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Journal of Obesity & Metabolic Syndrome

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J Obes Metab Syndr 2024; 33(4): 289-301

Published online December 30, 2024 https://doi.org/10.7570/jomes24035

Copyright © Korean Society for the Study of Obesity.

Obesity and Polycystic Ovary Syndrome

Jin Ju Kim 1,2,*

Author Affiliations

1Department of Obstetrics and Gynecology, Seoul National University Hospital Healthcare System Gangnam Center, Seoul; 2Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea

Correspondence to:
Jin Ju Kim
https://orcid.org/0000-0003-0879-8208
Department of Obstetrics and Gynecology, Seoul National University Hospital Healthcare System Gangnam Center, 152 Teheran-ro, Gangnam-gu, Seoul 06236, Korea
Tel: +82-2-2112-5637
Fax: +82-2-2112-5794
E-mail: tom7@snu.ac.kr

Received: September 24, 2024; Reviewed : November 29, 2024; Accepted: December 15, 2024

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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The core pathophysiology of polycystic ovary syndrome involves an overproduction of androgens primarily originating from ovarian thecal cells. Two major external triggers promote androgen overproduction in the ovaries: the increased secretion of luteinizing hormone, a consequence of aberrant hypothalamic gonadotropin-releasing hormone secretion dynamics, and compensatory hyperinsulinemia resulting from insulin resistance. Obesity interacts with polycystic ovary syndrome in multiple ways, but a major role of obesity in its pathophysiology is the exacerbation of insulin resistance. Additionally, obesity contributes to polycystic ovary syndrome by facilitating the conversion of precursor hormones to testosterone within adipose cells. Moreover, obesity can lead to relative hyperandrogenemia, which is marked by lower levels of sex hormone binding globulin and increased availability of free testosterone to target tissues. Also, obesity affects the secretion of gonadotropins, resulting in heightened luteinizing hormone secretion or increased sensitivity of thecal cells to luteinizing hormone. Obesity-related insulin resistance might be amplified by alterations in adipokine and inflammatory cytokine production. Ultimately, obesity and polycystic ovary syndrome might share a common genetic predisposition. The cornerstone of managing polycystic ovary syndrome is to address individual symptoms such as hyperandrogenism (hirsutism, acne, and female type boldness), menstrual irregularities, and infertility stemming from anovulation. However, obesity is integral to the pathophysiology of polycystic ovary syndrome and exacerbates all of its features. Therefore, lifestyle modifications aimed at weight reduction should be the primary strategy in overweight or obese women with polycystic ovary syndrome.

Keywords: Anovulation, Insulin resistance, Obesity, Polycystic ovary syndrome

INTRODUCTION

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Polycystic ovary syndrome (PCOS) is a prevalent (10% to 13%) endocrine disorder affecting reproductive-aged women.1,2 Its etiology is multifaceted and remains elusive; however, the overproduction of androgens by the ovaries (and to a lesser extent, the adrenal glands) is pivotal in the pathophysiology of PCOS, which often includes the occurrence of anovulation.

Historically, PCOS was perceived as a gynecological condition primarily characterized by menstrual irregularities. However, since the 1980s, a significant correlation between PCOS and insulin resistance (IR), along with resultant hyperinsulinemia, has been reported. Consequently, PCOS has been recognized not merely as a reproductive disorder but also as a metabolic disturbance associated with IR.

Obesity was once presumed to be a primary cause of PCOS, since many women with this syndrome were obese. However, obesity is neither necessary for the diagnosis of PCOS nor a sufficient explanation for the pathophysiology. This review delves into the interplay between PCOS and obesity and examines the management of PCOS with a focus on obesity.

