Metabolism Open 12 (2021) 100123

Contents lists available at ScienceDirect

Metabolism Open
journal homepage: www.sciencedirect.com/journal/metabolism-open

PCOS and nutritional approaches: Differences between lean and

obese phenotype
Luigi Barrea a, b, Evelyn Frias-Toral c, Ludovica Verde d, Florencia Ceriani e, Gabriela Cucalón f,
Eloisa Garcia-Velasquez g, Dino Moretti h, Silvia Savastano d, Annamaria Colao b, d,
Giovanna Muscogiuri b, d, *
a
Dipartimento di Scienze Umanistiche, Università Telematica Pegaso, 80143, Napoli, Italy
b
Cattedra Unesco “Educazione alla salute e allo sviluppo sostenibile”, Federico II, Napoli, Italy
c
Universidad Católica Santiago de Guayaquil, Av. Pdte. Carlos Julio Arosemena Tola, Guayaquil, 090615, Ecuador
d
Department of Clinical Medicine and Surgery, Endocrinology Unit, University Federico II, Italy
e
Escuela de Nutrición, Universidad de la República, Montevideo, Uruguay
f
ESPOL Polytechnic University, Escuela Superior Politécnica del Litoral, ESPOL, Lifescience Faculty, Campus Gustavo Galindo Km. 30.5 Vía Perimetral, P.O. Box 09-01-
5863, Guayaquil, Ecuador
g
Clinical Nutrition Service, Grupo Hospitalario Kennedy, Guayaquil, Ecuador
h
Hospital “Eva Perón”, Avenida San Martín, 1645, G. Baigorria, Santa Fe, Argentina

A R T I C L E I N F O A B S T R A C T

Keywords: Polycystic Ovary Syndrome (PCOS) is an endocrine/metabolic disorder with an ever-increasing prevalence. It has
Polycystic ovary syndrome various clinical characteristics; the cardinals are androgen excess, oligo-anovulatory infertility, polycystic
Body composition ovaries, insulin resistance (IR), and cardiometabolic alterations. These disturbances are a consequence of PCOS’s
Obesity
complex etiology. PCOS is mainly related to women with obesity; however, there are many PCOS lean patients
BMI
Diet modification
too. Even though they share some aspects in their metabolic profiles, each group has individual differences in
body composition and other parameters. Thus, in order to achieve successful therapeutic strategies, they should
be tailored to these details. The authors reviewed PubMed’s updated and related publications about body
composition and nutritional strategies for PCOS lean and obese patients. As previous reports have determined,
dietary patterns are essential in PCOS treatment. Several diets have been studied to control and improve IR,
infertility, and cardiometabolic dysfunctions in PCOS. This review will explain the specific features in metabolic
characterization and body composition among these patients. Finally, the diverse nutritional strategies used in
women with PCOS will be analyzed depending on their lean or obese phenotype.

1. Introduction excluded [2,3]. Multiple factors are implied to the onset of this syn­
drome. Many publications focus on the impact of developmental [4],
PCOS is a common endocrine dysfunction in women during their environmental, genetic [5], and epigenetic processes on PCOS patho­
fertile years. The estimated prevalence is between 10 and 15% world­ physiology [6]. Some of them are present during pregnancy, such as
wide [1]. The variety of signs and symptoms is characteristic of this anti-Müllerian hormone levels, intrauterine growth restriction,
syndrome. According to the Rotterdam 2003 diagnostic criteria, PCOS is androgen excess, and endocrine disruptors (e.g. bisphenol A) [7]. These
diagnosed if at least 2 of the following 3 criteria are present: Oligo- last two also occurred after birth [7]. All of them contribute to the
and/or anovulation; clinical and/or biochemical signs of hyper­ progress of IR and obesity.
androgenism; polycystic ovaries, taking into consideration that other Although the mechanism that associates them is not clear, it is
specific diagnoses such as congenital adrenal hyperplasias, known that obesity, IR, compensatory hyperinsulinemia coupled with a
androgen-secreting tumors, Cushing’s syndrome, have been studied and chronic low-grade inflammatory state often coexists with this syndrome

