Obesity Management in Women with Polycystic Ovary Syndrome

Abstract

Obesity and insulin resistance play an important role in initiating or maintaining ill health in polycystic ovary syndrome (PCOS). This implies that treatment that reduces body weight and insulin resistance would alleviate the symptoms of PCOS. Lifestyle modification has been found to be effective in restoring reproductive function in up to 80% of individuals who achieve at least 5% weight loss. However, long-term weight maintenance is a challenge. This article provides a review of reduced glycemic load diets, including low glycemic index, very low carbohydrate, high-protein and high monounsaturated fat diets, on metabolic and reproductive health in PCOS and non-PCOS populations. Dietary trials in non-PCOS women suggest that higher-protein, reduced glycemic load diets were probably more beneficial than the conventional low-fat, high-carbohydrate diet but further studies are required to confirm this in PCOS women. Similarly, the optimal exercise regime for PCOS women remains to be investigated.

Keywords

diet glycemic index high protein diet insulin resistance lifestyle low carbohydrate diet monounsaturated fat obesity overweight polycystic ovary syndrome

Obesity & polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is one of the most common endocrine conditions that affects obese and nonobese women during reproductive age. Its symptoms include irregular menses, infertility, acne and hirsutism (excessive hair growth). During pregnancy, PCOS probably also increases the risk of early miscarriages and complications such as pre-eclampsia and gestational diabetes [1]. As a result of these physical manifestations, women with PCOS tend to have poorer psychological health and lower quality of life [2]. Increasing evidence also suggests that women with PCOS may be at greater risk of developing metabolic diseases such as type 2 diabetes and cardiovascular disease in the long term [3,4].

Owing to its heterogeneity, the diagnostic criteria for PCOS have been a contentious issue among experts. The 1990 National Institutes of Health (NIH) meeting defined PCOS as the coexistence of chronic anovulation and hyperandrogenism, with the exclusion of other diseases such as thyroid disorder, hyperprolactinemia, congenital adrenal hyperplasia, androgen-secreting tumors and Cushing syndrome [5]. In 2003, this definition was broadened to include women with either hyperandrogenism or anovulation in addition to having polycystic ovaries. Using the previous NIH definition, the prevalence of PCOS was estimated to be 5–8% of women of reproductive age [6 –9]. This number is estimated to increase by 65% using the latest revised diagnostic criteria [10].

Obesity & fat distribution in PCOS women

It is estimated that 30–60% of women with PCOS are overweight or obese in the Western world [7,11 –14]. Some suggest that the prevalence of obesity is higher in PCOS women compared with healthy controls [7,15,16]. In a study involving 3094 women, Glueck and colleagues found that approximately 73–78% of women with PCOS aged between 20 and 41 years were obese (body mass index [BMI]>30 kg/m²) compared with 7–14% in the general population [16]. In addition to being potentially predisposed to obesity, PCOS women are also more likely to have central obesity. A number of studies have documented that both lean and obese PCOS women are more likely to have an upper-body fat distribution compared with weight-matched controls [17 –20]. The presence of obesity, especially central obesity, exacerbates the reproductive and metabolic profile of PCOS women. Obese PCOS women, when compared with lean PCOS women, tend to have lower insulin sensitivity, higher testosterone levels, lower sex-hormone binding globulin (SHBG) levels, as well as having a greater prevalence of infertility, hirsutism, menstrual irregularity and miscarriages [11,13,15,17,18,21 –26].

Obesity, insulin resistance & hyperandrogenism

The worsening of symptoms with increasing BMI and the improvement of symptoms with weight loss suggests that obesity plays a role in initiating or perpetuating the conditions of PCOS. Furthermore, weight gain in postadolescence and early adulthood also precipitates risks for developing PCOS, suggesting that obesity precedes PCOS [27]. Increasing evidence suggests that obesity promotes PCOS via hyperinsulinemia, a compensatory response during insulin resistance. PCOS women tend to be more insulin resistant compared with healthy, weight-matched controls [8,25,28]. The presence of insulin resistance also increases the severity of PCOS symptoms [21,22]. In addition, an increase in insulin level typically results in a concomitant increase in testosterone or androstenedione levels [29 –31]. Conversely, a decrease in circulating insulin levels either by weight loss or insulin-sensitizing treatment (e.g., through metformin) often leads to a reversal of hyperandrogenism [32 –34]. Several mechanisms have been identified to explain the observed relationship between hyperinsulinemia and hyperandrogenism ( Table 1 ). However, it is worth noting that not all PCOS women are insulin resistant [21,35]. Similarly, not all PCOS women are overweight or obese. In these individuals, other pathways may account for the presence of PCOS.

