Nutrition Research Reviews, page 1 of 9 doi:10.

1017/S0954422416000287
© The Authors 2017

Metabolic consequences of obesity and insulin resistance in polycystic

ovary syndrome: diagnostic and methodological challenges

Yvonne M. Jeanes and Sue Reeves*

Health Science Research Centre, Department of Life Sciences, University of Roehampton, London SW15 4JD, UK

Abstract
Women with polycystic ovary syndrome (PCOS) have a considerable risk of metabolic dysfunction. This review aims to present contemporary
knowledge on obesity, insulin resistance and PCOS with emphasis on the diagnostic and methodological challenges encountered in research
and clinical practice. Variable diagnostic criteria for PCOS and associated phenotypes are frequently published. Targeted searches were
conducted to identify all available data concerning the association of obesity and insulin resistance with PCOS up to September 2016. Articles
were considered if they were peer reviewed, in English and included women with PCOS. Obesity is more prevalent in women with PCOS, but
studies rarely reported accurate assessments of adiposity, nor split the study population by PCOS phenotypes. Many women with PCOS have
Nutrition Research Reviews

insulin resistance, though there is considerable variation reported in part due to not distinguishing subgroups known to have an impact on
insulin resistance as well as limited methodology to measure insulin resistance. Inflammatory markers are positively correlated with androgen
levels, but detailed interactions need to be identified. Weight management is the primary therapy; specific advice to reduce the glycaemic load
of the diet and reduce the intake of pro-inflammatory SFA and advanced glycation endproducts have provided promising results. It is
important that women with PCOS are educated about their increased risk of metabolic complications in order to make timely and appropriate
lifestyle modifications. Furthermore, well-designed robust studies are needed to evaluate the mechanisms behind the improvements observed
with dietary interventions.

Key words: Polycystic ovary syndrome: Obesity: Diabetes: Insulin resistance

Introduction to September 2016. PubMed and Science Direct were utilised in

order to locate relevant scientific reports and papers and ensure
Polycystic ovary syndrome (PCOS) is a common endocrine– an extensive review of the literature. Articles were considered if
metabolic disorder affecting 12–18 % of women, depending on they were peer reviewed, in English and included women with
the diagnostic criteria used(1). Women with PCOS are at lifelong PCOS (all diagnostic methods).
risk of metabolic dysfunction and have increased risk of insulin PCOS is a heterogeneous condition, the symptoms of which
resistance (IR), type 2 diabetes mellitus (T2DM), dyslipidaemia often first present during the teenage years(7), though the
and atherosclerosis(2). The pathophysiology of PCOS is com- symptoms vary in their severity and can also change with age.
plex and to some extent remains unclear; PCOS has a genetic The symptoms include: menstrual irregularity, acne, excess
heritability and several potential genes have been identified. male pattern hair (hirsutism), male pattern alopecia, central
However, research in this area is still in its infancy(3,4) and is adiposity and fertility issues. Many of the symptoms associated
influenced by environmental factors, most notably diet and with PCOS have been shown to lead to a reduction in health-
increased body weight(5). The progression of research and related quality of life(8) and consequently depression and anxiety
translation into clinical practice are hindered by the variability are commonly reported in women with PCOS, independent of
of diagnostic and methodological issues endemic in studies of body-weight status(9). Although obesity is a common feature of
PCOS(6). PCOS, lean women with PCOS are also at increased disease risk
Therefore the aim of this review is to present current when compared with matched controls and can also suffer
knowledge on the association between obesity, IR and PCOS debilitating symptoms(3). IR is not within any of the diagnostic
and in doing so highlight some of the diagnostic and metho- criteria; however, the majority of lean and overweight women
dological challenges encountered in research and clinical with PCOS have a form of IR intrinsic to PCOS and the com-
practice. Targeted searches were conducted to identify all pensatory hyperinsulinaemia drives many of the phenotypic
available data concerning the association of obesity and IR with features of PCOS(10). Hyperinsulinaemia promotes ovarian
PCOS in order to summarise current knowledge on this topic up hyperandrogenism which is present in 60–80 % of women with

