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Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2008-0751
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The Journal of Clinical Endocrinology & Metabolism Vol. 93, No. 9 3373-3380
Copyright © 2008 by The Endocrine Society

The Effect of a Hypocaloric Diet with and without Exercise Training on Body Composition, Cardiometabolic Risk Profile, and Reproductive Function in Overweight and Obese Women with Polycystic Ovary Syndrome

Rebecca L. Thomson, Jonathan D. Buckley, Manny Noakes, Peter M. Clifton, Robert J. Norman and Grant D. Brinkworth

Australian Technology Network Centre for Metabolic Fitness and Nutritional Physiology Research Centre (R.L.T., J.D.B.), Sansom Institute for Health Research, University of South Australia, Adelaide, Australia 5001; Preventative Health Flagship (R.L.T., M.N., P.M.C., G.D.B.), Commonwealth Scientific and Industrial Research Organisation, Human Nutrition, Adelaide, Australia 5000; and Research Centre for Reproductive Health (R.J.N.), Discipline of Obstetrics and Gynaecology, University of Adelaide, Adelaide, Australia 5005

Address all correspondence and requests for reprints to: Dr. Grant Brinkworth, Commonwealth Scientific and Industrial Research Organisation, Human Nutrition, P.O. Box 10041 BC, Adelaide, South Australia 5000. E-mail: grant.brinkworth{at}csiro.au.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Context: In overweight women with polycystic ovary syndrome (PCOS), the benefits of the addition of exercise to an energy-restricted diet in further improving cardiometabolic risk factors and reproductive function has not been extensively studied.

Objective: The objective was to evaluate the effects of aerobic and aerobic-resistance exercise when combined with an energy-restricted high protein diet (5000–6000 kJ/d) on metabolic risk factors and reproductive function in women with PCOS.

Design and Setting: A 20-wk outpatient, randomized, parallel study was conducted in a metropolitan research clinic.

Patients and Intervention: Ninety-four overweight and obese women with PCOS (age 29.3 ± 0.7 yr; body mass index 36.1 ± 0.5 kg/m2) were randomized to diet only (DO; n = 30), diet and aerobic exercise (DA; n = 31), or diet and combined aerobic-resistance exercise (DC; n = 33).

Main Outcome Measures: Weight, body composition, cardiometabolic risk factors, hormonal status, menstrual cyclicity, and ovulatory function were assessed.

Results: All interventions reduced weight (DO 8.9 ± 1.6%, DA 10.6 ± 1.7%, and DC 8.7 ± 1.7%; P < 0.001) with no difference between treatments (P = 0.7, time x treatment). Fat mass decreased more (3 kg) and fat-free mass decreased less (2 kg) in DA and DC compared with DO (P ≤ 0.03). Reductions in blood pressure (5.6/2.7 mm Hg), triglycerides (0.4 mmol/liter), total cholesterol (0.5 mmol/liter), low-density lipoprotein cholesterol (0.1 mmol/liter), glucose (0.2 mmol/liter), fasting insulin (4.3 mIU/liter), testosterone (0.4 nmol/liter), and free androgen index (2.8) (P < 0.001) and improvements in SHBG (7.0 nmol/liter) and reproductive function occurred in all groups, with no difference between treatments.

Conclusion: In overweight and obese women with PCOS, the addition of aerobic or combined aerobic-resistance exercise to an energy-restricted diet improved body composition but had no additional effect on improvements in cardiometabolic, hormonal, and reproductive outcomes relative to diet alone.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, presenting in approximately 7% of this population (1). PCOS is associated with a number of reproductive disorders and is characterized by the presence of polycystic ovaries, menstrual dysfunction, infertility or reduced fertility, and biochemical or clinical hyperandrogenism. PCOS also increases the prevalence and risk of a number of cardiometabolic disturbances including insulin resistance, hypertension, dyslipidemia, and diabetes (2, 3).

Although the pathogenesis of PCOS is complex and not entirely understood, obesity (particularly abdominal obesity) is mediated by the development of insulin resistance (4) and is closely linked to the development of this condition and its clinical features, particularly menstrual irregularities and increased serum androgens (5, 6, 7). The central role of insulin resistance in the manifestations of PCOS has led to it becoming a primary target for PCOS management.

Lifestyle modification focusing predominantly on diet and exercise behavior is considered the preferred first-line treatment for PCOS management with the primary goal to normalize serum androgens and restore reproductive function (4). Several studies have shown that weight loss of 5–10% of weight in overweight women with PCOS via energy restriction can reduce circulating insulin levels and hyperandrogenism (8, 9) and improve menstrual cyclicity (10, 11), fertility, and cardiovascular disease risk factors (8). It is considered that the primary determinant underlying many of these reported weight-loss benefits is the accompanying reduction in circulating insulin concentrations (12).

