Reproductive Health and Rheumatoid Arthritis 

Reproductive Health and Rheumatoid Arthritis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Reproductive Health and Rheumatoid Arthritis Mohammad Erfan Ranjbaran, Maryam kazemi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4777941/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 15 Oct, 2024 Read the published version in BMC Rheumatology → Version 1 posted 15 You are reading this latest preprint version Abstract Introduction: The prevalence of Rheumatoid Arthritis (RA) has been steadily increasing over the last thirty years, particularly among women. Due to the conflicting results of various studies on the link between rheumatoid arthritis and reproductive health, we have undertaken this study to explore their relationship. Method: This cross-sectional study utilized primary data from women involved in the Fasa Persian Cohort. The study examined the frequency of RA and its association with various factors related to reproductive health, including age at first pregnancy, number of alive children, history of abortion, and infertility. SPSS software was utilized for data analysis, with the significance level set at p < 0.05. Results: 5557 women with an average age of 48.6 ± 9.5 years participated. Of these women, 7.2% were diagnosed with rheumatoid disease, with an average onset age of 38.2 ± 15.2. The study did not find a significant correlation between RA and factors such as number of pregnancies, age at first pregnancy, duration of breastfeeding and number of children. Conclusion: The study suggests that the experience of RA is independent of gynecological, obstetric factors, or reproductive life. This finding may provide reassurance to women affected by RA. Introduction Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the joints. The burden of RA has increased globally over the past 30 years and is projected to continue rising(1). Rheumatoid arthritis (RA) primarily affects women; In fact, being female is considered a risk factor for this disorder(2–4). RA, the most common chronic systemic autoimmune disease, exhibits a female-to-male prevalence ratio greater than 4 before age 50, and below 2 after 60(3, 5, 6). Such a gender tendency raises questions about the possible relationship between immune dysregulation, hormonal fluctuations, and reproductive health(2–4). Approximately 50% of RA cases occur during the reproductive years, emphasizing the importance of understanding the effect of hormonal and reproductive factors on disease development(6). There are much evidence regarding the impact of estrogen and progesterone, the two main female sex hormones, on the immune system, and several molecular mechanisms have been proposed(3). However, studying the influence of female hormonal factors on RA is complex. Pregnancy, breastfeeding and parity of any number have been shown in some studies to be protective, while the incidence and severity of RA is higher in the postpartum period and perimenopause(6–8). Women with RA are more likely to have coexisting reproductive disorders such as infertility, endometriosis, and premature ovarian insufficiency, or to develop them later on(9). There is also a known connection between RA and abortion as well as polycystic ovary syndrome (PCOS), although the evidence is somewhat controversial(9). During the peak incidence of rheumatoid arthritis (RA), which typically occurs during the female reproductive period, women often confront significant decisions concerning pregnancy and the potential for having a child; and the stress experienced by RA patients may somewhat influence their reproductive choices(9). Therefore, it is essential to have a comprehensive understanding of how RA is associated with female reproductive factors in order to provide the best possible care and consultation for women. Despite progress, controversies still exist(3). Understanding the impact of reproductive factors on the development and trajectory of RA is important. This knowledge informs society and guides medical expectations. Tailoring preventive interventions for high-risk populations may mitigate disease burden and improve outcomes(10). This article explores the intricate connections between rheumatoid disease (RA) and reproductive factors, shedding light on potential implications for patient care and preventive strategies. Methodology This cross-sectional study was conducted on baseline data of Fasa PERSIAN cohort, which is one of the 22 active cohorts in Iran. It started its activity in 2013 and includes about 10,000 people aged older than 35 from Sheshdeh and Qare-Balagh villages in Fasa (south east of Iran)(11). The entire female population of the Fasa PERSIAN cohort was included in the study. Subjects with incomplete information on study variables or any history of malignant gynecologic diseases were excluded. Rheumatoid disease was recorded based on a check list of diseases completed by the individual or in annual follow-ups, as self-reported that was confirmed by a doctor. The following variables are recorded: current age, years of education, socio-economic status(classified as low, middle, and high), marital status (classified as single, married, widowed, and divorced), obstetric history including gravidity, stillbirth, abortion, age at first pregnancy, alive child numbers and total breastfeeding duration (in months), gynecologic history including history of infertility, hysterectomy, and OCP use, physical activity (MET; minutes/week), BMI, waist circumference (in centimeter), calorie intake(per day), cigarette, other tobaccos, and opium use. Quantitative variables are described using mean and standard deviation, while qualitative variables are described using frequency and percentage. Univariate analysis was done by using chi-square, independent sample T test, Pearson correlation test and one-way analysis of variance (ANOVA). Logistic regression model was used to adjust confounding variables. variables were correlated with rheumatoid arthritis in univariate analysis with p-value < .2 enter to this model. Data analysis was done by SPSS 25 software at a significance level of 0.05. Results Among the 5557 women in the Fasa PERSIAN cohort study, the average age of the participants was 48.6 ± 9.5 years. 7.2% of the participants had rheumatoid disease, and the average age at which rheumatoid disease started was 38.2 ± 15.2. 81.9% of the participants were married, and the average years of education was 3.7 years. We analyzed the socio-demographic characteristics and reproductive factors of participants based on the presence or absence of rheumatoid disease. (Table 1 ) Reproductive factors such as number of pregnancies, abortions, live child number, infertility, contraceptive use and breastfeeding duration were analyzed with respect to the RA affliction. The mean pregnancy numbers in non-RA and RA groups were 5.15 ± 3.16 and 5.93 ± 3.34, respectively. Age at first pregnancy in non-RA and RA group was 20.45 ± 4.88 and 19.43 ± 4.04 respectively. Among the non-RA group, the live child number was 4.77 ± 2.67; and 5.6 ± 2.76 among the RA group. Our findings indicated that RA was significantly correlated with waist circumference (p < 0.001) but not correlated with BMI, calorie intake, and physical activity. Our analysis also revealed that among reproductive factors, RA was significantly correlated with pregnancy number, first pregnancy age, breastfeeding duration, and alive child number with a p-value of < .001 but was not correlated with abortion number, history of hysterectomy, stillbirth, infertility, and contraceptive use. In addition, our analysis showed a significant correlation between years of education and RA (p value < .001). Marital status did not reveal any significant correlation with RA in our study. Cigarette, tobacco and opium use did not have any significant correlation with RA. In the regression model (Table 2 ), it was observed that the years of education have correlations with RA in that people without rheumatoid disease had higher years of education (p value = .02) Other variables such as pregnancy number, first pregnancy age, alive child