Obesity and the Risk of Infertility, Gestational Diabetes, and Type 2 Diabetes in Polycystic Ovary Syndrome

Stephanie Pirotta; Anju Joham; Jessica A. Grieger; Chau Tien Tay; Mahnaz Bahri-Khomami; Marla Lujan; Siew S. Lim; Lisa J. Moran

doi:10.1055/s-0041-1726866

Seminars in Reproductive Medicine, Table of Contents

Semin Reprod Med 2020; 38(06): 342-351
DOI: 10.1055/s-0041-1726866

Review Article

Obesity and the Risk of Infertility, Gestational Diabetes, and Type 2 Diabetes in Polycystic Ovary Syndrome

Stephanie Pirotta

¹Health and Social Care Unit, SPHPM, Monash University, Victoria, Australia

,

Anju Joham

²Monash Centre for Health Research and Implementation, Monash University, Victoria, Australia

³Department of Diabetes and Vascular Medicine, Monash Health, Victoria, Australia

,

Jessica A. Grieger

⁴Adelaide Medical School, University of Adelaide, South Australia, Australia

⁵Robinson Research Institute, University of Adelaide, Adelaide, Australia

,

Chau Tien Tay

²Monash Centre for Health Research and Implementation, Monash University, Victoria, Australia

,

Mahnaz Bahri-Khomami

²Monash Centre for Health Research and Implementation, Monash University, Victoria, Australia

,

Marla Lujan

⁶Division of Nutritional Sciences, Cornell University, New York

,

Siew S. Lim

²Monash Centre for Health Research and Implementation, Monash University, Victoria, Australia

,

Lisa J. Moran

²Monash Centre for Health Research and Implementation, Monash University, Victoria, Australia

› Author Affiliations

Abstract

This review describes the relationship between obesity and the most common reproductive (infertility) and metabolic (gestational diabetes mellitus [GDM] and type 2 diabetes mellitus [T2DM]) consequences in polycystic ovary syndrome (PCOS). It also describes the vital role of lifestyle management for PCOS. PCOS is a heterogeneous endocrine disorder common in reproductive-age women. Consensus on the exact etiological mechanisms of PCOS is unreached. Overweight or obesity is present in at least 60% of the PCOS population, but the condition occurs irrespective of BMI, with excess BMI increasing both the prevalence and severity of clinical features. Use of lifestyle therapies (nutrition, physical activity, and/or behavioral) for the prevention and management of excess weight gain, infertility, GDM, and T2DM is a vital component of best-practice PCOS care. Lifestyle management is recommended for all women with PCOS as the first-line treatment with or without medications. Due to a lack of high-quality trials demonstrating the efficacy of specific lifestyle approaches, PCOS lifestyle recommendations are as those for the general population. This review summarizes current knowledge relating to obesity and its impact on fertility, GDM, and T2DM. It also summarizes the lifestyle recommendations to best manage these conditions in women with PCOS and obesity.

