KatCarney

Role of lifestyle modification in PCOS
Source: http://www.managingpcos.org.au/content/view/38/

(Written for Health Professionals)

In addition to the reproductive abnormalities of chronic anovulation and hyperandrogenism, a significant majority of women with PCOS are more insulin resistant than controls matched for body-mass index, fat free body mass, and body-fat distribution.1 Insulin resistance (IR) is now recognised as having an integral aetiological role in PCOS. IR underlies metabolic syndrome and 42% of young Australian Women with PCSO have metabolic syndrome with all needing screening for CVRF status. IR is also a risk factor for abnormal glucose metabolism. In young, obese women with PCOS the rates of abnormal glucose tolerance are very high; 15-20% have IGT in their 20’s and 30% to 40% have impaired glucose tolerance (IGT) and up to 10% have type 2 diabetes (DM) by their fourth decade.2,3 Lifestyle intervention improves insulin resistance and prevents progression to diabetes in non PCOS populations and is accepted first line intervention in PCOS. The literature in this area is summarized below.

Non-Pharmacological Management of IR in PCOS
Weight Loss
Amelioration of IR occurs with weight loss in obese subjects with and without PCOS.4 In PCOS, the reduction in IR with weight loss results in improved androgen levels, ovulation rate, menstrual cycle regulation, and improved fertility.5,6 Others have reported symptom improvement and related this to weight loss and more specifically reduction in IR.7,8 In the general population diet and exercise lead to preferential loss of visceral fat.9 In women with PCOS, visceral fat is highly correlated with IR and waist circumference.6,10 In PCOS the likely means by which weight loss improves IR is through loss of visceral fat with resultant metabolic improvements.

A number of different lifestyle strategies to reduce IR in obese women with PCOS (BMI 32-42 kg/m²) have been studied. However to date the prospective studies reported have been limited by small numbers (n=6-40), lack of controls or use of controls who had failed to finish study protocol and use of variable IR assessment tools. The evidence base is further limited by few head-to head comparison studies, and no long-term follow-up to assess effects of short-term decreases in IR on long-term complications such as DM2 and cardiovascular risk in PCOS.

Short-term weight loss strategies using very low calorie diets (<500kcal\day) for 4 weeks have achieved 6.6-9% loss of initial body weight11-14 and have been shown to decrease serum insulin levels13, OGTT stimulated-insulin14 and insulin sensitivity on the clamp test in patients with PCOS.12

As this type of weight loss program is not viable long term, other weight loss trials have used moderate caloric restriction (1000-1500kcal/day) for 2-15 months.6,15,16 In these studies weight loss of as little as 5% and up to 14% has resulted in improved fasting insulin16, OGTT-stimulated insulin15, HOMA17 and insulin sensitivity on clamp testing.6 Another study suggested that improvement in IR (HOMA) may be maximal in the acute catabolic phase of energy restriction rather than during weight maintenance.17

Few studies have combined energy restriction with physical activity. More recently a 6-month lifestyle modification was performed in a group of obese anovulatory PCOS women and obese ovulatory controls.7 The group program included 1 hour of weekly supervised exercise with encouragement to do a further two hours per week as well as one hour of diet and lifestyle education(18). In this study mean weight loss was only 2-5% of body weight however 9/15 still became ovulatory. This was associated with an improvement in insulin sensitivity of 71% using the “gold standard” euglycaemic hyperinsulinemic clamp. Significant improvements in fasting insulin, waist circumference and central abdominal fat but not in androgen levels were also seen in those that responded. There was no improvement in any of these measures in non-responders who remained anovulatory.

IR and Dietary composition
Despite evidence in other IR populations that high protein, low carbohydrate (CHO) diets increase lean body mass and increase insulin sensitivity19, in obese women with PCOS, 2 randomised controlled trials demonstrated no advantage of high versus low protein diet on a number of outcomes including IR.17, 20 Furthermore a diet high in polyunsaturated fatty acids (PUFA) had no effect on IR but increased glucose levels.21 A cross-over trial in 11 obese women with PCOS compared three diets with similar energy and protein contents.22 The diet low in CHO but high in PUFA, reduced fasting and post-challenge insulin levels on IVGTT, but not insulin sensitivity when compared with a standard diet high in monounsaturated fats (MUFA). It appears that caloric restriction is paramount and that no specific dietary composition can be recommended.