* Corresponding author. Dipartimento di Medicina Clinica e Chirurgia, Unit of Endocrinology, Federico II University Medical School of Naples, Via Sergio Pansini
5, 80131, Naples, Italy.
E-mail address: [email protected] (G. Muscogiuri).

https://doi.org/10.1016/j.metop.2021.100123
Received 1 September 2021; Accepted 4 September 2021
Available online 13 September 2021
2589-9368/© 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
L. Barrea et al. Metabolism Open 12 (2021) 100123

[8]. These same endocrines and metabolic disorders that develop from [24], and oxidative stress [25,26], cluttering the scene and preventing a
PCOS give these patients an increased risk of developing metabolic breakdown. It is needed a thorough and complete understanding that
syndrome, type 2 diabetes mellitus (T2D), infertility [8], cardiovascular encompasses the heterogeneity of PCOS [27,28].
diseases (CVD) [9], negative maternal/neonatal outcomes [10], adrenal Most of the studies that addressed excess body fat in PCOS relied on
incidentalomas [11], among others. approximate total or core fat mass indices, such as body mass index
It is important to note that PCOS is not exclusive to obese women; it (BMI) and waist circumference or waist-to-hip ratio [29]. In practice and
also occurs in lean women. A study by Satyaraddi et al. shows that obese research studies, the obese phenotype of PCOS differs from lean based
and lean women with PCOS, compared to the control group, are meta­ on BMI, that is, if it is above or below, respectively, the limit considered
bolically worse and have more visceral adiposity, concluding that non- normal for age and ethnicity [30].
obese PCOS presents a metabolic risk similar to that of obese patients It is important to note that BMI is not an accurate descriptor of body
because they present a similar amount of visceral adipose tissue [12]. composition and is widely surpassed by more specific techniques such as
It seems clear that environmental factors such as eating habits play computed tomography (CT), magnetic resonance imaging (MRI), and
an essential role in preventing and treating women with PCOS. Inter­ dual-energy X-ray Absorptiometry (DEXA) [31]. These tools allow the
national recommendations indicate that weight control is one of the assessment of individual differences in body composition, fat distribu­
main treatment strategies for PCOS since obesity worsens the clinical tion, and adipose tissue function [31]. In this sense, Carmina et al.,
presentation of this syndrome [13]. There is still no consensus on what is found an inverse correlation between adiposity assessed by DEXA (total
the best nutritional treatment for PCOS. However, according to Fagh­ or central fat) and insulin sensitivity (QUICKI) in patients with PCOS
foori et al., it is recommended to carry out a dietary treatment that has [32]. For their part, Barber et al. reported that visceral fat, assessed by
an impact on the control of IR, metabolic functions from a hypocaloric MRI, was correlated with IR (HOMA2) in a small group of overweight
diet, with a low contribution of simple sugars and refined carbohydrates, women with PCOS [33]. Consistent with these findings, Penaforte et al.
promoting the intake of foods with a low glycemic index (GI) [14]. reported that women with insulin-resistant PCOS, as defined by QUICKI,
Likewise, the reduction of the contribution of saturated and trans fatty had higher amounts of visceral and trunk abdominal fat, as measured by
acids will be sought, and attention should be paid to possible de­ CT, than non-insulin-resistant women [34]. In a large cohort of women
ficiencies such as vitamin D, chromium, and omega-3 [14]. In turn, it has with PCOS, Tosi et al. demonstrated that total or trunk fat mass is
been observed that, since PCOS can be the consequence of a strongly and inversely associated with insulin-induced glucose clearance
lipid-induced proinflammatory state, a healthy diet with adequate dis­ during clamping, considered the gold standard for evaluating IR [35].
tribution of macronutrients seems to be a good option [15]. Other diets This finding supports the hypothesis that excess body fat may be an
that have been studied are the low saturated fat weight-loss diet, low GI essential determinant of IR in PCOS [35]. Satyaraddi et al. in a
diet [16], the ketogenic Mediterranean with phytoextracts (KEMEPHY) case-control study with 81 patients with PCOS (42 obese and 39
diet [17], and the very low carbohydrate diet. non-obese), evaluated the disposition of fat using DEXA and concluded