Abbreviations: AGEs, advanced glycation endproducts; GI, glycaemic index; GL, glycaemic load; IGT, impaired glucose tolerance; IR, insulin resistance;
NAFLD, non-alcoholic fatty liver disease; PCOS, polycystic ovary syndrome; T2DM, type 2 diabetes mellitus; VAI, visceral adiposity index.
* Corresponding author: Dr Sue Reeves, email [email protected]

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 2 Y. M. Jeanes and S. Reeves

Table 1. Diagnostic criteria for polycystic ovary syndrome (PCOS)(18) between studies. There is also uncertainty as to whether PCOS
causes weight gain and obesity or if obesity is linked to the
NIH Rotterdam AE- development of PCOS(21,22). Furthermore, clarification of
Criteria 1990 2003* PCOS
the role of adiposity in PCOS entails measurements other than
Oligo-ovulation leading to oligomenorrhoea, + +/− +/− the measurement of BMI.
or anovulation leading to amenorrhoea A meta-analysis clearly indicated that overweight or obese
Hyperandrogenism: clinical (hirsutism, male + +/− +
pattern alopecia, acne) and/or biochemical women with PCOS had significantly worse metabolic and
Polycystic ovarian morphology on ultrasound +/− +/− +/− reproductive outcomes when compared with healthy-weight
women with PCOS(23). Palomba et al.(24) confirmed that obesity
NIH, National Institutes of Health; AE, androgen excess.
* The presence of two of the following three features with the exclusion of other has a bidirectional relationship with PCOS and noted that
endocrine disorders. excessive weight gain could unmask a latent PCOS condition.
IR promotes the development of visceral adiposity in women
with PCOS, whereas the role of androgens is less clear(25). Tosi
PCOS; the androgen excess predominately results from increased et al.(26) have recently shown adiposity to be correlated with IR
synthesis and release of ovarian androgens(10). In combination, and free testosterone levels (fat mass determined by dual-
hyperinsulinaemia and hyperandrogenaemia can disrupt follicle energy X-ray absorptiometry (DXA), IR with euglycaemic clamp
growth; this is accompanied by menstrual irregularity, anovula- and serum free testosterone by liquid chromatography–MS;
tory sub-fertility and accumulation of immature follicles(5). n 100 women with PCOS). However, insulin sensitivity, but not
The most widely used criteria for clinical diagnosis of PCOS adiposity, was found to be an independent predictor of free
involve the presence of two of the three features listed in testosterone concentrations. The central:peripheral fat ratio
Nutrition Research Reviews

