-lasting unopposed oestrogen exposure leads to endometrial hyperplasia, which increases the chance of development of atypical hyperplasia and eventually type-1 endometrial cancer. Albrektsen et al.25 and Lambe et al.5 suggest that mechanical shedding of malignant or premalignant endometrial cells at each delivery is the main factor in relation to reduced risk of endometrial cancer. Epub 2020 Nov 17. When adjusted for the other study variables, these trends slightly sharpened, and the model also suggested a slight protective effect with increasing intensity between births (Table II). Cancer Causes Control. Rather, our risk estimates might be too high because the use of oral contraceptive was more common in the reference population than in the GM cohort. Int J Gynecol Cancer. COVID-19 is an emerging, rapidly evolving situation. In 2007, 7536 new endometrial cancers were diagnosed in the UK, making it the fourth most common cancer in women after breast, lung, and colorectal cancers.2 Cancer of the … Immigration studies (migration studies), which examine the change in cancer risk in populations moving between countries with different rates of cancer, show that there is some environmental component to endometrial cancer. Multiple births, old age at first birth and a long birth period significantly reduced the risk of endometrial cancer in GM‐women. Even if a woman with endometrial cancer has one or more risk factors, there's no way to know which, if any, of them caused her cancer. Moreover, breastfeeding, multiparity, consumption of combined oral contraceptives for 1-2 years during once a lifetime has been found to reduce the risk of endometrial cancer. BRCA Mutations Increase Fertility in Families at Hereditary Breast/Ovarian Cancer Risk. [ncbi.nlm.nih.gov] Prepare for clinical challenges and save time in addressing them thanks to expert advice on treatment options from international contributors. Endometriosis most commonly involves your ovaries, fallopian tubes and the tissue lining your pelvis. Kwiatkowski F, Arbre M, Bidet Y, Laquet C, Uhrhammer N, Bignon YJ. We had no data about hysterectomies in our population, but there is no reason to believe that the frequency of hysterectomies among GM‐women would substantially differ from that in the national population.20 Therefore, there should be no marked bias due to hysterectomies. In an alternative analysis among GM‐women aged 50+ whose history of reproduction was considered practically finished, we replaced birth intensity by the variable birth period, which was defined as the length of time from the first to the last birth. Many factors affect the risk of developing endometrial cancer, including: Obesity Endometrial cancer has a very good prognosis amongst all other cancers in … Endometrial cancer is the most common gynecologic malignancy. 2017 Jun;28(6):579-588. doi: 10.1007/s10552-017-0880-4. Some women with endometrial cancer don't have any known risk factors. The SIR of papillary adenocarcinoma was 0.78 (95% CI 0.40–1.63), and the incidence of sarcomas was nearly the same as the national average (SIR = 1.02, 95% CI 0.63–1.56). Endometrial cancer is the most common gynecologic malignancy. The SIR of sarcomas in this population was similar to the national average. Our results are thus in agreement with those of Schwartz et al.,26, 27 but they conflict with observations from Norway.22, 25. The hormonal background of endometrial cancer is insufficiently characterised. The RR of endometrial cancer was 0.58 (95% CI 0.34-0.97) among women giving their first birth at an age of more than 30 years compared to women with first birth before the age of 20. The expected numbers of cancer cases were calculated by multiplying the number of person‐years in each stratum by the corresponding cancer incidence rate in Finland. The hormonal background of endometrial cancer is insufficiently characterised. Accessibility Our results support previous observations of the protective effect of old age at last pregnancy.5, 6, 25, The number of cancers of histologic subtypes other than adenocarcinoma was rather small for reliable conclusions. The SMRs among GM women were 0.73 (95% confidence intervals (CI) 0.66-0.80) for breast cancer, 0.54 (95% CI 0.29-0.79) for endometrial cancer and 0.64 (95% CI 0.49-0.79) for ovarian cancer. Because 79% of patients in our cohort were at least 55 years or older at the age of endometrial cancer diagnosis, the role of lactation remains minimal in this population. Using data from the Jerusalem Perinatal Cohort we were able to separate the components of mortality, comparing both incidence and survival after cancer onset. ... more years and grand multiparity. However, the number of cancer cases remained small in the subgroups of women who contracted cancer during the premenopausal period (n = 27), had histologic subtypes other than adenocarcinoma (n = 52) or had a clinically advanced malignancy (n = 58). A recent commentary in The Lancet summarized the available evidence based on data in nulliparous women and concluded that the risk … In this study, the findings of grand multiparous pa- Parity, age, and previous uterine abrasion increase the risk of adenomyosis (the abnormal presence of endometrial tissue within the uterus muscular layer). © 2002 Wiley‐Liss, Inc. Endometrial cancer is a hormone‐dependent malignancy. This site needs JavaScript to work properly. Bethesda, MD 20894, Copyright (2002). A population-based study on the risk of cervical cancer and cervical intraepithelial neoplasia among grand multiparous women in Finland. 