Natural history of polycystic ovary syndrome: A systematic review of cardiometabolic outcomes from longitudinal cohort studies

Behboudi-Gandevani et al. (2018)26 Iran Prospective Population based

Age, 26.4 ± 8.6 years, n = 178

Age, 28.9 ± 8.6 years, n = 1524 NIH 12.9 years (1998/2001 to 2010) Dyslipidemia, central obesity, obesity, hypertension Low Boudreaux et al. (2006)27 United States Prospective Academic practice (endocrine unit)

Age, 38.0 ± 5.9 years, n = 97

Age, 40.0 ± 5.2 years, n = 95

NIH 8 years (1992/94 to 2001/02 T2DM High Brown et al. (2011)28 Netherlands Retrospective Academic practice (out-patient clinic) Age, 28.6 years, n = 254 Age, 29.9 years, n = 41 Rotterdam 7 years (1991 through 2009)

BMI, WC,

glucose, insulin,

HOMA score

High Carmina et al. (2013)29 Italy Prospective Academic practice (Endocrine Unit) Age, 21.8 ± 2 years, n = 118 Age, 21.8 ± 2 years, n = 35 (not followed up) Rotterdam 20 years (baseline 1985/1990) BMI, WC, blood glucose, insulin, total cholesterol, HDL-C, LDL-C, non-HDL-C, TG High Carmina et al. (2012)30 Italy Prospective Academic practice Age, 37 ± 1 years, n = 54 Age, 37 ± 1 years, n = 20 Rotterdam 5 years (period not specified) BMI, insulin Moderate Carmina et al. (2012)31 Italy Prospective Academic practice (Endocrine Unit) Age, 21.9 ± 2.1 years, n = 193 Age, 21.9 ± 2.1 years, n = 35 (not followed up) Rotterdam 20 years (baseline 1985/1990) BMI, WC, insulin High Celik et al. (2014)32 Turkey Prospective Academic practice Age, 24.7 ± 5.6 years, n = 84 Age, 27.4 ± 6.5 years, n = 45 Rotterdam 2.6 median years (2009−2011) T2DM, IGT, BMI, fasting glucose, OGTT-2h glucose, fasting insulin High Choi et al. (2021)33 Korea Prospective cohort Tertiary hospital Age, 23.2 ± 5.7 to 25.5 ± 6.0 years, n = 252 Age, 20–29 years, n = 15,050 Rotterdam PCOS; 2.9 years, controls not followed up T2DM High Crumbach et al. (2016)34 Croatia Retrospective Hospital records (Reproduction Unit) Age, 26.5 ± 6.4 years, n = 36 No controls Rotterdam 9 years (2007–2016) BMI, glucose, insulin, HOMA-IR, total-C, TG, HDL-C, LDL-C High De Zegher et al. (2017)35 Spain and Germany Retrospective Academic practice (endocrinology and pediatric obesity units) Age, 15–16 years, n = 467 Age, 15 years, n = 87 NIH Not specified Difference in birth weight and BMI (z-score) at PCOS diagnosis High Ehrmann et al. (1999)36 United States Prospective Academic practice (Endocrinology, gynecology,and pediatrics Clinics) Age, 25.5 ± 0.7 years, n = 25 No controls NIH 2.4–6.3 years (1990–1996) Glucose (comparison with baseline), T2DM High Forslund et al. (2021)37 Sweden Prospective cohort Academic practice Age 49.4 ± 5.0 years, n = 21 Age 49.7 ± 5.6 years, n = 55 Rotterdam 32 years BMI, WHR Moderate Gambineri et al. (2012)38 Italy Prospective Academic practice Age, 23.4 ± 6.3 years, n = 249 No controls NIH 16.9 years (1978/99  to 2009) T2DM High Greenwood et al. (2019)39 United States Prospective Academic practice (PCOS clinic) Age, 29 years, n = 163 No controls Rotterdam 5.5 years (2006–2017 to consecutive) BMI Moderate Huddleston et al. (2017)40 United States Prospective Academic practice (PCOS clinic) Age, 30.4 ± 5.6 years, n = 38 Age, 35.7 ± 5.5 years, n = 296 Rotterdam 3–4 years (2004–2014 cohort) BMI, TG, HOMA, LDL, HDL, fasting glucose, total T, 2-h glucose, AUC glucose, SBP, and DBP Low Iftikhar et al. (2012)41 United States Retrospective Population-based (practice linked) Age, 25 years, n = 309 Age, 25 years, n = 343 Rotterdam 23.7 years (1966/88 to 2005/2007) Unstable angina, myocardial infarction, Coronary artery bypass grafting, stroke, at least 1 CV event, overall deaths, and deaths due to CVD Moderate Jacewicz-Święcka and Kowalska (2020)42 Poland Prospective cohort Endocrinology and gynaecology clinics Age, 25.5 years, n = 30 No controls Rotterdam 10 years (2003/2009 to 2015/2017) BMI, WC, WHR, TG, total cholesterol, LDL-C, HDL-C, SBP, DBP, abdominal obesity, pre DM, IFG, IGT, mean insulin, mean glucose, HOMA-IR score High Jakubowicz et al. (2002)43 Venezuela Retrospective nested in RCT Hospital (Endocrinology Clinic) Age, 30.0 ± 3.2, years, n = 31 No controls NIH 4.5 years (1996−2000) Serum insulin, glucose High Javed et al. (2015)44 United States Retrospective General hospital (paediatric and adolescent medicine department) Age, 15.7 years, n = 98 Age, 15.9 years, n = 150 NIH and Rotterdam 2.3 years (PCOS), 3.4 years (controls) [1997−2012] Impaired fasting glucose Low Kazemi Jaliseh et al. (2017)45 Iran Prospective Population based Age, 26.4 ± 8.5 years, n = (pre DM, 1449, DM 1619) Age, 28.9 ± 8.6 years, n = 1524 NIH 12.9 years (1998–2010) Prediabetes mellitus and diabetes mellitus Low Leelaphiwat et al. (2019)46 Thailand Retrospective Academic practice (Endocrinology unit) Age, 27.4 ± 5.4 years, n = 114 No controls Rotterdam 2–4 years (2004–2011) T2DM High Ng et al. (2019)47 Hong Kong Prospective cohort General hospital and community (controls) Age, 30.6 ± 6.5 years, n = 199 Age, 42.6 ± 7.0 years, n = 242 Rotterdam 10.6 ± 1.3 years (2003/2007 to 2016/2017) BMI, WC, WHR, TG, total cholesterol, LDL-C, HDL-C, SBP, DBP, HOMA-IR score, HTN, fasting insulin, fasting glucose, 2-hour glucose, dyslipidaemia T2DM Low Palomba et al. (2014)48 Italy Prospective Academic practice (Obstetrics and Gynecology department)