Table 1, with the exclusion of other endocrine disorders as identified by DXA was shown to be related to androgen levels
developed by the European Society of Human Reproduction in twenty-four women with PCOS(27). Details of the complex
and Embryology (ESHRE) and the American Society for relationship between androgens and obesity are gradually
Reproductive Medicine (ASRM)(11), and are otherwise known as unfolding(28); adipocytes seem to be prone to hypertrophy
the Rotterdam criteria. when exposed to androgen excess, and both adipose tissue
There are distinct phenotypic presentations associated with hypertrophy and hyperandrogenism are related to IR(29). What
PCOS, and over the years several sub-categories have been is known is that weight reduction, even as little as 5 %, improves
suggested. In 2012 at the National Institutes of Health workshop PCOS symptoms in overweight or obese women with
there was a general consensus(12) and these categories are as PCOS(30,31).
follows: Whether women with PCOS present with increased abdom-
Androgen excess + ovulatory dysfunction; inal adiposity compared with women in the general population
Androgen excess + polycystic ovarian morphology; continues to be debated. A diagnostic method of abdominal
Ovulatory dysfunction + polycystic ovarian morphology; obesity has not yet been defined and thus a range of methods is
Androgen excess + ovulatory dysfunction + polycystic used. Visceral adiposity index (VAI) is a simple surrogate marker
ovarian morphology. of visceral adiposity which utilises BMI, waist circumference, TAG
Several studies have highlighted that women with PCOS and HDL measurements and has been increasingly used since it
who have regular ovulatory cycles often have normal insulin was established in 2010(32). Anthropometric studies that include
sensitivity with milder metabolic abnormalities compared with waist circumference measurements have shown that, regardless
women with PCOS with ovulatory dysfunction(13,14). Women of BMI, women with PCOS typically have an increased abdominal
who are anovulatory with hyperandrogenism are considered to fat distribution(33–36). A meta-analysis by Lim et al.(20) also
be at the greatest metabolic risk(15). Women with hyperandro- reported that women with PCOS had increased prevalence of
genic PCOS generally present with a worse cardiometabolic central obesity (risk ratio 1·73; 95 % CI 1·31, 2·30; PCOS n 1191;
profile compared with women with non-hyperandrogenic controls n 2396) (Fig. 1).
PCOS(16–18). It is generally agreed that the heterogeneity in When body composition has been assessed by MRI, amounts
the PCOS population, studies not reporting specific PCOS of visceral adipose tissue have been found to be similar in
phenotypes, and the different methodologies used to report women with PCOS and controls with comparable BMI (n 31),
IR and obesity/visceral fat have led to controversy in the rela- despite increased waist:hip ratios(37) in the women with PCOS.
tionship between obesity, IR and PCOS(6,19). However, it is worth noting that in this study a number of
participants were only 1 week after ceasing the insulin-
sensitising agent, metformin, which has been shown to
Obesity and polycystic ovary syndrome
reduce visceral adiposity in women with PCOS(38,39). Until
Obesity is a common feature of PCOS. A meta-analysis of cross- relatively recently, studies infrequently reported PCOS pheno-
sectional and retrospective studies illustrated there is a greater types, which are known to have an impact on metabolic risk.
prevalence of obesity in PCOS; BMI > 30 kg/m2 (relative risk Panidis et al.(40), in a relatively small study (n 100 PCOS),
2·77; 95 % CI 1·88, 4·10; PCOS n 4165; controls n 4885) com- reported significantly higher VAI in the hyperandrogenism and
pared with healthy women(20). The variability of data reporting oligo/anovulation phenotype, when compared with other
the prevalence of obesity in women with PCOS is likely to phenotypes. Additionally, Androulakis et al.(41) reported that
reflect geographical, environmental and population variability women with PCOS with menstrual disorders had significantly

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 Obesity and polycystic ovary syndrome 3

PCOS Control Risk ratio Risk ratio

Study of subgroup Events Total Events Total Weight M-H, random, 95 % CI M-H, random, 95 % CI
Amato 2008(113) 113 170 21 34 17.8 % 1.08 (0.81, 1.43)
Bernasconi 1996(114) 32 52 21 40 15.9 % 1.17 (0.81, 1.63)
Chae 2008(115) 33 143 37 255 14.6 % 1.59 (1.04, 2.43)
Cheung 2008(116) 147 277 14 98 13.0 % 3.71 (2.26, 6.11)
Glueck 2003(117) 118 138 821 1887 21.3 % 1.97 (1.80, 2.14)
Hahn 2007(118) 306 411 29 82 17.5 % 2.11 (1.56, 2.84)

Total (95 % CI) 1191 2396 100.0 % 1.73 (1.31, 2.30)

Total events 749 943
Heterogeneity: tau2 = 0.10; 2 = 30.73, df = 5 (P < 0.0001); I 2 = 84 %
Test for overall effect: Z = 3.82 (P = 0.0001) 0.01 0.1 1 10 100
Lower risk for PCOS Higher risk for PCOS

Fig. 1. Meta-analysis(113–118) of the prevalence of central obesity in women with and without polycystic ovary syndrome (PCOS) (taken from Lim et al.(20)).
M-H, Mantel–Haenszel.