Table 1.

The effect of insulin on androgen production.

Target organ	Effect of insulin
Pituitary	Increases sensitivity to GnRH [36,37]
Ovaries	Increases the activity of 17,20 lyase [38]
	Increases the activity of 3β-hydroxysteroid dehydrogenase and aromatase in the granulosa cells [39]
	Increases LH receptor levels [36,37]
	Promotes ovarian growth and cyst formation [36,40]
Liver	Inhibits SHBG production [41]

GnRH: Gonadotrophin- releasing hormone; LH: Luteinizing hormone; SHBG: Sex hormone-binding globulin.

Weight loss & PCOS

Obesity and insulin resistance play an important, but not exclusive, role in the pathogenesis of PCOS. This implies that treatment that reduces body weight and increases insulin sensitivity should be beneficial for obese PCOS patients. For this reason, lifestyle modification is often regarded as the first-line treatment for PCOS women. In addition to providing the well-known metabolic benefits, dietary-induced weight loss has also been shown to improve reproductive hormone profile and clinical outcomes such as hirsutism, menstrual cyclicity, pregnancy rate and live births [42 –49]. Research studies have reported improvement in reproductive function following lifestyle treatment lasting 4–6 months. However, improvement in reproductive function was seen as early as 2 weeks after energy restriction in one study, suggesting that energy restriction per sé may have a role in improving reproductive function [44].

The proportion of PCOS women who had clinically significant improvements (either in menstrual cyclicity or ovulation) after lifestyle treatment was 44–57% [44,50,51]. When analysis included only those who had lost at least 5% of body weight, the proportion of responders increased to 67–82% [46,52]. The higher proportion of responders among those with greater weight loss suggests that a threshold of weight loss may be required for improvement in reproductive function, and such a threshold is likely to differ between individuals. However, it is possible that these nonresponders, if obese, have independent pathogenetic factors, and therefore will not respond to weight loss regardless of magnitude achieved. While it would be useful to have some prognostic factor to identify those who would benefit from weight loss, the majority of the studies have found no difference in baseline characteristics between responders and nonresponders [48,50,53,54]. Nevertheless, considering that up to 80% of individuals who achieve at least 5% weight loss have seen improvement in ovulation or menstrual cyclicity in addition to metabolic improvements, lifestyle treatment should be recommended as the first-line treatment for PCOS and remain as an adjunct when additional treatments are introduced.

The mechanism by which weight loss restores reproductive function is unclear. Previous research suggests that such improvements were due to the increase in insulin sensitivity resulting from weight loss. In support of this, an improvement in insulin sensitivity parameters (fasting insulin, Homeostasis Model Assessment and glucose infusion rate/mean clamp insulin) following lifestyle treatment was seen only among the responders but not in nonresponders [50,54]. In addition, the reduction in cytochrome P (CYP)450c17α activity as a result of dietary-induced weight loss was accompanied by a simultaneous decrease in fasting and glucose-stimulated insulin [55]. A similar reduction in CYP450c17α was also observed in lean PCOS women treated with an insulin-sensitizing agent, metformin [56,57]. These findings support the role of hyperinsulinemia in excess androgen production, as discussed earlier.

Lifestyle programs for women with PCOS

Lifestyle modification has been shown to be beneficial in the majority of women with PCOS. However, limited studies have investigated the optimal diet, exercise or behavior therapy for PCOS women. The present review aims to summarize the benefits of various lifestyle interventions in PCOS and non-PCOS populations. Due to limited studies conducted in PCOS women, studies conducted in non-PCOS will also be considered in this review. The effects of various dietary and exercise patterns on reproductive health will be discussed whenever data are available. Considering the important roles of obesity and insulin resistance in the pathogenesis of PCOS, the interventions will also be evaluated based on these outcomes. Finally, the effects of the reviewed interventions on conventional metabolic risk markers, such as on fasting blood lipid and glycemic response, will also be discussed.