A separate line of evidence has also shown that exercise training independent of weight loss in overweight and obese subjects with cardiometabolic disturbances and a wide range of insulin-resistant states decreases abdominal fat and improves insulin sensitivity and an array of cardiovascular disease risk factors (13). Moreover, recent studies suggest that compared with either aerobic or resistance training alone, combined aerobic-resistance training is more efficacious for improving insulin sensitivity and reducing abdominal fat in a range of obese patient groups (14, 15). However, despite the well established benefits of exercise training and regular exercise being recommended as a cornerstone of PCOS management (12), there is limited research evaluating the effects of exercise training and specific exercise regimes in overweight women with PCOS. Vigorito et al. (16) showed that a 3-month aerobic exercise training program improved fasting insulin but did not assess effects on reproductive function. More recently, Palomba et al. (17) found that although a 24-wk aerobic exercise program or a hypocaloric high-protein diet improved both menstrual cyclicity and fertility in overweight PCOS patients, the exercising subjects reported significantly higher ovulation rates and menses frequency as well as greater improvements in waist circumference (WC), sex hormones, and insulin levels. However, although this study assessed the relative effects of diet and exercise treatment, it was unable to determine the additive benefit of exercise when it is combined with energy restriction. A small preliminary study (18) showed that although 12-wk lifestyle modification programs consisting of nutritional counseling alone or nutritional counseling plus combined aerobic-resistance exercise both significantly reduced fasting insulin levels, the addition of exercise promoted more favorable changes in the sum of two skinfolds. However, this latter study was limited by a small sample size and the lack of any assessment of reproductive function.

The purpose of the present study was to assess the additive benefit of aerobic or aerobic-resistance exercise training, when it is combined with a moderate hypocaloric weight-loss diet on body composition, cardiometabolic and hormonal profiles, and reproductive function in overweight and obese women with PCOS.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Participants

One hundred four sedentary overweight and obese women with PCOS [age, 18–41 yr; body mass index (BMI): 25–55 kg/m2] were recruited by public advertisement and from specialist clinics. PCOS was diagnosed according to the Rotterdam criteria (19). Menstrual irregularity was defined as cycle length less than 21 d or greater than 35 d or variation between consecutive cycles of greater than 3 d. Potential participants were excluded if they were using fertility treatments or oral contraceptives; were smokers, pregnant, breastfeeding, or had history of cardiovascular, liver, kidney or respiratory disease, diabetes, uncontrolled hypertension, or malignancy; or were participating in regular physical activity. Subjects were also excluded if they had reproductive disorders unrelated to PCOS, thyroid abnormalities, or nonclassical adrenal hyperplasia. All experimental procedures were approved by the Human Ethics Committees of the Commonwealth Scientific and Industrial Research Organisation and the University of South Australia, and all subjects provided written informed consent.

Study design

In a parallel study design, subjects were randomly assigned by computer generation into three 20-wk lifestyle interventions; diet only (DO), diet and aerobic exercise (DA) and diet and combined aerobic-resistance exercise (DC). At baseline (wk 0), at the midpoint (wk 10), and at the end of the intervention (wk 20), subjects attended the clinic on two occasions. Subjects were advised not to consume alcohol or participate in vigorous physical activity during the 24 h prior to the clinic visits. One of the clinic visits occurred in the morning after an overnight fast, during which height (baseline only), weight, and blood pressure (BP) were measured before the collection of a venous blood sample for the measurement of metabolic and hormonal parameters. On a separate day, after a minimum 3-h fast, body composition was determined, and at baseline and wk 10, an incremental treadmill exercise test to exhaustion was performed and muscle strength assessed by one-repetition maximums (1RM) to set training loads. During the month before study commencement and throughout the intervention, menses calendars were recorded and first morning spot urine samples were collected twice weekly to assess pregnanediol-3-glucuronide (PDG) concentrations as a marker of ovulation. Subjects were requested not to modify their lifestyles during the intervention period other than as necessary to comply with study requirements.

Dietary intervention

All subjects were prescribed the same energy-restricted, high-protein diet (5000–6000 kJ/d) for a planned weight loss of 8–12 kg over the study period. The diet provided 30% of energy as protein, 40% as carbohydrate, and 30% as fat (<8% saturated fat). To facilitate compliance, the diet included specific daily quantities of foods in a checklist that subjects completed daily. Volunteers met with a dietician in small groups or individually fortnightly throughout the study to discuss dietary issues, nutrition guidelines, and the importance of compliance with the diet to promote weight loss.