In addition, it has been postulated that the Mediterranean diet (MD) that both obese and non-obese women with PCOS, in compared to their
can be an adequate dietary treatment for PCOS due to its anti- age controls with the same BMI, were metabolically worse and had more
inflammatory effect and its relationship with the decrease in body visceral adiposity [12]. Non-obese PCOS has a similar risk to obese PCOS
weight [8]. The MD is based on the regular consumption of unsaturated by having a similar amount of visceral adipose tissue (corrected for body
fats, low-glycemic carbohydrates, fiber, vitamins, antioxidants, and a weight) [12].
moderate animal protein intake [18]. Also, a more elevated adhesion to Beyond obesity, the metabolic abnormalities found in PCOS include
the MD related to larger Phase Angle has been published as evidence of dyslipidemias, IR, hyperinsulinemia, and glucose intolerance [36].
cell stability, as another positive effect of MD on PCOS [19]. When it comes to characterizing the metabolic profiles of the obese and
Given the high prevalence of PCOS worldwide and its associated lean phenotypes of women with PCOS, it is essential to do so through the
health consequences, the present work aims to know the different differential patterns of insulin physiology [37]. While non-obese women
nutritional approaches that should be carried out in women with PCOS have lower insulin levels and IR [38] associated with higher levels of sex
based on the lean or obese phenotype to take actions to control this hormone-binding globulin [39], hyperinsulinemia remains a common
syndrome. So, it will be analyzed the specific characteristics in body finding in this population [40]. A primary alteration in β-cell function
composition and metabolic profile between these two groups. Later it has been suggested as a weight-independent pathophysiological
will be developed the nutritional approach for each of them. component in women with PCOS [41]. Insulin hypersecretion is the
probable underlying mechanism in this scenario, present in both lean
2. Differences in body composition and metabolic profile and obese subjects [42]. A possible link between adipose tissue and
between lean PCOS and obese PCOS insulin sensitivity is provided by mediating adipokines, products of
adipose secretory activity. Among them, adiponectin, a protein pro­
Adipose tissue is a highly complex organ with profound effects on duced almost exclusively by adipocytes, is considered to exert
physiology and pathophysiology. In fact, in recent decades, it has come insulin-sensitizing, anti-atherogenic and anti-inflammatory actions. It
to be considered a central endocrine organ in energy homeostasis with has been proposed that adiponectin expression is down-regulated by
implications in metabolic disorders [20]. The most common classifica­ obesity [43]. In a systematic review and meta-analysis by Toulis et al.,
tion scheme distinguishes between subcutaneous and visceral fat, regarding adiponectin levels in women with PCOS, they conclude that
mainly because the latter deposit has a well-known association with after controlling for BMI-related effects, adiponectin levels appear to be
metabolic disease, while the former does not [21]. lower in women with PCOS than in controls without PCOS [44]. Low
Weight gain and central obesity, although not a diagnostic criterion, adiponectin levels in PCOS are likely related to IR, but not testosterone
are common features of PCOS [22]. Visceral adiposity in PCOS is asso­ [44]. Lean women with PCOS have shown decreased sensitivity to
ciated with increased IR, leading to exacerbation of reproductive and catecholamine-mediated lipolysis in subcutaneous adipose tissue (SAT),
metabolic abnormalities [23]. In turn, androgens promote visceral fat which results in the preservation of this tissue [45]. Because leptin is
accumulation and IR by inhibiting lipolysis and promoting lipogenesis. secreted primarily from SAT, this may partially explain the hyper­
Additionally, obesity significantly impacts the PCOS phenotype since it leptinemia found in normal-weight women with PCOS, and although
is associated with a higher prevalence of menstrual irregularity, intrinsic dysregulation of its secretion mechanisms may also be
hyperandrogenemia, and hirsutism [23]. However, this process has involved, the precise chain of events remains unclear [46]. The role of
several vicious circles, with two-way relationships between androgen vitamin D in the pathogenesis of IR associated with PCOS has been
excess, adipose dysfunction, IR, and other actors, such as inflammation postulated, regardless of BMI. The insulin receptor mRNA genomic input