Diet

It is generally agreed that energy restriction is required for weight loss. In fact, early improvements in reproductive function in the absence of apparent weight loss were probably due to energy restriction per sé. Aside from this, there is little agreement on what constitutes the optimal diet for PCOS women. A range of dietary approaches have been shown to be effective in weight loss and in improving reproductive function ( Table 2 ), but only two randomized, controlled trials have compared the effect between different dietary patterns in PCOS women [45,50]. These studies did not find that dietary patterns differentially affect reproductive outcomes in PCOS women. However, increasing evidence in non-PCOS studies suggest that diets with reduced glycemic load may be beneficial in alleviating hyperinsulinemia and its metabolic consequences [58]. This is of particular relevance to PCOS women due to the close association between insulin resistance and reproductive health. A summary of the findings from randomized, controlled trials of these diets is shown in Table 3.

Table 2.

Dietary trials conducted in PCOS women.

Study	n	Duration	Intervention	Weight loss	Metabolic	Reproductive	Ref.
Kiddy et al. (1989)	5	4 weeks	Diet (non-RCT) 1386 KJ/day for 4 weeks 42.7% C, 33% P, 29% F	−7.1 kg	Decreased fasting insulin	Increased SHBG, decreased free T	[59]
Pasquali et al. (1989)	20	6–12 months	Diet (non-RCT) 4200–6300 KJ/day 50% C, 20% P, 30% F	85.9→76.1 kg	Decreased fasting insulin	Improved ovulation and pregnancy, decreased T, progesterone and LH	[53]
Kiddy et al. (1992)	24	7 months	Diet (non-RCT) Low fat, low cal BMI>30: 1386 KJ/day for 4 weeks, then 4200 KJ/day low-fat for 6 months BMI<30: 4200 KJ/day for 7 months	91.9→85 kg	Decreased fasting insulin	Decreased free T Among those who lost >5% weight: increase SHBG, decreased hirsutism, improved ovulation and menstrual cyclicity	[60]
Holte et al. (1995)	13	14.9 months (mean)	Diet (non-RCT) 5000 KJ/day – continued until no further weight loss, and weight stable for 1 month	−14%	Decreased fasting insulin	7/13 had improved menstrual cyclicity Decreased T and FAI, increased SHBG	[51]
Andersen et al. (1995)	9	24 weeks	Diet (non-RCT) 4 weeks 1800 KJ/day; 25 g C, 51 g P, 5 g F/100 g 20 weeks 4200–6300 KJ/day 59% C, 22% P, 20% F Exercise: advised to take walks	−9% fat mass	Decreased fasting insulin, PAI-1, fibrinolysis	Two had normal menstrual cyclicity and became pregnant	[61]
Jakubowicz and Nestler (1997)	12	8 weeks	Diet (non-RCT) 4200–5000 KJ/day, 43% C, 23% P, 35% F	32→29.6 kg/m²	Decreased fasting insulin	Decreased T, increased SHBG, decreased basal and stimulated 17α hydroxyprogesterone	[55]
Huber-Bucholz et al. (1999)	18	6 months	Combined therapy (non-RCT) Diet: low fat, low Gl, high-fibre diet Exercise: Group sessions Behaviour: Group sessions	2–5%	Decreased fasting insulin in responders	50% resumed ovulation Decreased FAI and LH in responders	[54]
Van Dam et al. (2002)	15	7 days	Diet (non-RCT) 4200 KJ/day replacement drinks 42% C, 43% P, 15% F	115→112 kg	Decreased fasting insulin, fasting blood glucose	Decreased T	[43]
Van Dam et al. (2004)	15	7 days then follow-up for 29 weeks	Diet (non-RCT) 4200 KJ/day replacement drinks 42% C, 43% P, 15% F	37.5→33.4 kg/m² in responders 41.9→37.2 kg/m² in non responders	Decreased fasting blood glucose in responders	Increased SHBG. Decreased FAI and FSH in responders	[62]
Moran et al. (2003)	28	16 weeks	Diet (RCT) 6000 KJ/day HP: 40% C, 30% P, 30% F LP: 55% C,15% P, 30% F	−7.7 kg	Decreased fasting insulin, LDL cholesterol, triglyceride	44% had improvement in ovulation	[50]
Crosignani et al. (2003)	33	12 months	Diet (non-RCT) 5000 KJ/day 55% C, 20% P, 25% F Exercise: Advised to do some swimming or aerobics at least twice weekly	76% lost >5% 33% lost >10%	NA	Among those who lost >5% weight: 7% had resumed normal menstrual cyclicity, 10 were pregnant, 8 live births	[52]
Moran et al. (2004)	10	16 weeks	Diet (RCT) 6000 KJ each HP: 40% C, 30% P, 30% F LP: 55% C, 15% P, 30% F	94.8→87.7	NA	NA	[63]
Stamets et al. (2004)	26	1 month	Diet (RCT) 4200 KJ deficit/day HP: 40% C, 30% P, 30% F LP: 55% C, 15% P, 30% F	−4 kg	Decreased fasting insulin	Decreased T	[45]
Mavropoulos et al. (2005)	11	24 weeks	Diet (non-RCT) Very low C diet (< 20 g C/day) Exercise: encouraged to exercise three-times weekly	−12.1%	Decreased fasting insulin	Decreased free T and LH:FSH ratio	[42]
Tolino et al. (2005)	144	7 months	Diet: (non-RCT) BMI >30: 1400 KJ for 4 weeks, then 4200 KJ low fat for 6 months	92→86 kg	Decreased fasting insulin	Among those who lost >5% weight: Decreased free T, increased SHBG, decreased hirsutism, 25% conceived. Improved ovulation and menstrual cyclicity	[46]
Hoeger et al. (2005)	6	48 weeks	Combined therapy (RCT) Diet: 2100–4200 KJ deficit a day Individualised healthy meal plan 50% C, 25% P, 25% F; low GI Exercise: Group sessions Behaviour: Group sessions	−6.8kg	NS	NS	[64]
Bruner et al. (2006)	12	12 weeks	Diet: (RCT) Canadian Food Guide to Healthy Eating Exercise: a combination of endurance and resistance activities 3 days/week	NS	Decreased fasting insulin	NS	[65]
Moran et al. (2006)	23	8 weeks and 6 months	Diet: (RCT) 8 weeks (5000 KJ/day) 2 meal replacements plus low-fat dinner and snacks for 8 weeks 6 months fat counting (<50 g/day) or carbohydrate counting (<120 g/day) Exercise: 8000 steps/day	−4.7kg	Decreased fasting insulin and blood glucose, decreased systolic blood pressure	Decreased T. 57% had improved menstrual cyclicity	[44]

