Polycystic ovary syndrome (PCOS) is the main cause of female infertility worldwide and is associated with a substantially increased lifetime risk of comorbidities, including type 2 diabetes mellitus, ...psychiatric disorders and gynaecological cancers. Despite its high prevalence (~15%) and substantial economic burden, the aetiology of PCOS remains elusive. The genetic loci linked to PCOS so far account for only ~10% of its heritability, which is estimated at 70%. However, growing evidence suggests that altered epigenetic and developmental programming resulting from hormonal dysregulation of the maternal uterine environment contributes to the pathogenesis of PCOS. Male as well as female relatives of women with PCOS are also at an increased risk of developing PCOS-associated reproductive and metabolic disorders. Although PCOS phenotypes are highly heterogenous, hyperandrogenism is thought to be the principal driver of this condition. Current treatments for PCOS are suboptimal as they can only alleviate some of the symptoms; preventative and targeted treatments are sorely needed. This Review presents an overview of the current understanding of the aetiology of PCOS and focuses on the developmental origin and epigenetic inheritance of this syndrome.
Introduction
The knowledge regarding eating behavior and disorders in women with polycystic ovary syndrome (PCOS) and severe obesity is limited. This study aimed to assess eating behavior and ...lifestyle factors in women with severe obesity (BMI ≥35 kg/m2), with and without PCOS, and the effect of weight loss on these behaviors.
Material and Methods
A prospective clinical trial with participants screened for PCOS using National Institutes of Health criteria. Participants completed the Food Frequency Questionnaire, International Physical Activity Questionnaire, Three‐Factor Eating Questionnaire, and Questionnaire of Eating and Weight Patterns‐revised, and were evaluated regarding binge eating disorder using DSM‐5 criteria before and after a 12‐month weight loss intervention. Clinicaltrials.gov: NCT01319162.
Results
246 women were included (PCOS n = 63, age 33.0 ± 8.4, BMI 39.9 ± 4.7; non‐PCOS n = 183, age 37.7 ± 8.7, BMI 39.6 ± 4.3). Women with PCOS showed elevated baseline scores in cognitive restraint eating (50.0 33.3–63.2) compared to women without PCOS (38.9 27.8–55.6; p = 0.012). No differences were observed between groups in emotional and uncontrolled eating. In both groups, cognitive restraint eating was negatively correlated with energy intake (PCOS: r = −0.315, p < 0.05; non‐PCOS: r = −0.214, p < 0.001), while uncontrolled eating displayed a positive correlation with energy intake (PCOS: r = 0.263, p = 0.05; non‐PCOS: r = 0.402, p < 0.001). A positive correlation was found between emotional eating and energy intake only in women without PCOS (r = 0.400, p < 0.001). Baseline self‐reported energy intake and physical activity did not differ between groups. At 12‐month follow‐up, women with PCOS reported reduced fat intake. Women without PCOS reported reduced energy intake, carbohydrates and sugar, increased protein, reduced scores for emotional and uncontrolled eating, and heightened scores for cognitive restraint eating. Comparing changes from baseline to follow‐up, differences were found between groups in cognitive restraint, intake of fat, carbohydrates, and sugar. The mean weight loss was 12–14 kg, with no between‐group difference (p = 0.616).
Conclusions
Women with severe obesity and PCOS showed elevated cognitive restraint eating behaviors compared to women without PCOS. Although significant weight loss was seen in both groups, alterations in eating behavior more favorable for weight loss were only seen in women without PCOS.
In women with severe obesity (BMI ≥35 kg/m2), those with PCOS have more conscious control of eating (higher cognitive restraint eating behavior). A 12% weight loss in both women with and without PCOS led to an altered eating behavior in those without PCOS with a greater change in cognitive restraint eating, which is in favor of further weight loss.
Objective
Existing data are contradictory on the prevalence of polycystic ovary syndrome (PCOS) and metabolic syndrome (MetS) in women with severe obesity (body mass index BMI ≥ 35 kg/m2), and there ...are few studies investigating the effect of weight reduction in women with severe obesity and PCOS. The aim was to study the prevalence of PCOS and MetS among women with severe obesity and to evaluate the effect of a 12‐months weight loss programme on the prevalence of PCOS and MetS.
Design/Participants
In total, 298 women with severe obesity were enrolled whereof 246 women had complete screening data for PCOS and MetS before commencing treatment. Weight loss intervention included very low energy diet. At 12‐months follow‐up, 72 women with complete data remained and were re‐examined with baseline parameters.
Results
At baseline, the prevalence of PCOS was 25.6% and in this group, the prevalence of MetS was 43.4% in PCOS vs 43.3% in controls (ns). At 12‐months follow‐up, weight loss in women with PCOS was 12.3 ± 10.7 kg (P < .001) and in non‐PCOS 13.9 ± 13.4 kg (P < .001) with no between group difference. Women without PCOS decreased in total bone mass.