Keywords

polycystic ovary syndrome - lifestyle management - fertility

Full Text

References

References
1 Rosenfield RL, Ehrmann DA. The pathogenesis of polycystic ovary syndrome (PCOS): the hypothesis of PCOS as functional ovarian hyperandrogenism revisited. Endocr Rev 2016; 37 (05) 467-520
2 Wolf WM, Wattick RA, Kinkade ON, Olfert MD. Geographical prevalence of polycystic ovary syndrome as determined by region and race/ethnicity. Int J Environ Res Public Health 2018; 15 (11) 2589
3 Bozdag G, Mumusoglu S, Zengin D, Karabulut E, Yildiz BO. The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod 2016; 31 (12) 2841-2855
4 Boomsma CM, Eijkemans MJ, Hughes EG, Visser GH, Fauser BC, Macklon NS. A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome. Hum Reprod Update 2006; 12 (06) 673-683
5 Apridonidze T, Essah PA, Iuorno MJ, Nestler JE. Prevalence and characteristics of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2005; 90 (04) 1929-1935
6 Thannickal A, Brutocao C, Alsawas M. et al. Eating, sleeping and sexual function disorders in women with polycystic ovary syndrome (PCOS): a systematic review and meta-analysis. Clin Endocrinol (Oxf) 2020; 92 (04) 338-349
7 Cooney LG, Lee I, Sammel MD, Dokras A. High prevalence of moderate and severe depressive and anxiety symptoms in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod 2017; 32 (05) 1075-1091
8 Pirotta S, Barillaro M, Brennan L. et al. Disordered eating behaviours and eating disorders in women in Australia with and without polycystic ovary syndrome: a cross-sectional study. J Clin Med 2019; 8 (10) E1682
9 Lim SS, Davies MJ, Norman RJ, Moran LJ. Overweight, obesity and central obesity in women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update 2012; 18 (06) 618-637
10 Bahri Khomami M, Joham AE, Boyle JA. et al. The role of maternal obesity in infant outcomes in polycystic ovary syndrome—a systematic review, meta-analysis, and meta-regression. Obes Rev 2019; 20 (06) 842-858
11 World Health Organization. Waist Circumference and Waist-Hip Ratio: Report of a WHO Expert Consultation. December 8–11, 2008. Geneva, Switzerland: WHO; 2008
12 Ramlau-Hansen CH, Thulstrup AM, Nohr EA, Bonde JP, Sørensen TI, Olsen J. Subfecundity in overweight and obese couples. Hum Reprod 2007; 22 (06) 1634-1637
13 Silvestris E, de Pergola G, Rosania R, Loverro G. Obesity as disruptor of the female fertility. Reprod Biol Endocrinol 2018; 16 (01) 22-22
14 Corbould A, Dunaif A. The adipose cell lineage is not intrinsically insulin resistant in polycystic ovary syndrome. Metabolism 2007; 56 (05) 716-722
15 Sirotkin AV, Fabian D, Babeľová Kubandová J, Vlčková R, Alwasel S, Harrath AH. Body fat affects mouse reproduction, ovarian hormone release, and response to follicular stimulating hormone. Reprod Biol 2018; 18 (01) 5-11
16 Malini NA, Roy George K. Evaluation of different ranges of LH:FSH ratios in polycystic ovarian syndrome (PCOS) - clinical based case control study. Gen Comp Endocrinol 2018; 260: 51-57
17 Bertoldo MJ, Caldwell ASL, Riepsamen AH. et al. A hyperandrogenic environment causes intrinsic defects that are detrimental to follicular dynamics in a PCOS mouse model. Endocrinology 2019; 160 (03) 699-715
18 Zhang Y, Sun X, Sun X. et al. Molecular characterization of insulin resistance and glycolytic metabolism in the rat uterus. Sci Rep 2016; 6 (01) 30679
19 Pierre A, Taieb J, Giton F. et al. Dysregulation of the anti-Müllerian hormone system by steroids in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2017; 102 (11) 3970-3978
