Introduction

The prevalence of obesity is increasing at alarming rates in Australia. Obesity is associated with increased risk of metabolic complications such as hypertension, dyslipidaemia and insulin resistance (IR).

IR is often inextricably linked with ovarian function, leading to clinical reproductive manifestations such as subfertility and polycystic ovary syndrome (PCOS) with these presentations preceding metabolic
complications of IR.

Reproductive and metabolic health implications

Lifestyle-related metabolic diseases are underpinned by inadequate physical activity and excess dietary intake, and often form a continuum of health consequences across the lifespan.

Women who are obese, especially those with reproductive complications including PCOS, have been identified as specific highrisk subgroups for progression to pre-diabetes, type 2 diabetes mellitus and potentially cardiovascular disease (CVD).¹

Risk of lifestyle-related disease is further elevated among high-risk ethnic groups, including Indigenous, Asian and Pacific Islander women. Life stages are also relevant, with increased weight gain occurring after puberty, in pregnancy and at menopause.

Young Australian women are currently gaining the most weight²and efforts targeting prevention of weight gain are critical to limit reproductive and metabolic impacts and optimise health.

Obesity may affect women throughout their reproductive years, beginning in adolescence, with earlier menarche in obese girls.³ It contributes to menstrual irregularities and oligo/anovulation, lower conception rates, higher miscarriage rates, reduced response to assisted reproductive technologies and higher rates of pregnancy complications.^4-5

Obese women have a threefold risk of infertility compared with lean women,⁶ both via direct effects on ovarian function and through increased risk of PCOS. Once pregnant, obese women have high-risk pregnancies with greater complications, including gestational diabetes mellitus (GDM).

GDM is closely related to obesity and IR. Its prevalence has increased dramatically in parallel with rising obesity rates,⁷ with a 45% increased incidence in Australian women between 1995 and 2005.⁸

Polycystic ovary syndrome

Obesity impairs female reproduction, both independently and by exacerbating the common condition of PCOS,⁹ which affects 12 to18 percent of reproductive aged women.¹⁰ Diagnosis is based on oligo- or amenorrhoea, clinical or biochemical hyperandrogenism and the appearance of polycystic ovaries on ultrasound.¹¹

Screening in unselected obese women showed 28 percent had PCOS, compared to 5 per cent of lean women.¹² Recent data from the Australian Longitudinal Women's Health Study has shown greater weight gain in PCOS women compared with non-PCOS women and shows that excess weight is the key longitudinal predictor of PCOS risk.

The clinical expression of PCOS is largely dependent on weight¹³ and therefore obese women express greater manifestations of PCOS, including hyperandrogenism, IR and subfertility. IR is recognised to be a key pathophysiological feature of PCOS and a significant contributor to its reproductive and metabolic complications.¹⁴

Link between metabolic and reproductive disorders

In obese states, in particular abdominal obesity,¹⁵ women have impaired reproduction even in the absence of PCOS. This may be due to IR with its compensatory hyperinsulinaemia stimulating ovarian androgen production, and lower circulating levels of sex hormone binding globulin leading to higher levels of bioavailable testosterone.

Women with PCOS may have abnormal levels and patterns of gonadotrophin pulsatility, with excessive luteinising hormone (LH) secretion, but normal levels of follicle stimulating hormone (FSH).

Impaired ovarian follicle development may occur due to hyperandrogenaemia and/or excess stimulation by insulin¹⁶ or LH11 leading to arrested follicle development and anovulation.

Prevention and treatment

In lifestyle-related conditions, lifestyle intervention and weight loss are first-line treatments,^17-18 with efficacy in improving metabolic abnormalities, ovulation and fertility and reducing long-term diabetes and cardiovascular complications.¹³

Clinicians must undertake focused measures to recognise early weight gain and optimise prevention of further weight gain in young women.

We also have the opportunity to recognise and treat women with early reproductive manifestations of obesity and IR and to intervene to prevent high-risk women with PCOS and GDM from progressing to diabetes and CVD later in life. Also, there is a vital public health need to improve pre-conception health to improve fertility and healthy pregnancy outcomes.

