Female reproductive factors and risk of joint replacement arthroplasty of the knee and hip due to osteoarthritis in postmenopausal women: a nationwide cohort study of 1.13 million women

  • Author Footnotes
    a Drs. Yeonghee Eun and Jung Eun Yoo contributed equally to this work as co-first authors.
    Y. Eun
    Footnotes
    a Drs. Yeonghee Eun and Jung Eun Yoo contributed equally to this work as co-first authors.
    Affiliations
    Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
    Search for articles by this author
  • Author Footnotes
    a Drs. Yeonghee Eun and Jung Eun Yoo contributed equally to this work as co-first authors.
    J.E. Yoo
    Footnotes
    a Drs. Yeonghee Eun and Jung Eun Yoo contributed equally to this work as co-first authors.
    Affiliations
    Department of Family Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, South Korea
    Search for articles by this author
  • K. Han
    Affiliations
    Department of Statistics and Actuarial Science, Soongsil University, Seoul, South Korea
    Search for articles by this author
  • D. Kim
    Affiliations
    Department of Statistics and Actuarial Science, Soongsil University, Seoul, South Korea
    Search for articles by this author
  • K.N. Lee
    Affiliations
    Department of Biomedicine and Health Science, The Catholic University of Korea, Seoul, South Korea
    Search for articles by this author
  • J. Lee
    Affiliations
    Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
    Search for articles by this author
  • D.-Y. Lee
    Affiliations
    Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
    Search for articles by this author
  • D.-H. Lee
    Affiliations
    Department of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
    Search for articles by this author
  • Author Footnotes
    b Drs. Hyungjin Kim and Dong Wook Shin contributed equally to this work as corresponding authors.
    H. Kim
    Correspondence
    Address correspondence and reprint requests to: H. Kim, Department of Medical Humanities, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul 06351, South Korea. Tel.: 82-2 3410-1879; fax: 82-2 3410-0231.
    Footnotes
    b Drs. Hyungjin Kim and Dong Wook Shin contributed equally to this work as corresponding authors.
    Affiliations
    Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Department of Medical Humanities, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
    Search for articles by this author
  • Author Footnotes
    b Drs. Hyungjin Kim and Dong Wook Shin contributed equally to this work as corresponding authors.
    D.W. Shin
    Correspondence
    Address correspondence and reprint requests to: D.W. Shin, Department of Family Medicine/Supportive Care Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-gu, Seoul 06351, South Korea. Tel.: 82-2 3410-5252; fax: 82-2 3410-0388.
    Footnotes
    b Drs. Hyungjin Kim and Dong Wook Shin contributed equally to this work as corresponding authors.
    Affiliations
    Department of Family Medicine and Supportive Care Centre, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Department of Clinical Research Design and Evaluation/ Department of Digital Health, Samsung Advanced Institute for Health Science and Technology (SAIHST), Sungkyunkwan University, Seoul, South Korea
    Search for articles by this author
  • Author Footnotes
    a Drs. Yeonghee Eun and Jung Eun Yoo contributed equally to this work as co-first authors.
    b Drs. Hyungjin Kim and Dong Wook Shin contributed equally to this work as corresponding authors.
Published:November 09, 2021DOI:https://doi.org/10.1016/j.joca.2021.10.012

      Summary

      Objectives

      Previous studies of the relationships between female reproductive factors and osteoarthritis (OA) have shown conflicting results. In this study, we aimed to explore the relationships between reproductive factors and joint replacement arthroplasty of the knee (TKRA) and hip (THRA) in a large nationwide population-based cohort of postmenopausal Korean women.

      Methods

      We included 1,134,680 subjects who participated in national health examinations in 2009 in the study. The study outcomes were incident THRA or TKRA due to severe hip or knee OA. The relationships between reproductive factors and THRA or TKRA were evaluated using a multivariable-adjusted proportional hazards model.