20 Sim KA, Partridge SR, Sainsbury A. Does weight loss in overweight or obese women improve fertility treatment outcomes? A systematic review. Obes Rev 2014; 15 (10) 839-850
21 Conway G, Dewailly D, Diamanti-Kandarakis E. et al; ESE PCOS Special Interest Group. The polycystic ovary syndrome: a position statement from the European Society of Endocrinology. Eur J Endocrinol 2014; 171 (04) 1-29
22 Lizneva D, Suturina L, Walker W, Brakta S, Gavrilova-Jordan L, Azziz R. Criteria, prevalence, and phenotypes of polycystic ovary syndrome. Fertil Steril 2016; 106 (01) 6-15
23 Azziz R, Carmina E, Dewailly D. et al; Task Force on the Phenotype of the Polycystic Ovary Syndrome of The Androgen Excess and PCOS Society. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril 2009; 91 (02) 456-488
24 Escobar-Morreale HF. Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol 2018; 14 (05) 270-284
25 Yilmaz M, Isaoglu U, Delibas IB, Kadanali S. Anthropometric, clinical and laboratory comparison of four phenotypes of polycystic ovary syndrome based on Rotterdam criteria. J Obstet Gynaecol Res 2011; 37 (08) 1020-1026
26 Ezeh U, Yildiz BO, Azziz R. Referral bias in defining the phenotype and prevalence of obesity in polycystic ovary syndrome. J Clin Endocrinol Metab 2013; 98 (06) E1088-E1096
27 Lizneva D, Kirubakaran R, Mykhalchenko K. et al. Phenotypes and body mass in women with polycystic ovary syndrome identified in referral versus unselected populations: systematic review and meta-analysis. Fertil Steril 2016; 106 (06) 1510-1520 , e1512
28 Luque-Ramírez M, Alpañés M, Sanchón R, Fernández-Durán E, Ortiz-Flores AE, Escobar-Morreale HF. Referral bias in female functional hyperandrogenism and polycystic ovary syndrome. Eur J Endocrinol 2015; 173 (05) 603-610
29 Teede HJ, Joham AE, Paul E. et al. Longitudinal weight gain in women identified with polycystic ovary syndrome: results of an observational study in young women. Obesity (Silver Spring) 2013; 21 (08) 1526-1532
30 Laitinen J, Taponen S, Martikainen H. et al. Body size from birth to adulthood as a predictor of self-reported polycystic ovary syndrome symptoms. Int J Obes Relat Metab Disord 2003; 27 (06) 710-715
31 Kakoly NS, Khomami MB, Joham AE. et al. Ethnicity, obesity and the prevalence of impaired glucose tolerance and type 2 diabetes in PCOS: a systematic review and meta-regression. Hum Reprod Update 2018; 24 (04) 455-467
32 He Y, Tian J, Blizzard L. et al. Associations of childhood adiposity with menstrual irregularity and polycystic ovary syndrome in adulthood: the Childhood Determinants of Adult Health Study and the Bogalusa Heart Study. Hum Reprod 2020; 35 (05) 1185-1198
33 Moran C, Arriaga M, Rodriguez G, Moran S. Obesity differentially affects phenotypes of polycystic ovary syndrome. Int J Endocrinol 2012; 2012: 317241-317241
34 Ewens KG, Jones MR, Ankener W. et al. FTO and MC4R gene variants are associated with obesity in polycystic ovary syndrome. PLoS One 2011; 6 (01) e16390
35 Liu AL, Xie HJ, Xie HY. et al. Association between fat mass and obesity associated (FTO) gene rs9939609 A/T polymorphism and polycystic ovary syndrome: a systematic review and meta-analysis. BMC Med Genet 2017; 18 (01) 89
36 Barr S, Hart K, Reeves S, Sharp K, Jeanes YM. Habitual dietary intake, eating pattern and physical activity of women with polycystic ovary syndrome. Eur J Clin Nutr 2011; 65 (10) 1126-1132
37 Moran LJ, Ranasinha S, Zoungas S, McNaughton SA, Brown WJ, Teede HJ. The contribution of diet, physical activity and sedentary behaviour to body mass index in women with and without polycystic ovary syndrome. Hum Reprod 2013; 28 (08) 2276-2283