number, abortion number, stillbirth, breastfeeding duration, waist circumference, BMI, and cigarette smoking had no significant statistical correlation with having or not having RA. Meanwhile, in linear regression, the relationship between variables and the age of onset of RA was investigated. However, there was almost no relationship between the two except for education level & marital status with p values of .001 & .03 respectively. (Table 3 ) Table 1 socio- demographic characteristics and reproductive factors of participants of study No Rheumatoid disease Rheumatoid disease P value Years of education mean ± SD 3.77 ± 3.4 2.85 ± 2.75 < .001 Marital status n(%) .39 single 265(94) 6(17) married 4227(92.9) 323(7.1) widow 581(91.4) 55(8.6) divorce 82(91.1) 8(8.9) Socioeconomic status n(%) .75 low 1720(92.8) 133(7.2) middle 1707(92.4) 140(7.6) high 1726(93) 129(7) Waist circumference(cm) mean ± SD 96.02 ± 11.43 97.93 ± 12.04 < .001 BMI (kg/m2) mean ± SD 26.82 ± 4.78 27.33 ± 5.15 .05 Calorie intake(cal) mean ± SD 2838.77 ± 1110.07 2890.5 ± 1146.44 .36 Physical activity (MET min/week) mean ± SD 38.41 ± 6.51 38.78 ± 8.13 .36 Pregnancy number mean ± SD 5.15 ± 3.16 5.93 ± 3.34 < .001 Alive child number mean ± SD 4.77 ± 2.67 5.6 ± 2.76 < .001 Abortion number mean ± SD 0.44 ± 0.81 0.52 ± 0.79 .09 First pregnancy age mean ± SD 20.45 ± 4.88 19.43 ± 4.04 < .001 Breast feeding duration (months) mean ± SD 90.08 ± 57.38 104.17 ± 58.57 < .001 Hysterectomy n (%) .25 yes 203(91.4) 19(8.6) no 4952(92.8) 384(7.2) Still birth n (%) .13 yes 701(91.8) 63(8.2) no 3997(93) 302(7) Infertility n (%) .50 yes 1349(92.7) 106(7.3) no 3573(92.7) 283(7.3) Used contraceptive n (%) .31 yes 3432(92.9) 263(7.1) no 1723(92.5) 140(7.5) smoke Cigarette n (%) .07 Yes 253(90.4) 27(9.6) no 4902(92.2) 376(7.1) Other tobacco usage n (%) .31 yes 58(90.6) 6(9.4) no 5096(92.8) 397(7.2) Opium usage n (%) .23 yes 41(89.1) 5(10.9) no 5114(92.8) 398(7.2) Table 2 logistic regression model for rheumatoid arthritis B S.E. P value Exp(B) Years of Education − .050 .022 .025 .951 Pregnancy Number − .190 .204 .352 .827 Alive Childbirth Number .242 .206 .241 1.273 First Pregnancy Age − .026 .015 .072 .974 Abortion Number .238 .215 .269 1.268 Breast feeding Duration .000 .001 .964 1.000 Waist Circumference .016 .010 .125 1.016 BMI − .008 .024 .753 .993 Smoke Cigarette .115 .218 .597 1.122 Has Stillbirth − .258 .298 .387 .773 Constant -3.213 .711 .000 .040 Table 3 Linear regression model for age of rheumatoid arthritis Unstandardized coefficients Standardized coefficients P value B Std. Error Beta (Constant) 26.888 7.848 .001 Use Contraceptive Drug -2.243 1.635 − .068 .171 Smoke Cigarette .074 2.733 .001 .978 Marital Status 3.664 1.764 .100 .039 Years of Education -1.012 .311 − .185 .001 Pregnancy Number .066 .720 .014 .927 Alive Childbirth Number 1.547 .844 .285 .068 Breast feeding Duration .005 .017 .019 .775 Physical activity − .041 .089 − .021 .648 Discussion In this cross -sectional study women had average age of more than 45 years; 7 out of 100 of them were found to be suffering from RA. The average body mass index of the population was in the overweight range. Additionally, the average number of pregnancies was more than 5, and the number of live children was over 4. The average age of RA onset was 38.2 years. The average age at first pregnancy was 20.37 years within our population. This study showed that the number of pregnancies, the age of the first pregnancy, the duration of breastfeeding, the number of children, the number of abortions, and stillbirths, had no statistically significant correlation with RA. However, a review article by Alpízar and colleagues highlighted controversies in different studies regarding whether these factors are associated with RA. Some studies suggested a protective effect, while others considered them as risk factors for developing RA(6). Our study supported previous research findings regarding the relationship between years of education and rheumatoid arthritis (RA). Years of education had an inverse relationship with RA. Previous studies have shown an association between higher levels of education and a decreased risk of RA; However, the findings have been inconsistent, and the reasons behind this association remain unclear (12). In our analysis, we found that marital status did not show a significant correlation with RA. It seems to be more of a prognostic factor rather than a causal or protective factor (13). Many studies have shown that married individuals tend to have fewer health problems and lower mortality rates compared to those who are not married, including divorced, widowed, separated, or never married individuals (13). Being in a well-adjusted or nondistressed marriage seems to be associated with less pain and better functioning for individuals with RA(14). In our study, we did not find a link between waist circumference and body mass index (BMI) with rheumatoid arthritis (RA). However, a review and meta-analysis showed that overweight and obese individuals have a higher risk of developing RA compared to those with a normal BMI(15). Specifically, women with a waist circumference greater than 102 cm had 2–3 times the risk of developing RA, while those with a waist circumference greater than 88 cm did not show the same association(16). This association may not have been observed due to the cross-sectional nature of our study. Regarding physical activity, Azeez and colleagues found that exercise led to reductions in weight, waist circumference, and BMI in RA patients (17). Low-intensity leisure-time physical activity (LTPA) was inversely associated with BMI, while moderate/vigorous LTPA showed an inverse relationship with both BMI and waist circumference(18). The analysis of our population did not show a significant correlation between smoking and rheumatoid arthritis (RA), even though smoking is widely recognized as a significant risk factor for the development of RA(19). The prevalence of smoking was 6% in the RA group and 5% in the non-RA group. Likely due to the low prevalence of smoking in this rural society, no significant relationship between smoking, tobacco use, and rheumatoid arthritis was observed. Cigarette smoking is associated with the risk of chronic inflammatory diseases (CIDs) like RA (20). Heated tobacco products (HTPs) are being promoted as a potentially less harmful alternative to traditional cigarettes, but their impact on CIDs is still under ongoing research(20). In literature, opioids are generally considered for pain management and are not regarded as a risk factor or a protective factor(21). The age of disease onset was only correlated with marital status and years of education, not any other mentioned variables. The average age of onset of rheumatoid arthritis in our population was 38.2 years, and the average age at first pregnancy was 20 years. This suggests that the participants in our society completed their reproductive history and family formation before developing rheumatoid arthritis. Therefore, it can be inferred that initiating and completing the reproductive history at a younger age for females does not seem to have an impact on the incidence of rheumatoid arthritis. We believe that the high average age of disease in our society has led to a lack of correlation between women's reproductive factors and RA. This is because the majority of women's history of childbearing occurs before the average age of the disease in our population, especially considering that the age of marriage and pregnancy is lower in our rural population. The Fasa Persian cohort comprised individuals over 35 years of age. The average age of the participants in our study was over 45 years old, indicating that our study population had nearly completed its reproductive history. This aspect can be considered both a strength and a weakness of our study. The study did not include individuals of childbearing age who had not completed their reproductive history. However, it focused on people who had completed their reproductive history on a cross-sectional basis, thereby strengthening the study. Additionally, the study population was limited to rural