DIAGNOSIS OF PCOS

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PCOS is usually diagnosed following the Rotterdam consensus criteria, which appears in the updated international evidence-based PCOS guidelines (Table 1).3,4 These guidelines suggest a diagnosis of PCOS when a woman exhibits two of the following three criteria; (1) anovulation, presenting as irregular menstruation or amenorrhea; (2) clinical or biochemical signs of hyperandrogenism (HA) (such as hirsutism, acne, female type boldness, and/or elevated testosterone levels); and (3) the presence of polycystic ovary morphology on pelvic ultrasonography or increased serum anti-Müllerian hormone levels. The application of the third criterion for diagnosing PCOS is not recommended for those with a gynecological age of less than 8 years (less than 8 years post-menarche) due to the absence of definitive normative data during this period. Before confirming a diagnosis of PCOS, it is essential to rule out other causes of HA (such as nonclassical congenital adrenal hyperplasia, androgen-secreting tumors, or Cushing syndrome) and irregular menstruation (primarily due to thyroid disorders and hyperprolactinemia).

PATHOPHYSIOLOGY OF PCOS

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The major circulating androgens in women are dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), androstenedione (ADD), and testosterone. DHEA, DHEA-S, and ADD are considered prehormones since they have little or no intrinsic activity and require conversion to testosterone to exert androgenic effects.

In women, ovary and adrenal cortex are the two major sources of circulating androgens. Moderate adrenal androgen excess is commonly observed in women with PCOS;5-10 approximately 20% to 30% of women with PCOS demonstrate adrenal androgen excess using DHEA-S and ADD as markers.8 Thus, studies have reported that simultaneous measurement of DHEA-S or ADD alongside testosterone can increase the sensitivity of PCOS-related androgen excess detection.8,10 Nevertheless, it is excessive ovary androgen production that is fundamental to PCOS. The ovarian follicle consists of inner granulosa cells and outer theca cells. Steroidogenesis in the ovaries is contingent on the collaborative efforts of granulosa and theca cells, with androgen synthesis primarily occurring within thecal cells. The potential mechanisms for heightened androgen production in thecal cells among women with PCOS include: (1) a degree of intrinsic functional defect in theca cells11-14 and (2) elevated extrinsic stimulation of theca cells by luteinizing hormone (LH) or insulin. Among these, extrinsic stimulations by LH or insulin serve as the predominant pathway for thecal cell androgen hyperproduction (Fig. 1).

Increased LH concentration originating from increased gonadotropin-releasing hormone pulse frequency can cause theca cell androgen hyperproduction

LH, a pituitary hormone, activates androgen production in the ovarian theca cells. Elevated serum LH levels in women with PCOS drive increased androgen production in theca cells, thereby serving as a crucial factor in PCOS pathogenesis. Augmented LH production in women with PCOS arises from intensified gonadotropin-releasing hormone (GnRH) secretion frequency within the hypothalamus. While typical frequency in normal women is about 16 times in 24 hours, women with PCOS exhibit frequencies of around 22–24, roughly one per hour. This increase in GnRH pulsatility promotes LH secretion from the pituitary gland, whereas decreased pulsatility enhances follicle stimulating hormone (FSH) secretion. It is presumed that genetic and/or environmental factors might be involved in GnRH pulse generator system abnormalities.15-17

IR and resultant hyperinsulinemia can cause HA in PCOS

IR is present in 75% of lean patients and 95% of patients with a body mass index (BMI) over 25 kg/m2.4 Longitudinal observations have demonstrated that IR may even exacerbate over time in women with PCOS.18 Increased circulating insulin levels secondary to IR contribute to HA of PCOS in at least two important ways, by stimulating theca cell androgen hyperproduction and by inhibiting hepatic sex hormone binding globulin (SHBG) production.

Numerous in vitro studies involving theca cells have shown that insulin stimulates androgen production.19 Interestingly, theca cells from PCOS patients exhibited heightened insulin sensitivity compared to those from normal women. Consequently, in women with PCOS, androgen overproduction can even occur at physiological insulin concentrations, unlike in normal women where high insulin levels are required for increased androgen synthesis.13,20 In vivo investigations have also demonstrated that insulin stimulates ovarian androgen production. The cumulative insulin response during an oral glucose tolerance test (OGTT) correlates positively with the rise in serum ADD and testosterone.21 Moreover, suppression of serum insulin levels with diazoxide (which blocks the release of insulin from the pancreas) or troglitazone (an insulin-sensitizing agent) decreased serum ADD and testosterone levels in women with PCOS.22