2004 Mar 8;90(5):1025-9. doi: 10.1038/sj.bjc.6601650. Eight women were older than 50 years during their last birth. (2002). We investigated the significance of parity, age at first birth, intensity between births, length of time from the first to the last birth and length of delivery-free premenopausal period in a cohort of grand multiparous (GM) women, i.e., women with at least 5 births. We investigated the significance of parity, age at first birth, intensity between births, length of time from the first to the last birth and length of delivery‐free premenopausal period in a cohort of grand multiparous (GM) women, i.e., women with at least 5 births. Grand multiparity and the risk of breast cancer: population-based study in Finland. 2,3. A practitioner's guide to meta‐analysis, Prolonged lactation and endometrial cancer. A case‐control study of risk factors for sarcomas of the uterus, Incidence of histological types of uterine sarcoma in relation to menstrual and reproductive history, Endometrial carcinoma; ovarian dysfunction—a risk factor in young women, Infertility‐associated endometrial cancer risk may be limited to specific subgroups of infertile women, Cancer incidence in a cohort of infertile women, Birth period, years from first to last birth, Premenopausal delivery‐free period (years). KC: Surgical stage I endometrial cancer: … Follow‐up for endometrial cancer was done automatically through the files of the national, population‐based Finnish Cancer Registry with personal identifiers. Type II endometrial cancer is diagnosed more often in elderly and nonwhite women who have a history of multiparity, tobacco smoking, and tamoxifen-treated breast carcinoma. and you may need to create a new Wiley Online Library account. Unable to load your collection due to an error, Unable to load your delegates due to an error. Advanced age at first birth (30+ years) significantly decreased the risk of endometrial cancer in postmenopausal women. Enter your email address below and we will send you your username, If the address matches an existing account you will receive an email with instructions to retrieve your username, By continuing to browse this site, you agree to its use of cookies as described in our, I have read and accept the Wiley Online Library Terms and Conditions of Use, Increased cell division as a cause of human cancer, Reproductive, menstrual, and medical risk factors for endometrial cancer: results from a case‐control study, Childbearing at older age and endometrial cancer risk (Sweden), Reproductive factors and risk of endometrial cancer, Role of reproductive factors on the risk of endometrial cancer, Reproductive factors and risk of endometrial cancer. A reasonable definition of "grand multiparity" is a patient who has had ≥5 births (live or stillborn) at ≥20 weeks of gestation, with "great grand multiparity" defined as ≥10 births (live or stillborn) ≥20 weeks of gestation . 2 Similarly, women who undergo estrogen replacement without progesterone have an increased risk of endometrial cancer… The term grand multiparity (GM) defines women who have undergone at least 5 full‐term pregnancies.9 The Population Register of Finland contains detailed information on the births and children of all GM mothers. Please check your email for instructions on resetting your password. Standardised incidence ratios (SIRs) were calculated by dividing the number of observed cancer cases by the expected number based on the national incidence rates. 1, 2 Lending support to this hypothesis, during the follicular phase of the menstrual cycle, progesterone levels are low, estradiol levels are at normal premenopausal levels, and increased endometrial proliferation is observed. Clipboard, Search History, and several other advanced features are temporarily unavailable. Am J Epidemiol. Obesity and diabetes mellitus are well‐known risk factors for endometrial cancer, especially in postmenopausal women.14-16 Obesity and diabetic disorders are common in women with several pregnancies.17-19 Hence, the actual risk reduction of endometrial cancer in our population would have been larger than that shown, if we had been able to adjust our results for obesity and diabetes. The Iowa Women's Health Study, Data quality and quality control of a population‐based cancer