Exercise intervention

Apart from the energy-restricted diet, subjects randomized to the DA group undertook a walking/jogging program comprising five sessions per week. The training heart rate (HR) was based on a percentage of the maximum HR (HRmax) achieved in the treadmill tests conducted at wk 0 and 10. Exercise intensity progressed from 25–30 min at 60–65% HRmax during the first week to 45 min at 75–80% HRmax by study end. To assist with compliance, HR during exercise was monitored using a personal HR monitor (FS1 Polar Heart Rate Monitor; Polar Electro Oy, Kempele, Finland). Subjects randomized to the DC group performed the same aerobic exercise program as the DA group three times per week, and undertook a progressive resistance training program twice per week on nonconsecutive days. The resistance training program consisted of five resistance exercises: bench press, lat pulldown, leg press, knee extension, and sit-ups. The training load was set using a percentage of 1RM, which was assessed for each exercise. For the first 2 wk, the training load was 50–60% 1RM and increased to 65–75% 1RM for the following weeks. The training load was increased progressively once subjects could successfully perform three sets of 12 repetitions at that load.

Clinical measurements

Height was measured using a stadiometer (SECA, Hamburg, Germany), and weight was measured using electronic digital scales (Mercury, AMZ 14, Tokyo, Japan). BMI was calculated as weight(kg)/height(m)2. Fat mass (FM), fat-free mass (FFM), and percent body fat (BF%) were determined by dual-energy x-ray absorptiometry (Lunar Prodigy; Lunar Radiation Corp., Madison, WI). Abdominal fat mass (AbFM) was measured as previously described (20). WC was measured 2 cm above the uppermost lateral border of the iliac crest using an anthropometric tape (model W606PM; Lufkin, Cooper Industries Ltd., Houston, TX). Seated BP was measured by automated oscillometry (model T8; Omron Corp., Tokyo, Japan).

Biochemical measurements

Fasting plasma and serum samples were collected and stored at –80 C for analysis after study completion. Serum total cholesterol, high-density lipoprotein cholesterol, triglycerides, and plasma glucose were measured on a Hitachi 902 autoanalyzer (Roche Diagnostics, Indianapolis, IN) using commercial enzymatic kits (Roche Diagnostics, Basel, Switzerland). Low-density lipoprotein cholesterol was calculated using the modified Friedewald equation (21). Plasma insulin concentrations were determined using a commercial ELISA kit (Mercodia ELISA; ALPCO Diagnostics, Uppsala, Sweden). Insulin resistance was estimated using the homeostatic model assessment (HOMA2) online calculator (22). Serum SHBG was measured by coated-tube immunoradiometric assay using commercial kits (Diagnostic Systems Laboratories, Webster, TX). Testosterone was measured by RIA using commercial enzymatic kits (Diagnostic Systems Laboratories). Free androgen index (FAI) was calculated as testosterone/SHBG x 100.

Spot urine samples were stored at –20 C until analysis at completion of the study. Urinary PDG was measured according to the method of Santoro et al. (23). Menstrual cyclicity was assessed using completed menses calendars. Improvements in menstrual cyclicity were defined as a change from nonovulatory to ovulatory cycles or from irregular to regular cycles or an improvement in consecutive intercycle variation.

Data analysis

Data were checked for normality. Between-group differences in baseline characteristics were assessed using one-way ANOVA. Effects of the treatments on dependent variables and their interactions over time were analyzed using random-effects mixed modeling, making efficient use of all available measurements (24). Where a statistically significant main effect was found, differences between means were determined by post hoc analysis using Bonferroni adjustments for multiple comparisons. Linear regression was used to assess relationships between variables using raw data (i.e. non-model-predicted values). {chi}2 tests were used to assess changes for categorical variables. An {alpha}-level of significance was set at P < 0.05. All values reported are model-predicted values ± SD except for age and BMI at baseline, which are the mean of the raw data ± SD. The differences between treatments [with 95% confidence intervals (95% CI)] for changes from baseline to wk 20 are presented for each outcome.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Subjects

Of the 104 subjects recruited, 10 withdrew before commencement, and 94 subjects commenced the study (age 29.3 ± 6.8 yr; BMI 36.1 ± 4.8 kg/m2). Sixty-three subjects completed to wk 10, and 52 completed to wk 20 (Fig. 1Go). There were no significant differences in baseline characteristics between treatments (Table 1Go and 3Go) and between subjects who completed or dropped out of the study. The percentages of subjects who completed the study were not different between treatment groups.