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L. Barrea et al. Metabolism Open 12 (2021) 100123

is improved by Vitamin D signaling through vitamin D receptor (VDR) (hyperandrogenemia, IR, oxidative stress, chronic inflammation) [4].
[47]. This action initiates insulin synthesis and discharge. It also re­
strains some pro-inflammatory cytokines directly related to the IR 3. Nutritional approach to lean PCOS
pathogenesis. There is evidence implying that vitamin D deficiency oc­
curs commonly in obese PCOS patients [48,49]. Furthermore, this PCOS is the most common endocrinopathy of females during
condition is also related to several other alterations such as cancer reproductive age. Hyperandrogenism, IR chronic anovulation, and
progression [50], CVD, autoimmune disorders (e.g., autoimmune thy­ pathogenesis are still unclear, but there is solid evidence that genetic
roid disease) [51], and sleep disruptions. Dyslipidemia is probably the factors are part of PCOS’s etiology since there is a high prevalence of this
most common metabolic disorder in PCOS detected in 70% of patients syndrome in members of the same family. IR, high androgen levels, and
according to the National Cholesterol Education Program (NCEP) dyslipidemia have been found even in non-obese members of patients’
guidelines [52]. Most studies report a decrease in HDL cholesterol and families [36].
an increase in triglyceride levels, the same lipid profile that is known to There is a broad differential disparity of PCOS diagnosis, and it is due
be associated with IR. Lean PCOS women had more diminished HDL and to the different criteria used for the syndrome and differences in
HDL2 levels than their counterparts with normal ovarian function, while geographical and environmental factors in relevant studies. PCOS is
obese PCOS individuals also presented increased triglyceride levels [53]. usually more commonly found in obese women [36]. Obesity is reported
Finally, oxidative stress and low-grade inflammation are two charac­ in 25–70% of women with PCOS, but a significant proportion of patients
teristics shared equally by obese and non-obese patients with PCOS [54]. have it despite having a normal BMI (≤25 kg/m2) [36]. These findings
In PCOS women, a particular biological pattern is found worthy of complicate its diagnostics and therapeutic approach more difficult to
analyzing a complex combination of the consequences of androgen determine. These lean PCOS patients may or may not have the cardinal
excess, dyslipidemia, and IR (Fig. 1). In general, obese phenotypes have symptoms such as irregular menstrual cycles and acne [30].
more severe clinical forms of PCOS than their lean equivalent. However, Despite androgen and adiposity levels, the majority of PCOS patients
both share many central pathophysiological processes have increased serum insulin and IR. Several reports showed the
different metabolic disturbances characteristics in PCOS patients, like
increased plasma insulin levels 2 h after glucose administration to lean
PCOS patients, correlated with the lean, healthy participants. Also,
important risen low-density lipoprotein (LDL) and total cholesterol have
been associated in lean PCOS women versus controls [1,30,55].
Nutrition is one of the major modifiable environmental risk factors
for several non-communicable diseases and plays an essential role in
their prevention and initial treatment [56]. Weight loss is usually
considered the first-line treatment in women exhibiting the obese
phenotype, which in lean women is not needed to lose weight. Instead,
for lean PCOS women, the main goal is to maintain their weight. Many
lifestyle modifications such as dietary interventions and regular physical
activity have demonstrated improved IR and ameliorated hyper­
androgenism amongst other beneficial effects on PCOS symptoms [57].