38 Jeanes YM, Reeves S, Gibson EL, Piggott C, May VA, Hart KH. Binge eating behaviours and food cravings in women with polycystic ovary syndrome. Appetite 2017; 109: 24-32
39 Larsson I, Hulthén L, Landén M, Pålsson E, Janson P, Stener-Victorin E. Dietary intake, resting energy expenditure, and eating behavior in women with and without polycystic ovary syndrome. Clin Nutr 2016; 35 (01) 213-218
40 Dokras A, Stener-Victorin E, Yildiz BO. et al. Androgen excess- Polycystic Ovary Syndrome Society: position statement on depression, anxiety, quality of life, and eating disorders in polycystic ovary syndrome. Fertil Steril 2018; 109 (05) 888-899
41 Lim SS, Norman RJ, Davies MJ, Moran LJ. The effect of obesity on polycystic ovary syndrome: a systematic review and meta-analysis. Obes Rev 2013; 14 (02) 95-109
42 Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes 1989; 38 (09) 1165-1174
43 Stepto NK, Cassar S, Joham AE. et al. Women with polycystic ovary syndrome have intrinsic insulin resistance on euglycaemic-hyperinsulaemic clamp. Hum Reprod 2013; 28 (03) 777-784
44 Milutinović DV, Nikolić M, Veličković N. et al. Enhanced inflammation without impairment of insulin signaling in the visceral adipose tissue of 5α-dihydrotestosterone-induced animal model of polycystic ovary syndrome. Exp Clin Endocrinol Diabetes 2017; 125 (08) 522-529
45 Torre-Villalvazo I, Bunt AE, Alemán G. et al. Adiponectin synthesis and secretion by subcutaneous adipose tissue is impaired during obesity by endoplasmic reticulum stress. J Cell Biochem 2018; 119 (07) 5970-5984
46 Chow LS, Mashek DG, Wang Q, Shepherd SO, Goodpaster BH, Dubé JJ. Effect of acute physiological free fatty acid elevation in the context of hyperinsulinemia on fiber type-specific IMCL accumulation. J Appl Physiol (1985) 2017; 123 (01) 71-78
47 Park E, Wong V, Guan X, Oprescu AI, Giacca A. Salicylate prevents hepatic insulin resistance caused by short-term elevation of free fatty acids in vivo. J Endocrinol 2007; 195 (02) 323-331
48 Baskind NE, Balen AH. Hypothalamic-pituitary, ovarian and adrenal contributions to polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol 2016; 37: 80-97
49 Wu S, Divall S, Nwaopara A. et al. Obesity-induced infertility and hyperandrogenism are corrected by deletion of the insulin receptor in the ovarian theca cell. Diabetes 2014; 63 (04) 1270-1282
50 Moret M, Stettler R, Rodieux F. et al. Insulin modulation of luteinizing hormone secretion in normal female volunteers and lean polycystic ovary syndrome patients. Neuroendocrinology 2009; 89 (02) 131-139
51 Nestler JE, Powers LP, Matt DW. et al. A direct effect of hyperinsulinemia on serum sex hormone-binding globulin levels in obese women with the polycystic ovary syndrome. J Clin Endocrinol Metab 1991; 72 (01) 83-89
52 Tosi F, Negri C, Brun E. et al. Insulin enhances ACTH-stimulated androgen and glucocorticoid metabolism in hyperandrogenic women. Eur J Endocrinol 2011; 164 (02) 197-203
53 Cassar S, Misso ML, Hopkins WG, Shaw CS, Teede HJ, Stepto NK. Insulin resistance in polycystic ovary syndrome: a systematic review and meta-analysis of euglycaemic-hyperinsulinaemic clamp studies. Hum Reprod 2016; 31 (11) 2619-2631
54 Evans DJ, Barth JH, Burke CW. Body fat topography in women with androgen excess. Int J Obes 1988; 12 (02) 157-162
55 Corbould AM, Bawden MJ, Lavranos TC, Rodgers RJ, Judd SJ. The effect of obesity on the ratio of type 3 17beta-hydroxysteroid dehydrogenase mRNA to cytochrome P450 aromatase mRNA in subcutaneous abdominal and intra-abdominal adipose tissue of women. Int J Obes Relat Metab Disord 2002; 26 (02) 165-175