higher VAI when compared with PCOS without menstrual dis- presenting PCOS phenotypes. In particular, visceral fat plays a
orders. A more recent, albeit relatively small, study(15) reported key role in generating the insulin-resistant state which leads to
a higher VAI in PCOS women with hyperandrogenism and impaired glucose tolerance (IGT) and is a significant and
Nutrition Research Reviews

oligo/annovulation compared with other phenotypes. Further independent risk factor for T2DM(49).
research is clearly warranted with more accurate assessments of
adiposity for different PCOS phenotypes to help clarify the link
Insulin resistance in polycystic ovary syndrome
between obesity and PCOS.
Visceral adipose tissue is an important endocrine organ, A link between PCOS and IR was first highlighted in 1980,
producing and releasing several adipokines; any specific dif- whereby obese women with PCOS were shown to have an
ferences in resistin, leptin and visfatin in PCOS women com- increased insulin response to an oral glucose tolerance test
pared with controls remain uncertain; however, a clear role for compared with obese controls(50). Prevalence rates of IR have
adiponectin in PCOS has been reported. Adiponectin is down- been reported between 44 and 85 %(10,51). This variability is in
regulated in obesity and is associated with IR; it also has strong part due to differences in PCOS phenotype and ethnicity(15,17).
insulin-sensitising, anti-inflammatory and anti-diabetic func- Reports of the prevalence of IR are limited by the methods used
tions. Adiponectin circulates in different polymer complexes; it to determine insulin sensitivity; the euglycaemic insulin clamp
has been suggested that its actions are mediated primarily by technique is the most accurate method to diagnose IR, but its
the high-molecular-weight form of adiponectin(42). In 2014(43), high cost limits use; thus the surrogate markers, fasting insulin
a meta-analysis based on thirty-eight trials (n 1944 PCOS; and homeostasis model assessment of insulin resistance
n 1654 healthy controls) highlighted significantly lower total (HOMA-IR)(52), are often reported.
adiponectin levels in PCOS women compared with healthy IR and compensatory hyperinsulinaemia are fundamental to the
controls, independent of BMI (weighted mean difference −2·67; exacerbation of PCOS symptoms and metabolic complications(53).
95 % CI −3·22, −2·13). Visceral fat secretes less adiponectin Several studies have shown that the majority of women with
compared with subcutaneous fat(44), so the proposed increased PCOS, both lean and overweight, have a form of IR that is
visceral adiposity in women with PCOS could be a reason intrinsic to the syndrome(10). Researchers have shown that
behind decreased high-molecular-weight adiponectin levels. obesity and PCOS have a separate and synergistic relationship
Metformin, a common treatment option for PCOS, was with IR(54). Defects in both insulin sensitivity and secretion are
associated with significantly elevated serum adiponectin present in lean women with PCOS(55). The pathogenesis of IR in
concentrations in women with PCOS (standard mean differ- PCOS is complex and incompletely understood, though it
ences −0·43, 95 % CI −0·75, −0·11)(45). In addition, it is likely that is agreed there is a post-binding defect in insulin receptor
adiponectin levels are different in the PCOS phenotypes as signalling(51). There is an increasing body of evidence to
suggested by Cankaya et al.(46); in a small study (n 40), suggest a genetic susceptibility to PCOS and its associated IR as
adolescents with androgen excess PCOS phenotype had well as evidence to suggest tha PCOS may also have fetal
significantly lower high-molecular-weight adiponectin levels origins due to androgen exposure at critical periods of growth
compared with non-hyperandrogenic women. Testosterone has or due to intra-uterine growth restrictions(4).
been found to contribute to high-molecular-weight adiponectin IR is a common feature in annovulatory women with PCOS;
variance(47); however, in a 2009 meta-analysis testosterone however, it is not as frequently observed in ovulatory women
levels were not associated with adiponectin levels(48). Further with PCOS, even when hyperandrogenism is present(56).
high-quality studies are needed to help clarify the role of Bil et al.(15) reported significantly greater HOMA-IR in the
testosterone and adiponectin in PCOS. androgen excess PCOS phenotype compared with non-
Obesity is evidently complex and the location of excess hyperandrogenic women (n 100). Some older studies have
adiposity is key and all too rarely measured in combination with failed to demonstrate IR in lean women with PCOS(57,58),

