Depressive symptoms among women with endometriosis: a systematic review and meta-analysis

  • Pietro Gambadauro
    Corresponding author: Pietro Gambadauro, MD, MSc, PhD.
    National Centre for Suicide Research and Prevention of Mental Ill-Health (NASP), Department of Learning, Informatics, Management and Ethics (LIME), Karolinska Institutet, Stockholm, Sweden

    Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden

    Res Medica Sweden, Uppsala, Sweden
    Search for articles by this author
  • Vladimir Carli
    National Centre for Suicide Research and Prevention of Mental Ill-Health (NASP), Department of Learning, Informatics, Management and Ethics (LIME), Karolinska Institutet, Stockholm, Sweden
    Search for articles by this author
  • Gergö Hadlaczky
    National Centre for Suicide Research and Prevention of Mental Ill-Health (NASP), Department of Learning, Informatics, Management and Ethics (LIME), Karolinska Institutet, Stockholm, Sweden
    Search for articles by this author
Published:November 09, 2018DOI:


      To evaluate whether endometriosis is associated with depressive symptoms, and whether the association is modulated by pelvic pain.

      Data Sources

      PubMed, Embase, PsychINFO, and the Cochrane Library, were systematically searched through September 2017.

      Study Eligibility Criteria

      The following eligibility criteria applied: full-text original article; quantitative data about depressive symptoms or depression; comparison of women with and without endometriosis, or women with endometriosis with and without pelvic pain. Articles reporting duplicated data were excluded.

      Study Appraisal and Synthesis Methods

      Two reviewers selected and reviewed the studies. Disagreements were resolved through discussion or a third opinion. Qualitative synthesis was performed through tabulation and assessment using a modified version of the Newcastle−Ottawa Scale. Effect sizes were pooled through meta-analysis, and moderator analyses were performed to identify potential confounders with several variables: region of the sample, method of ascertainment of endometriosis, method of measurement of depression, year of publication, and quality score.


      A meta-analysis of 24 studies (99,614 women) showed higher levels of depression among women with endometriosis compared to controls (standardized mean difference [SMD], 0.22, 95% confidence interval [CI], 0.13–0.32). The heterogeneity in this analysis (I2 = 68%) was not explained by any of the moderating variables. When only healthy controls were considered, a larger endometriosis-depression effect was found (11 studies, SMD, 0.49; 95% CI, 0.24–0.73; I2 = 69%). Endometriosis patients reporting pelvic pain had significantly higher levels of depression compared to those without pain (4 studies; SMD, 1.01; 95% CI, 0.71–1.31; I2 = 0%). No significant difference was found between women with pelvic pain and endometriosis and those with pelvic pain but without endometriosis (11 studies, SMD, −0.11; 95% CI, −0.25 to 0.04; I2 = 0%).


      The association between endometriosis and depressive symptoms is largely determined by chronic pain but may also be modulated by individual and context vulnerabilities. Awareness of the complex relationship between endometriosis and depressive symptoms informs tailored care and patient-centered research outcomes.