56 Jena D, Choudhury AK, Mangaraj S, Singh M, Mohanty BK, Baliarsinha AK. Study of visceral and subcutaneous abdominal fat thickness and its correlation with cardiometabolic risk factors and hormonal parameters in polycystic ovary syndrome. Indian J Endocrinol Metab 2018; 22 (03) 321-327
57 Horejsi R, Möller R, Rackl S. et al. Android subcutaneous adipose tissue topography in lean and obese women suffering from PCOS: comparison with type 2 diabetic women. Am J Phys Anthropol 2004; 124 (03) 275-281
58 Kirchengast S, Huber J. Body composition characteristics and body fat distribution in lean women with polycystic ovary syndrome. Hum Reprod 2001; 16 (06) 1255-1260
59 Carey DG, Jenkins AB, Campbell LV, Freund J, Chisholm DJ. Abdominal fat and insulin resistance in normal and overweight women: direct measurements reveal a strong relationship in subjects at both low and high risk of NIDDM. Diabetes 1996; 45 (05) 633-638
60 Tay CT, Teede HJ, Hill B, Loxton D, Joham AE. Increased prevalence of eating disorders, low self-esteem, and psychological distress in women with polycystic ovary syndrome: a community-based cohort study. Fertil Steril 2019; 112 (02) 353-361
61 Tay CT, Teede HJ, Loxton D, Kulkarni J, Joham AE. Psychiatric comorbidities and adverse childhood experiences in women with self-reported polycystic ovary syndrome: an Australian population-based study. Psychoneuroendocrinology 2020; 116: 104678
62 Teede HJ, Misso ML, Costello MF. et al; International PCOS Network. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Hum Reprod 2018; 33 (09) 1602-1618
63 Monash University. International Evidence Based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. Melbourne: Monash University; 2018
64 Moran LJ, Pasquali R, Teede HJ, Hoeger KM, Norman RJ. Treatment of obesity in polycystic ovary syndrome: a position statement of the Androgen Excess and Polycystic Ovary Syndrome Society. Fertil Steril 2009; 92 (06) 1966-1982
65 Practice Committee of the American Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss: a committee opinion. Fertil Steril 2013; 99 (01) 63
66 World Health Organization. Multiple Definitions of Infertility. Geneva: World Health Organization; 2020
67 Mascarenhas MN, Flaxman SR, Boerma T, Vanderpoel S, Stevens GA. National, regional, and global trends in infertility prevalence since 1990: a systematic analysis of 277 health surveys. PLoS Med 2012; 9 (12) e1001356
68 Wild S, Pierpoint T, Jacobs H, McKeigue P. Long-term consequences of polycystic ovary syndrome: results of a 31 year follow-up study. Hum Fertil (Camb) 2000; 3 (02) 101-105
69 Al-Jefout M, Alnawaiseh N, Al-Qtaitat A. Insulin resistance and obesity among infertile women with different polycystic ovary syndrome phenotypes. Sci Rep 2017; 7 (01) 5339-5339
70 Reyes-Muñoz E, Ortega-González C, Martínez-Cruz N. et al. Association of obesity and overweight with the prevalence of insulin resistance, pre-diabetes and clinical-biochemical characteristics among infertile Mexican women with polycystic ovary syndrome: a cross-sectional study. BMJ Open 2016; 6 (07) e012107
71 van der Steeg JW, Steures P, Eijkemans MJ. et al. Obesity affects spontaneous pregnancy chances in subfertile, ovulatory women. Hum Reprod 2008; 23 (02) 324-328
72 Wise LA, Rothman KJ, Mikkelsen EM, Sørensen HT, Riis A, Hatch EE. An internet-based prospective study of body size and time-to-pregnancy. Hum Reprod 2010; 25 (01) 253-264
73 Joham AE, Teede HJ, Ranasinha S, Zoungas S, Boyle J. Prevalence of infertility and use of fertility treatment in women with polycystic ovary syndrome: data from a large community-based cohort study. J Womens Health (Larchmt) 2015; 24 (04) 299-307
