Hyperandrogenic anovulation (PCOS): A unique disorder of insulin action associated with an increased risk of non-insulin-dependent diabetes mellitus

doi:10.1016/S0002-9343(99)80057-6

The American Journal of Medicine

Volume 98, Issue 1, Supplement 1, 16 January 1995, Pages S33-S39

https://doi.org/10.1016/S0002-9343(99)80057-6 Get rights and content

Polycystic ovary syndrome is the most common endocrine disorder in women of reproductive age. Recent prevalence estimates suggest that 5–10% of premenopausal women have the full-blown syndrome of hyperandrogenism, chronic anovulation, and polycystic ovaries. Evidence suggests that women with polycystic ovary syndrome have a unique disorder of insulin action and are at increased risk to develop non-insulin-dependent diabetes mellitus. Further, non-insulin-dependent diabetes mellitus in women with polycystic ovary syndrome has a substantially earlier age of onset (third to fourth decades) than it does in the general population (sixth to seventh decades). Studies assessing whether abnormalities in insulin action are intrinsic or secondary to the hormonal milieu have found that insulin-induced receptor autophosphorylation is markedly diminished in approximately 50% of polycystic ovary syndrome women. This defect is unique to women with polycystic ovary syndrome and is not seen in other common insulin-resistant states of obesity and non-insulin-dependent diabetes mellitus. In polycystic ovary syndrome women who have normal receptor autophosphorylation, it remains likely that signaling mechanisms downstream of the receptor are abnormal, since these women are also insulin resistant. This distinctive post-insulin-binding defect appears to be genetic, since it is present in cells removed from the in vivo environment for generations.

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Cited by (234)