areas, so its findings may not apply to urban populations. Despite these weaknesses, our study was conducted on a large population. Furthermore, many reproductive factors in a woman’s life were included and studied in our research. Given the higher prevalence of rheumatoid arthritis (RA) in women and the increased incidence of RA in middle age (50–60 years)(4), it is recommended that multi-centered longitudinal studies, encompassing both rural and urban populations and conducted as either prospective or retrospective studies, should be undertaken to establish the exact relationship between reproductive factors and rheumatoid arthritis. Additionally, since there are varying results from studies on the impact of female hormones on rheumatoid arthritis(3) and considering the higher prevalence of this disease in women compared to men, it is advisable to assess testosterone levels in men with rheumatoid arthritis. Low testosterone levels may potentially play a greater role than female hormones in the development of the disease. Conclusion According to the findings of this research paper, there is no significant link between reproductive factors and RA, regardless of gynecologic and obstetric history. Additionally, the onset age of RA is not associated with reproductive factors. Due to the chronic nature of RA and its mental and emotional burden, it is comforting for affected women to know that suffering from RA is unrelated to gynecological and obstetric factors or their reproductive life. Although longitudinal studies are recommended, women can be advised that having children at a younger age result in better outcomes and fewer consequences on reproductive health following autoimmune diseases, especially rheumatoid arthritis, which is at its peak in middle age. Abbreviations RA Rheumatoid disease or Rheumatoid arthritis PCOS Polycystic ovarian syndrome OCP Oral contraceptives BMI Body mass index MET Metabolic equivalent LTPA Low-intensity leisure-time physical activity HTPs Heated tobacco products CIDs Chronic inflammatory diseases Declarations Ethics approval and consent to participate Manuscripts reporting studies involving human participants. Accordance to the Helsinki Declaration the study protocol was approved by the National and Regional Ethics Committee of FUMS (code: IR.FUMS.REC. 1402.112) .Written and informed consent was obtained from each participant to enter the first phase of a cohort study and is available on the fa-ncdrc.fums.ac.ir website. Consent for publication Not Applicable Competing Interests None declared. Funding The authors declare that there is no funding regarding the publication of this paper. Author Contribution All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by [ [M.K]. The first draft of the manuscript was written by[M.E.R] and [M.K] commented on previous versions of the manuscript. All authors read and approved the final manuscript. Acknowledgements None declared. Data Availability The datasets analyzed during the study are available from the corresponding author upon reasonable request. References Black RJ, Cross M, Haile LM, Culbreth GT, Steinmetz JD, Hagins H, et al. Global, regional, and national burden of rheumatoid arthritis, 1990–2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021. The Lancet Rheumatology. 2023;5(10):e594-e610. Orellana C, Saevarsdottir S, Klareskog L, Karlson EW, Alfredsson L, Bengtsson C. Oral contraceptives, breastfeeding and the risk of developing rheumatoid arthritis: results from the Swedish EIRA study. Ann Rheum Dis. 2017;76(11):1845-52. Raine C, Giles I. What is the impact of sex hormones on the pathogenesis of rheumatoid arthritis? Front Med (Lausanne). 2022;9:909879. Sparks JA. Rheumatoid Arthritis. Ann Intern Med. 2019;170(1):Itc1-itc16. Salliot C, Nguyen Y, Gusto G, Gelot A, Gambaretti J, Mariette X, et al. Female hormonal exposures and risk of rheumatoid arthritis in the French E3N-EPIC cohort study. Rheumatology (Oxford). 2021;60(10):4790-800. Alpízar-Rodríguez D, Pluchino N, Canny G, Gabay C, Finckh A. The role of female hormonal factors in the development of rheumatoid arthritis. Rheumatology. 2017;56(8):1254-63. Jeong HS, Hong SJ, Choi SJ, Kim JH, Song GG, Jung JH. Effects of oral contraceptives on rheumatoid arthritis in Korean menopausal women: A nationwide cross-sectional study. Maturitas. 2018;112:24-8. Adab P, Jiang CQ, Rankin E, Tsang YW, Lam TH, Barlow J, et al. Breastfeeding practice, oral contraceptive use and risk of rheumatoid arthritis among Chinese women: the Guangzhou Biobank Cohort Study. Rheumatology (Oxford). 2014;53(5):860-6. Li P-F, Li S, Zheng P-S. Reproductive Effect by Rheumatoid Arthritis and Related Autoantibodies. Rheumatology and Therapy. 2024;11(2):239-56. Lopane CM, Comstock B, Nagel AK, Gandhi MA. Combined oral contraceptive use in rheumatoid arthritis for the purpose of pregnancy prevention and additional benefits: A narrative review. J Obstet Gynaecol Res. 2022;48(2):306-12. Poustchi H, Eghtesad S, Kamangar F, Etemadi A, Keshtkar A-A, Hekmatdoost A, et al. Prospective Epidemiological Research Studies in Iran (the PERSIAN Cohort Study): Rationale, Objectives, and Design. American Journal of Epidemiology. 2018;187(4):647-55. Bae S-C, Lee YH. Causal relationship between years of education and the occurrence of rheumatoid arthritis. Postgraduate Medical Journal. 2019;95(1125):378-81. Reisine S. Marital status and social support in rheumatoid arthritis. Arthritis Rheum. 1993;36(5):589-92. Reese JB, Somers TJ, Keefe FJ, Mosley-Williams A, Lumley MA. Pain and functioning of rheumatoid arthritis patients based on marital status: Is a distressed marriage preferable to no marriage? The Journal of Pain. 2010;11(10):958-64. Qin B, Yang M, Fu H, Ma N, Wei T, Tang Q, et al. Body mass index and the risk of rheumatoid arthritis: a systematic review and dose-response meta-analysis. Arthritis Research & Therapy. 2015;17(1):86. Ljung L, Rantapää-Dahlqvist S. Abdominal obesity, gender and the risk of rheumatoid arthritis – a nested case–control study. Arthritis Research & Therapy. 2016;18(1):277. Azeez M, Clancy C, O’Dwyer T, Lahiff C, Wilson F, Cunnane G. Benefits of exercise in patients with rheumatoid arthritis: a randomized controlled trial of a patient-specific exercise programme. Clinical Rheumatology. 2020;39(6):1783-92. Cárdenas Fuentes G, Bawaked RA, Martínez González MÁ, Corella D, Subirana Cachinero I, Salas-Salvadó J, et al. Association of physical activity with body mass index, waist circumference and incidence of obesity in older adults. European Journal of Public Health. 2018;28(5):944-50. Di Giuseppe D, Discacciati A, Orsini N, Wolk A. Cigarette smoking and risk of rheumatoid arthritis: a dose-response meta-analysis. Arthritis Research & Therapy. 2014;16(2):R61. Isaji H, Yamada K. A Survey on the Actual Use of and Reasons for Heated Tobacco Products in Patients with Rheumatoid Arthritis. International Journal of Environmental Research and Public Health [Internet]. 2022; 19(19). Day AL, Curtis JR. Opioid use in rheumatoid arthritis: trends, efficacy, safety, and best practices. Curr Opin Rheumatol. 2019;31(3):264-70. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 15 Oct, 2024 Read the published version in BMC Rheumatology → Version 1 posted Editorial decision: Revision requested 16 Sep, 2024 Reviews received at journal 09 Sep, 2024 Reviews received at journal 31 Aug, 2024 Reviewers agreed at journal 31 Aug, 2024 Reviewers agreed at journal 31 Aug, 2024 Reviewers agreed at journal 29 Aug, 2024 Reviewers agreed at journal 29 Aug, 2024 Reviewers agreed at journal 28 Aug, 2024 Reviews received at journal 25 Aug, 2024 Reviewers agreed at journal 24 Aug, 2024 Reviewers invited by journal 23 Aug, 2024 Editor invited by journal 21 Aug, 2024 Editor assigned by journal 21 Aug, 2024 Submission checks completed at journal 21 Aug, 2024 First submitted to journal 21 Jul, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4777941","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":354501408,"identity":"e14ce4df-ffc4-4c1f-b606-3a02c74a5741","order_by":0,"name":"Mohammad Erfan Ranjbaran","email":"","orcid":"","institution":"Noncommunicable Disease Research Center, Fasa University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Mohammad","middleName":"Erfan","lastName":"Ranjbaran","suffix":""},{"id":354501409,"identity":"41368081-f060-4de3-8b2c-988160c333e7","order_by":1,"name":"Maryam kazemi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABB0lEQVRIiWNgGAWjYPCCBDB5+E+FDZBibDxAtJYDPGfSQFoaiNfCwNt2GKIXn1rd9rPPJH7mpMnLt3cnHpA4c95ubfthoC01NtG4tJidSTeT7N2WY9jYc3bDAYOK28nbziQCtRxLy23ApeVAGpsE77YKxmaJ3A0HEs7cTjY7ANTC2HAYt5bzz9gk/26rsG+Tf7vhwMG2c8lm5x8S0HIjjU2ad1tOYo8E74aDjW0H7MxuELLlxjNma9ltackzeHI3HGY4k5xgdgNoSwI+v5xPY7z5dluy7fz2s5s/M1TY2ZudT3/44EONDU4tQMAigcxLBKtMwK0cBJg/IPPs8SseBaNgFIyCkQgAAlFr5mdkUaMAAAAASUVORK5CYII=","orcid":"","institution":"Noncommunicable Disease Research Center, Fasa University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Maryam","middleName":"","lastName":"kazemi","suffix":""}],"badges":[],"createdAt":"2024-07-21 18:53:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4777941/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4777941/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s41927-024-00429-z","type":"published","date":"2024-10-15T15:57:48+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":67149538,"identity":"7f3a4305-a84d-4a8b-aa93-4254614755f6","added_by":"auto","created_at":"2024-10-21 16:13:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":435639,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4777941/v1/29de7f66-cdb5-449a-8749-867c49ae826c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Reproductive Health and Rheumatoid Arthritis ","fulltext":[{"header":"Introduction","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eRheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the joints. The burden of RA has increased globally over the past 30 years and is projected to continue rising(1).\u003c/p\u003e \u003cp\u003eRheumatoid arthritis (RA) primarily affects women; In fact, being female is considered a risk factor for this disorder(2\u0026ndash;4). RA, the most common chronic systemic autoimmune disease, exhibits a female-to-male prevalence ratio greater than 4 before age 50, and below 2 after 60(3, 5, 6). Such a gender tendency raises questions about the possible relationship between immune dysregulation, hormonal fluctuations, and reproductive health(2\u0026ndash;4).\u003c/p\u003e \u003cp\u003eApproximately 50% of RA cases occur during the reproductive years, emphasizing the importance of understanding the effect of hormonal and reproductive factors on disease development(6). There are much evidence regarding the impact of estrogen and progesterone, the two main female sex hormones, on the immune system, and several molecular mechanisms have been proposed(3). However, studying the influence of female hormonal factors on RA is complex. Pregnancy, breastfeeding and parity of any number have been shown in some studies to be protective, while the incidence and severity of RA is higher in the postpartum period and perimenopause(6\u0026ndash;8). Women with RA are more likely to have coexisting reproductive disorders such as infertility, endometriosis, and premature ovarian insufficiency, or to develop them later on(9). There is also a known connection between RA and abortion as well as polycystic ovary syndrome (PCOS), although the evidence is somewhat controversial(9).\u003c/p\u003e \u003cp\u003eDuring the peak incidence of rheumatoid arthritis (RA), which typically occurs during the female reproductive period, women often confront significant decisions concerning pregnancy and the potential for having a child; and the stress experienced by RA patients may somewhat influence their reproductive choices(9). Therefore, it is essential to have a comprehensive understanding of how RA is associated with female reproductive factors in order to provide the best possible care and consultation for women. Despite progress, controversies still exist(3). Understanding the impact of reproductive factors on the development and trajectory of RA is important. This knowledge informs society and guides medical expectations. Tailoring preventive interventions for high-risk populations may mitigate disease burden and improve outcomes(10). This article explores the intricate connections between rheumatoid disease (RA) and reproductive factors, shedding light on potential implications for patient care and preventive strategies.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003eMethodology\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eThis cross-sectional study was conducted on baseline data of Fasa PERSIAN cohort, which is one of the 22 active cohorts in Iran. It started its activity in 2013 and includes about 10,000 people aged older than 35 from Sheshdeh and Qare-Balagh villages in Fasa (south east of Iran)(11).\u003c/p\u003e\u003cp\u003eThe entire female population of the Fasa PERSIAN cohort was included in the study.\u003c/p\u003e\u003cp\u003eSubjects with incomplete information on study variables or any history of malignant gynecologic diseases were excluded.\u003c/p\u003e\u003cp\u003eRheumatoid disease was recorded based on a check list of diseases completed by the individual or in annual follow-ups, as self-reported that was confirmed by a doctor.\u003c/p\u003e\u003cp\u003eThe following variables are recorded: current age, years of education, socio-economic status(classified as low, middle, and high), marital status (classified as single, married, widowed, and divorced), obstetric history including gravidity, stillbirth, abortion, age at first pregnancy, alive child numbers and total breastfeeding duration (in months), gynecologic history including history of infertility, hysterectomy, and OCP use, physical activity (MET; minutes/week), BMI, waist circumference (in centimeter), calorie intake(per day), cigarette, other tobaccos, and opium use.\u003c/p\u003e\u003cp\u003eQuantitative variables are described using mean and standard deviation, while qualitative variables are described using frequency and percentage. Univariate analysis was done by using chi-square, independent sample T test, Pearson correlation test and one-way analysis of variance (ANOVA). Logistic regression model was used to adjust confounding variables. variables were correlated with rheumatoid arthritis in univariate analysis with p-value\u0026thinsp;\u0026lt;\u0026thinsp;.2 enter to this model.\u003c/p\u003e\u003cp\u003eData analysis was done by SPSS 25 software at a significance level of 0.05.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eAmong the 5557 women in the Fasa PERSIAN cohort study, the average age of the participants was 48.6\u0026thinsp;\u0026plusmn;\u0026thinsp;9.5 years. 7.2% of the participants had rheumatoid disease, and the average age at which rheumatoid disease started was 38.2\u0026thinsp;\u0026plusmn;\u0026thinsp;15.2. 81.9% of the participants were married, and the average years of education was 3.7 years.\u003c/p\u003e \u003cp\u003eWe analyzed the socio-demographic characteristics and reproductive factors of participants based on the presence or absence of rheumatoid disease. (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) Reproductive factors such as number of pregnancies, abortions, live child number, infertility, contraceptive use and breastfeeding duration were analyzed with respect to the RA affliction. The mean pregnancy numbers in non-RA and RA groups were 5.15\u0026thinsp;\u0026plusmn;\u0026thinsp;3.16 and 5.93\u0026thinsp;\u0026plusmn;\u0026thinsp;3.34, respectively. Age at first pregnancy in non-RA and RA group was 20.45\u0026thinsp;\u0026plusmn;\u0026thinsp;4.88 and 19.43\u0026thinsp;\u0026plusmn;\u0026thinsp;4.04 respectively. Among the non-RA group, the live child number was 4.77\u0026thinsp;\u0026plusmn;\u0026thinsp;2.67; and 5.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.76 among the RA group.