74 Dunaif A, Graf M. Insulin administration alters gonadal steroid metabolism independent of changes in gonadotropin secretion in insulin-resistant women with the polycystic ovary syndrome. J Clin Invest 1989; 83 (01) 23-29
75 Burghen GA, Givens JR, Kitabchi AE. Correlation of hyperandrogenism with hyperinsulinism in polycystic ovarian disease. J Clin Endocrinol Metab 1980; 50 (01) 113-116
76 Steingold KA, Lobo RA, Judd HL, Lu JK, Chang RJ. The effect of bromocriptine on gonadotropin and steroid secretion in polycystic ovarian disease. J Clin Endocrinol Metab 1986; 62 (05) 1048-1051
77 Willis D, Mason H, Gilling-Smith C, Franks S. Modulation by insulin of follicle-stimulating hormone and luteinizing hormone actions in human granulosa cells of normal and polycystic ovaries. J Clin Endocrinol Metab 1996; 81 (01) 302-309
78 Willis DS, Watson H, Mason HD, Galea R, Brincat M, Franks S. Premature response to luteinizing hormone of granulosa cells from anovulatory women with polycystic ovary syndrome: relevance to mechanism of anovulation. J Clin Endocrinol Metab 1998; 83 (11) 3984-3991
79 Franks S, Mason H, Willis D. Follicular dynamics in the polycystic ovary syndrome. Mol Cell Endocrinol 2000; 163 (1-2): 49-52
80 Owens LA, Kristensen SG, Lerner A. et al. Gene expression in granulosa cells from small antral follicles from women with or without polycystic ovaries. J Clin Endocrinol Metab 2019; 104 (12) 6182-6192
81 Kumar P, Sait SF. Luteinizing hormone and its dilemma in ovulation induction. J Hum Reprod Sci 2011; 4 (01) 2-7
82 Bahri Khomami M, Joham AE, Boyle JA. et al. Increased maternal pregnancy complications in polycystic ovary syndrome appear to be independent of obesity—a systematic review, meta-analysis, and meta-regression. Obes Rev 2019; 20 (05) 659-674
83 Plows JF, Stanley JL, Baker PN, Reynolds CM, Vickers MH. The pathophysiology of gestational diabetes mellitus. Int J Mol Sci 2018; 19 (11) 3342
84 Popova PV, Klyushina AA, Vasilyeva LB. et al. Effect of gene-lifestyle interaction on gestational diabetes risk. Oncotarget 2017; 8 (67) 112024-112035
85 Li F, Hu Y, Zeng J. et al. Analysis of risk factors related to gestational diabetes mellitus. Taiwan J Obstet Gynecol 2020; 59 (05) 718-722
86 Mustaniemi S, Vääräsmäki M, Eriksson JG. et al. Polycystic ovary syndrome and risk factors for gestational diabetes. Endocr Connect 2018; 7 (07) 859-869
87 West S, Ollila M-M, Franks S. et al. Overweight, obesity and hyperandrogenemia are associated with gestational diabetes mellitus: a follow-up cohort study. Acta Obstet Gynecol Scand 2020; 99 (10) 1311-1319
88 Goldstein RF, Abell SK, Ranasinha S. et al. Association of gestational weight gain with maternal and infant outcomes: a systematic review and meta-analysis. JAMA 2017; 317 (21) 2207-2225
89 Barnes RA, Wong T, Ross GP. et al. Excessive weight gain before and during gestational diabetes mellitus management: What is the impact?. Diabetes Care 2020; 43 (01) 74-81
90 Kent J, Dodson WC, Kunselman A. et al; Reproductive Medicine Network. Gestational weight gain in women with polycystic ovary syndrome: a controlled study. J Clin Endocrinol Metab 2018; 103 (11) 4315-4323
91 Palomba S, Falbo A, Russo T, Tolino A, Orio F, Zullo F. Pregnancy in women with polycystic ovary syndrome: the effect of different phenotypes and features on obstetric and neonatal outcomes. Fertil Steril 2010; 94 (05) 1805-1811
92 Durie DE, Thornburg LL, Glantz JC. Effect of second-trimester and third-trimester rate of gestational weight gain on maternal and neonatal outcomes. Obstet Gynecol 2011; 118 (03) 569-575