      Key words

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

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to American Journal of Obstetrics & Gynecology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Kuznetsov L.
        • Dworzynski K.
        • Davies M.
        • Overton C.
        • Guideline Committee
        Diagnosis and management of endometriosis: summary of NICE guidance.
        BMJ. 2017; 358: j3935
        • DiVasta A.D.
        • Vitonis A.F.
        • Laufer M.R.
        • Missmer S.A.
        Spectrum of symptoms in women diagnosed with endometriosis during adolescence vs adulthood.
        Am J Obstet Gynecol. 2018; 218: 324
        • Hirsch M.
        • Duffy J.M.N.
        • Kusznir J.O.
        • Davis C.J.
        • Plana M.N.
        • Khan K.S.
        • International Collaboration to Harmonize Outcomes and Measures for Endometriosis
        Variation in outcome reporting in endometriosis trials: a systematic review.
        Am J Obstet Gynecol. 2016; 214: 452-464
        • Hickey M.
        • Ballard K.
        • Farquhar C.
        BMJ. 2014; 348: 1752
        • Culley L.
        • Law C.
        • Hudson N.
        • et al.
        The social and psychological impact of endometriosis on women's lives: a critical narrative review.
        Hum Reprod Update. 2013; 19: 625-639
        • Ofer A.
        • Shulman L.P.
        • Singh S.S.
        Improving the treatment and management of endometriosis: an overview of current and novel approaches.
        Am J Obstet Gynecol. 2016; 214: 672
        • Simoens S.
        • Dunselman G.
        • Dirksen C.
        • et al.
        The burden of endometriosis: costs and quality of life of women with endometriosis and treated in referral centres.
        Hum Reprod. 2012; 27: 1292-1299
        • World Health Organization
        Depression and other common mental disorders: global health estimates.
        World Health Organization, Geneva2017
        • Kessler R.C.
        • Bromet E.J.
        The epidemiology of depression across cultures.
        Annu Rev Public Health. 2013; 34: 119-138
        • Salk R.H.
        • Hyde J.S.
        • Abramson L.Y.
        Gender differences in depression in representative national samples: meta-analyses of diagnoses and symptoms.
        Psychol Bull. 2017; 143: 783-822
        • Bair M.J.
        • Robinson R.L.
        • Katon W.
        • Kroenke K.
        Depression and pain comorbidity: a literature review.
        Arch Intern Med. 2003; 163: 2433-2445
        • Warnock J.K.
        • Bundren J.C.
        • Morris D.W.
        Depressive mood symptoms associated with ovarian suppression.
        Fertil Steril. 2000; 74: 984-986
        • Wilkins K.M.
        • Warnock J.K.
        • Serrano E.
        Depressive symptoms related to infertility and infertility treatments.
        Psychiatr Clin North Am. 2010; 33: 309-321
        • Mirkin D.
        • Murphy-Barron C.
        • Iwasaki K.
        Actuarial analysis of private payer administrative claims data for women with endometriosis.
        J Manag Care Pharm. 2007; 13: 262-272
        • Pope C.J.
        • Sharma V.
        • Sharma S.
        • Mazmanian D.
        A systematic review of the association between psychiatric disturbances and endometriosis.
        J Obstet Gynaecol Can. 2015; 37: 1006-1015
        • Lee Y.Y.
        • Stockings E.A.
        • Harris M.G.
        • et al.
        The risk of developing major depression among individuals with subthreshold depression: a systematic review and meta-analysis of longitudinal cohort studies.
        Psychol Med. 2019; 49: 92-102
        • National Collaborating Centre for Mental Health (UK)
        The management of subthreshold depressive symptoms.
        in: NICE Clinical Guidelines, No. 90. Depression: the treatment and management of depression in adults (updated edition). British Psychological Society, Leicester, UK2010
        • Liberati A.
        • Altman D.G.
        • Tetzlaff J.
        • et al.
        The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.
        J Clin Epidemiol. 2009; 62: e1-e34
        • Gambadauro P.
        • Magos A.
        Office 2.0: a Web 2.0 tool for international collaborative research.
        Lancet. 2008; 371: 1837-1838
        • Lipsey M.W.
        • Wilson D.B.
        Practical meta-analysis. Applied social research methods vol.49.
        Sage, Thousand Oaks, CA2001
      1. Wilson DB. Practical meta-analysis effect size calculator. Available at: Accessed Oct. 5, 2018.