\u003c/p\u003e \u003cp\u003eOur findings indicated that RA was significantly correlated with waist circumference (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) but not correlated with BMI, calorie intake, and physical activity. Our analysis also revealed that among reproductive factors, RA was significantly correlated with pregnancy number, first pregnancy age, breastfeeding duration, and alive child number with a p-value of \u0026lt;\u0026thinsp;.001 but was not correlated with abortion number, history of hysterectomy, stillbirth, infertility, and contraceptive use. In addition, our analysis showed a significant correlation between years of education and RA (p value\u0026thinsp;\u0026lt;\u0026thinsp;.001). Marital status did not reveal any significant correlation with RA in our study. Cigarette, tobacco and opium use did not have any significant correlation with RA.\u003c/p\u003e \u003cp\u003eIn the regression model (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), it was observed that the years of education have correlations with RA in that people without rheumatoid disease had higher years of education (p value\u0026thinsp;=\u0026thinsp;.02)\u003c/p\u003e \u003cp\u003eOther variables such as pregnancy number, first pregnancy age, alive child number, abortion number, stillbirth, breastfeeding duration, waist circumference, BMI, and cigarette smoking had no significant statistical correlation with having or not having RA.\u003c/p\u003e \u003cp\u003eMeanwhile, in linear regression, the relationship between variables and the age of onset of RA was investigated. However, there was almost no relationship between the two except for education level \u0026amp; marital status with p values of .001 \u0026amp; .03 respectively. (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003esocio- demographic characteristics and reproductive factors of participants of study\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo Rheumatoid disease\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRheumatoid disease\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYears of education\u003c/p\u003e \u003cp\u003emean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.77\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.85\u0026thinsp;\u0026plusmn;\u0026thinsp;2.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMarital status n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e.39\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003esingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e265(94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emarried\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4227(92.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e323(7.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ewidow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e581(91.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55(8.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003edivorce\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e82(91.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8(8.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSocioeconomic status n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e.75\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003elow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1720(92.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e133(7.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emiddle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1707(92.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e140(7.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ehigh\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1726(93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e129(7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWaist circumference(cm) mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e96.02\u0026thinsp;\u0026plusmn;\u0026thinsp;11.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e97.93\u0026thinsp;\u0026plusmn;\u0026thinsp;12.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m2) mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.82\u0026thinsp;\u0026plusmn;\u0026thinsp;4.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.33\u0026thinsp;\u0026plusmn;\u0026thinsp;5.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCalorie intake(cal) mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2838.77\u0026thinsp;\u0026plusmn;\u0026thinsp;1110.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2890.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1146.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.36\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysical activity (MET min/week) mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38.41\u0026thinsp;\u0026plusmn;\u0026thinsp;6.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.78\u0026thinsp;\u0026plusmn;\u0026thinsp;8.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.36\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePregnancy number mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.15\u0026thinsp;\u0026plusmn;\u0026thinsp;3.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.93\u0026thinsp;\u0026plusmn;\u0026thinsp;3.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlive child number mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.77\u0026thinsp;\u0026plusmn;\u0026thinsp;2.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbortion number mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.44\u0026thinsp;\u0026plusmn;\u0026thinsp;0.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFirst pregnancy age mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20.45\u0026thinsp;\u0026plusmn;\u0026thinsp;4.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.43\u0026thinsp;\u0026plusmn;\u0026thinsp;4.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreast feeding duration (months) mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e90.08\u0026thinsp;\u0026plusmn;\u0026thinsp;57.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e104.17\u0026thinsp;\u0026plusmn;\u0026thinsp;58.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHysterectomy n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e203(91.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19(8.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4952(92.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e384(7.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStill birth n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e.13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e701(91.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63(8.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3997(93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e302(7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInfertility n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e.50\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1349(92.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e106(7.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3573(92.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e283(7.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUsed contraceptive n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e.31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3432(92.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e263(7.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1723(92.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e140(7.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003esmoke Cigarette n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e253(90.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27(9.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4902(92.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e376(7.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther tobacco usage n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e.31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58(90.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(9.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5096(92.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e397(7.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOpium usage n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41(89.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(10.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5114(92.