registry. It was not feasible to put both variables into the model at the same time because they were highly correlated. Worldwide, endometrial cancer is the seventh most common malignant disorder, but incidence varies among regions. Prevention and treatment information (HHS). The SIR for endometrial cancer among GM‐women was low [419 cases; SIR=0.57, 95% confidence interval (CI) 0.52–0.63]. Epub 2019 Feb 20. Learn more. Most women with endometrial cancer are diagnosed after menopause. Including this factor into the model clearly weakened the risk coefficients associated with increased risk compared to the model shown in Table II, and the risk decrease associated with higher age at first birth almost disappeared. Future investigations should focus on hormonal alterations underlying multiparity and late ages at a first birth in order to clarify processes involved in endometrial carcinogenesis. Our findings, however, that a long birth period and a short premenopausal delivery‐free period reduce the risk for endometrial cancer, appear to support the hormonal factor hypothesis of endometrial cancer. Conclusion. If you do not receive an email within 10 minutes, your email address may not be registered, The average intensity between the first 5 births and the length of the premenopausal delivery‐free period were new and novel variables in our study. The SIR for endometrial cancer among GM-women was low [419 cases; SIR=0.57, 95% confidence interval (CI) 0.52-0.63]. doi: 10.1371/journal.pone.0127363. In the univariate analysis, the SIR decreased by increasing parity and increasing age at first birth (Table I). This finding is line with most,5, 24 but not all,4, 8 previous findings. This study showed that six pregnancy-related factors—advanced maternal age, multiparity, multifetal pregnancy, cesarean section, delivery of a large-for-gestational-age infant, and preeclampsia—are positively correlated with future development of endometrial neoplasia, including endometrial hyperplasia or cancer. The prevalence of the disease is highest at around 60 years of age and most commonly presents with painless, post-menopausal bleeding. In premenopausal women, the trend appeared to be even stronger, though it was based on very sparse observations among those with first birth at higher ages and was not statistically significant. In ages 50+ (94% of endometrial cancer cases), the RR for women with at least 8 births was 0.63 (95% CI 0.44-0.92) compared to those with 5 births, and those with a birth period of 20+ years had RR=0.57 (95% CI 0.34-0.96) compared to those with a period of <10 years, while prolonged average intensity between births showed only a small protective effect. The hormonal background of endometrial cancer is insufficiently characterised. Data of the Population Register of Finland (86,978 GM‐women) and the population‐based Finnish Cancer Registry were combined. The beneficial endometrial effect of old age at first birth and a long birth period are likely associated with a shortened delivery‐free premenopausal period. Rosenblatt and Thomas 13 demonstrated that the protective effect of lactation against endometrial cancer does not extend beyond the age of 55 years, even in women who had breast‐fed for over 5 years. A birth period of over 20 years significantly decreased the risk of endometrial cancer in postmenopausal women, and adding this variable to the Poisson regression model markedly weakened the significance of parity. The malignancy was localised in 84% of the 361 cases with a known stage. Oral contraceptives protect women from endometrial cancer.12 They do not explain, however, the low incidence of endometrial cancer in our study as many of the women belonged to a religious minority, the Laestadius movement within the Lutheran church, which does not accept any kind of contraception. The RR of endometrial cancer was 0.58 (95% CI 0.34–0.97) among women giving their first birth at an age of more than 30 years compared to women with first birth before the age of 20. Use the link below to share a full-text version of this article with your friends and colleagues. The relationships between parity and the RR of endometrial cancer were different in pre‐ and postmenopausal GM‐women: in premenopausal women, the RR increased with the sixth birth or more, while in postmenopausal women, the RR decreased significantly (Table II). The present cohort of nearly 90,000 GM‐women with 1.7 million follow‐up years and 737 expected endometrial cancer patients is large enough for epidemiologic investigations in the main categories. Information about the histologic subtype of carcinoma was known for all cases and clinical stage for 86% of cases. Hinkula M, Pukkala E, Kyyrönen P, Kauppila A. For women with a period shorter than 10 years, the RR was 39% smaller than that for women with a period longer than 15 years. The relationships between parity and the RR of endometrial cancer were