Figure 1
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  		FIG. 1. Study flow diagram.

 

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  		TABLE 1. Weight and body composition at baseline and after 10 and 20 wk of DO, DA, and DC

 

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  		TABLE 3. Cardiometabolic risk factors and sex hormone concentrations at baseline and after 10 and 20 wk of DO, DA, and DC

 
Weight and body composition

Overall mean weight loss was 9.4 ± 1.9% of weight (P < 0.001) with no difference between treatments (P = 0.7; Table 1Go). Similarly, WC was reduced 11.1% by wk 20 (P < 0.001), with no difference between treatments (P > 0.5). There was a significant time by treatment interaction for BF%, FM, and FFM (P ≤ 0.04), such that DA and DC had 45% greater reduction in FM (P < 0.01) and 60% lesser reduction in FFM (P < 0.03) compared with DO (Tables 1Go and 2Go). There was some evidence for a time by treatment effect for AbFM, although this did not reach statistical significance (P = 0.08). Also for the exercising groups (DC and DA), there was greater FFM maintenance from wk 10–20 compared with DO, despite continued significant weight loss during this time. Only the exercising groups experienced continual weight loss and reductions in FM and AbFM and BF% from wk 10–20.


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  		TABLE 2. Difference between DO, DA, and DC for the change in body composition measures from wk 20 to wk 0

 
Cardiometabolic and hormonal outcomes

There were significant reductions in BP, fasting glucose and insulin, insulin resistance (HOMA), lipids, testosterone, and FAI and increases in SHBG in all treatment groups at wk 20 (P < 0.05), with no difference between treatments (P > 0.3; Table 3Go).

Increases in SHBG were inversely related to weight loss (r = –0.43; P = 0.002) and reductions in BF% (r = –0.42; P = 0.002), AbFM (r = –0.64; P < 0.001), and WC (r = –0.46; P = 0.001). Reductions in testosterone were positively related to reductions in BF% (r = 0.30; P = 0.03), AbFM (r = 0.33; P = 0.02), WC (r = 0.29; P = 0.04) and weight loss (r = 0.25; P = 0.07), as was the reduction in FAI (weight loss: r = 0.30, P = 0.04; BF%: r = 0.36, P = 0.01; WC: r = 0.29, P = 0.04; AbFM: r = 0.27, P = 0.06).

Reproductive function

Data on reproductive function were included only for 59 subjects due to inconclusive results from PDG analysis and menses calendars for the remaining subjects. At baseline, 53 subjects reported menstrual irregularities (28 irregular cycle length, 13 anovulatory, 12 amenorrheic), and six had regular ovulating periods.

Of the 53 subjects with menstrual irregularities, 49.1% reported improvements in ovulation [DO 50% (6 of 12), DA 50.0% (3 of 6), DC 42.9% (3 of 7)] and/or menstrual cyclicity [DO 21.4% (3 of 14), DA 42.9% (9 of 21), DC 44.4% (8 of 18)], with no difference between treatments (P > 0.1). There was no difference between groups in the number of menstrual cycles that occurred during the 20-wk study period (DO 2.25 ± 1.35; DA 3.30 ± 1.97; DC 3.00 ± 1.61; P > 0.3), but subjects in DA reported a greater number of ovulatory cycles compared with DO (DO 1.33 ± 1.63, DA 3.10 ± 1.97, DC 2.65 ± 1.70; P = 0.04). For the subjects that improved in menstrual cycle length, there was an average reduction of 13.8 ± 28.3 d (49.6 ± 25.0 to 32.7 ± 4.3 d), and for those that improved in consecutive intercycle variation, there was an average reduction of 16.0 ± 19.7 d (19.5 ± 20.7 to 3.5 ± 3.5 d). After the intervention, 18 subjects had regular ovulating cycles, five were anovulatory, 27 had irregular cycle lengths, and nine were amenorrheic.

Responders (R) vs. nonresponders (NR)

There were no differences in baseline characteristics between subjects who improved reproductive function, determined by improvements in ovulation and menstrual cyclicity (R, n = 26) and those that did not (NR, n = 27) (P > 0.1). Women who experienced improvements had greater reductions in weight (R vs. NR, 12.2 ± 4.0 vs. 6.7 ± 3.8 kg; P < 0.001), FM (8.2 ± 3.4 vs. 4.7 ± 3.2 kg; P < 0.01), AbFM (0.5 ± 0.3 vs. 0.3 ± 0.2 kg; P < 0.02), and WC (13.4 ± 5.1 vs. 10.0 ± 4.8 cm; P < 0.02) compared with women who did not. There were no differences in changes in any cardiometabolic or hormonal parameters between R and NR (P > 0.1).