BMI: Body mass index; C: Carbohydrate; F: Fat; FAI: Free androgen index; FSH: Follicle stimulating hormone; GI: Glycemic index; HP: High protein; LDL: Low-density lipoprotein; LH: Leutenizing hormone; LP: Low protein; NA: Not available; NS: Not significant changes from baseline. P: Protein; PAI-1: Plasminogen activator inhibitor Type 1; PCOS: Polycystic ovarian syndrome; RCT: Randomized, controlled trial; SHBG: Sex hormone-binding globulin; T: Testosterone.

Table 3.

The effect of reduced glycemic load diets on body weight, body composition and metabolic profile compared with low-fat, high-carbohydrate diet in randomized, controlled trials.

	Low GI diet [66 68,70,71]	VLC diet [42,82,88,100]	HP diet [45,50,67,72 76,82,86,87]	HF diet [89 –96,98,99]
Diet composition	55% C, 15% P, 30% F	20–30 g C /day	40% C, 30% P, 30% F	45% C, 15% P, 40% F
Weight loss	Similar or greater	Similar or greater	Similar or greater	Similar or less
Body composition	Similar or greater fat mass loss	Similar or greater fat mass loss	Similar or greater fat mass loss, similar or greater lean mass retention	Similar or greater fat mass loss
Total cholesterol	Lower	Higher	Inconsistent*	Similar or lower
LDL cholesterol	Similar or lower	Higher	Inconsistent*	Similar or lower
HDL cholesterol	Similar	Similar or higher	Similar or higher	Similar or higher
Triglyceride	Similar	Lower	Similar or lower	Similar or lower
Fasting insulin	Similar or lower	Similar or lower	Similar or lower	Similar
Fasting glucose	Inconsistent*	Similar or lower	Similar or higher	Inconsistent*

Studies showed either lower, similar or higher results compared with high-carbohydrate.