In women with PCOS, IR exhibits tissue selectivity. Classical insulin actions are mediated via its receptor, and there are two distinct intracellular pathways. The phosphatidyl-inositol 3-kinase (PI3K) pathway is responsible for the metabolic effects of insulin (such as glucose disposal into skeletal muscle), and the mitogen-activated protein kinase (MAPK) pathway mediates mitotic actions. Studies on cultured skin fibroblasts, muscles, and adipocytes from women with PCOS have displayed resistance in the PI3K metabolic pathway.23-26 Nonetheless, the MAPK pathway remains unaffected in these women, allowing compensatory hyperinsulinemia due to IR to stimulate the intact MAPK pathway. Consequently, through impaired PI3K and intact MAPK post-receptor insulin pathways, insulin actions can be simultaneously inhibited and enhanced, explaining how insulin can stimulate HA in women who are ‘insulin-resistant.’

Insulin is a major regulator of SHBG production in the liver. Insulin diminishes SHBG production, thereby increasing the availability of free testosterone and heightening bioavailable androgens for target tissues. This phenomenon represents yet another pathway through which IR contributes to HA in women with PCOS.

Finally, insulin augments the effect of LH on thecal cells through the activation of CYP17 (P450c17α), a crucial enzyme in androgen biosynthesis within the ovary.27-29 Consequently, increased LH levels and hyperinsulinemia may act synergistically to further escalate theca cell androgen production.

Why does excess production of androgens cause anovulation in women with PCOS?

The core tenet of PCOS is excess androgen production originating from the ovaries, but why oligo-or amenorrhea occur simultaneously? Ovulation encompasses the development of one among many ovarian follicles into a dominant follicle, culminating in oocyte release. Follicular growth involves two types of cells surrounding the ovarian follicles: the inner granulosa cells, which produce estradiol, and the outer thecal cells, which are responsible for androgen production. Stimulated by LH, theca cells generate testosterone from cholesterol, which then serves as a substrate for estradiol production through aromatase activity within granulosa cells. This sequence fosters an estrogenic microenvironment essential for continued follicular growth and ovulation. Upon reaching full maturity, the follicle’s estradiol levels surpass the threshold for positive feedback effects (primarily inducing the LH surge), triggering ovulation. However, elevated androgen levels in the ovarian microenvironment inhibit aromatase activity, preventing testosterone’s conversion to estrogen. Instead, testosterone converts to more potent 5α-reduced androgens through 5α-reductase, which cannot be converted to estradiol. Therefore, the local concentration of androgens within the ovary is critically important for ovulation, with abnormally high local androgen levels contributing to a chronic state of anovulation.

OBESITY AND PCOS

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Obesity frequently accompanies PCOS, yet its exact prevalence remains unclear due to the lack of representative population data. Studies conducted in the United States indicate a prevalence of obesity of approximately 35% in the general female population, in contrast to roughly 60% among those diagnosed with PCOS; in addition, 87.5% exhibit a BMI ≥26 kg/m2, nearly double the prevalence found in the general population.30-32 On the other hand, in a study involving 1,741 women diagnosed with PCOS in the United Kingdom, only 38.4% presented with a BMI ≥25 kg/m2.33 Moreover, an Italian study revealed that merely 14% of women suffering from PCOS were obese.34 In a multi-institutional Korean study, which included 865 women with PCOS averaging 24.9 years of age, approximately 20% were categorized as obese with a BMI of 25 kg/m2 or higher.35 For reference, the prevalence of obesity among Korean women in their 20s during the same timeframe approximated 10%.36 In a recent study using the Korean National Health Insurance Service, the prevalence of obesity was also 20.8% in 137,416 women with PCOS aged 15 to 44 years.37 Consequently, obesity prevalence among PCOS patients fluctuates significantly depending on the population.38

The disparity in obesity prevalence is mirrored by mean BMI—mean BMI in East Asian women with PCOS ranges from 20 to 22 kg/m2, which is substantially lower than that of Caucasians, with reported averages from 27.5 to 31.5 kg/m2.39-44 Despite recommendations for ethnicity-specific BMI criteria, East Asian women may present PCOS symptoms at lower BMI compared to Caucasians, indicating that a lower BMI may not always be a benign indicator in Asian patients.