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e398(7.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003elogistic regression model for rheumatoid arthritis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eS.E.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eExp(B)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYears of Education\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.050\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.951\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePregnancy Number\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.190\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.204\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.352\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.827\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlive Childbirth Number\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e.242\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.206\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.241\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.273\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFirst Pregnancy Age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.026\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.072\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.974\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbortion Number\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e.238\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.215\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.269\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.268\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreast feeding Duration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.964\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWaist Circumference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e.016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.016\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.753\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.993\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoke Cigarette\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e.115\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.218\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.597\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.122\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHas Stillbirth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.258\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.298\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.387\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.773\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConstant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-3.213\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.711\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.040\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLinear regression model for age of rheumatoid arthritis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUnstandardized coefficients\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eStandardized coefficients\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStd. Error\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBeta\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e(Constant)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.888\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.848\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUse Contraceptive Drug\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-2.243\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.635\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.068\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.171\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoke Cigarette\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e.074\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.733\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.978\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMarital Status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.664\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.764\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.039\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYears of Education\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-1.012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.311\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.185\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePregnancy Number\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e.066\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.720\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.927\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlive Childbirth Number\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.547\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.844\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.285\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.068\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreast feeding Duration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.775\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysical activity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.041\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e.089\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;.021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.648\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eIn this cross -sectional study women had average age of more than 45 years; 7 out of 100 of them were found to be suffering from RA. The average body mass index of the population was in the overweight range. Additionally, the average number of pregnancies was more than 5, and the number of live children was over 4. The average age of RA onset was 38.2 years. The average age at first pregnancy was 20.37 years within our population.\u003c/p\u003e \u003cp\u003eThis study showed that the number of pregnancies, the age of the first pregnancy, the duration of breastfeeding, the number of children, the number of abortions, and stillbirths, had no statistically significant correlation with RA. However, a review article by Alp\u0026iacute;zar and colleagues highlighted controversies in different studies regarding whether these factors are associated with RA. Some studies suggested a protective effect, while others considered them as risk factors for developing RA(6).\u003c/p\u003e \u003cp\u003eOur study supported previous research findings regarding the relationship between years of education and rheumatoid arthritis (RA). Years of education had an inverse relationship with RA. Previous studies have shown an association between higher levels of education and a decreased risk of RA; However, the findings have been inconsistent, and the reasons behind this association remain unclear (12).\u003c/p\u003e \u003cp\u003eIn our analysis, we found that marital status did not show a significant correlation with RA. It seems to be more of a prognostic factor rather than a causal or protective factor (13). Many studies have shown that married individuals tend to have fewer health problems and lower mortality rates compared to those who are not married, including divorced, widowed, separated, or never married individuals (13). Being in a well-adjusted or nondistressed marriage seems to be associated with less pain and better functioning for individuals with RA(14).\u003c/p\u003e \u003cp\u003eIn our study, we did not find a link between waist circumference and body mass index (BMI) with rheumatoid arthritis (RA). However, a review and meta-analysis showed that overweight and obese individuals have a higher risk of developing RA compared to those with a normal BMI(15). Specifically, women with a waist circumference greater than 102 cm had 2\u0026ndash;3 times the risk of developing RA, while those with a waist circumference greater than 88 cm did not show the same association(16). This association may not have been observed due to the cross-sectional nature of our study. Regarding physical activity, Azeez and colleagues found that exercise led to reductions in weight, waist circumference, and BMI in RA patients (17). Low-intensity leisure-time physical activity (LTPA) was inversely associated with BMI, while moderate/vigorous LTPA showed an inverse relationship with both BMI and waist circumference(18).