93 Siega-Riz AM, Viswanathan M, Moos MK. et al. A systematic review of outcomes of maternal weight gain according to the Institute of Medicine recommendations: birthweight, fetal growth, and postpartum weight retention. Am J Obstet Gynecol 2009; 201 (04) 339.e1-339.e14
94 Zheng W, Huang W, Zhang L. et al. Early pregnancy metabolic factors associated with gestational diabetes mellitus in normal-weight women with polycystic ovary syndrome: a two-phase cohort study. Diabetol Metab Syndr 2019; 11 (01) 71
95 Gilmore LA, Klempel-Donchenko M, Redman LM. Pregnancy as a window to future health: excessive gestational weight gain and obesity. Semin Perinatol 2015; 39 (04) 296-303
96 Oken E, Kleinman KP, Belfort MB, Hammitt JK, Gillman MW. Associations of gestational weight gain with short- and longer-term maternal and child health outcomes. Am J Epidemiol 2009; 170 (02) 173-180
97 Lo JC, Feigenbaum SL, Escobar GJ, Yang J, Crites YM, Ferrara A. Increased prevalence of gestational diabetes mellitus among women with diagnosed polycystic ovary syndrome: a population-based study. Diabetes Care 2006; 29 (08) 1915-1917
98 Hedderson MM, Darbinian JA, Ferrara A. Disparities in the risk of gestational diabetes by race-ethnicity and country of birth. Paediatr Perinat Epidemiol 2010; 24 (05) 441-448
99 Jaffe A, Giveon S, Rubin C, Novikov I, Ziv A, Kalter-Leibovici O. Gestational diabetes risk in a multi-ethnic population. Acta Diabetol 2020; 57 (03) 263-269
100 Read S, Berger H, Feig D. et al. 1362-P: Influence of ethnicity on the association between body mass index and prevalence of gestational diabetes. Diabetes 2020; 69 (Suppl. 01) 1362-P
101 Lao TT, Ho L-F, Chan BCP, Leung W-C. Maternal age and prevalence of gestational diabetes mellitus. Diabetes Care 2006; 29 (04) 948-949
102 Ehrmann DA, Barnes RB, Rosenfield RL, Cavaghan MK, Imperial J. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care 1999; 22 (01) 141-146
103 Legro RS, Kunselman AR, Dodson WC, Dunaif A. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab 1999; 84 (01) 165-169
104 Joham AE, Ranasinha S, Zoungas S, Moran L, Teede HJ. Gestational diabetes and type 2 diabetes in reproductive-aged women with polycystic ovary syndrome. J Clin Endocrinol Metab 2014; 99 (03) E447-E452
105 Kakoly NS, Earnest A, Teede HJ, Moran LJ, Joham AE. The impact of obesity on the incidence of type 2 diabetes among women with polycystic ovary syndrome. Diabetes Care 2019; 42 (04) 560-567
106 Shorakae S, Teede H, de Courten B, Lambert G, Boyle J, Moran LJ. The emerging role of chronic low-grade inflammation in the pathophysiology of polycystic ovary syndrome. Semin Reprod Med 2015; 33 (04) 257-269
107 González F, Sia CL, Bearson DM, Blair HE. Hyperandrogenism induces a proinflammatory TNFα response to glucose ingestion in a receptor-dependent fashion. J Clin Endocrinol Metab 2014; 99 (05) E848-E854
108 Glintborg D, Andersen M. An update on the pathogenesis, inflammation, and metabolism in hirsutism and polycystic ovary syndrome. Gynecol Endocrinol 2010; 26 (04) 281-296
109 Cerf ME. Developmental programming and glucolipotoxicity: insights on beta cell inflammation and diabetes. Metabolites 2020; 10 (11) 444
110 Salley KE, Wickham EP, Cheang KI, Essah PA, Karjane NW, Nestler JE. Glucose intolerance in polycystic ovary syndrome—a position statement of the Androgen Excess Society. J Clin Endocrinol Metab 2007; 92 (12) 4546-4556
111 Moran LJ, Ko H, Misso M. et al. Dietary composition in the treatment of polycystic ovary syndrome: a systematic review to inform evidence-based guidelines. J Acad Nutr Diet 2013; 113 (04) 520-545