IR and Exercise
Exercise training is a potential safe first line alternative in the management of IR in PCOS. Mechanistically, immediately after an acute period of exercise, glucose transport in skeletal muscle is increased through insulin-independent translocation of the GLUT4 glucose transporters to the cell membrane.23 The molecular mechanisms for enhanced insulin sensitivity with exercise training may be related to increased expression/activation of key proteins in the insulin signalling pathway that regulate glucose metabolism in skeletal muscle.24,25

Lifestyle studies to date have focused on diet in conjunction with moderate low intensity exercise in a group environment. These studies have had high drop-out rates with difficulty in maintaining compliance. No studies have examined the role of exercise alone. Whilst the mechanisms require further exploration, regular moderate intensity exercise is known to improve quality of life and insulin action in health and disease including in non-obese women26 and diabetic men27, and is likely to be beneficial in PCOS.

Lifestyle intervention remains first line treatment in POCS, however there are still research questions to be answered especially on the role of exercise, mechanisms to improve the feasibility and sustainability of lifestyle change. In the interim it should be remembered that realistic achievable goals (5-10% wt loss) are important to focus on and have proven health benefits.

References
1.
Dunaif A, Segal K, Futterweit W, Dobrjansky A. Profound insulin resistance independent of obesity in polycystic ovary syndrome. Diabetes. 1989;38:1165.

2.
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 January 1, 1999;22(1):141-6.

3.
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 January 1, 1999;84(1):165-8.

4.
Goodyear PLJ, Kahn MDBB. EXERCISE, GLUCOSE TRANSPORT, AND INSULIN SENSITIVITY. Annu Rev Med. 1998;49(1):235-61.

5.
Moran LJ, Noakes M, Clifton PM, Tomlinson L, Norman RJ. Dietary composition in restoring reproductive and metabolic physiology in overweight women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003 Feb;88(2):812-9.

6.
Holte J, Bergh T, Berne C, Wilde L, Lithell H. Restored insulin sensitivity but persistently increased early insulin secretion after weight loss in obese women with polycystic ovary syndrome. J Clin Endocrinol Metab. 1995;80:2586-93.

7.
Huber-Burchholz M-M, Carey DPG, Norman RJ. Restoration of reproductive potential by lifestyle modification in obese polycystic ovary syndrome: Role of insulin sensitivity and luteinizing hormone. Journal of Clinical Endocrinology and Metabolism. 1999;84:1470 - 4.

8.
Balen A, Rajkowha M. Polycystic ovary syndrome--a systemic disorder? Best Pract Res Clin Obstet Gynaecol. 2003 Apr;17(2):263-74.

9.
Goodpaster BBH, Kelley DDE, Wing RRR, Meier AA, Thaete FFL. Effects of weight loss on regional fat distribution and insulin sensitivity in obesity. Diabetes. 1999;48(4):839-47.

10.
Lord J, Thomas R, Fox B, Acharya U, Wilkin T. The central issue? Visceral fat mass is a good marker of insulin resistance and metabolic disturbance in women with polycystic ovary syndrome. BJOG: An International Journal of Obstetrics and Gynaecology. 2006;0(0):???-???

11.
Wahrenberg HH, Ek II, Reynisdottir SS, Carlström KK, Bergqvist AA, Arner PP. Divergent effects of weight reduction and oral anticonception treatment on adrenergic lipolysis regulation in obese women with the polycystic ovary syndrome. The Journal of clinical endocrinology & metabolism. 1999;84(6):2182-7.

12.
Andersen P, Seljeflot I, Abdelnoor M, Arnesen H, Dale P, Lovik A, et al. Increased insulin sensitivity and fibrinolytic capacity after dietary intervention in obese women with polycystic ovary syndrome. Metabolism. 1995;44(5):611-6.

13.
Polson DW, Kiddy DS, Mason HD, Franks S. Induction of ovulation with clomiphene citrate in women with polycystic ovary syndrome: the difference between responders and nonresponders. Fertil Steril. 1989 Jan;51(1):30-4.