C: Carbohydrate; F: Fat; GI: Glycemic index; HDL: High-density lipoprotein; HF: High monounsaturated fat; HP: High protein; LDL: Low-density lipoprotein; P: Protein; VLC: Very low carbohydrate.

Low glycemic index diets (~55% carbohydrate, 15% protein & 30% fat)

The glycemic index (GI) is calculated based on the area under a 2 h glucose response curve following the consumption of a 50 g carbohydrate portion of individual foods compared with the 2 h glucose response for white bread. Glycemic load can be reduced by choosing foods with low glycemic index (LGI). The efficacy of LGI diets on reproductive function is unclear as the effects of GI on PCOS women have not been investigated.

In non-PCOS studies, Kelly and colleagues have examined the effect of LGI diets on body weight and cardiovascular health in a review that includes 13 weight maintenance and two weight-loss studies published between 1966 and May 2003 [66]. The meta-analysis concluded that LGI diets did not differ significantly from high GI diets in inducing weight loss and improving fasting insulin [66]. Several other weight-loss or weight-maintaining studies have also shown that LGI diets result in greater weight or fat loss, although this was not consistently shown in other studies [67 –69]. Some suggests that LGI diets also result in lower postprandial glucose and insulin levels at energy-balance [68,70].

In terms of metabolic outcomes, the meta-analysis found that LGI diets result in a small reduction in total cholesterol (−0.17 mmol/l, p <0.05) when compared with high GI diets, without any significant effect on other cardiovascular health markers including triglyceride, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, body weight or fasting glucose [66]. In more recent publications, LGI diets have been shown to result in greater decreases in LDL cholesterol compared with high GI diets at energy balance [70,71].

Moderate carbohydrate, high-protein, low-fat diets (~40% carbohydrate, 30% protein & 30% fat)

Glycemic load can also be reduced by restricting carbohydrate intake. In PCOS women, the effects of high-protein (HP) and high-carbohydrate (HC) diets were found to be equally effective in inducing weight loss and improving reproductive health in two studies, with possibly better metabolic outcome with HP diet (higher HDL levels and lower postprandial insulin levels) [45,50].

In a non-PCOS-specific meta-regression of 87 studies, Krieger and colleagues found that lower-carbohydrate diets were associated with greater weight loss, fat mass loss, and decrease in percentage body fat [72]. On the other hand, diets high in protein (>1.05 g/kg per day) were associated with better fat-free mass retention [72]. This could be due to an increase in protein requirement during weight loss as the recommended daily intake of 0.8 g/kg per day was determined at energy balance [72]. Together, evidence to date suggests that replacing carbohydrate with protein is beneficial for individuals undergoing weight loss, particularly in retaining lean mass. In support of this, some studies in the non-PCOS population have found that HP diets resulted in greater weight loss and/or fat loss compared with low-fat HC diets (~55% carbohydrate, 15% protein and 30% fat) under energy-restricted or ad libitum conditions [67,73 –78]. Better outcomes with HP diets compared with HC diets in ad libitum setting may be related to the greater acute satiety associated with protein compared with glucose or fat [79 –81]. HP diets have also been shown to produce lower fasting and postprandial insulin levels [50,82 –85].

In terms of metabolic outcomes, studies in non-PCOS patients have found that HP diets are associated with lower triglyceride [75,76,82,86] and higher HDL cholesterol levels compared with HC diets [74,82,87]. The effect of protein:carbohydrate manipulation on cholesterol was inconsistent. While most studies found that HP and HC diets had no differential effects on total and LDL cholesterol levels, some have shown that either HP or HC diets produced better outcomes [67,73,74,86,87]. HP diets were also found to result in higher fasting glucose levels compared with HC diets during weight loss [82 –84,87]. Replacing carbohydrate with protein resulted in an inconsistent effect on postprandial glucose. Studies have shown that HP diets had greater decrease in postprandial glucose during weight maintenance but not during weight loss [63,83 –85]. Studies that investigated the combination of LGI and HP (LGIHP) diet in non-PCOS women have reported better body weight, triglyceride, HDL cholesterol, fasting insulin and postprandial insulin and glucose outcomes compared with HC diet [67,81].