        • Shatford L.A.
        • Hearn M.T.
        • Yuzpe A.A.
        • Brown S.E.
        • Casper R.F.
        Psychological correlates of differential infertility diagnosis in an in vitro fertilization program.
        Am J Obstet Gynecol. 1988; 158: 1099-1107
        • Walker E.
        • Katon W.
        • Jones L.M.
        • Russo J.
        Relationship between endometriosis and affective disorder.
        Am J Psychiatry. 1989; 146: 380-381
        • Low W.Y.
        • Edelmann R.J.
        • Sutton C.
        A psychological profile of endometriosis patients in comparison to patients with pelvic pain of other origins.
        J Psychosom Res. 1993; 37: 111-116
        • Waller K.G.
        • Shaw R.W.
        Endometriosis, pelvic pain, and psychological functioning.
        Fertil Steril. 1995; 63: 796-800
        • Peveler R.
        • Edwards J.
        • Daddow J.
        • Thomas E.
        Psychosocial factors and chronic pelvic pain: a comparison of women with endometriosis and with unexplained pain.
        J Psychosom Res. 1996; 40: 305-315
        • Lorençatto C.
        • Petta C.A.
        • Navarro M.J.
        • Bahamondes L.
        • Matos A.
        Depression in women with endometriosis with and without chronic pelvic pain.
        Acta Obstet Gynecol Scand. 2006; 85: 88-92
        • Tietjen G.E.
        • Bushnell C.D.
        • Herial N.A.
        • Utley C.
        • White L.
        • Hafeez F.
        Endometriosis is associated with prevalence of comorbid conditions in migraine.
        Headache. 2007; 47: 1069-1078
        • Eriksen H.L.
        • Gunnersen K.F.
        • Sorensen J.A.
        • Munk T.
        • Nielsen T.
        • Knudsen U.B.
        Psychological aspects of endometriosis: differences between patients with or without pain on four psychological variables.
        Eur J Obstet Gynecol Reprod Biol. 2008; 139: 100-105
        • Siedentopf F.
        • Tariverdian N.
        • Rücke M.
        • Kentenich H.
        • Arck P.C.
        Immune status, psychosocial distress and reduced quality of life in infertile patients with endometriosis.
        Am J Reprod Immunol. 2008; 60: 449-461
        • Kumar A.
        • Gupta V.
        • Maurya A.
        Mental health and quality of life of chronic pelvic pain and endometriosis patients.
        J Proj Psychol Ment Health. 2010; 17: 153-157
        • Baron Y.M.
        • Dingli M.
        • Agius R.C.
        • Neville C.
        • Brincat M.
        Gastro-intestinal symptoms and dietary intolerance in women with endometriosis.
        J Endometriosis. 2011; 3: 99-104
        • Kumar V.
        • Khan M.
        • Vilos G.A.
        • Sharma V.
        Revisiting the association between endometriosis and bipolar disorder.
        J Obstet Gynaecol Can. 2011; 33: 1141-1145
        • Roth R.S.
        • Punch M.
        • Bachman J.E.
        Psychological factors in chronic pelvic pain due to endometriosis: a comparative study.
        Gynecol Obstet Invest. 2011; 72: 15-19
        • Souza C.A.
        • Oliveira L.M.
        • Scheffel C.
        • et al.
        Quality of life associated to chronic pelvic pain is independent of endometriosis diagnosis—a cross-sectional survey.
        Health Qual Life Outcomes. 2011; 9: 41
        • As-Sanie S.
        • Harris R.E.
        • Napadow V.
        • et al.
        Changes in regional gray matter volume in women with chronic pelvic pain: a voxel-based morphometry study.
        Pain. 2012; 153: 1006-1014
        • Issa B.
        • Onon T.S.
        • Agrawal A.
        • et al.
        I—Visceral hypersensitivity in endometriosis: a new target for treatment?.
        Gut. 2012; 61: 367-372
        • Hansen K.E.
        • Kesmodel U.S.
        • Baldursson E.B.
        • Schultz R.
        • Forman A.
        The influence of endometriosis-related symptoms on work life and work ability: a study of Danish endometriosis patients in employment.
        Eur J Obstet Gynecol Reprod Biol. 2013; 169: 331-339
        • Cavaggioni G.
        • Lia C.
        • Resta S.
        • et al.
        Are mood and anxiety disorders and alexithymia associated with endometriosis? A preliminary study.
        Biomed Res Int. 2014; 2014: 786830
        • Facchin F.
        • Barbara G.
        • Saita E.
        • et al.
        Impact of endometriosis on quality of life and mental health: pelvic pain makes the difference.
        J Psychosom Obstet Gynaecol. 2015; 36: 135-141
        • Friedl F.
        • Riedl D.
        • Fessler S.
        • et al.
        Impact of endometriosis on quality of life, anxiety, and depression: an Austrian perspective.