   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
This study showed that substantial weight loss and improvements in cardiometabolic risk factors, hormonal status, and reproductive function occurred after a structured energy-restricted high-protein diet in overweight and obese women with PCOS. There was no additive benefit from the addition of exercise training in these parameters, but exercise did provide more beneficial changes in body composition with an approximately 45% greater reduction in FM and a 60% better preservation of FFM.

Several studies have shown that weight loss after energy restriction improves body composition by reducing FM, AbFM, and WC in overweight women with PCOS (8, 10), but to date this is the first known study evaluating the added effects of exercise on body composition in these women. The lack of marked additional weight loss after the exercise programs in the present study is not surprising given that numerous short-term studies in other overweight and obese populations have consistently shown exercise alone induces modest weight loss (<5 kg) (25, 26, 27), and when combined with dietary restriction, any greater weight loss observed is minimal (13, 27). Nevertheless, the current study showed the addition of exercise to diet provided significantly favorable effects on body composition rather than facilitating weight loss per se. Lean tissue loss that often occurs with energy restriction is associated with reductions in resting metabolic rate, acting to preserve fat stores and prevent further weight loss (28). The greater preservation of FFM has important potential implications for long-term weight-loss maintenance (29, 30) because it maintains resting metabolic rate and assists with continued weight (i.e. fat) loss and/or weight maintenance (31). The effect of exercise training on resting metabolic rate was not assessed in the current study and warrants further investigation in PCOS. A small preliminary study (18) has also reported greater reductions in the sum of two skinfolds despite an absence of weight loss in women with PCOS when aerobic exercise was added to nutritional counseling. Furthermore, two recent studies in healthy overweight middle-aged women and postmenopausal women with type 2 diabetes reported greater reductions in abdominal fat in subjects who performed combined aerobic-resistance training compared with aerobic exercise only or nonexercise controls (14, 15), suggesting that the incorporation of resistance exercise training may be most beneficial for reducing abdominal fat. In contrast, no differences in effects on body composition were observed between the different exercise treatments in the current study. Previous studies have shown greater preservation of FFM with resistance training compared with aerobic training when combined with energy restriction (32, 33). Resistance training preserves the loss of FFM associated with energy restriction through muscular hypertrophy (33), whereas aerobic exercise is thought to maintain FFM as a result of increased energy expended as fat (34). Possible reasons for the lack of difference between the exercising treatments may be attributed to the earlier studies using more intensive resistance training programs (15, 32, 33, 34). Furthermore, the absence of energy restriction in two of the earlier studies may contribute to differing effects on body composition (14, 15).

The lack of difference in the improvements in cardiometabolic or hormonal parameters between treatment groups suggests the improvements were primarily related to energy restriction and weight loss. Previous studies have also shown similar improvements in blood lipid profiles and fasting insulin levels after short-term energy restriction in overweight women with PCOS (6, 8, 10, 35, 36). Reductions in fasting insulin, but not blood lipids, after exercise training alone with minimal weight loss have also been reported in overweight PCOS patients (16, 18). Taken together, these findings suggest exercise training may be effective in women with PCOS for improving insulin resistance even without weight loss, but not for improving blood lipid profile. Previous studies have also reported that combined aerobic-resistance exercise is more effective for improving insulin sensitivity compared with aerobic exercise in overweight women (14, 15). Resistance exercise improves insulin sensitivity by increasing muscle mass and the number of glucose transporter proteins, and aerobic exercise enhances glucose disposal through increases in skeletal muscle capillarization, blood flow, and hexokinase and glycogen synthase activities (37, 38). In the present study, despite greater FFM preservation and FM reductions in the exercising groups compared with DO, no difference in insulin resistance was observed. The reason for the lack of any additional insulin-sensitizing effect of exercise is not clear; however, the indirect assessment of insulin resistance (HOMA) used may not have been sensitive enough to detect additional exercise effects, and a more sensitive assessment (hyperinsulinemic-euglycemic clamp) may have been appropriate. Alternatively, the lack of difference between the treatment groups may be due to the insulin-sensitizing effect of energy restriction being larger than those achieved through exercise (27), resulting in a masking of the benefits of exercise.