Very low carbohydrate, high-fat diets (20–30 g carbohydrate/day)

The resurgence of the Atkins diet has generated considerable interest in very low carbohydrate (VLC) diets in recent years. Recently, a VLC diet was studied in PCOS women and was found to significantly decrease body weight (−12% body weight in 24 weeks) and free testosterone while increasing leutenizing hormone:follicle-stimulating hormone ratio with no significant changes in lipid profile [42]. However, this single-arm study was unable to determine if this dietary pattern was more advantageous than other dietary patterns.

In a non-PCOS population, the effect of VLC diets on weight loss and cardiovascular effect was considered in a recent meta-analysis by Nordmann and colleagues [88]. At 6 months, VLC diets produced greater weight loss than HC diets but differences were no longer significant by 12 months. One study found that VLC diets also result in lower fasting insulin [82].

In terms of metabolic profile, VLC diets resulted in higher total and LDL cholesterol values and lower fasting glucose levels, but lower triglyceride and higher HDL cholesterol levels compared with HC diets after 6 months of treatment [82,88]. Differences in total cholesterol, LDL cholesterol and triglyceride remained significant despite similar weight loss after 12 months [88].

Moderate carbohydrate, high monounsaturated fat diet (~45% carbohydrate, 40% fat & 15% protein)

Replacing carbohydrate with monounsaturated fat may be a way to attain the benefits of carbohydrate restriction without the adverse effect on blood cholesterol. However, there has been concern for its effect on body weight due to the high monounsaturated fat (HF) recommendation, especially in ad libitum setting. One study in PCOS women found that a HC diet led to a small but significantly greater decrease in androstenedione compared with a HF diet (−0.1 ng/ml versus +0.1 ng/ml, p <0.05) [89]. As this study was designed to examine the effect of diets during energy balance, it would be interesting to see how the HF diet compares with HC diet during weight loss in PCOS women.

In agreement with critics of this diet, most non-PCOS studies found that moderate carbohydrate, HF diets were equal or less beneficial than HC diets in weight or fat mass loss [90 –97]. A smaller weight loss with HF diets could be due to the greater intake of energy-dense food in energy-controlled or ad libitum settings [90 –97]. Some studies have shown that HF diets resulted in lower fasting and postprandial insulin compared with HC diets [90,92 –94,98,99].

Replacing carbohydrate with monounsaturated fat does improve the circulating lipid profile. A number of studies have found that subjects on HF diets had lower total cholesterol and triglyceride and higher HDL cholesterol than those on HC diets [90,91,93,96,99]. HF diets have inconsistent effects on fasting glucose [92 –94,98,99]. A meta-analysis suggests some evidence of HF diets resulting in better postprandial or 24-h glucose levels [90].

Comparison of dietary patterns

Several non-PCOS studies have compared the weight loss and metabolic benefits of these reduced glycemic load diets. McAuley and colleagues have compared the effect between VLC, HP and HC diets in an 8-week study [76]. Both VLC and HP diets produced greater weight loss compared with a HC diet [76]. At 12-month follow-up, the HP group had a greater retention rate, lower body weight and body fat, and lower triglyceride level compared with the other dietary patterns [97].

In another study, a VLC diet was compared with very low fat (67% carbohydrate, 20% protein, 13% fat) and high unsaturated fat (46% carbohydrate, 26% protein, 28% fat) diets [100]. The VLC diet produced a greater weight and lean mass loss as well as lower postprandial insulin levels compared with the high unsaturated fat diet [100]. In addition, the VLC diet resulted in higher HDL cholesterol, lower triglyceride, lower postprandial and glucose levels, but also higher LDL cholesterol and homocysteine levels compared with the other diets [100].