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 4 Y. M. Jeanes and S. Reeves

although this may be accounted for by the inability to distin- studies reported an OR of 2·54 (95 % CI 1·44, 4·47) for OGT and
guish between the different PCOS phenotypes which resulted in 4·00 (95 % CI 1·97, 8·10) for T2DM(72). Differences in the diag-
the inclusion of women who were ovulatory. nostic criteria for IGT and PCOS were evident, and there were
Chronic inflammation and its role in IR in PCOS continues to inadequate data to allow for PCOS phenotype sub-analysis;
be investigated(59). The increase in multiple markers of additionally, differences in ethnicity and BMI have resulted in
inflammation such as leucocyte count, C-reactive protein, IL-18, variable risk estimates between PCOS studies. Studies in the
protein-1, and monocyte chemo-attractant in addition to USA have indicated a prevalence of 23–35 % for IGT and 4–10 %
increased oxidative stress and endothelial dysfunction are evi- for T2DM(67,68), whereas in non-US studies prevalence rates in
dence that PCOS is commonly coupled with low-level systemic women with PCOS are elevated although not all to the same
inflammation(60). However, there are limited studies that assess extent, with prevalence rates of 16 % for IGT and 2·5 % for
the presence of chronic inflammation independent of adiposity T2DM described in an Italian cohort(73). In the US studies, even
in women with PCOS. Circulating markers of oxidative stress lean women with PCOS had increased rates of IGT and T2DM
are abnormal in women with PCOS independent of weight compared with healthy controls(67), the onset of IGT occurring
excess and IR(61). The close association between oxidative in their thirties and forties which is earlier than the normal
stress and inflammation make it difficult to determine their population(74). A more recent longitudinal study following
individual contribution to PCOS and the mechanism of oxida- women for at least 10 years reported that the age-standardised
tive stress-induced IR remains unclear(62). Oxidative stress and prevalence of diabetes at the end of follow-up was 39·3 %,
inflammation markers are positively correlated with androgen significantly higher than in healthy women (prevalence of
levels in PCOS patients(63); thus they seem to contribute to 5·8 %)(75).
hyperandrogenaemia, but detailed interactions still need to be The Royal College of Obstetrics and Gynaecology 2014
Nutrition Research Reviews

identified, and as of yet few investigations have been done. guidelines(76) state that women presenting with PCOS with a
Insulin acts directly on the ovary by stimulating the thecal BMI ≥ 25 kg/m2 and lean women with PCOS, but who have
cells to increase androgen production and by activation of the additional risk factors such as advanced age (> 40 years),
cytochrome P450c17α(57,64). Hyperinsulinaemia further exacer- personal history of gestational diabetes or family history of
bates the pathogenesis of PCOS by inhibiting the production of T2DM, should have a 2-h post-75 g oral glucose tolerance test.
insulin-like growth factor-1 (IGF-1) binding protein in the liver,
leading to elevated circulating levels of IGF-1, which in
Metabolic syndrome and non-alcoholic liver disease in
turn stimulates ovarian thecal cell androgen production(65).
polycystic ovary syndrome
Hyperinsulinaemia reduces hepatic production of sex
hormone-binding globulin, thus increasing free testosterone PCOS commonly includes many metabolic syndrome compo-
levels(66). In combination, hyperinsulinaemia and hyperandro- nents, such as abdominal obesity, dyslipidaemia, hyperglycae-
genaemia can disrupt follicle growth; this is accompanied by mia and hypertension, which predispose women with PCOS to
menstrual irregularity, anovulatory sub-fertility and accumula- the development of T2DM and CVD. There is a higher pre-
tion of immature follicles(51). Diamanti-Kandarakis & Dunaif(51) valence of the metabolic syndrome in women with PCOS
in a review described the modulating action of insulin on compared with women in the general population(77), estimated
ovarian steroidogenesis as well as the importance of the insulin to be between 34 and 46 %, based on studies of Caucasian
signalling pathway in the control of ovulation. women with PCOS from the USA using the National Cholesterol
Women with PCOS commonly have postprandial Education Program Adult Treatment Panel III criteria(78–80).
dysglycaemia(67,68), which reflects peripheral, primarily skeletal Women diagnosed with PCOS using National Institutes of
muscle, IR. In lean women with PCOS hyperinsulinaemia is Health criteria are more likely to have a higher prevalence of
often evident postprandially but not in the fasted state(69). the metabolic syndrome compared with controls, compared
IR and compensatory hyperinsulinaemia have also been with women diagnosed with PCOS using the ESHRE/ASRM
proposed as a cause of reactive hypoglycaemia in women with guidelines(72,81). Studies that clearly indicate the prevalence of
PCOS. A cross-sectional study of sixty-four lean young women the metabolic syndrome in differing PCOS phenotypes are
with PCOS reported the rate of reactive hypoglycaema to be lacking.
50 %(70). A survey of clinical practice (n 88) also indicated a high IR and obesity are strong predictors of non-alcoholic fatty
prevalence of hypoglycaemia; self-reported in 71 % of women liver disease (NAFLD)(82,83); thus it is not surprising that there is
with PCOS(36). A recent study also indicated a higher prevalence a higher prevalence of NAFLD in women with PCOS compared
of reactive hypoglycaemia in PCOS (n 88) compared with with age- and BMI-matched controls; prevalence rates ranging
age- and BMI-matched controls (n 34), though a much lower from 27 to 62 %(84–87). This variation can be attributed to dif-
prevalence of 17 %(71). Robust studies investigating hypo- ferences in laboratory diagnostic criteria (for example, liver
glycaemia are sparse. function tests, liver imaging studies, liver biopsy) and differ-
ences in study populations relating to ethnicity, age, BMI and
PCOS diagnostic criteria(88). Vassilatou(88) has highlighted the
Impaired glucose tolerance and type 2 diabetes mellitus
increasing evidence that hyperandrogenism is related to NAFLD
The prevalence of IGT and T2DM in women with PCOS is in PCOS and suggested that hyperandrogensim should be
substantially higher compared with age- and weight-matched considered as an additional link in the synergy with obesity
healthy women; a meta-analysis of cross-sectional and cohort and IR for the development of NAFLD in PCOS. However,