Lean individuals with PCOS must be encouraged to consume a healthier
diet in its composition, like increasing vegetables and fruit daily to
ensure they have an adequate supply of various minerals, vitamins, and
nutrients [30].
Evidence-based guidelines recommend that lifestyle modification
regimens incorporate a dietary intake consistent with usual healthy
Fig. 1. Pathophysiology of polycystic ovary syndrome (PCOS) nutritional recommendations that include modified macronutrient
PCOS: polycystic ovary syndrome; DM: Diabetes mellitus; OH: ovarian hyper­ composition. These recommendations can be followed for weight
androgenism; IR: insulin resistance; LH: luteinizing hormone; T2D: type 2 maintenance and body composition improvement and the prevention of
diabetes. weight gain and fat mass increase in lean women with PCOS [30].
Fig. 1. Diagram describing the pathophysiology of polycystic ovary syndrome It is essential to mention and remark that lean women with PCOS
(PCOS) and the amplifying factor of visceral adiposity in metabolic disorders. need various nutrients, minerals, and vitamins in their diet since they do
The common denominator in PCOS seems to be OH, with IR and consequent
not need to lose weight or be restricted with their food consumption.
counterbalancing hyperinsulinemia, a nonessential but common aggravating
PCOS is also associated with low-grade inflammation. This relation
factor in this pathophysiology. The propensity for obesity appears to be sec­
ondary to the underlying OH and hyperinsulinism. OH can explain the funda­
could support and demonstrate the therapeutic role of foods and nutri­
mental clinical features of PCOS: hirsutism, oligoanovulation, and polycystic ents such as the Mediterranean dietary pattern in the PCOS pathogenesis
ovaries. Hyperinsulinemia affects the ovary selectively, which persists insulin that likely involving their inflammatory status, IR, and hyper­
sensitive, while liver and skeletal muscle evidence IR. In the ovary, hyperin­ androgenemia [8]. Nevertheless, the exact dietary macro and micro­
sulinism cooperates with LH to up-regulate androgen generation. These effects nutrient combination needed for a good nutritional plan to improve
cause premature luteinization of granulosa cells complicating hyper­ PCOS clinical characteristics are undetermined.
androgenism. Obesity worsens the clinical severity of OH by increasing IR. The The MD is a plant-based, antioxidant-rich diet known for its several
mechanisms may include a deficiency of insulin-sensitizing adipokines such as health benefits. It is characterized by a high intake of whole grains,
adiponectin in favor of pro-inflammatory cytokines such as TNF-alpha; in turn, fruits, vegetables, tree nuts, legumes, and olive oil daily; a moderate
hyperinsulinemia also promotes adiposity, closing the vicious circle. Due to its
intake of fish and poultry, and low consumption of dairy products, red
increased lipolytic response to catecholamines, visceral fat gives more IR than
meat, processed meat and sweets, and finally a moderate consumption
subcutaneous abdominal fat. Androgens oppose the effects of insulin on sub­
cutaneous fat stores, while hyperandrogenemia promotes the accumulation of of wine with meals. This dietary pattern is considered nutritionally
visceral fat. These situations lead to chronic inflammation that mediates long- complete and adequate since it is very easy to follow; it is based on the
term cardiometabolic complications and comorbidities seen in women with traditional foods that people used to eat in their countries. Higher
POCS, including dyslipidemia, metabolic syndrome, T2D, and cardiovascu­ adherence to this nutritional approach has also been proven to be
lar disease. effective in preserving the skeletal muscle mass in healthy women, likely