        Arch Gynecol Obstet. 2015; 292: 1393-1399
        • Fuldeore M.
        • Yang H.
        • Du E.X.
        • Soliman A.M.
        • Wu E.Q.
        • Winkel C.
        Healthcare utilization and costs in women diagnosed with endometriosis before and after diagnosis: a longitudinal analysis of claims databases.
        Fertil Steril. 2015; 103: 163-171
        • Lagana A.S.
        • Condemi I.
        • Retto G.
        • et al.
        Analysis of psychopathological comorbidity behind the common symptoms and signs of endometriosis.
        Eur J Obstet Gynecol Reprod Biol. 2015; 194: 30-33
        • Melis I.
        • Litta P.
        • Nappi L.
        • Agus M.
        • Melis G.B.
        • Angioni S.
        Sexual function in women with deep endometriosis: correlation with quality of life, intensity of pain, depression, anxiety, and body image.
        Int J Sex Health. 2015; 27: 175-185
        • Rocha M.G.
        • Gomes V.A.
        • Tanus-Santos J.E.
        • et al.
        Reduction of blood nitric oxide levels is associated with clinical improvement of the chronic pelvic pain related to endometriosis.
        Braz J Med Biol Res. 2015; 48: 363-369
        • Stratton P.
        • Khachikyan I.
        • Sinaii N.
        • Ortiz R.
        • Shah J.
        Association of chronic pelvic pain and endometriosis with signs of sensitization and myofascial pain.
        Obstet Gynecol. 2015; 125: 719-728
        • De Graaff A.A.
        • Van Lankveld J.
        • Smits L.J.
        • Van Beek J.J.
        • Dunselman G.A.J.
        Dyspareunia and depressive symptoms are associated with impaired sexual functioning in women with endometriosis, whereas sexual functioning in their male partners is not affected.
        Hum Reprod. 2016; 31: 2577-2586
        • Chen L.C.
        • Hsu J.W.
        • Huang K.L.
        • et al.
        Risk of developing major depression and anxiety disorders among women with endometriosis: a longitudinal follow-up study.
        J Affect Disord. 2016; 190: 282-285
        • Gambassi G.
        Pain and depression: the egg and the chicken story revisited.
        Arch Gerontol Geriatr. 2009; 49: 103-112
        • Steele A.
        Opioid use and depression in chronic pelvic pain.
        Obstet Gynecol Clin North Am. 2014; 41: 491-501
        • Seng J.S.
        • Clark M.K.
        • McCarthy A.M.
        • Ronis D.L.
        PTSD and physical comorbidity among women receiving Medicaid: results from service-use data.
        J Trauma Stress. 2006; 19: 45-56
        • Smorgick N.
        • Marsh C.A.
        • As-Sanie S.
        • Smith Y.R.
        • Quint E.H.
        Prevalence of pain syndromes, mood conditions, and asthma in adolescents and young women with endometriosis.
        J Pediatr Adolesc Gynecol. 2013; 26: 171-175
        • Facchin F.
        • Barbara G.
        • Dridi D.
        • et al.
        Mental health in women with endometriosis: searching for predictors of psychological distress.
        Hum Reprod. 2017; 32: 1855-1861
        • van Aken M.A.W.
        • Oosterman J.M.
        • van Rijn C.M.
        • et al.
        Pain cognition versus pain intensity in patients with endometriosis: toward personalized treatment.
        Fertil Steril. 2017; 108: 679-686
        • Carey E.T.
        • Martin C.E.
        • Siedhoff M.T.
        • Bair E.D.
        • As-Sanie S.
        Biopsychosocial correlates of persistent postsurgical pain in women with endometriosis.
        Int J Gynaecol Obstet. 2014; 124: 169-173
        • Facchin F.
        • Saita E.
        • Barbara G.
        • Dridi D.
        • Vercellini P.
        “Free butterflies will come out of these deep wounds”: a grounded theory of how endometriosis affects women's psychological health.
        J Health Psychol. 2018; 23: 538-549
        • Naushad N.
        • Dunn L.B.
        • Muñoz R.F.
        • Leykin Y.
        Depression increases subjective stigma of chronic pain.
        J Affect Disord. 2018; 229: 456-462
        • Katon W.
        • Lin E.H.
        • Kroenke K.
        The association of depression and anxiety with medical symptom burden in patients with chronic medical illness.
        Gen Hosp Psychiatry. 2007; 29: 147-155
        • Benton T.
        • Staab J.
        • Evans D.L.
        Medical co-morbidity in depressive disorders.
        Ann Clin Psychiatry. 2007; 19: 289-303
      2. American College of Obstetricians and Gynecologists (ACOG). Management of endometriosis. Practice bulletin Nr 114. 2010 (reaffirmed 2018). Available at: Accessed July 10, 2018.