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 Obesity and polycystic ovary syndrome 5

sub-analyses with the PCOS phenotypes were not reported and insulin resistant. However, exploring the mechanisms behind
would seem prudent for further evaluation. the intervention and assessing IR with the euglycaemic clamp
Of clinical importance, the prevalence of non-alcoholic technique and evaluating the effect of modifying dietary GI in a
steatohepatitis (NASH) in women with PCOS is particularly subgroup of IR women with PCOS is prudent to improving the
high(89). Bariatric surgery has shown beneficial outcomes on evidence base for dietary recommendations.
NASH(90). With the exception of weight loss through lifestyle Inflammation is implicated in the pathogenesis of PCOS;
modification and encouraging exercise in obese women, few dietary constituents such as SFA can influence inflammatory
evidence-based effective treatments specifically target NAFLD/ mediators, such as TNF-α and IL-1β and disrupt insulin
NASH in women with PCOS(91). signalling(103,104). Conversely, MUFA and PUFA do not interrupt
metabolism and inflammation to the same extent. SFA intake
has been shown to influence glucose metabolism through the
Dietary influences of the metabolic aspects of polycystic
altering of insulin signalling and cell membrane function, with a
ovary syndrome
diet high in SFA associated with a decrease in insulin sensitivity
With no cure for PCOS, clinical management focuses on treating when compared with a high-MUFA diet(103). Of interest, it has
the presenting symptoms. Lifestyle management is advocated as been reported that 68 % of women with PCOS had a total fat
the primary therapy in overweight and obese women with intake greater than a 35 % contribution to total energy, with
PCOS since even a modest weight loss of just 5–10 %, without SFA intake accounting for 12 % of total energy, substantially
medical intervention, improves many of the symptoms asso- exceeding the reference nutrient intake (<10 % energy)(105,106).
ciated with PCOS(30,92,93). Thus, a reduction of total fat intake should focus on lowering
The optimal method of achieving sustainable weight loss is SFA intake concurrently with the encouragement of the main-
Nutrition Research Reviews