Conclusions
Polycystic ovary syndrome occurs in one out of four women with severe obesity. The prevalence of MetS does not differ between women with or without PCOS with severe obesity. There was a significant weight loss in both groups but no difference between groups regarding change in metabolic parameters.
ABSTRACT
A single bout of low‐frequency electroacupuncture (EA) causing muscle contractions increases whole‐body glucose uptake in insulin‐resistant rats. We explored the underlying mechanism of this ...finding and whether it can be translated into clinical settings. Changes in glucose infusion rate (GIR) were measured by euglycemic–hyperinsulinemic clamp during and after 45 min of low‐frequency EA in 21 overweight/obese women with polycystic ovary syndrome (PCOS) and 21 controls matched for age, weight, and body mass index (experiment 1) and in rats receiving autonomic receptor blockers (experiment 2). GIR was higher after EA in controls and women with PCOS. Plasma serotonin levels and homovanillic acid, markers of vagal activity, decreased in both controls and patients with PCOS. Adipose tissue expression of pro‐nerve growth factor (proNGF) decreased, and the mature NGF/proNGF ratio increased after EA in PCOS, but not in controls, suggesting increased sympathetic‐driven adipose tissue metabolism. Administration of a‐/β‐adrenergic receptor blockers in rats blocked the increase in GIR in response to EA. Muscarinic and dopamine receptor antagonist also blocked the response but with slower onset. In conclusion, a single bout of EA increases whole‐body glucose uptake by activation of the sympathetic and partly the parasympathetic nervous systems, which could have important clinical implications for the treatment of insulin resistance.—Benrick, A., Kokosar, M., Hu, M., Larsson, M., Maliqueo, M., Marcondes, R. R., Soligo, M., Protto, V., Jerlhag, E., Sazonova, A., Behre, C. J., Højlund, K., Thorén, P., Stener‐Victorin, E. Autonomic nervous system activation mediates the increase in whole‐body glucose uptake in response to electroacupuncture. FASEB J. 31, 3288–3297 (2017). www.fasebj.org
Abstract
More than 1 out of 10 women worldwide are diagnosed with polycystic ovary syndrome (PCOS), the leading cause of female reproductive and metabolic dysfunction. Despite its high prevalence, ...PCOS and its accompanying morbidities are likely underdiagnosed, averaging > 2 years and 3 physicians before women are diagnosed. Although it has been intensively researched, the underlying cause(s) of PCOS have yet to be defined. In order to understand PCOS pathophysiology, its developmental origins, and how to predict and prevent PCOS onset, there is an urgent need for safe and effective markers and treatments. In this review, we detail which animal models are more suitable for contributing to our understanding of the etiology and pathophysiology of PCOS. We summarize and highlight advantages and limitations of hormonal or genetic manipulation of animal models, as well as of naturally occurring PCOS-like females.
Graphical Abstract
Graphical Abstract
Polycystic ovary syndrome (PCOS) is a heterogeneous and complex disorder that has both adverse reproductive and metabolic implications for affected women. However, there is generally poor ...understanding of its etiology. Varying expert-based diagnostic criteria utilize some combination of oligo-ovulation, hyperandrogenism, and the presence of polycystic ovaries. Criteria that require hyperandrogenism tend to identify a more severe reproductive and metabolic phenotype. The phenotype can vary by race and ethnicity, is difficult to define in the perimenarchal and perimenopausal period, and is exacerbated by obesity. The pathophysiology involves abnormal gonadotropin secretion from a reduced hypothalamic feedback response to circulating sex steroids, altered ovarian morphology and functional changes, and disordered insulin action in a variety of target tissues. PCOS clusters in families and both female and male relatives can show stigmata of the syndrome, including metabolic abnormalities. Genome-wide association studies have identified a number of candidate regions, although their role in contributing to PCOS is still largely unknown.
Hyperandrogenism is the main characteristic of polycystic ovary syndrome, which affects placental function and fetal growth, and leads to reproductive and metabolic dysfunction in female offspring. ...Adiponectin acts on the placenta and may exert endocrine effects on the developing fetus. This study aims to investigate if maternal and/or fetal adiponectin can prevent metabolic and reproductive dysfunction in prenatal androgenized (PNA) female offspring. Adiponectin transgenic (APNtg) and wild‐type dams received dihydrotestosterone/vehicle injections between gestational days 16.5‐18.5 to induce PNA offspring, which were followed for 4 months. Offspring from APNtg dams were smaller than offspring from wild‐type dams, independent of genotype. Insulin sensitivity was higher in wild‐type mice from APNtg dams compared to wild‐types from wild‐type dams, and insulin sensitivity correlated with fat mass and adipocyte size. PNA increased visceral fat% and adipocyte size in wild‐type offspring from wild‐type dams, while wild‐type and APNtg offspring from APNtg dams were protected against this effect. APNtg mice had smaller adipocytes than wild‐types and this morphology was associated with an increased expression of genes regulating adipogenesis (Ppard, Pparg, Cebpa, and Cebpb) and metabolism (Chrebp and Lpl). Anogenital distance was increased in all PNA‐exposed wild‐type offspring, but there was no increase in PNA APNtg offspring, suggesting that adiponectin overexpression protects against this effect. In conclusion, elevated adiponectin levels in utero improve insulin sensitivity, reduce body weight and fat mass gain in the adult offspring and protect against PNA‐induced visceral adiposity. In conclusion, these data suggest that PNA offspring benefit from prenatal adiponectin supplementation.