Previous studies have also shown that lifestyle modifications improve hormonal profile in overweight women with PCOS, through reductions in serum testosterone and FAI and increases in SHBG after weight loss (5, 6, 8, 36, 39, 40). Alternatively, exercise interventions in PCOS show mixed results in their effects on hormonal profiles, with two studies reporting no changes after 12–24 wk of combined nutritional counseling and aerobic or resistance exercise (16, 18) and another study showing improved testosterone, SHBG, and FAI levels in ovulating patients after a 24-wk energy-restricted diet or aerobic exercise (17). Reductions in abdominal fat have been associated with improved insulin sensitivity and hormonal profile and restored ovarian function (6, 10) as shown by the moderate associations seen between reductions in AbFM and WC and improvements in hormonal profile. Central body fat may contribute to hyperandrogenemia indirectly through adverse effects on insulin sensitivity and consequent effects of hyperinsulinemia on the ovaries (7).

Improvements in reproductive function have also been shown after weight loss in overweight women with PCOS. Previous studies have observed that during 12–24 wk of energy restriction or lifestyle modification, 44–92% of previously anovulatory overweight women resumed spontaneous ovulation (5, 10, 11, 40) or improved menstrual cyclicity (6, 8, 39) after relatively modest weight loss (2–8 kg). Patients with restored ovarian function display improvements in fasting insulin and insulin sensitivity and a redistribution of body fat, particularly central fat, and a more favorable endocrine environment (5, 8, 10, 11, 40), with NR showing no improvements (8, 10, 17). R in the present study experienced significantly greater reductions in weight, FM, AbFM, and WC compared with NR, but both groups experienced similar significant reductions in insulin and hormones. It is difficult to explain why NR also showed improvements in insulin and hormone profile, suggesting that other factors are responsible for changes in reproductive function. Additional research is needed to further explain the improvements in reproductive function in women with PCOS.

In conclusion, weight loss via energy restriction improved reproductive function, cardiometabolic abnormalities, and hormonal parameters in overweight and obese women with PCOS. Addition of regular aerobic or combined aerobic-resistance exercise provided no additional improvement for cardiometabolic, hormonal, or reproductive outcomes but resulted in more favorable changes on body composition. Thus, lifestyle modifications that combine energy restriction for weight loss and regular exercise would appear to be a preferred treatment strategy in overweight women with PCOS. However, these results are limited to overweight and obese women with PCOS, and further research is required to assess the benefits of exercise in lean and normal-weight women with PCOS. Additional studies are also required to evaluate the individual effects of different exercise modalities and the long-term effects of diet and exercise treatment in women with PCOS.


   Acknowledgments
 
We gratefully acknowledge Julia Weaver for assisting with trial management; Lindy Lawson and Rosemary McArthur for their assistance in the nursing activities; Gemma Williams, Xenia Cleanthous, Siew Lim, and Julianne McKeough for their dietetic guidance; Mark Mano, Cathryn Seccafien, and Candita Sullivan for laboratory assistance; and John Petkov and Kylie Lange for their statistical analysis advice.


   Footnotes
 
This project was funded by a grant from the National Health and Medical Research Council of Australia. R.T. was funded by a postgraduate scholarship from the South Australia Department of Health.

Disclosure Summary: R.T., J.B., P.C., R.N., and G.B. have nothing to declare. M.N. has received lecture fees from Meat and Livestock Australia.

First Published Online June 26, 2008

Abbreviations: AbFM, Abdominal fat mass; BF%, percent body fat; BMI, body mass index; BP, blood pressure; CI, confidence interval; DA, diet and aerobic exercise; DC, diet and combined aerobic-resistance exercise; DO, diet only; FAI, free androgen index; FFM, fat-free mass; FM, fat mass; HR, heart rate; HOMA, homeostatic model assessment of insulin resistance; NR, nonresponder; PCOS, polycystic ovary syndrome; PDG, pregnanediol-3-glucuronide; R, responder; 1RM, one-repetition maximum; WC, waist circumference.

Received April 4, 2008.