      3. National Institute for Health and Care Excellence (NICE). Endometriosis: diagnosis and management. NICE guideline [NG73]. 2017. Available at: Accessed July 10, 2018.

      4. European Society of Human Reproduction and Embryology (ESHRE). Management of women with endometriosis. 2013. Available at: Accessed July 10, 2018.

        • Practice Committee of the American Society for Reproductive Medicine (ASRM)
        Endometriosis and infertility: a committee opinion.
        Fertil Steril. 2012; 98: 591-598
        • O'Connor E.A.
        • Whitlock E.P.
        • Beil T.L.
        • Gaynes B.N.
        Screening for depression in adult patients in primary care settings: a systematic evidence review.
        Ann Intern Med. 2009; 151: 793-803
        • National Collaborating Centre for Mental Health (UK)
        The identification of depression in people with a chronic physical health problem.
        in: NICE clinical guidelines, no. 91. Depression in adults with a chronic physical health problem: treatment and management. British Psychological Society, Leicester, UK2010
        • Becker C.M.
        • Gattrell W.T.
        • Gude K.
        • Singh S.S.
        Reevaluating response and failure of medical treatment of endometriosis: a systematic review.
        Fertil Steril. 2017; 108: 125-136
        • Hirsch M.
        • Duffy J.M.
        • Barker C.
        • et al.
        International Collaboration to Harmonize Outcomes and Measures for Endometriosis (iHOME). Protocol for developing, disseminating and implementing a core outcome set for endometriosis.
        BMJ Open. 2016; 6: e013998
        • Greenberg P.E.
        • Leong S.A.
        • Birnbaum H.G.
        • Robinson R.L.
        The economic burden of depression with painful symptoms.
        J Clin Psychiatry. 2003; 64: 17-23
        • Hassa H.
        • Tanir H.M.
        • Uray M.
        Symptom distribution among infertile and fertile endometriosis cases with different stages and localisations.
        Eur J Obstet Gynecol Reprod Biol. 2005; 119: 82-86
        • Pasch L.A.
        • Holley S.R.
        • Bleil M.E.
        • Shehab D.
        • Katz P.P.
        • Adler N.E.
        Addressing the needs of fertility treatment patients and their partners: are they informed of and do they receive mental health services?.
        Fertil Steril. 2016; 106: 209-215
        • Cesta C.E.
        • Viktorin A.
        • Olsson H.
        • et al.
        Depression, anxiety, and antidepressant treatment in women: association with in vitro fertilization outcome.
        Fertil Steril. 2016; 105: 1594-1602
        • Gambadauro P.
        • Iliadis S.
        • Bränn E.
        • Skalkidou A.
        Conception by means of in-vitro fertilization is not associated with maternal depressive symptoms during pregnancy and postpartum.
        Fertil Steril. 2017; 108: 325-332