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L. Barrea et al. Metabolism Open 12 (2021) 100123

due to the potential anti-inflammatory and antioxidant properties of appropriate nutritional interventions that would be highly appealing as
micronutrients or through their direct role in muscle metabolism and a therapeutic lifestyle approach to clinically managing this pathology
physiology, such as with magnesium and potassium [56]. [58] (Fig. 2).
As stated before, inflammation and IR are often associated with
PCOS. This type of inflammation and hyperandrogenism are linked to 4. Nutritional approach to obese PCOS
saturated fat. As stated before, inflammation and IR are often associated
with PCOS. This type of inflammation and hyperandrogenism are linked The frequency of obese women with PCOS is greater than that of the
to saturated fat. A lipid-stimulated proinflammatory status may cause general female population compared to their lean counterparts [1].
the characteristic IR, hyperandrogenism, and dyslipidemia frequently Excessive adiposity in PCOS is associated with increased IR rates,
found in PCOS women. A better macronutrient distribution of the diet resulting in reproductive and metabolic abnormalities aggravation.
despite not being intended for weight loss may improve the constant Also, excessive weight has a significant impact on the PCOS phenotype
inflammatory state. So, there is a strategic relevance and importance of since it is associated with a greater prevalence of menstrual and hor­
the nutritional assessment and body composition evaluation of women monal irregularity, and hirsutism [1].
with PCOS that needs to be considered a crucial step in managing this As for PCOS, no universal treatment is available, and therefore,
syndrome [15]. treatment must always be individualized to the actual needs of the in­
A better macronutrient distribution of the diet despite not being dividual patient. Considering that IR is a major issue on PCOS, first-line
intended for weight loss may improve the constant inflammatory state. therapy treatment are lifestyle changes, including modifications of diet
So, there is a strategic relevance and importance of the nutritional and/or physical activity levels should be recommended, given the pos­
assessment and body composition evaluation of women with PCOS that itive effect that has on improving body composition (abdominal
needs to be considered a crucial step in managing this syndrome [15]. adiposity and obesity), glucose, and/or lipid profile [3,14].
One of the goals of patients with PCOS is on supporting their body by As for dietary treatment, should be taken into consideration a
promoting healthy hormonal balance, a good uterine lining, regular negative energy balance in order to achieve an energy deficit. The
ovulation, improving estrogen metabolism, and these could be achieved specific dietary composition that should be implemented remains quite
by vitamins and minerals such as calcium and vitamin D, as well as some controversial, which can be considered a challenge for clinicians. In the
medicinal herbs that promote hormonal balance and support regular general population, research evaluating the effects of varying dietary
ovulation [58]. recommendations differs from low-calorie diets with fat modifications,
There is promising evidence from several studies suggesting that MD, ketogenic diet (KD) and reduction in the dietary GI in addition to
vitamin D may be involved in several features of PCOS, such as infertility overall calorie reduction to induce weight loss may have a positive effect
[59], hirsutism, IR [60], and CVD risk. For example, vitamin D supple­ on IR (Table 1) [64,65]. Also, studies that converge weight-loss strate­
mentation may improve reproductive function in women with PCOS by gies and the use of inositol have shown that they could bring weight loss
restoring regular menstrual cycles [61,62]. There is a need for more in subjects with PCOS [66]. PCOS has been associated with an increased
randomized trials in well-delineated and determined populations that frequency of weight management methods [67]. These findings may be
will help in defining the role of vitamin D in PCOS. related to women with PCOS being more likely to perceive themselves at
Some publications state that decreased vitamin D levels and IR are risk of excessive weight gain [67–69].
independent body size characteristics in PCOS patients. This assertion is Weight loss, by 5–10%, can improve insulin and testosterone levels
highly relevant since many PCOS women have IR but are not obese [48, and improve menstrual hormones [64,68]. Among the different nutri­
49,54]. Lifestyle intervention has been helpful as it improves body tional strategies, the MD is recognized as a dietary pattern due to its
composition, hyperandrogenism, and IR in women with PCOS. How­ characteristics, like consumption of fatty acids, omega-3 unsaturated
ever, there is a lack of evidence regarding the effect of this lifestyle fatty acids, and diminished consumption of animal-derived proteins that
intervention on improving glucose tolerance or lipid profiles and may decrease many risk factors for metabolic disorders such as endo­
assessing clinical reproductive outcomes, such as quality of life and thelial dysfunction, fatty acids alterations and IR [56,67]. The main
treatment satisfaction [63]. impact on inflammatory activity is due to the microbiota modulation as
There is still the need for more robust evidence to present a foun­ a result of the dietary fiber and the high intake of both polyunsaturated
dation for verifiable nutritional approaches that can help and improve fatty acids (PUFA) omega 3 and antioxidants [56].
PCOS treatment in this specific population. It is of great interest to find In the last couple of years, there has been observed that women