Accepted June 16, 2008.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Norman RJ, Dewailly D, Legro RS, Hickey TE 2007 Polycystic ovary syndrome. Lancet 370:685–697[CrossRef][Medline]
  2. Apridonidze T, Essah PA, Iuorno MJ, Nestler JE 2005 Prevalence and characteristics of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab 90:1929–1935[Abstract/Free Full Text]
  3. Ehrmann DA, Liljenquist DR, Kasza K, Azziz R, Legro RS, Ghazzi MN 2006 Prevalence and predictors of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab 91:48–53[Abstract/Free Full Text]
  4. Moran L, Norman RJ 2004 Understanding and managing disturbances in insulin metabolism and body weight in women with polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol 18:719–736[CrossRef][Medline]
  5. Clark AM, Ledger W, Galletly C, Tomlinson L, Blaney F, Wang X, Norman RJ 1995 Weight loss results in significant improvement in pregnancy and ovulation rates in anovulatory obese women. Hum Reprod 10:2705–2712[Abstract/Free Full Text]
  6. Holte J, Bergh T, Berne C, Wide L, Lithell H 1995 Restored insulin sensitivity but persistently increased early insulin secretion after weight loss in obese women with polycystic ovary syndrome. J Clin Endocrinol Metab 80:2586–2593[Abstract]
  7. Barber TM, McCarthy MI, Wass JAH, Franks S 2006 Obesity and polycystic ovary syndrome. Clin Endocrinol (Oxf) 65:137–145[CrossRef][Medline]
  8. Moran LJ, Noakes M, Clifton PM, Tomlinson L, Norman RJ 2003 Dietary composition in restoring reproductive and metabolic physiology in overweight women with polycystic ovary syndrome. J Clin Endocrinol Metab 88:812–819[Abstract/Free Full Text]
  9. Hoeger KM 2006 Role of lifestyle modification in the management of polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol 20:293–310
  10. Huber-Buchholz MM, Carey DG, Norman RJ 1999 Restoration of reproductive potential by lifestyle modification in obese polycystic ovary syndrome: role of insulin sensitivity and luteinizing hormone. J Clin Endocrinol Metab 84:1470–1474[Abstract/Free Full Text]
  11. Crosignani PG, Colombo M, Vegetti W, Somigliana E, Gessati A, Ragni G 2003 Overweight and obese anovulatory patients with polycystic ovaries: parallel improvements in anthropometric indices, ovarian physiology and fertility rate induced by diet. Hum Reprod 18:1928–1932[Abstract/Free Full Text]
  12. Norman RJ, Davies MJ, Lord J, Moran LJ 2002 The role of lifestyle modification in polycystic ovary syndrome. Trends Endocrinol Metab 13:251–257[CrossRef][Medline]
  13. Carroll S, Dudfield M 2004 What is the relationship between exercise and metabolic abnormalities? A review of the metabolic syndrome. Sports Med 34:371–418[CrossRef][Medline]
  14. Cuff DJ, Meneilly GS, Martin A, Ignaszewski A, Tildesley HD, Frohlich JJ 2003 Effective exercise modality to reduce insulin resistance in women with type 2 diabetes. Diabetes Care 26:2977–2982[Abstract/Free Full Text]
  15. Park SK, Park JH, Kwon YC, Kim HS, Yoon MS, Park HT 2003 The effect of combined aerobic and resistance exercise training on abdominal fat in obese middle-aged women. J Physiol Anthropol Appl Human Sci 22:129–135[CrossRef][Medline]
  16. Vigorito C, Giallauria F, Palomba S, Cascella T, Manguso F, Lucci R, De Lorenzo A, Tafuri D, Lombardi G, Colao A, Orio F 2007 Beneficial effects of a three-month structured exercise training program on cardiopulmonary functional capacity in young women with polycystic ovary syndrome. J Clin Endocrinol Metab 92:1379–1384[Abstract/Free Full Text]
  17. Palomba S, Giallauria F, Falbo A, Russo T, Oppedisano R, Tolino A, Colao A, Vigorito C, Zullo F, Orio F 2007 Structured exercise training programme versus hypocaloric hyperproteic diet in obese polycystic ovary syndrome patients with anovulatory infertility: a 24-week pilot study. Hum Reprod 23:642–650[CrossRef][Medline]
  18. Bruner B, Chad K, Chizen D 2006 Effects of exercise and nutritional counseling in women with polycystic ovary syndrome. Appl Physiol Nutr Metab 31:384–391[CrossRef][Medline]
  19. The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group 2004 Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 19:41–47[Abstract/Free Full Text]