      Results

      During a mean follow-up duration of 8.2 years, 1,610 incident THRA cases and 60,670 incident TKRA cases were observed. Later age at menarche, longer breastfeeding, HRT and OC use were associated with increased risk of TKRA for severe knee OA, while later age at menopause and longer reproductive span were associated with decreased risk. With regard to THRA for severe hip OA, later menarche, longer breastfeeding, HRT more than 5 years, and OC use more than 1 year were associated with higher risk. The associations between reproductive factors and severe OA were more pronounced in underweight and younger subjects.

      Conclusion

      We found that shorter estrogen exposure was associated with higher risk of TKRA due to severe knee OA, and such associations were more pronounced in underweight and younger subjects. The association between shorter estrogen exposure and THRA was not robust.

      Keywords

      To read this article in full you will need to make a payment

      Subscribe:

      Subscribe to Osteoarthritis and Cartilage
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • McDonough C.M.
        • Jette A.M.
        The contribution of osteoarthritis to functional limitations and disability.
        Clin Geriatr Med. 2010; 26: 387-399
        • Safiri S.
        • Kolahi A.A.
        • Smith E.
        • Hill C.
        • Bettampadi D.
        • Mansournia M.A.
        • et al.
        Global, regional and national burden of osteoarthritis 1990-2017: a systematic analysis of the Global Burden of Disease Study 2017.
        Ann Rheum Dis. 2020; 79: 819-828
        • Srikanth V.K.
        • Fryer J.L.
        • Zhai G.
        • Winzenberg T.M.
        • Hosmer D.
        • Jones G.
        A meta-analysis of sex differences prevalence, incidence and severity of osteoarthritis.
        Osteoarthritis Cartilage. 2005; 13: 769-781
        • Zhou M.
        • Chen J.
        • Wang D.
        • Zhu C.
        • Wang Y.
        • Chen W.
        Combined effects of reproductive and hormone factors and obesity on the prevalence of knee osteoarthritis and knee pain among middle-aged or older Chinese women: a cross-sectional study.
        BMC Publ Health. 2018; 18: 1192
        • Jung J.H.
        • Bang C.H.
        • Song G.G.
        • Kim C.
        • Kim J.H.
        • Choi S.J.
        Knee osteoarthritis and menopausal hormone therapy in postmenopausal women: a nationwide cross-sectional study.
        Menopause. 2018; 26: 598-602
        • Jung Y.H.
        • Shin J.S.
        • Lee J.
        • Kim M.R.
        • Park K.B.
        • Choi A.
        • et al.
        Influence of parity-related factors adjusted for abortion on knee osteoarthritis in Korean women aged 50 or older: a cross-sectional study.
        Maturitas. 2015; 82: 176-183
        • Park C.Y.
        Breastfeeding for one month or longer is associated with higher risk of osteoarthritis in older adults: NHANES 1999-2012.
        Clin Nutr Res. 2017; 6: 277-284
        • Von Muhlen D.
        • Morton D.
        • Von Muhlen C.A.
        • Barrett-Connor E.
        Postmenopausal estrogen and increased risk of clinical osteoarthritis at the hip, hand, and knee in older women.
        J Womens Health Gend Based Med. 2002; 11: 511-518
        • Jorgensen K.T.
        • Pedersen B.V.
        • Nielsen N.M.
        • Hansen A.V.
        • Jacobsen S.
        • Frisch M.
        Socio-demographic factors, reproductive history and risk of osteoarthritis in a cohort of 4.6 million Danish women and men.
        Osteoarthritis Cartilage. 2011; 19: 1176-1182
        • Cirillo D.J.
        • Wallace R.B.
        • Wu L.
        • Yood R.A.
        Effect of hormone therapy on risk of hip and knee joint replacement in the Women's Health Initiative.
        Arthritis Rheum. 2006; 54: 3194-3204
        • Karlson E.W.
        • Mandl L.A.