However, the bulk of PCOS research has focused on individuals attending specialty clinics, who may exhibit more severe symptoms and higher obesity rates than those identified from medically unbiased (unselected) populations. Evidence suggests that obesity levels in PCOS patients from the general unselected population might not be as high as previously thought.45 In one particular study, the rates of obesity and overweight status were virtually indistinguishable between PCOS patients and unaffected women, or were, at most, modestly different.46 Additionally, some research found negligible differences in adiposity distribution between women with PCOS and those with similar BMI without the condition.47,48 Given the referral bias to specialty clinics, the actual population-based severity of obesity may be less pronounced than currently perceived.

The impact of obesity on PCOS: obesity aggravates the degree of IR and hyperinsulinemia

At one time, obesity was suspected as a primary cause of PCOS, but is no longer viewed as an essential feature. The excess of androgens characteristic of PCOS is largely attributed to either LH or insulin stimulating ovarian theca cells. Since adipose tissue does not release agents that activate thecal cells, obesity’s role as the central PCOS mechanism is questionable. It is conceivable that in women genetically predisposed to PCOS, weight gain and obesity frequently trigger clinical and biochemical manifestations by worsening the extent of IR and hyperinsulinemia. Furthermore, epidemiological studies indicate that not all obese women are diagnosed with PCOS, and, vice versa, not every woman with PCOS is obese. Notably, the prevalence of obesity significantly varies across populations, yet global PCOS prevalence remains relatively consistent at approximately 7% to 10%.49-53 One study examining PCOS prevalence across different obesity levels found no significant alterations in PCOS occurrence based on the BMI classification.54 These epidemiological findings also suggest that the connection between obesity and PCOS is neither necessary nor sufficient.

Central obesity is of particular concern for IR, and women with PCOS not only show increased generalized obesity, as indicated by BMI, but also exhibit heightened central obesity.55-58 In a study involving 410 American patients, about 80% were found to have abdominal obesity, as defined by a waist circumference exceeding 88 cm.59 Moreover, non-obese PCOS women have been observed to possess an elevated body fat percentage, waist-hip ratio, and visceral obesity compared to normal control women matched based on BMI.60

The impact of obesity on PCOS: obesity itself may be involved in PCOS beyond the worsening of IR

While the conventional understanding suggests that obesity facilitates PCOS pathophysiology through elevating IR, obesity can also influence PCOS pathophysiology via alternate pathways. Obesity can cause relative hyperandrogenemia, marked by diminished SHBG levels and an increase in the free form of testosterone available to target tissues.61,62 Moreover, adipose tissue can serve as an endocrine organ, converting the precursor ADD into testosterone.63-65 Thus, obesity by itself can account for the excess peripheral production rate of testosterone independent of PCOS. Owing to peripheral aromatization, estrogen levels, particularly estrone, might also increase in obese women with PCOS.66

Additionally, obesity can induce changes in hypothalamic-pituitary-ovarian axis functioning. As previously described, a core aspect of PCOS pathophysiology is the increase in LH and relative decrease in FSH. Elevated androgen levels, paired with chronically high estrogen levels, can disrupt the normal pattern of gonadotropin release, intensifying LH pulse frequency and amplitude while suppressing FSH secretion.67 Consequently, obesity can itself correlate with elevated LH levels.