\u003c/p\u003e \u003cp\u003eThe analysis of our population did not show a significant correlation between smoking and rheumatoid arthritis (RA), even though smoking is widely recognized as a significant risk factor for the development of RA(19). The prevalence of smoking was 6% in the RA group and 5% in the non-RA group. Likely due to the low prevalence of smoking in this rural society, no significant relationship between smoking, tobacco use, and rheumatoid arthritis was observed. Cigarette smoking is associated with the risk of chronic inflammatory diseases (CIDs) like RA (20). Heated tobacco products (HTPs) are being promoted as a potentially less harmful alternative to traditional cigarettes, but their impact on CIDs is still under ongoing research(20). In literature, opioids are generally considered for pain management and are not regarded as a risk factor or a protective factor(21).\u003c/p\u003e \u003cp\u003eThe age of disease onset was only correlated with marital status and years of education, not any other mentioned variables.\u003c/p\u003e \u003cp\u003eThe average age of onset of rheumatoid arthritis in our population was 38.2 years, and the average age at first pregnancy was 20 years. This suggests that the participants in our society completed their reproductive history and family formation before developing rheumatoid arthritis. Therefore, it can be inferred that initiating and completing the reproductive history at a younger age for females does not seem to have an impact on the incidence of rheumatoid arthritis. We believe that the high average age of disease in our society has led to a lack of correlation between women's reproductive factors and RA. This is because the majority of women's history of childbearing occurs before the average age of the disease in our population, especially considering that the age of marriage and pregnancy is lower in our rural population.\u003c/p\u003e \u003cp\u003eThe Fasa Persian cohort comprised individuals over 35 years of age. The average age of the participants in our study was over 45 years old, indicating that our study population had nearly completed its reproductive history. This aspect can be considered both a strength and a weakness of our study. The study did not include individuals of childbearing age who had not completed their reproductive history. However, it focused on people who had completed their reproductive history on a cross-sectional basis, thereby strengthening the study. Additionally, the study population was limited to rural areas, so its findings may not apply to urban populations. Despite these weaknesses, our study was conducted on a large population. Furthermore, many reproductive factors in a woman\u0026rsquo;s life were included and studied in our research.\u003c/p\u003e \u003cp\u003eGiven the higher prevalence of rheumatoid arthritis (RA) in women and the increased incidence of RA in middle age (50\u0026ndash;60 years)(4), it is recommended that multi-centered longitudinal studies, encompassing both rural and urban populations and conducted as either prospective or retrospective studies, should be undertaken to establish the exact relationship between reproductive factors and rheumatoid arthritis. Additionally, since there are varying results from studies on the impact of female hormones on rheumatoid arthritis(3) and considering the higher prevalence of this disease in women compared to men, it is advisable to assess testosterone levels in men with rheumatoid arthritis. Low testosterone levels may potentially play a greater role than female hormones in the development of the disease.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eAccording to the findings of this research paper, there is no significant link between reproductive factors and RA, regardless of gynecologic and obstetric history. Additionally, the onset age of RA is not associated with reproductive factors.\u003c/p\u003e \u003cp\u003eDue to the chronic nature of RA and its mental and emotional burden, it is comforting for affected women to know that suffering from RA is unrelated to gynecological and obstetric factors or their reproductive life.\u003c/p\u003e \u003cp\u003eAlthough longitudinal studies are recommended, women can be advised that having children at a younger age result in better outcomes and fewer consequences on reproductive health following autoimmune diseases, especially rheumatoid arthritis, which is at its peak in middle age.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRheumatoid disease or Rheumatoid arthritis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePCOS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePolycystic ovarian syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOCP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOral contraceptives\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBMI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBody mass index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMET\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMetabolic equivalent\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLTPA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLow-intensity leisure-time physical activity\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHTPs\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHeated tobacco products\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCIDs\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eChronic inflammatory diseases\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e \u003cp\u003eManuscripts reporting studies involving human participants. Accordance to the Helsinki Declaration the study protocol was approved by the National and Regional Ethics Committee of FUMS (code: IR.FUMS.REC. 1402.112) .Written and informed consent was obtained from each participant to enter the first phase of a cohort study and is available on the fa-ncdrc.fums.ac.ir website.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eNot Applicable\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting Interests\u003c/h2\u003e \u003cp\u003eNone declared.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThe authors declare that there is no funding regarding the publication of this paper.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by [ [M.K]. The first draft of the manuscript was written by[M.E.R] and [M.K] commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eNone declared.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets analyzed during the study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBlack RJ, Cross M, Haile LM, Culbreth GT, Steinmetz JD, Hagins H, et al. Global, regional, and national burden of rheumatoid arthritis, 1990\u0026amp;#x2013;2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021. The Lancet Rheumatology. 2023;5(10):e594-e610.\u003c/li\u003e\n\u003cli\u003eOrellana C, Saevarsdottir S, Klareskog L, Karlson EW, Alfredsson L, Bengtsson C. Oral contraceptives, breastfeeding and the risk of developing rheumatoid arthritis: results from the Swedish EIRA study. Ann Rheum Dis. 2017;76(11):1845-52.\u003c/li\u003e\n\u003cli\u003eRaine C, Giles I. What is the impact of sex hormones on the pathogenesis of rheumatoid arthritis? Front Med (Lausanne). 2022;9:909879.\u003c/li\u003e\n\u003cli\u003eSparks JA. Rheumatoid Arthritis. Ann Intern Med. 2019;170(1):Itc1-itc16.\u003c/li\u003e\n\u003cli\u003eSalliot C, Nguyen Y, Gusto G, Gelot A, Gambaretti J, Mariette X, et al. Female hormonal exposures and risk of rheumatoid arthritis in the French E3N-EPIC cohort study. Rheumatology (Oxford). 2021;60(10):4790-800.\u003c/li\u003e\n\u003cli\u003eAlp\u0026iacute;zar-Rodr\u0026iacute;guez D, Pluchino N, Canny G, Gabay C, Finckh A. The role of female hormonal factors in the development of rheumatoid arthritis. Rheumatology. 