112 Kite C, Lahart IM, Afzal I. et al. Exercise, or exercise and diet for the management of polycystic ovary syndrome: a systematic review and meta-analysis. Syst Rev 2019; 8 (01) 51
113 Thomson RL, Buckley JD, Brinkworth GD. Exercise for the treatment and management of overweight women with polycystic ovary syndrome: a review of the literature. Obes Rev 2011; 12 (05) e202-e210
114 Haqq L, McFarlane J, Dieberg G, Smart N. Effect of lifestyle intervention on the reproductive endocrine profile in women with polycystic ovarian syndrome: a systematic review and meta-analysis. Endocr Connect 2014; 3 (01) 36-46
115 Kataoka J, Tassone EC, Misso M. et al. Weight management interventions in women with and without PCOS: a systematic review. Nutrients 2017; 9 (09) 996
116 Kazemi M, McBreairty LE, Zello GA. et al. A pulse-based diet and the therapeutic lifestyle changes diet in combination with health counseling and exercise improve health-related quality of life in women with polycystic ovary syndrome: secondary analysis of a randomized controlled trial. J Psychosom Obstet Gynaecol 2020; 41 (02) 144-153
117 Lim SS, Hutchison SK, Van Ryswyk E, Norman RJ, Teede HJ, Moran LJ. Lifestyle changes in women with polycystic ovary syndrome. Cochrane Database Syst Rev 2019, Issue 3. Art. No.: CD007506. DOI: 10.1002/14651858.CD007506.pub4. Accessed 16 March 2021
118 Lan L, Harrison CL, Misso M. et al. Systematic review and meta-analysis of the impact of preconception lifestyle interventions on fertility, obstetric, fetal, anthropometric and metabolic outcomes in men and women. Hum Reprod 2017; 32 (09) 1925-1940
119 Legro RS. Effects of obesity treatment on female reproduction: results do not match expectations. Fertil Steril 2017; 107 (04) 860-867
120 Knowler WC, Barrett-Connor E, Fowler SE. et al; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346 (06) 393-403
121 Tuomilehto J, Lindström J, Eriksson JG. et al; Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001; 344 (18) 1343-1350
122 Goveia P, Cañon-Montañez W, Santos DP. et al. Lifestyle intervention for the prevention of diabetes in women with previous gestational diabetes mellitus: a systematic review and meta-analysis. Front Endocrinol (Lausanne) 2018; 9: 583
123 Thangaratinam S, Rogozińska E, Jolly K. et al. Effects of interventions in pregnancy on maternal weight and obstetric outcomes: meta-analysis of randomised evidence. BMJ 2012; 344: e2088
124 Martis R, Brown J, McAra-Couper J, Crowther CA. Enablers and barriers for women with gestational diabetes mellitus to achieve optimal glycaemic control - a qualitative study using the theoretical domains framework. BMC Pregnancy Childbirth 2018; 18 (01) 91
125 Nicklas JM, Zera CA, Seely EW, Abdul-Rahim ZS, Rudloff ND, Levkoff SE. Identifying postpartum intervention approaches to prevent type 2 diabetes in women with a history of gestational diabetes. BMC Pregnancy Childbirth 2011; 11 (01) 23
126 National Health and Medical Research Council. Clinical Practice Guidelines for the Management of Overweight and Obesity in Adults, Adolescents and Children in Australia. Melbourne: National Health and Medical Research Council; 2013
127 The National Institute for Health and Care Excellence (NICE). NICE Guidance: Fertility, Pregnancy and Childbirth. London: NICE; 2017
128 The Fertility Society of Australia. The Role of Exercise in Improving Fertility, Quality of Life and Emotional Well-Being. Canberra: Australian Government Department of Health and Ageing; 2015