Alterations in adipokine and inflammatory cytokine production within visceral fat may contribute to PCOS pathophysiology.68 Notably, adiponectin levels, an insulin-sensitizing adipokine, are lower in women with PCOS, as demonstrated in a comprehensive meta-analysis of over 3,400 subjects, even after BMI adjustment.69 Additionally, diminished adiponectin levels could lead to hyperandrogenemia as adiponectin inhibits sex steroid production by thecal cells.70 Adiponectin genetic variants have also been linked to PCOS.71 Elevated tumor necrosis factor in obese women with PCOS can encourage theca cell proliferation and ovarian steroidogenesis.72,73 Increased interleukin 6 levels have also been implicated in escalating adrenal steroidogenesis and fostering hyperandrogenemia.74-76

Finally, obesity tends to be more prevalent within families affected by PCOS,77,78 suggesting that obesity and PCOS might share an underlying genetic predisposition, such as the FTO gene.79-82

Central obesity, catch-up growth, and PCOS

Women with PCOS typically begin to exhibit hallmark symptoms such as hirsutism and irregular menstruation during adolescence. This observation suggests that genetic factors, rather than lifestyle habits, have a prominent role in this syndrome. However, studies have suggested that the intrauterine environment also contributes to PCOS pathophysiology.

Ibáñez and de Zegher83 suggested that a mismatch between (reduced) prenatal weight gain (fetal growth restriction) and (augmented) postnatal weight can precipitate an early predisposition and subsequent necessity for lipid storage. Girls experiencing catch-up weight gain are prone to lipid deposition primarily in ectopic locations (the liver and viscera), leading to the development of ‘central obesity,’ which is accompanied by IR from an early age. To surpass increased ectopic fatness, accelerated growth and bone maturation ensue, resulting in either precocious pubarche or precocious puberty. Neuroendocrine mechanisms linking ectopic fat and accelerated maturation are well documented.84,85 Upregulation of the adrenarchal axis (marked by elevated levels of DHEA-S, which are associated with early pubarche)86-90 and the gonadal axis (elevated LH and estradiol levels, indicating early puberty),91,92 thyroid axis activation,93 and elevated free testosterone levels94 have been observed in girls with such mismatch growth. Ultimately, the fusion of growth plates curtails further height increases, causing the growth-accelerating response to ectopic fat to diminish. The persistence of central obesity and maladaptive increases in LH, DHEA-S, and testosterone in late adolescence or early adulthood become detrimental, leading to PCOS. Accordingly, the authors proposed that the PCOS acronym could represent ‘postpubertal central obesity syndrome.’ They also emphasized that treating adolescent PCOS should not solely aim to control symptoms, but should also target reduction of ectopic fat volume.

Impact of obesity on the phenotype of PCOS

Obesity exacerbates all reproductive and metabolic characteristics in comparison to women of normal weight with PCOS. Menstrual disorders are frequently encountered when an excess weight gain occurs during puberty.95 Furthermore, incidents of chronic anovulation and menstrual irregularities are more common in overweight and obese women with PCOS during adulthood than in normal-weight counterparts.62 The severity of clinical manifestations, including ovulatory dysfunction, glucose intolerance, dyslipidemia, metabolic syndrome, and cardiovascular disease risk factors, escalates with the degree of obesity in women with PCOS.18,59,96-98 A systematic review and meta-analysis encompassing 30 studies highlighted the negative effects of obesity on the phenotype of PCOS.99 Overweight or obese women with PCOS were found to have diminished SHBG, elevated total testosterone, free androgen index, hirsutism scores, fasting glucose, fasting insulin, homeostatic model assessment-insulin resistance index, and an adverse lipid profile.

Moreover, obese women with PCOS demonstrate diminished responsiveness to pharmacological ovulation induction, diminished pregnancy outcomes, heightened miscarriage rates, and lower live birth rates following infertility treatments.4,100-102 Thus, the presence of obesity has additional negative impacts on clinical manifestations beyond those attributed to PCOS alone.