2017;56(8):1254-63.\u003c/li\u003e\n\u003cli\u003eJeong HS, Hong SJ, Choi SJ, Kim JH, Song GG, Jung JH. Effects of oral contraceptives on rheumatoid arthritis in Korean menopausal women: A nationwide cross-sectional study. Maturitas. 2018;112:24-8.\u003c/li\u003e\n\u003cli\u003eAdab P, Jiang CQ, Rankin E, Tsang YW, Lam TH, Barlow J, et al. Breastfeeding practice, oral contraceptive use and risk of rheumatoid arthritis among Chinese women: the Guangzhou Biobank Cohort Study. Rheumatology (Oxford). 2014;53(5):860-6.\u003c/li\u003e\n\u003cli\u003eLi P-F, Li S, Zheng P-S. Reproductive Effect by Rheumatoid Arthritis and Related Autoantibodies. Rheumatology and Therapy. 2024;11(2):239-56.\u003c/li\u003e\n\u003cli\u003eLopane CM, Comstock B, Nagel AK, Gandhi MA. Combined oral contraceptive use in rheumatoid arthritis for the purpose of pregnancy prevention and additional benefits: A narrative review. J Obstet Gynaecol Res. 2022;48(2):306-12.\u003c/li\u003e\n\u003cli\u003ePoustchi H, Eghtesad S, Kamangar F, Etemadi A, Keshtkar A-A, Hekmatdoost A, et al. Prospective Epidemiological Research Studies in Iran (the PERSIAN Cohort Study): Rationale, Objectives, and Design. American Journal of Epidemiology. 2018;187(4):647-55.\u003c/li\u003e\n\u003cli\u003eBae S-C, Lee YH. Causal relationship between years of education and the occurrence of rheumatoid arthritis. Postgraduate Medical Journal. 2019;95(1125):378-81.\u003c/li\u003e\n\u003cli\u003eReisine S. Marital status and social support in rheumatoid arthritis. Arthritis Rheum. 1993;36(5):589-92.\u003c/li\u003e\n\u003cli\u003eReese JB, Somers TJ, Keefe FJ, Mosley-Williams A, Lumley MA. Pain and functioning of rheumatoid arthritis patients based on marital status: Is a distressed marriage preferable to no marriage? The Journal of Pain. 2010;11(10):958-64.\u003c/li\u003e\n\u003cli\u003eQin B, Yang M, Fu H, Ma N, Wei T, Tang Q, et al. Body mass index and the risk of rheumatoid arthritis: a systematic review and dose-response meta-analysis. Arthritis Research \u0026amp; Therapy. 2015;17(1):86.\u003c/li\u003e\n\u003cli\u003eLjung L, Rantap\u0026auml;\u0026auml;-Dahlqvist S. Abdominal obesity, gender and the risk of rheumatoid arthritis \u0026ndash; a nested case\u0026ndash;control study. Arthritis Research \u0026amp; Therapy. 2016;18(1):277.\u003c/li\u003e\n\u003cli\u003eAzeez M, Clancy C, O\u0026rsquo;Dwyer T, Lahiff C, Wilson F, Cunnane G. Benefits of exercise in patients with rheumatoid arthritis: a randomized controlled trial of a patient-specific exercise programme. Clinical Rheumatology. 2020;39(6):1783-92.\u003c/li\u003e\n\u003cli\u003eC\u0026aacute;rdenas Fuentes G, Bawaked RA, Mart\u0026iacute;nez Gonz\u0026aacute;lez M\u0026Aacute;, Corella D, Subirana Cachinero I, Salas-Salvad\u0026oacute; J, et al. Association of physical activity with body mass index, waist circumference and incidence of obesity in older adults. European Journal of Public Health. 2018;28(5):944-50.\u003c/li\u003e\n\u003cli\u003eDi Giuseppe D, Discacciati A, Orsini N, Wolk A. Cigarette smoking and risk of rheumatoid arthritis: a dose-response meta-analysis. Arthritis Research \u0026amp; Therapy. 2014;16(2):R61.\u003c/li\u003e\n\u003cli\u003eIsaji H, Yamada K. A Survey on the Actual Use of and Reasons for Heated Tobacco Products in Patients with Rheumatoid Arthritis. International Journal of Environmental Research and Public Health [Internet]. 2022; 19(19).\u003c/li\u003e\n\u003cli\u003eDay AL, Curtis JR. Opioid use in rheumatoid arthritis: trends, efficacy, safety, and best practices. Curr Opin Rheumatol. 2019;31(3):264-70.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-rheumatology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"brhm","sideBox":"Learn more about [BMC Rheumatology](http://bmcrheumatol.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/brhm/default.aspx","title":"BMC Rheumatology","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-4777941/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4777941/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIntroduction: The prevalence of Rheumatoid Arthritis (RA) has been steadily increasing over the last thirty years, particularly among women. Due to the conflicting results of various studies on the link between rheumatoid arthritis and reproductive health, we have undertaken this study to explore their relationship.\u003c/p\u003e \u003cp\u003eMethod: This cross-sectional study utilized primary data from women involved in the Fasa Persian Cohort. The study examined the frequency of RA and its association with various factors related to reproductive health, including age at first pregnancy, number of alive children, history of abortion, and infertility. SPSS software was utilized for data analysis, with the significance level set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003cp\u003eResults: 5557 women with an average age of 48.6\u0026thinsp;\u0026plusmn;\u0026thinsp;9.5 years participated. Of these women, 7.2% were diagnosed with rheumatoid disease, with an average onset age of 38.2\u0026thinsp;\u0026plusmn;\u0026thinsp;15.2. The study did not find a significant correlation between RA and factors such as number of pregnancies, age at first pregnancy, duration of breastfeeding and number of children.\u003c/p\u003e \u003cp\u003eConclusion: The study suggests that the experience of RA is independent of gynecological, obstetric factors, or reproductive life. This finding may provide reassurance to women affected by RA.\u003c/p\u003e","manuscriptTitle":"Reproductive Health and Rheumatoid Arthritis ","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-09-20 05:04:17","doi":"10.21203/rs.3.rs-4777941/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-09-16T07:26:49+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-09T11:03:42+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-31T14:00:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"277488668802178809699639564656510989149","date":"2024-08-31T13:31:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"167798304190614389712226585642877996040","date":"2024-08-31T05:04:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"253434272242478857552259984003156782061","date":"2024-08-29T09:40:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"256384695525208230294832518120538336264","date":"2024-08-29T06:49:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"60780482384103842619540231449548851119","date":"2024-08-29T02:45:30+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-25T13:48:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"57435694633346586261324823856292563821","date":"2024-08-24T05:18:05+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-08-23T18:43:51+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-08-21T17:57:32+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-08-21T17:55:47+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-08-21T17:54:35+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Rheumatology","date":"2024-07-21T18:47:36+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-rheumatology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"brhm","sideBox":"Learn more about [BMC Rheumatology](http://bmcrheumatol.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/brhm/default.aspx","title":"BMC Rheumatology","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fadc7c13-9952-4387-bb63-51b291c598e9","owner":[],"postedDate":"September 20th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-10-21T16:08:27+00:00","versionOfRecord":{"articleIdentity":"rs-4777941","link":"https://doi.org/10.1186/s41927-024-00429-z","journal":{"identity":"bmc-rheumatology","isVorOnly":false,"title":"BMC Rheumatology"},"publishedOn":"2024-10-15 15:57:48","publishedOnDateReadable":"October 15th, 2024"},"versionCreatedAt":"2024-09-20 05:04:17","video":"","vorDoi":"10.1186/s41927-024-00429-z","vorDoiUrl":"https://doi.org/10.1186/s41927-024-00429-z","workflowStages":[]},"version":"v1","identity":"rs-4777941","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4777941","identity":"rs-4777941","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}