When compared with LGI or HP diets, HF diets were found to elicit comparable weight loss, although greater satiety was reported with HP diets at energy balance [79,91]. In contrast, a cross-over study found that a HP diet produced a greater decrease in total cholesterol, HDL cholesterol and triglyceride compared with HF diet [86].

In summary, studies in the non-PCOS population suggest that reduced glycemic load diets are more beneficial than the conventional low-fat, HC diet commonly prescribed for weight loss, based on the parameters considered in this review. Due to the limited number of studies conducted in PCOS women, it remains inconclusive if dietary patterns have a differential effect on the reproductive health of this population. Future studies with larger sample size and longer follow-up period are required to determine the optimal dietary treatment for PCOS women.

Exercise

Research has identified that physical activity plays a central role in the secondary prevention of obesity [101 –103]. While at least 150 min of exercise/week has been shown to produce clinically significant improvements in body composition and insulin sensitivity [104 –106], physical activity levels up to 60–90 min a day were found to be necessary for weight maintenance [101,102,107]. At the time this review was prepared, there has only been one published study on the effect of physical activity on PCOS women. Randeva and colleagues investigated the effect of a 6-month brisk walking program on overweight and obese women with PCOS [108]. An improvement in homocysteine level and waist:hip ratio was seen, without changes in free androgen index (FAI). Other reproductive outcomes were not reported in this study. Among the studies from non-PCOS women, some suggest that endurance training led to a greater improvement in insulin sensitivity while aerobics training resulted in greater fat loss [109,110]. Others suggest that a combination of both would be beneficial in terms of both fat loss and improving insulin sensitivity [104,105]

As with dietary interventions, there is a lack of evidence on whether endurance, resistance or a combination of these exercises would be more beneficial for women with PCOS. Therefore, further research is required to determine the suitable exercise regime for PCOS women.

Behavior therapy

As changes with diet and exercise can be stressful and complicated, psychological support such as the codelivery of cognitive–behavior therapy can improve patient's compliance with lifestyle intervention by providing self-regulation skills such as self-monitoring, goal setting, planning, relapse coping, as well as developing positive body image and managing stress [111,112]. In support of this, the NIH recommends a combined therapy consisting of diet, exercise and behavior therapy for long-term weight management [111]. In view of the poorer psychological health and lower quality of life among PCOS women [2], interventions that provide psychological support will be of great benefit to this group.

Putting it together: comprehensive lifestyle programs

Among the lifestyle modification trials conducted in PCOS women, relatively few had included the combination of diet, exercise and behavioral therapy in a structured manner ( Table 2 ). The Fertility Fitness program in South Australia, developed in the 1990s, was the first comprehensive lifestyle program investigated for its effect on improving reproductive function. This program involves a multidisciplinary team of psychiatrist, obstetrician/gynecologist, dietitian, nurse and fitness instructor [113]. Participants of this program had significant weight loss, increased pregnancy and ovulation rates, decreased testosterone, increased SHBG, decreased systolic blood pressure, improved physical fitness and nutrition intake and improved psychological health as measured in self-esteem and depression scores [47 –49,54]. Recently, a pilot study has similarly reported significant weight loss (−6.8 kg) among the six subjects who completed a 48-week comprehensive lifestyle program [64]. However, no significant changes in reproductive or metabolic measures were seen, possibly due to the small sample size. Low compliance and high drop-out rate (39%) in this study highlighted some of the difficulties in conducting lifestyle trials in young women with PCOS in recent times.

Despite the efficacy of lifestyle intervention in improving the metabolic and reproductive profile of PCOS women, the use of lifestyle modification as a long-term strategy is still a challenge. Moran and colleagues have looked at weight maintenance over 6 months after an 8-week weight loss trial [44]. The proportion of subjects with weight loss greater than 5% decreased from 74–44% during the 6-month period, suggesting that approximately half of the subjects who had initially lost greater than 5% weight had regained weight in the maintenance phase. Weight regain is often accompanied by the return of metabolic and reproductive disturbances [44]. Therefore, effective strategies for weight maintenance are crucial for the long-term effectiveness of lifestyle treatment in PCOS women.