PCOS as a risk factor for the development of obesity

To date, the influence of obesity on PCOS has been well documented. While the natural progression of weight gain in women with PCOS remains unclear, there is potential for PCOS to either contribute to further weight gain or obstruct successful weight loss efforts. In a longitudinal study involving 66 adolescent girls diagnosed with PCOS, 37 girls presenting with either HA or irregular menstruation, and 161 non-PCOS counterparts, aged 14 to 16 years demonstrated that the group with PCOS experienced a higher long-term increase in BMI compared to the latter two groups.103 Although the underlying mechanisms remain uncertain, factors such as altered energy expenditure, androgen-induced abnormalities in the lipolytic function of adipocytes, mental health challenges, and decreased physical activity have been identified as contributing to the propensity for weight gain in women with PCOS.104 The 2023 international evidence-based PCOS guideline also acknowledges that, despite the lack of clarity on specific mechanisms, many women with PCOS display predispositions that facilitate higher BMI and more significant longitudinal weight gain.4 Consequently, the guideline development group has underscored the necessity for a lifelong commitment to a healthy lifestyle and the prevention of excessive weight gain, while highlighting the amplified difficulties encountered in weight management.

MANAGEMENT OF PCOS FOCUSED ON OBESITY

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In women genetically predisposed to PCOS or those who are at high risk but might remain asymptomatic, weight gain and obesity often lead to clinical and biochemical manifestations of PCOS. Obesity’s primary role in PCOS lies in exacerbating IR, thereby worsening the overproduction of androgens in ovarian theca cells, which leads to anovulation. This underscores the critical importance of identifying and managing obesity in women with PCOS.

In women with PCOS, it is essential to address individual symptoms such as HA (manifested by hirsutism, acne, and female type boldness), menstrual irregularities, and anovulation-related infertility. Nonetheless, initiating lifestyle modifications stands as a fundamental approach for overweight and obese women with PCOS. Although the precise BMI threshold that corresponds to an increased risk for each manifestation of PCOS remains undefined, a modest weight loss of approximately 2% to 5% has been shown to lower insulin and androgen levels, thereby ameliorating PCOS symptoms.105-111 Improvements in central adiposity, such as reductions in waist circumference and waist-hip ratio, serve as reliable predictors of the benefits derived from weight loss. While there is ongoing debate regarding the superiority of low-fat versus low-carbohydrate diets for women with PCOS, the paramount importance of a significant reduction in net caloric intake is universally acknowledged.

The 2023 international evidence-based PCOS guideline highlights the lifelong importance of preventing additional weight gain.4 In particular, among PCOS patients who are not overweight in the adolescence period and at key life points such as trial of pregnancy, focusing on a healthy lifestyle and weight gain prevention becomes particularly critical.

Obesity, compounded by IR, significantly elevates the risk for metabolic syndrome, impaired glucose tolerance, and type 2 diabetes mellitus in women with PCOS. Consequently, upon diagnosing PCOS, it is imperative to screen women for cardiovascular disease risk factors such as obesity (BMI and waist circumference), blood pressure, lipid profile (cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride level), cigarette smoking habits, and glycemic status (assessed through fasting plasma glucose, glycosylated hemoglobin levels, and the 75-g OGTT). The 75-g OGTT is recommended as the most accurate method for evaluating glycemic status in women with PCOS, regardless of BMI.4

Premenopausal women with PCOS are at a substantially increased risk of developing endometrial hyperplasia and endometrial cancer. Although the principal cause of endometrial pathology in these women is chronic exposure to unopposed estrogen due to prolonged anovulation, obesity independently raises the risk of endometrial cancer. In adipose tissue, aromatase activity converts androgens to estrogens, directly fostering endometrial cell proliferation and the transcription of genes that promote cell growth.112 Accordingly, weight management also plays a vital role in preventing endometrial cancer among women with PCOS. Management of PCOS focused on obesity is delineated in Table 2.

CONCLUSION

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The core pathology of PCOS involves an overproduction of androgens primarily from ovarian thecal cells. There are two main external contributors to this overproduction of androgens in the ovaries: one is the increased secretion of LH arising from the aberrant hypothalamic GnRH secretion dynamics, and the other is compensatory hyperinsulinemia resulting from IR.