Fig. 2. Nutritional management for polycystic ovary

syndrome (PCOS) lean patients.
PCOS: polycistic ovary syndrome; IR: insulin resis­
tance.
Fig. 2. Nutritional management for PCOS lean pa­
tients. Lifestyle modifications such as dietary in­
terventions and regular physical activity have
demonstrated improved IR and ameliorated hyper­
androgenism amongst other beneficial effects on
PCOS symptoms in PCOS lean patients. These patients
must be encouraged to consume a healthier diet in its
composition, like increasing vegetables and fruit daily
to ensure they have an adequate supply of various
minerals, vitamins, and nutrients and prevent weight
gain and fat mass increase. Nutritional macro and
micronutrient composition have positive effects on
glucose and lipid metabolism, inflammation, and
hormonal balance. For example, vitamin D supple­
mentation may improve reproductive function in
women with PCOS by restoring regular menstrual
cycles.

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L. Barrea et al. Metabolism Open 12 (2021) 100123

Table 1 D may cause inflammatory responses, thus worsening IR. Therefore,

Characteristics of reviewed studies assessing the effect of different dietary weight loss should be kept in mind in the management of obese PCOS to
compositions on obesity in PCOS. restore regular 25(OH)D levels, insulin-sensitivity as a result of total fat
Reference Population Interventions Outcomes mass loss [14,48]. Intervention studies of vitamin D supplementation in
Marsh PCOS Low saturated fat Low-GI vs healthy diet:
women with PCOS have shown improvements in reproductive function,
et al., Mean BMI weight-loss diet Greater improvement glucose metabolism, and lipid profile by improving reproductive func­
2010 >34 Low GI: 1,576 kcal, 50% in insulin sensitivity, tion [48,61,74,75]. Ongoing research is expected to provide answers to
[16] Mean age carbohydrate, 23% lower fibrinogen, whether vitamin D supplementation around 600–800 IU/day depending
>30 yo protein, 27% fat, 34 g improved menstrual
on age and gender, may be effective [48].
Sydney, fiber, 40%GI, 74 g GL regularity.
Australia Standard healthy: 1,569 No significant Another micronutrient that is worth discussing is cyclohexane-
Low GI: n > kcal, 50% carbohydrate, differences in other 1,2,3,4,5,6-hexol (Inositol) belongs to the vitamin B complex. The ste­
29 completed 23% protein, 27% fat, outcomes reoisomers of inositol such as Myo-inositol (MYO-INS) and D-chiro-
Healthy diet: 34 g fiber, 59% GI, 109 inositol (DCI) are currently being used for the treatment of PCOS by
n > 20 g GL
completed
improving IR and reducing CVD risk factors [51,76].
Paoli et al., n: 14 PCOS A modified KD protocol Improvement in levels: Bariatric surgery does appear to change the PCOS complications such
J 2020 BMI: 28.84 was used. The Testosterone, DHEAs, as ovulation rates, menstrual regularity, CVD, decreasing waist
[17] KEMEPHY diet LH, FSH. circumference, and total fat mass. A study of women with PCOS who
(Mediterranean Weight loss: 9,43 kg
underwent laparoscopic bypass, lowering androgen levels and men­
eucaloric ketogenic) BMI at the end of
1600/1700 kcal/day) intervention: 25,49 strual cycles, insulin sensitivity, and blood pressure demonstrated that
with phytoextracts, kg/m2 obesity significantly impacts the pathophysiology of obesity-related
Food supplements are infertility [72]. The indications for bariatric surgery are not different
high proteins (19 g/ in women with PCOS (BMI ≥40 kg/m2 or ≥35 kg/m2 and severe
portion) and very low
morbidity presence. In 2017 a study concluded that weight loss in
carbohydrate (3.5 g/
portion) women with severe obesity and PCOS with gastric surgery resulted in
Le Donne n: 43 PCOS 3 groups Weight loss: 8.1, 8.5 improvement of male hormones like testosterone, hirsutism, and men­
et al., 3 groups Group 1(n = 21) diet and 9.8 kg for Group strual dysfunction [17].
2019 BMI: 31,8 kg/ only 1,2,3 respectively and
[64] m2 Group 2 (n = 10) Diet significant fat mass
and MI lost for Group 1 5. Conclusions
Group 3 (n = 12) diet
inositols (MI + DCI). Even though of the high prevalence of PCOS women with obesity, it
Duration: 6 months for is not unusual to find a significant proportion of patients with normal
all groups.
The diet (1200 Kcal)
BMI. Regardless of androgen concentrations and adiposity levels, these
administered to all three women have elevated serum insulin and IR.