        • Aweh G.N.
        • Sangha O.
        • Liang M.H.
        • Grodstein F.
        Total hip replacement due to osteoarthritis: the importance of age, obesity, and other modifiable risk factors.
        Am J Med. 2003; 114: 93-98
        • Liu B.
        • Balkwill A.
        • Cooper C.
        • Roddam A.
        • Brown A.
        • Beral V.
        • et al.
        Reproductive history, hormonal factors and the incidence of hip and knee replacement for osteoarthritis in middle-aged women.
        Ann Rheum Dis. 2009; 68: 1165-1170
        • Hellevik A.I.
        • Nordsletten L.
        • Johnsen M.B.
        • Fenstad A.M.
        • Furnes O.
        • Storheim K.
        • et al.
        Age of menarche is associated with knee joint replacement due to primary osteoarthritis (The HUNT Study and the Norwegian Arthroplasty Register).
        Osteoarthritis Cartilage. 2017; 25: 1654-1662
        • Leung Y.Y.
        • Talaei M.
        • Ang L.W.
        • Yuan J.M.
        • Koh W.P.
        Reproductive factors and risk of total knee replacement due to severe knee osteoarthritis in women, the Singapore Chinese Health Study.
        Osteoarthritis Cartilage. 2019; 27: 1129-1137
        • Hussain S.M.
        • Wang Y.
        • Giles G.G.
        • Graves S.
        • Wluka A.E.
        • Cicuttini F.M.
        Female reproductive and hormonal factors and incidence of primary total knee arthroplasty due to osteoarthritis.
        Arthritis Rheum. 2018; 70: 1022-1029
        • Wise B.L.
        • Niu J.
        • Zhang Y.
        • Felson D.T.
        • Bradley L.A.
        • Segal N.
        • et al.
        The association of parity with osteoarthritis and knee replacement in the multicenter osteoarthritis study.
        Osteoarthritis Cartilage. 2013; 21: 1849-1854
        • Wang A.
        • Zawadzki N.
        • Hedlin H.
        • LeBlanc E.
        • Budrys N.
        • Van Horn L.
        • et al.
        Reproductive history and osteoarthritis in the Women's health initiative.
        Scand J Rheumatol. 2021; 50: 58-67
        • Riyazi N.
        • Rosendaal F.R.
        • Slagboom E.
        • Kroon H.M.
        • Breedveld F.C.
        • Kloppenburg M.
        Risk factors in familial osteoarthritis: the GARP sibling study.
        Osteoarthritis Cartilage. 2008; 16: 654-659
        • Lee J.
        • Lee J.S.
        • Park S.H.
        • Shin S.A.
        • Kim K.
        Cohort profile: the national health insurance service–national sample cohort (NHIS-NSC), South Korea.
        Int J Epidemiol. 2017; 46: e15
        • Lee Y.H.
        • Han K.
        • Ko S.H.
        • Ko K.S.
        • Lee K.U.
        Taskforce team of diabetes fact sheet of the Korean diabetes association. Data analytic process of a nationwide population-based study using national health information database established by national health insurance service.
        Diabetes Metab J. 2016; 40: 79-82
        • Yoo K.Y.
        Cancer control activities in the Republic of Korea.
        Jpn J Clin Oncol. 2008; 38: 327-333
        • Eun Y.
        • Jeon K.H.
        • Han K.
        • Kim D.
        • Kim H.
        • Lee J.
        • et al.
        Menopausal factors and risk of seropositive rheumatoid arthritis in postmenopausal women: a nationwide cohort study of 1.36 million women.
        Sci Rep. 2020; 10: 20793
        • Yoo J.E.
        • Shin D.W.
        • Han K.
        • Kim D.
        • Yoon J.W.
        • Lee D.Y.
        Association of female reproductive factors with incidence of fracture among postmenopausal women in Korea.
        JAMA Netw Open. 2021; 4e2030405
        • Groenwold R.H.H.
        • White I.R.
        • Donders A.R.T.
        • Carpenter J.R.
        • Altman D.G.
        • Moons K.G.M.
        Missing covariate data in clinical research: when and when not to use the missing-indicator method for analysis.