different in pre‐ and postmenopausal GM‐women: in premenopausal women, the RR increased with the sixth birth or more, while in postmenopausal women, the RR decreased significantly (Table II). WHO Collaborative Study of Neoplasia and Steroid Contraceptives, Association of incident carcinoma of the endometrium with body weight and fat distribution in older women: early findings of the Iowa Women's Health Study, Diabetes mellitus and cancer risk: a multisite case‐control study, New metabolic‐endocrine risk markers in endometrial cancer, Parity‐associated weight gain and its modification by sociodemographic and behavioral factors: a prospective analysis in US women, Sociodemographic factors associated with long‐term weight gain, current body fatness and central adiposity in Swedish women, Socioeconomic variations in hysterectomy: evidence from a linkage study of the Finnish hospital discharge register and population census, Grand multiparity and risk of breast cancer; population‐based study in Finland, Reproductive factors and risk of cancer of the uterine corpus: a prospective study, The epidemiology of endometrial cancer in young women, Endometrial cancer and age at last delivery: evidence for an association, Is the risk of cancer of the corpus uteri reduced by a recent pregnancy? Gynecol Oncol. All calculations were performed using SAS (Cary, NC) statistical software. Would you like email updates of new search results? Epub 2017 Mar 30. Using this national population register of GM‐women and data of Finnish Cancer Registry, we studied the significance of parity, age at first birth, average intensity between births, birth period and premenopausal delivery‐free period as risk determinants of endometrial cancer. FOIA 2015 Feb 5;12(2):1864-73. doi: 10.3390/ijerph120201864. In addition, it is likely that the protective effect of multiple pregnancies on endometrial cancer extends at least to the sixth or even up to the eighth birth, i.e., higher than previously reported.4, 5, 8, 23 A study from Sweden showed that in childless women compared to uniparous women, the increase in risk for endometrial cancer is stronger in premenopausal than postmenopausal women.5 Our cohort, consisting only of GM‐ women, suggests that the protective effect of parity manifests only during the postmenopausal years. These environmental risk factors are not well characterized. There were 419 cases of endometrial cancer among GM‐women, while 737 cases would have been expected on the basis of average incidence rates among the entire Finnish female population (SIR = 0.57, 95% CI 0.52–0.63). Pregnancy outcomes and risk of endometrial cancer: A pooled analysis of individual participant data in the Epidemiology of Endometrial Cancer Consortium. This reduction is similar to that previously observed for breast cancer (45%) in the same cohort.21 In agreement with earlier results,8, 22 we found that multiparity powerfully reduced the risk of endometrial cancer. The SIRs for local (n = 303) and nonlocal (n = 58) endometrial cancers were identical at 0.58, and the respective 95% CIs were 0.51–0.65 and 0.44–0.76. Breast cancer Endometrial cancer Multiparity Cohort study Survival Electronic supplementary material The online version of this article (doi: 10.1007/s10552-015-0701-6 ) contains supplementary material, which is available to authorized users. The computerised files of the Finnish Population Register, which includes links between parents and their children who were living at the same address in 1974 or later, revealed 86,978 GM‐ women during the period 1974 until the end of 1997. Careers. 2021 May 1;148(9):2068-2078. doi: 10.1002/ijc.33360. Risk factors for endometrial cancer include obesity, diabetes mellitus, breast cancer, use of tamoxifen, never having had a child, late menopause, high levels of estrogen, and increasing age. 2006 Oct;103(1):207-11. doi: 10.1016/j.ygyno.2006.02.025. Experience in Finland, Time trends in socio‐economic differences in incidence rates of cancers of the breast and female genital organs (Finland, 1971–1995), Risk of endometrial cancer in relation to use of combined oral contraceptives. Data of the Population Register of Finland (86,978 GM-women) and the population-based Finnish Cancer Registry were combined. Unopposed estrogen promotes malignant transformation of the endometrium, an action that is counteracted by progesterone.1 Pregnancy is characterised by continuous progesterone production from the early weeks of gestation until delivery.2 Possibly for this reason, at least partly, parous women have a markedly lower risk of endometrial cancer than nulliparous women.3-8. RESULT(S): Multiparity had no effect on the progression of PD, and treatment of the disease during pregnancy appears to have been safe. A prospective study of 765,756 Norwegian women, World Health Organization Collaborative Study of Neoplasia and Steroid Contraceptives. Learn about our remote access options, Department of Obstetrics and Gynaecology, Oulu University Hospital, Oulu, Finland, Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland. Multivariate relative risks (RRs) were estimated by Poisson regression analysis. Int J Cancer. 