Obesity is implicated in PCOS pathophysiology primarily through exacerbating IR. Moreover, obesity contributes to PCOS by facilitating the conversion of precursor hormones to testosterone within adipose cells. Additionally, obesity induces relative hyperandrogenemia, characterized by diminished levels of SHBG and increased free testosterone availability to target tissues. Furthermore, obesity influences gonadotropin secretion, leading to heightened LH secretion or increased sensitivity of thecal cells to LH stimulation. The IR associated with obesity may be further intensified by changes in adipokine and inflammatory cytokine production. Lastly, obesity and PCOS might share underlying genetic factors.

Addressing individual symptoms such as hirsutism, acne, and menstrual irregularities, as well as infertility due to anovulation, is paramount in managing PCOS. However, recognizing obesity as a contributory factor to PCOS’s pathophysiology and its aggravating effect on reproductive and metabolic features in PCOS women is essential. Therefore, lifestyle modifications targeting weight reduction should be an initial treatment step for overweight or obese women with PCOS.

Figures

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Fig. 1. Pathophysiology of polycystic ovary syndrome (PCOS). The fundamental pathophysiology of PCOS encompasses excessive production of androgens primarily from the ovaries (and, to a lesser extent, the adrenal glands). There are two major external factors driving ovarian androgen overproduction: one is the elevated secretion of luteinizing hormone (LH) via the hypothalamic-pituitary axis, and the other is increased insulin levels stemming from insulin resistance. Obesity significantly contributes to PCOS pathophysiology primarily by worsening insulin resistance, but it also plays a role by converting precursor androgens to testosterone within adipose tissues directly. Furthermore, obesity influences gonadotropin release, leading to a rise in LH secretion or enhancing the sensitivity of thecal cells to LH stimulation. Obesity-induced insulin resistance may be further exacerbated by variation in adipokine and inflammatory cytokine levels. Lastly, obesity and PCOS may share an underlying genetic predisposition. GnRH, gonadotropin-releasing hormone.

Tables

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Diagnostic criteria for polycystic ovary syndrome

Rotterdam criteria (2 out of 3)3 International evidence-based guideline (2 out of 3 except adolescents)4
1. Oligo- and/or anovulation* 1. Oligo- and/or anovulation*
Irregular menstrual cycles are defined as follows:
• Normal in the first year post-menarche as part of the pubertal transition
• 1 to < 3 years post-menarche: < 21 or > 45 days
• 3 years post-menarche to perimenopause: < 21 or > 35 days or < 8 cycles per year
• 1 year post-menarche > 90 days for any one cycle
• Primary amenorrhea by age 15 or > 3 years post-thelarche
2. Clinical and/or biochemical signs of hyperandrogenism* 2. Clinical and/or biochemical signs of hyperandrogenism*
3. Polycystic ovary morphology 3. Either polycystic ovary morphology on ultrasound or elevated serum anti-Müllerian hormone Ultrasound criteria or anti-Müllerian hormone should not be used for the diagnosis of PCOS in those with a gynecological age of < 8 years ( < 8 years after menarche)

*Provided other causes are excluded.

PCOS, polycystic ovary syndrome.

Management of polycystic ovary syndrome focused on obesity4

General strategies If weight loss is a goal, a tailored energy deficit could be prescribed.
A lifelong effort on prevention of further weight gain is emphasized.
Diet There is no evidence that any one type of diet is superior to others for anthropometric, hormonal, metabolic, or reproductive outcomes.
Any diet composition conforming to general healthy eating guidelines will have benefits.
Exercise There is no evidence that any one type of exercise is superior to others for anthropometric, hormonal, metabolic, or reproductive outcomes.
Any physical activity conforming to general guidelines will have benefits, and doing some physical activity is better than none.
Anti-obesity pharmacological agents In addition to lifestyle intervention, anti-obesity medications could be considered for the management of weight in adult women with PCOS per general population guidelines.
Bariatric surgery In women with PCOS, bariatric/metabolic surgery could be considered per general population guidelines.
Preconception Women with PCOS should be counseled on the adverse impacts of obesity on pregnancy outcomes.

PCOS, polycystic ovary syndrome.

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