        CMAJ – Canadian Medical Association journal = journal de l'Association medicale canadienne. 2012; 184: 1265-1269
        • Sniekers Y.H.
        • Weinans H.
        • van Osch G.J.
        • van Leeuwen J.P.
        Oestrogen is important for maintenance of cartilage and subchondral bone in a murine model of knee osteoarthritis.
        Arthritis Res Ther. 2010; 12: R182
        • Huang J.G.
        • Xia C.
        • Zheng X.P.
        • Yi T.T.
        • Wang X.Y.
        • Song G.
        • et al.
        17beta-Estradiol promotes cell proliferation in rat osteoarthritis model chondrocytes via PI3K/Akt pathway.
        Cell Mol Biol Lett. 2011; 16: 564-575
        • Xu X.
        • Li X.
        • Liang Y.
        • Ou Y.
        • Huang J.
        • Xiong J.
        • et al.
        Estrogen modulates cartilage and subchondral bone remodeling in an ovariectomized rat model of postmenopausal osteoarthritis.
        Med Sci Monit. 2019; 25: 3146-3153
        • Ge Y.
        • Zhou S.
        • Li Y.
        • Wang Z.
        • Chen S.
        • Xia T.
        • et al.
        Estrogen prevents articular cartilage destruction in a mouse model of AMPK deficiency via ERK-mTOR pathway.
        Ann Transl Med. 2019; 7: 336
        • Robinson J.L.
        • Soria P.
        • Xu M.
        • Vrana M.
        • Luchetti J.
        • Lu H.H.
        • et al.
        Estrogen promotes mandibular condylar fibrocartilage chondrogenesis and inhibits degeneration via estrogen receptor alpha in female mice.
        Sci Rep. 2018; 8: 8527
        • Zheng H.
        • Chen C.
        Body mass index and risk of knee osteoarthritis: systematic review and meta-analysis of prospective studies.
        BMJ Open. 2015; 5e007568
        • Brix N.
        • Ernst A.
        • Lauridsen L.L.B.
        • Parner E.T.
        • Arah O.A.
        • Olsen J.
        • et al.
        Childhood overweight and obesity and timing of puberty in boys and girls: cohort and sibling-matched analyses.
        Int J Epidemiol. 2020; 49: 834-844
        • Marnach M.L.
        • Ramin K.D.
        • Ramsey P.S.
        • Song S.W.
        • Stensland J.J.
        • An K.N.
        Characterization of the relationship between joint laxity and maternal hormones in pregnancy.
        Obstet Gynecol. 2003; 101: 331-335
        • Fell D.B.
        • Joseph K.S.
        • Armson B.A.
        • Dodds L.
        The impact of pregnancy on physical activity level.
        Matern Child Health J. 2009; 13: 597-603
        • Jaffe D.H.
        • Neumark Y.D.
        • Eisenbach Z.
        • Manor O.
        Parity-related mortality: shape of association among middle-aged and elderly men and women.
        Eur J Epidemiol. 2009; 24: 9-16
        • Zeng Y.
        • Ni Z-m
        • Liu S-y
        • Gu X.
        • Huang Q.
        • Liu J-a
        • et al.
        Parity and all-cause mortality in women and men: a dose-response meta-analysis of cohort studies.
        Sci Rep. 2016; 6: 19351
        • Melo A.S.
        • Ferriani R.A.
        • Navarro P.A.
        Treatment of infertility in women with polycystic ovary syndrome: approach to clinical practice.
        Clinics (Sao Paulo). 2015; 70: 765-769
        • Sanchez-Santos M.T.
        • Rubin K.H.
        • Glintborg D.
        • Andersen M.S.
        • Kluzek S.
        • Abrahamsen B.
        Prevalence and incidence of clinically diagnosed knee, hip and hand osteoarthritis in women with polycystic ovary syndrome: a national register-based study.
        Osteoarthritis Cartilage. 2018; 26: S200
        • Kim M.Y.
        • Kim H.J.
        • Noh J.H.
        • Kim S.A.
        • Hwang D.S.
        • Lee C.H.
        • et al.
        Relationship of breastfeeding duration with joint pain and knee osteoarthritis in middle-aged Korean women: a cross-sectional study using the Korea National Health and Nutrition Examination Survey.