14.
Hamilton-Fairley DD, Kiddy DD, Anyaoku VV, Koistinen RR, Seppälä MM, Franks SS. Response of sex hormone binding globulin and insulin-like growth factor binding protein-1 to an oral glucose tolerance test in obese women with polycystic ovary syndrome before and after calorie restriction. Clinical endocrinology. 1993;39(3):363-7.

15.
Pasquali R, Antenucci D, Casimirri F, Venturoli S, Paradisi R, Fabbri R, et al. Clinical and hormonal characteristics of obese amenorrheic hyperandrogenic women before and after weight loss. J Clin Endocrinol Metab. 1989 January 1, 1989;68(1):173-658.

16.
Jakubowicz DJ, Nestler JE. 17 alpha-Hydroxyprogesterone responses to leuprolide and serum androgens in obese women with and without polycystic ovary syndrome offer dietary weight loss. J Clin Endocrinol Metab. 1997 Feb;82(2):556-60.

17.
Moran L, Noakes M, Clifton P, Tomlinson L, Norman R. Dietary composition in restoring reproductive and metabolic phsiology in overweight women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003;88:812-19.

18.
Clark AM, Ledger W, Galletly C, Tomlinson L, Blaney F, Wang X, et al. Weight loss results in significant improvement in pregnancy and ovulation rates in anovulatory obese women. Human Reproduction. 1995;10(10):2705 - 12.

19.
O'Dea KK, Traianedes KK, Ireland PP, Niall MM, Sadler JJ, Hopper JJ, et al. The effects of diet differing in fat, carbohydrate, and fiber on carbohydrate and lipid metabolism in type II diabetes. Journal of the American Dietetic Association. 1989;89(8):1076-86.

20.
Stamets K, Taylor DS, Kunselman A, Demers LM, Pelkman CL, Legro RS. A randomized trial of the effects of two types of short-term hypocaloric diets on weight loss in women with polycystic ovary syndrome. Fertil Steril. 2004 Mar;81(3):630-7.

21.
Kasim-Karakas SE, Almario RU, Gregory L, Wong R, Todd H, Lasley BL. Metabolic and endocrine effects of a polyunsaturated fatty acid-rich diet in polycystic ovary syndrome. Journal of Clinical Endocrinology and Metabolism. 2004 Feb;89(2):615-20.

22.
Douglas CC, Gower BA, Darnell BE, Ovalle F, Oster RA, Azziz R. Role of diet in the treatment of polycystic ovary syndrome. Fertility & Sterility. 2006 Mar;85(3):679-88.

23.
Krook A, Wallberg-Henriksson H, Zierath JR. Sending the signal: molecular mechanisms regulating glucose uptake. Med Sci Sports Exerc. 2004 Jul;36(7):1212-7.

24.
Chibalin AV, Yu M, Ryder JW, Song XM, Galuska D, Krook A, et al. Exercise induced changes in expression and activity of proteins involved in insulin signal transduction in skeletal muscle: differential effects on insulin receptor substrates1 and 2. Proc Natl Acad Sci USA. 2000;97:38-43.

25.
Houmard JA, Shinebarger MH, Dolan PL, Leggett-Frazier N, Bruner RK, McCammon MR, et al. Exercise training increases GLUT4 concentration in previously sedentary middle-aged men. Am J Physiol Endocrinol Metab. 1993;264:E896-E901.

26.
Poehlman ET, Dvorak RV, DeNino WF, Brochu M, Ades PA. Effects of Resistance Training and Endurance Training on Insulin Sensitivity in Nonobese, Young Women: A Controlled Randomized Trial. Journal of Clinical Endocrinology and Metabolism. 2000 July 1, 2000;85(7):2463-8.

27.
Bruce CR, Kriketos AD, Cooney GJ, Hawley JA. Dissociation of muscle triglyceride content and insulin sensitivity after exercise training in patients with type 2 diabetes. Diabetologia. 2004;47:23 - 30.


Content updated February 27, 2007

Last Updated ( Thursday, 01 March 2007 )

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