  20. Carey DG, Jenkins AB, Campbell LV, Freund J, Chisholm DJ 1996 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 45:633–638[Abstract]
  21. Friedewald WT, Levy RI, Fredrickson DS 1972 Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502[Abstract]
  22. Wallace TM, Levy JC, Matthews DR 2004 Use and abuse of HOMA modeling. Diabetes Care 27:1487–1495[Abstract/Free Full Text]
  23. Santoro N, Crawford SL, Allsworth JE, Gold EB, Greendale GA, Korenman S, Lasley BL, McConnell D, McGaffigan P, Midgely R, Schocken M, Sowers M, Weiss G 2003 Assessing menstrual cycles with urinary hormone assays. Am J Physiol Endocrinol Metab 284:521–530
  24. Cnaan A, Laird NM, Slasor P 1997 Using the general linear mixed model to analyse unbalanced repeated measures and longitudinal data. Stat Med 16:2349–2380[CrossRef][Medline]
  25. Miller WC, Koceja DM, Hamilton EJ 1997 A meta-analysis of the past 25 years of weight loss research using diet, exercise or diet plus exercise intervention. Int J Obes Relat Metab Disord 21:941–947[CrossRef][Medline]
  26. Douketis JD, Macie C, Thabane L, Williamson DF 2005 Systematic review of long-term weight loss studies in obese adults: clinical significance and applicability to clinical practice. Int J Obes Relat Metab Disord 29:1153–1167[CrossRef][Medline]
  27. Shaw K, Gennat H, O'Rourke P, Del Mar C 2006 Exercise for overweight or obesity. Cochrane Database Syst Rev 18:CD003817
  28. Leibel RL, Rosenbaum M, Hirsch J 1995 Changes in energy expenditure resulting from altered body weight. N Engl J Med 332:621–628[Abstract/Free Full Text]
  29. Tremblay A, Doucet E, Imbeault P 1999 Physical activity and weight maintenance. Int J Obes 23:S50–S54
  30. Svendsen OL, Hassager C, Christiansen C 1993 Effect of an energy-restrictive diet, with or without exercise, on lean tissue mass, resting metabolic rate, cardiovascular risk factors, and bone in overweight postmenopausal women. Am J Med 95:131–140[CrossRef][Medline]
  31. Stiegler P, Cunliffe A 2006 The role of diet and exercise for the maintenance of fat-free mass and resting metabolic rate during weight loss. Sports Med 36:239–262[CrossRef][Medline]
  32. Bryner RW, Ullrich IH, Sauers J, Donley D, Hornsby G, Kolar M, Yeater R 1999 Effects of resistance vs. aerobic training combined with an 800 calorie liquid diet on lean body mass and resting metabolic rate. J Am Coll Nutr 18:115–121[Abstract/Free Full Text]
  33. Geliebter A, Maher MM, Gerace L, Gutin B, Heymsfield SB, Hashim SA 1997 Effects of strength or aerobic training on body composition, resting metabolic rate, and peak oxygen consumption in obese dieting subjects. Am J Clin Nutr 66:557–563[Abstract/Free Full Text]
  34. Ballor DL, Katch VL, Becque MD, Marks CR 1988 Resistance weight training during caloric restriction enhances lean body weight maintenance. Am J Clin Nutr 47:19–25[Abstract/Free Full Text]
  35. Andersen P, Seljeflot I, Abdelnoor M, Arnesen H, Dale PO, Lovik A, Birkeland K 1995 Increased insulin sensitivity and fibrinolytic capacity after dietary intervention in obese women with polycystic ovary syndrome. Metabolism 44:611–616[CrossRef][Medline]
  36. Jakubowicz DJ, Nestler JE 1997 17{alpha}-Hydroxyprogesterone responses to leuprolide and serum androgens in obese women with and without polycystic ovary syndrome after dietary weight loss. J Clin Endocrinol Metab 82:556–560[Abstract/Free Full Text]
  37. Cauza E, Hanusch-Enserer U, Strasser B, Ludvik B, Metz-Schimmerl S, Pacini G, Wagner O, Georg P, Prager R, Kostner K, Dunky A, Haber P 2005 The relative benefits of endurance and strength training on the metabolic factors and muscle function of people with type 2 diabetes mellitus. Arch Phys Med Rehabil 86:1527–1533[CrossRef][Medline]
  38. Ivy JL 1997 Role of exercise training in the prevention and treatment of insulin resistance and non-insulin-dependent diabetes mellitus. Sports Med 24:321–336[Medline]
  39. Kiddy DS, Hamilton-Fairley D, Bush A, Short F, Anyaoku V, Reed MJ, Franks S 1992 Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome. Clin Endocrinol (Oxf) 36:105–111[Medline]
  40. Guzick DS, Wing R, Smith D, Berga SL, Winters SJ 1994 Endocrine consequences of weight loss in obese, hyperandrogenic, anovulatory women. Fertil Steril 61:598–604[Medline]




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