        BMC Wom Health. 2020; 20: 213
        • Gust K.
        • Caccese C.
        • Larosa A.
        • Nguyen T.V.
        Neuroendocrine effects of lactation and hormone-gene-environment interactions.
        Mol Neurobiol. 2020; 57: 2074-2084
        • Karsdal M.A.
        • Bay-Jensen A.C.
        • Henriksen K.
        • Christiansen C.
        The pathogenesis of osteoarthritis involves bone, cartilage and synovial inflammation: may estrogen be a magic bullet?.
        Menopause Int. 2012; 18: 139-146
        • Bjornerem A.
        • Ghasem-Zadeh A.
        • Wang X.
        • Bui M.
        • Walker S.P.
        • Zebaze R.
        • et al.
        Irreversible deterioration of cortical and trabecular microstructure associated with breastfeeding.
        J Bone Miner Res. 2017; 32: 681-687
        • Tanko L.B.
        • Sondergaard B.C.
        • Oestergaard S.
        • Karsdal M.A.
        • Christiansen C.
        An update review of cellular mechanisms conferring the indirect and direct effects of estrogen on articular cartilage.
        Climacteric. 2008; 11: 4-16
        • Nevitt M.C.
        • Felson D.T.
        • Williams E.N.
        • Grady D.
        The effect of estrogen plus progestin on knee symptoms and related disability in postmenopausal women: the Heart and Estrogen/Progestin Replacement Study, a randomized, double-blind, placebo-controlled trial.
        Arthritis Rheum. 2001; 44: 811-818
        • Hansen M.
        • Miller B.F.
        • Holm L.
        • Doessing S.
        • Petersen S.G.
        • Skovgaard D.
        • et al.
        Effect of administration of oral contraceptives in vivo on collagen synthesis in tendon and muscle connective tissue in young women.
        J Appl Physiol (1985). 2009; 106: 1435-1443
        • Stegeman B.H.
        • de Bastos M.
        • Rosendaal F.R.
        • van Hylckama Vlieg A.
        • Helmerhorst F.M.
        • Stijnen T.
        • et al.
        Different combined oral contraceptives and the risk of venous thrombosis: systematic review and network meta-analysis.
        BMJ. 2013; 347: f5298
        • Wang Q.
        • Wurtz P.
        • Auro K.
        • Morin-Papunen L.
        • Kangas A.J.
        • Soininen P.
        • et al.
        Effects of hormonal contraception on systemic metabolism: cross-sectional and longitudinal evidence.
        Int J Epidemiol. 2016; 45: 1445-1457
        • Sowers M.R.
        • Karvonen-Gutierrez C.A.
        The evolving role of obesity in knee osteoarthritis.
        Curr Opin Rheumatol. 2010; 22: 533-537
        • Kershaw E.E.
        • Flier J.S.
        Adipose tissue as an endocrine organ.
        J Clin Endocrinol Metab. 2004; 89: 2548-2556
        • Hugle T.
        • Geurts J.
        • Nuesch C.
        • Muller-Gerbl M.
        • Valderrabano V.
        Aging and osteoarthritis: an inevitable encounter?.
        J Aging Res. 2012; 2012: 950192
        • Rezus E.
        • Cardoneanu A.
        • Burlui A.
        • Luca A.
        • Codreanu C.
        • Tamba B.I.
        • et al.
        The link between inflammaging and degenerative joint diseases.
        Int J Mol Sci. 2019; 20: 614
        • Westreich D.
        • Greenland S.
        The table 2 fallacy: presenting and interpreting confounder and modifier coefficients.
        Am J Epidemiol. 2013; 177: 292-298
        • Bandoli G.
        • Palmsten K.
        • Chambers C.D.
        • Jelliffe-Pawlowski L.L.
        • Baer R.J.
        • Thompson C.A.
        Revisiting the Table 2 fallacy: a motivating example examining preeclampsia and preterm birth.
        Paediatr Perinat Epidemiol. 2018; 32: 390-397
        • Green M.J.
        • Popham F.
        Interpreting mutual adjustment for multiple indicators of socioeconomic position without committing mutual adjustment fallacies.
        BMC Publ Health. 2019; 19: 10