2015 Jun 5;10(6):e0127363. 2019 Oct 1;145(7):1719-1730. doi: 10.1002/ijc.31961. Parity and hormonal contraception use are risk factors for cervical cancer. 2014 Mar;24(3):384-93. doi: 10.1097/IGC.0000000000000075. Prognosis of endometrial cancer. The rest represented sarcomas (5%), papillary adenocarcinomas (3%) and other rare histologic subtypes (4%). Women with Lynch syndrome tend to develop endometrial cancer at an earlier age, with the median age at diagnosis of 48 years. Only 15% of women are diagnosed with endometrial cancer before age 50 years, and fewer than 5% are diagnosed before age 40 years. For women 50 years or older, most of whom had already had their last child, we also analysed the significance of the length of (i) the entire birth period, i.e., years from the first to last birth in 4 categories (<10, 10–14.9, 15–19.9 and 20+ years) and (ii) the period between the last birth and age 50 years (approximate age of menopause) in 3 categories (<10, 10–14.9 and 15+ years). Hence, part of the protective effect associated in earlier studies with multiparity7, 24 may actually be attributable to a long birth period. Multiple multiparous women significantly more often presented with lower educational level, more often were diagnosed with comorbidities and a history of other malignancies, while breast cancer and colon cancer were of lesser evidence in multiple multiparous endometrial cancer patients. Int J Cancer 98 : … Nearly 88% of patients had adenocarcinoma. In postmenopausal women, the increase in parity from 5 to 6 decreased approximately 30% the RR of endometrial cancer, and the further births slightly strengthened this trend (p = 0.01). To analyse the association between the length of the delivery‐free premenopausal period and endometrium cancer, we used individually matched case‐control data and the conditional logistic model. Reproductive factors and the risk of endometrial cancer. Endometrial adenocarcinoma or cancer of the uterine corpus accounts for more than 80% of endometrial cancers and is one of the most common female genital tract malignancies. Ninety‐four percent of the malignancies were diagnosed in women of 50 years or older. Protective factors include prior use of combined oral contraceptives for one or more years and grand multiparity.2, 3. A short premenopausal delivery‐free period was also protective, and it weakened the significance of parity. The mean length of follow‐up was 19.3 years. In ages 50+ (94% of endometrial cancer cases), the RR for women with at least 8 births was 0.63 (95% CI 0.44–0.92) compared to those with 5 births, and those with a birth period of 20+ years had RR=0.57 (95% CI 0.34–0.96) compared to those with a period of <10 years, while prolonged average intensity between births showed only a small protective effect. High parity is associated with reduced mortality from reproductive cancers. It suggests that the development of sarcomas (or at least of the most common subtypes of sarcoma) is not affected by reproductive factors. Poisson regression modelling, which takes into account the effects of other variables as confounding factors, was used in the relative risk (RR) calculations. Privacy, Help In the whole population of GM‐women, the endometrial cancer risk was 43% smaller than in the national reference population. Sponholtz TR, Palmer JR, Rosenberg L, Hatch EE, Adams-Campbell LL, Wise LA. Reproductive factors and incidence of endometrial cancer in U.S. black women. 2001 Aug;12(6):491-500. doi: 10.1023/a:1011253527605. Endometrial cancer risk did not appear to be substantially influenced by incomplete pregnancies, histories of infertility, or years of breastfeeding. Epub 2006 Apr 3. Hinkula M, Pukkala E, Kyyrönen P, Laukkanen P, Koskela P, Paavonen J, Lehtinen M, Kauppila A. Br J Cancer. The standardised incidence ratio (SIR) was calculated by dividing the number of observed cases by the number of expected cancers. The ACS recommends that all women older Follow‐up for cancer started on 1 January 1974 or at the birth of the fifth child, whichever was later, and ended at death, emigration or on 31 December 1997, whichever was first. Raglan O, Kalliala I, Markozannes G, Cividini S, Gunter MJ, Nautiyal J, Gabra H, Paraskevaidis E, Martin-Hirsch P, Tsilidis KK, Kyrgiou M. Int J Cancer. Cases of endometrial cancer and person‐years at risk were counted by 5‐year age groups and separately for 4 parity categories (5, 6, 7 and 8+ children), 4 categories by age at first birth (<20, 20–24, 25–29 and 30+ years) and 3 birth‐intensity categories (average interval between the first 5 deliveries <2.0, 2.0–3.0 and >3.0 years).

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