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References

1. Rachon D, Teede H 2010 Ovarian function and obesity--interrelationship, impact on women's reproductive lifespan and treatment options. Mol Cell Endocrinol 316:172-179

2. Lombard C, Deeks A, Jolley D, Ball K, Teede H 2010 A low intensity, community based lifestyle programme to prevent weight gain in women with young children: cluster randomised controlled trial. BMJ 341:c3215

3. Pelusi C, Pasquali R 2003 Polycystic ovary syndrome in adolescents: pathophysiology and treatment implications. Treat Endocrinol 2:215-230

4. Brewer CJ, Balen AH 2010 The adverse effects of obesity on conception and implantation. Reproduction 140:347-364

5. Pasquali R, Patton L, Gambineri A 2007 Obesity and infertility. Curr Opin Endocrinol Diabetes Obes 14:482-487

6. Rich-Edwards JW, Goldman MB, Willett WC, Hunter DJ, Stampfer MJ, Colditz GA, Manson JE 1994 Adolescent body mass index and infertility caused by ovulatory disorder. Am J Obstet Gynecol 171:171-177

7. Ferrara A 2007 Increasing prevalence of gestational diabetes mellitus: a public health perspective. Diabetes Care 30 Suppl 2:S141-146

8. Anna V, van der Ploeg HP, Cheung NW, Huxley RR, Bauman AE 2008 Sociodemographic correlates of the increasing trend in prevalence of gestational diabetes mellitus in a large population of women between 1995 and 2005. Diabetes Care 31:2288-2293

9. Wilkes S, Murdoch A 2009 Obesity and female fertility: a primary care perspective. J Fam Plann Reprod Health Care 35:181-185

10. March WA, Moore VM, Willson KJ, Phillips DI, Norman RJ, Davies MJ 2010 The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod 25:544-551

11. Norman RJ, Dewailly D, Legro RS, Hickey TE 2007 Polycystic ovary syndrome. Lancet 370:685-697

12. Alvarez-Blasco FF, Botella-Carretero JIJI, San Millán JLJL, Escobar-Morreale HFHF 2006 Prevalence and characteristics of the polycystic ovary syndrome in overweight and obese women. Archives of internal medicine 166:2081-2086

13. Pasquali R, Gambineri A, Pagotto U 2006 The impact of obesity on reproduction in women with polycystic ovary syndrome. BJOG 113:1148-1159

14. Diamanti-Kandarakis E, Papavassiliou AG 2006 Molecular mechanisms of insulin resistance in polycystic ovary syndrome. Trends Mol Med 12:324-332

15. Zaadstra BM, Seidell JC, Van Noord PA, te Velde ER, Habbema JD, Vrieswijk B, Karbaat J 1993 Fat and female fecundity: prospective study of effect of body fat distribution on conception rates. BMJ 306:484-487

16. Pasquali R, Gambineri A 2006 Metabolic effects of obesity on reproduction. Reprod Biomed Online 12:542-551

17. Norman RJ, Davies MJ, Lord JM, Moran LJ 2002 The role of lifestyle modifications in polycystic ovary syndrome. Trends Endocrinol Metab 13:235 - 237

18. Norman RJ, Wu R, Stankiewicz MT 2004 Polycystic ovary syndrome. Medical Journal of Australia 180:132-137

19. Wing RR, Papandonatos G, Fava JL, Gorin AA, Phelan S, McCaffery J, Tate DF 2008 Maintaining large weight losses: the role of behavioral and psychological factors. J Consult Clin Psychol 76:1015-1021

20. Vanwormer JJ, French SA, Pereira MA, Welsh EM 2008 The impact of regular self-weighing on weight management: a systematic literature review. Int J Behav Nutr Phys Act 5:54

21. VanWormer JJ, Martinez AM, Martinson BC, Crain AL, Benson GA, Cosentino DL, Pronk NP 2009 Self-weighing promotes weight loss for obese adults. Am J Prev Med 36:70-73

22. Jeffery RW, French SA 1999 Preventing weight gain in adults: the pound of prevention study. Am J Public Health 89:747-751

23. French SA, Jeffery RW 1994 Consequences of dieting to lose weight: effects on physical and mental health. Health Psychol 13:195-212

Content Updated March 25, 2011