Medication

Besides lifestyle modification, pharmacotherapy is another noninvasive option for obesity management. However, limited studies have been conducted to describe the effects of various obesity drugs specifically in PCOS women. In one study, sibutramine produced significant weight loss and reduction in hyperandrogenism in 40 obese PCOS women after 5 months of treatment [114]. Similarly, treating PCOS women with orlistat resulted in weight loss and reduction in testosterone [115]. However, as these studies were not placebo-controlled, the placebo weight loss effect of these drugs on PCOS women remains unknown. In non-PCOS studies, a Cochrane review has found that orlistat resulted in an additional 2.7 kg weight loss, while sibutramine resulted in 4.3 kg weight loss at 1 year compared with placebo [116]. On the other hand, rimonabant has been found to produce weight loss of 5% after 1 year in non-PCOS patients [116]. In terms of adverse effects, orlistat was associated with gastrointestinal disturbances, sibutramine with small increases in blood pressure and pulse rate, and rimonabant with nervous, psychiatric or gastrointestinal-related effects [116]

Metformin is increasingly prescribed for PCOS women to treat PCOS-related symptoms. While some studies in PCOS women found that metformin resulted in greater weight loss and fat loss compared with placebo [34,117 –119], a recent meta-analysis found that metformin has no net effect on BMI or waist:hip ratio in this population [120]. In contrast, studies in younger non-PCOS patients have consistently shown a beneficial effect of metformin on body weight and body composition [121 –124]. It is unclear if metformin has an age-specific effect on body weight and composition. A comparison between metformin and sibutramine in chronically anovulating women found that sibutramine was more effective in weight loss but metformin was more effective in restoring reproductive function [125].

Bariatric surgery

Surgical options are often prescribed for patients with morbid obesity. A study has found that bariatric surgery produced 41 kg weight loss in morbidly obese PCOS women after 1 year, which is accompanied by a reduction in hyperandrogenism and restoration of menstrual cycle and ovulation [126]. Similar results were observed by Eid and colleagues with roux-en-Y gastric bypass surgery in PCOS women. These studies suggest that bariatric surgery is an effective treatment for PCOS women with morbid obesity.

Conclusion

PCOS is a common obesity-related endocrine condition which affects women of reproductive age with symptoms such as menstrual irregularity, hirsutism and ovarian dysfunction. Increasing evidence suggests that obesity may play a causal role in developing or maintaining PCOS, possibly through compensatory hyperinsulinemia. Studies have shown that even modest weight loss can result in improvement in fertility and reproductive hormones. However, weight regain can lead to rebound of metabolic and reproductive disturbances. Thus, future research effort should focus on effective ways to achieve and maintain long-term weight loss. To date, relatively few studies have looked at the efficacy and effectiveness of various dietary and exercise regimes in PCOS women, especially in conjunction with behavioral therapy. Thus, the optimal lifestyle intervention for PCOS women remains a question for future research.

Future perspective

Increasingly, lifestyle interventions are progressing towards more holistic approaches, which include not only diet, but also exercise and psychological support to improve physical, mental and emotional well-being of individuals. However, such comprehensive intervention can be burdensome for both clinicians and patients. This may in turn encourage research in novel approaches for longer-term lifestyle management, such as the use of telephone, internet, computer programs, hand-held devices or other tools. Research in the PCOS population has been lacking in this area in the past, and a greater focus in this area would greatly benefit this group.

Executive summary

Obesity & PCOS women

PCOS women are more likely to be obese and insulin resistant.

Hyperinsulinemia is associated with hyperandrogenism through several mechanisms.

Weight loss & PCOS

Up to 80% of individuals who achieved weight loss of at least 5% experienced clinically significant improvements in reproductive function.

Lifestyle program for PCOS women

The NIH recommends a combined therapy consisting of diet, exercise and behavior therapy for long-term weight management.

A number of reduced glycemic load diets have shown potential in inducing weight loss and conferring metabolic benefits to dieters. The optimal exercise regime remains to be investigated.

Challenges with lifestyle modification in PCOS women

Biological and psychosocial factors such as altered appetite responses and high social or family demands poses challenges to lifestyle modification in this group.

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Escobar-Morreale

Botella-Carretero

Alvarez-Blasco

Sancho

Millan

San JL

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