under constant debate; studies demonstrating the clinical ben- tenance of MUFA and PUFA in women with PCOS. There is
efits of weight loss in women with PCOS incorporate a variety some evidence to show that by reducing the consumption of
of methods to reduce energy intake and achieve a negative saturated fat(107) and reducing the GI and GL of the diet(107),
energy balance(94). Behaviour-change strategies have long been insulin sensitivity can be improved in insulin-resistant popula-
recognised as being instrumental in managing chronic condi- tions; however, there remains a paucity of studies in women
tions, particularly weight management. However, lifestyle with PCOS(108).
modification programmes are often reported to have low Advanced glycation end products (AGEs) are elevated in
compliance and high dropout rates(95). Furthermore, many PCOS(109); these pro-inflammatory molecules trigger a state of
overweight or obese women with PCOS are not following a diet intracellular oxidative stress and inflammation after binding to
that would promote weight loss(96). Bariatric surgery, on the their cell membrane receptors (RAGE). They are highly reactive
other hand, in women with PCOS has resulted in substantial molecules formed by non-enzymic reactions of carbonyl group
weight loss and marked improvement of multiple biochemical of carbohydrates with free amino groups of proteins, nucleic
abnormalities(97,98). A recent meta-analysis of thirteen studies acids or lipids. AGEs within the body are from endogenous
(2130 women) reported a reduction in the incidence of PCOS production or ingested in high amounts from cooked fast
preoperatively from 45·6 %, to 6·8 % at 12-month follow-up(99). food(110). A small study(111) (twenty-three PCOS participants)
Dietary modification to improve IR may produce benefits has shown that a 2-month intervention of a low dietary intake of
greater than those achieved by modest weight loss and would AGEs is associated with improved levels of serum testosterone,
also be suitable for lean IR women with PCOS. Modifying the oxidative stress and HOMA-IR in PCOS. The role of dietary
carbohydrate content and fatty acid content of the diet have AGEs as mediators of metabolic and reproductive alterations in
both been proposed as methods to improve insulin sensitivity. PCOS is an exciting and emerging area of dietary modification
The concept of a low-glycaemic index (GI) diet aims to reduce for PCOS.
the glycaemic load (GL) and hence insulin response to ingested An area yet to be explored in PCOS is the role of the gut
foods and drinks. Greater improvement in insulin sensitivity microbiota(112), which could influence glucose homeostasis and
and regular menses were reported after weight loss with a low insulin sensitivity by fermenting indigestible dietary compo-
dietary GI approach (n 29) compared with weight loss through nents to produce SCFA. These SCFA have been shown to
conventional healthy eating (n 20)(100). In this study, women beneficially modulate adipose tissue, skeletal muscle and liver
were followed for 12 months or until they achieved 7 % weight tissue function. Furthermore, research, including well-designed
loss. Barr et al.(101) also demonstrated an improvement in robust studies, is needed to evaluate the mechanisms behind
insulin sensitivity after following an isoenergetic diet with a the improvements observed with dietary modification and
reduction in dietary GI in twenty-one women with PCOS over a inherent with all weight-reduction interventions to improve
12-week intervention period. Furthermore, one study(102) adherence to interventions and weight maintenance.
reported a reduction in IR after a 12-week hypoenergetic diet,
high in protein (30 % protein: n 23), with a low GL compared
Conclusion
with a conventional hypoenergetic healthy eating intervention
(15 % protein: n 26). A low-GL diet in lean women with PCOS PCOS is a diverse condition that manifests itself in a variety of
(n 41) resulted in a reduction in waist circumference(36). These symptoms linked to ovulatory dysfunction and the over-
small studies suggest a benefit for promoting lower GI dietary production of androgens. Women with PCOS are at a greater
advice to lean women with PCOS, many of whom are also risk of metabolic dysfunction and consequently need regular

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 6 Y. M. Jeanes and S. Reeves

monitoring for risk of diabetes and CVD. Whilst treatment is endocrine and metabolic disorders in PCOS patients. Eur J
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No funding was received for this review. Both authors were
18 Azziz R, Carmina E, Dewailly D, et al. (2006) Position
involved at all stages and contributed equally. Statement: criteria for defining polycystic ovary syndrome as
There are no conflicts of interest. a predominantly hyperandogenic syndrome: an Androgen
Excess Society Guideline. J Clin Endocrinol Metab 91,
4237–4245.
19 Teede H, Deeks A & Moran L (2010) Polycystic ovary
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