Polycystic ovary syndrome (PCOS) affects about 12% of women of reproductive age. In 2018, the first evidence‐based guideline on assessment and management of PCOS was published, and an updated ...extended guideline was released in August 2023. These guidelines followed best practice and are endorsed by 39 organizations worldwide, making them the most robust source of evidence to guide clinical practice. In the 2023 guideline, diagnostic criteria have been further refined as polycystic ovary morphology can now be assessed with gynecological ultrasound or elevated anti‐Müllerian hormone levels. A healthy lifestyle should be at the focus of care for all women with PCOS; however, with no specific diet or physical exercise recommended. The latest evidence on medical treatments and fertility management are reviewed, including special considerations regarding long‐term follow‐up of metabolic and psychiatric comorbidities and pregnancy in women with PCOS. Here we summarize the recommendations from a Nordic perspective.
In 2018, the firstevidence‐based guideline on assessment and management of PCOS was published,and an updated version was released in August 2023.Here we summarize the recommendations from a Nordic perspective.
Maternal polycystic ovary syndrome (PCOS), a condition associated with hyperandrogenism, is sug‐gested to increase anxiety‐like behavior in the offspring. Because PCOS is closely linked to obesity, ...we investigated the impact of an adverse hormonal or metabolic maternal environment and offspring obesity on anxiety in the offspring. The obese PCOS phenotype was induced by chronic high‐fat‐high‐sucrose (HFHS) consumption together with prenatal dihydrotestosterone exposure in mouse dams. Anxiety‐like behavior was assessed in adult offspring with the elevated‐plus maze and open‐field tests. The influence of maternal androgens and maternal and offspring diet on genes implicated in anxiety were analyzed in the amygdala and hypothalamus with real‐time PCR (n = 47). Independent of diet, female offspring exposed to maternal androgens were more anxious and displayed up‐regulation of adrenoceptor a 1B in the amygdala and up‐regulation of hypothalamic corticotropin‐releasing hor‐mone (Crh). By contrast, male offspring exposed to a HFHS maternal diet had increased anxiety‐like behavior and showed up‐regulation of epigenetic markers in the amygdala and up‐regulation of hypothalamic Crh. Overall, there were substantial sex differences in gene expression in the brain. These findings provide novel insight into how maternal androgens and obesity exert sex‐specific effects on behavior and gene expression in the offspring of a PCOS mouse model.—Manti, M., Fornes, R., Qi, X., Folmerz, E., Lindén Hirschberg A., de Castro Barbosa T., Maliqueo, M., Benrick, A., Stener‐Victorin E. Maternal androgen excess and obesity induce sexually dimorphic anxiety‐like behavior in the offspring. FASEB J. 32, 4158–4171 (2018). www.fasebj.org
To compare the metabolic profiles of normo- and hyperandrogenic women with polycystic ovary syndrome (PCOS) with those of control women at different ages during reproductive life.
Case-control study.
...Not applicable.
In all, 1,550 women with normoandrogenic (n = 686) or hyperandrogenic (n = 842) PCOS and 447 control women were divided into three age groups: <30, 30-39, and >39 years).
None.
Body mass index (BMI), waist circumference, blood pressure, glucose, insulin, cholesterol, lipoproteins, triglycerides and high-sensitivity C-reactive protein.
Both normo- and hyperandrogenic women with PCOS were more obese, especially abdominally. They had increased serum levels of insulin (fasting and in oral glucose tolerance tests), triglycerides, low-density lipoprotein, and total cholesterol, higher blood pressure, and lower high-density lipoprotein levels independently from BMI compared with the control population as early as from young adulthood until menopause. The prevalence of metabolic syndrome was two- to fivefold higher in women with PCOS compared with control women, depending on age and phenotype, and the highest prevalence was observed in hyperandrogenic women with PCOS at late reproductive age.
When evaluating metabolic risks in women with PCOS, androgenic status, especially abdominal obesity and age, should be taken into account, which would allow tailored management of the syndrome from early adulthood on.
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