groups 25% fats, The first line of treatment for PCOS is a decrease in body weight of at
15–18% proteins and least 5–10% in those women who are obese, or if it is a PCOS lean pa­
the remaining portion
tient, it is recommended to maintain it. A healthy dietary pattern with
glucids; low GI foods
were recommended satisfactory macronutrient distribution is essential in these patients
since IR, dyslipidemia, and hyperandrogenism might result from a lipid-
induced pro-inflammatory state. Various diets have been studied to treat
population presented lower intake of energy-dense nutrient-poor foods PCOS, such as the low saturated fat weight-loss diet, low GI diet, the
and soda drinks, and higher intake of fruits and legumes thus higher KEMEPHY diet with phytoextracts, and a very low carbohydrate diet. All
adherence to the MD that could support a therapeutic role that has the of them have positively improved some aspects of the PCOS character­
dietary pattern on PCOS [8,56]. istics. Some of them have reached a significant weight loss in those PCOS
Physical exercise has been shown to improve several factors related obese patients. However, the MD has been proposed as a possible eating
to PCOS such as ovulation rates, menstrual regularity, CVD [9], guide that leads to better results in PCOS individuals because of its anti-
decreasing waist circumference, weight, and total fat mass making ex­ inflammatory effect and its relationship with decreased body weight.
ercise a positive non-pharmacological lifestyle change for PCOS [70]. In obese women who have undergone bariatric surgery, an
Physical activity has shown improvement in infertility in women. In a improvement has been found by reducing androgen levels and men­
retrospective cohort study of obese infertile women undergoing cycles of strual cycles, insulin sensitivity, and blood pressure. Notably, an in­
in-vitro fertilization, the results of patients with regular physical activity crease in the frequency of body weight control methods has been
were compared with those who were inactive. There were significantly observed, so health personnel must evaluate this aspect in their follow-
more elevated pregnancy rates in the first group [71,72]. International up visits. Also, vitamin D supplementation has been reported to improve
guidelines for assessing and managing PCOS (2018) indicate that vari­ reproductive function in women with PCOS. In itself, cyclohexane-
ations on intensity and time of exercise are recommended as a lifestyle 1,2,3,4,5,6-hexol (Inositol) is another of the nutrients being studied
change to improve overall health in individuals with PCOS [73]. Daily for its possible benefits in the treatment of this syndrome. Within the
high-intensity interval training and strength training for at least two strategies to improve the lifestyle for PCOS treatment, physical activity
nonconsecutive days for a minimum of 150 min per week of has a fundamental role. It has been demonstrated that it improves
moderate-intensity, 75 min per week of vigorous-intensity, or an several factors related to PCOS.
equivalent of both [70]. Since the dramatically increased prevalence of this syndrome in the
As for micronutrient studies, several studies have suggested that 25 last years and considering the consequences for women’s health both in
(OH)D may be involved in complications related to PCOS, such as the short and long term, it is essential to continue investigating possible
fertility, hirsutism, glucose metabolism, and CVD risk [48,61]. Vitamin non-pharmacological treatments and their impact on PCOS.
D plays a role in various metabolic pathways, including glucose meta­
bolism. 25(OH)D levels are an independent predictor of total fat mass in CRediT authorship contribution statement
PCOS patients. The mechanism behind this effect is still unknown, but
the immunomodulatory role is well documented, and the lack of 25(OH) Luigi Barrea: Conceptualization, Methodology, Formal analysis,

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Declaration of competing interest [9] Orio F, Muscogiuri G, Giallauria F, Savastano S, Bottiglieri P, Tafuri D, Predotti P,
Colarieti G, Colao A, Palomba S. Oral contraceptives versus physical exercise on
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No conflict of interest has been declared by the authors.
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