Age, 27.8 ± 3.6 years, n = 150,

Gestational age (5.4 weeks)

Age, 27.4 ± 4.0 years, n = 150

Gestational age (5.4 weeks)

Rotterdam 27 gestational weeks (2003 to 2012) Fasting glucose, fasting insulin, HOMA, SBP, DBP, total C, HDL, LDL, TG Low Palomba et al. (2007)49 Italy Prospective nested in RCT Academic practice Age, 24.8 ± 2.7 years, n = 13 Age, 25.6 ± 2.7 years, n = 10 NIH 24 months (recruited 2003/04 to 2005/06) BMI, LDL-C, and AUC glucose to AUC insulin ratio Moderate Ramezani Tehrani et al. (2015)50 Iran Prospective Population based Age, 29.8 ± 9.2 years, n = 85 Age, 29.3 ± 9.0 years, n = 552 NIH 9.4 years (1999/2001 to 2009/2011) BMI, WC,TC, LDL-C HDL-C, TG, SBP, DBP FPG, Insulin, HOMA-IR, HOMA-%β, pre DM, DM, pre HTN, HTN Low Schmidt et al. (2011)51 Sweden Prospective Academic practice Age, 49.4 ± 4.9 years, n = 25 Age, 49.7 ± 5.6 years, n = 68 Rotterdam 21 years (1987–2008) BMI,WHR Moderate Schmidt et al. (2011)52 Sweden Prospective Academic practice Age, 49.4 ± 4.9 years, n = 25 Age, 49.7 ± 5.6 years, n = 68 Rotterdam 21 years (1987–2008) TG, cholesterol, HDL, LDL, serum insulin, SBP, DBP, MI hospitalizations and age,stroke hospitalizations and age, all CVD (MI and stroke) Moderate Tay et al. (2020)53 Australia prospective cohort Community 1–22 years, n = 37 1–22 years, n = 190 Rotterdam 22 years (at ages 1, 2, 3, 5, 8,  10, 14, 16, 20, 22 years) Change in BMI Low Udesen et al. (2019)54 Denmark Prospective Fertility clinic Age, 29.1 ± 4.1 years, n = 40 Age, 30.0 ± 5.2 years, n = 8 Rotterdam 5.8 ± 0.8 years (recruited 2010/2012) BMI, WHR, SBP, DBP, fasting s-glucose, s-insulin, HOMA-IR, total-C, LDL-C, HDL-C and TG High Velija-Asimi et al. (2016)55 Bosnia and Herzegovina Prospective Academic practice Age, 28.6 years, n = 148 No controls Rotterdam 3 ± 1.6 years (2010–2015) Pre-T2DM and T2DM High Wang et al. (2011)56 United States Retrospective Population/multisite Age, 27.3 ± 3.6 years, n = 53 Age, 26.8 ± 3.7 years, n = 1074 NIH 18 years (recruited 1985/86) Diabetes, dyslipidemia and hypertension Moderate

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