MIF-mediated NF-κB signaling pathway regulates the pathogenesis of polycystic ovary syndrome in rats
2021, Cytokine
Citation Excerpt :
Polycystic ovary syndrome (PCOS) resulting from abnormal glucose metabolism is a relatively common and complex endocrine disorder among women in their reproductive years, occurring in 5% and 10% of the patient population [1]. Women with PCOS suffer from reproductive dysfunction which is characterized by anovulation, infertility, obesity, hyperandrogenism, insulin resistance, and compensatory hyperinsulinemia [2]. However, the pathogenesis of PCOS is still unclear.
Polycystic ovary syndrome (PCOS) resulting from abnormal glucose metabolism is a relatively common and complex endocrine disorder among women in their reproductive years, However, the pathogenesis of PCOS is still unclear. The purpose of this study is to investigate the macrophage migration inhibitory factor (MIF) involvement of the nuclear factor (NF)-κB in rats with PCOS. Results indicated that testosterone promoted the increase in the levels of MIF and luteinizing hormone (LH) but inhibited the increase in the level of follicular stimulating hormone (FSH). The MIF antibody could alleviate the process of PCOS to a certain extent. Testosterone promoted the expression of interleukin 1-beta (IL-1β), interleukin 6 (IL-6), Inducible nitric oxide synthase (iNOS), and tumor necrosis factor alpha (TNF-α); the MIF antibody could reverse this effect. Testosterone could inhibit the expression of NF-κB protein whereas MIF antibody could promote the expression in the ovarian cytoplasm. Testosterone promoted the expression of NF-κB protein in the nucleus, this effect also could be reversed by the MIF antibody. Hyperandrogenism activated the NF-κB pathway. After using the MIF antibody, this effect was reversed. This finding suggested that hyperandrogenism activated the NF-κB pathway through MIF. In short, increased MIF levels activated the NF-κB pathway in ovaries, leading to inflammation and the increase in the levels of relevant inflammatory indicators, which might be one of the important factors in the pathogenesis of PCOS.
A Ketogenic Diet may Restore Fertility in Women With Polycystic Ovary Syndrome: A Case Series
2018, AACE Clinical Case Reports
Objective: Polycystic ovary syndrome (PCOS) is the most common cause of infertility in women. We report the clinical course of 4 women with PCOS trying to conceive while following a ketogenic diet and assess their fecundity after a period of 6 months.
Methods: The patients were followed once monthly in a shared medical appointment setting for total of 6 months. During each visit, the patients were assessed for weight loss progression, menstrual regularity, and ovulation.
Results: The patients' ages ranged from 24 to 29 years old, their body mass indexes from 30.75 to 42.46 kg/m², and their duration of infertility from 1 to 4.5 years. All patients were interested in pregnancy. The diagnosis of PCOS was confirmed by an endocrinology consultation, and the patients initiated a protein-sparing modified fast (PSMF) diet. The PSMF diet entails a maximum daily total carbohydrate intake of 20 g, fat intake up to 50 g, and an approximate protein intake of about 1.5 g for each 1 kg of ideal body weight. Metformin was continued if they were already taking it, otherwise it was initiated with the PSMF diet and titrated up to 500 mg twice daily. All 4 patients adhered to the PSMF diet and were able to lose weight (ranging from 19 to 36 lbs). All 4 also had irregular periods prior to the PSMF diet, and resumed regular menstruation shortly after starting the PSMF diet (ranging from 4 to 8 weeks). Two women were able to conceive spontaneously with no ovulation induction needed.
Conclusion: The PSMF diet may have a promising benefit for women with PCOS by inducing weight loss and facilitating ovulation.
Abbreviations: BMI = body mass index;HSG = hysterosalpingogram;PCOS = polycystic ovary syndrome;PSMF = protein-sparing modified fast;SMA = shared medical appointment
Adolescents with Classical Polycystic Ovary Syndrome Have Alterations in the Surrogate Markers of Cardiovascular Disease but Not in the Endothelial Function. The Possible Benefits of Metformin
2016, Journal of Pediatric and Adolescent Gynecology
Citation Excerpt :
Polycystic ovary syndrome (PCOS) is a complex endocrine disorder, affecting up to 10% of women of reproductive age, characterized by chronic anovulation, oligomenorrhea, and hyperandrogenism.1,2
To study whether adolescents with the classical form of polycystic ovary syndrome (PCOS) have alterations in metabolic and vascular structure and function. The effect of metformin was evaluated.
Controlled study.
University outpatient clinic.
Eighteen nonobese adolescents with PCOS were enrolled. Seventeen healthy age-matched adolescents were recruited as control subjects.
The metabolic profile and the endothelial structure and function were evaluated.
Hormonal and lipid profile, blood pressure (BP) measurement, fasting glucose and insulin levels, C-reactive protein (CRP), homocysteine, tissue-type plasminogen activator, plasminogen activator inhibitor-1 (PAI-1), and plasmin-antiplasmin complexes (PAP) were measured. Flow mediated dilation (FMD), central pulse wave velocity (PWV), radial artery pulse wave, and common carotid intima-media thickness (IMT) were also assessed. Girls with PCOS were also studied 6 months after treatment with metformin (850 mg twice per day).
Adolescents with PCOS were insulin resistant and/or hyperinsulinemic and they had higher BP values and levels of CRP and PAI-1 than the control subjects. The levels of tissue-type plasminogen activator and PAP were similar in both groups. FMD, PWV, and IMT were also similar. Metformin significantly (P < .05) reduced insulin, BP, CRP, and PAI-1 levels. The PAP levels significantly (P < .05) increased. Radial artery pulse wave was significantly reduced after metformin treatment. No modifications in FMD, PWV, and IMT were observed.
Adolescents with classical PCOS have alterations in some surrogate markers of cardiovascular risk and they are ameliorated by metformin. No deterioration of vascular structure and function has been detected, probably because of the short duration of exposure to the disease.
Obesity may be the common pathway for sleep-disordered breathing in women with polycystic ovary syndrome
2016, Sleep Medicine
Polycystic ovary syndrome (PCOS) is one of the most common endocrinological disorders in women of reproductive age, and is characterized by hyperandrogenism. It is associated with long-term metabolic dysfunctions including sleep-disordered breathing (SDB). We hypothesized that the increased prevalence of SDB in PCOS results from raised testosterone levels.
This was a prospective, cross-sectional, case–control study in which 50 case patients with untreated PCOS and 100 control subjects were included. All the case patients and control subjects went through a detailed clinical, biochemical, and hormonal evaluation. Overnight polysomnography was performed in all case patients and the snorers (16 of 100) in the control group.
SDB was seen in 66% of the case patients and in 4% of control group with (odds ratio [OR] = 46.5, 95% confidence interval [CI] = 14.6–148.4; p <0.001). After adjustment for body mass index (BMI) and waist circumference (WC), the difference was not significant (p = 0.993 and p = 0.931, respectively). The SDB patients with PCOS showed significantly higher respiratory distress index (RDI) values than SDB patients in the control group (22.5 ± 21.5 vs 9.0 ± 5.6, p = 0.01). On the Epworth Sleepiness Scale the PCOS case patients reported feeling more sleepy than did the control subjects (12.5 ± 3.2 vs 9.32 ± 1.7, p <0.001). Free testosterone levels were also significantly higher in the PCOS group than in the control subjects (2.95 ± 3.44 vs 1.5 ± 1.0, p <0.001). There was a significant correlation between free testosterone level and RDI values (r = 0.377; p = 0.007), WC (r = 0.315; p = 0.026), and BMI (r = 0.398; p = 0.004). A significant correlation of WC (r = 0.551; p <0.001) and BMI (r = 0.572; p <0.001) was observed with RDI.
Testosterone-induced obesity is probably the common pathway for the development of SDB in PCOS.
Sex and Gender Differences in Body Composition, Lipid Metabolism, and Glucose Regulation
2016, Sex Differences In Physiology
Women have more body fat and less muscle mass than men. Women also have less visceral fat and more subcutaneous fat, particularly in the abdominal and gluteal-femoral regions, than men. These sex-specific differences in body composition are associated with sex-based differences in energy substrate-utilization patterns; that is, females store more lipids and have higher whole-body insulin sensitivity than males, while men tend to oxidize more lipids than females. These patterns are influenced by the unique actions of sex hormones and adipokines in each sex as well as by nutritional status and physical fitness in both sexes. This chapter focuses on sex-specific differences in body fat deposition, lipid metabolism, and glucose homeostasis and their regulation by sex hormones and adipokines, with an emphasis on studies in humans as well as relevant preclinical animal models. Readers will gain a better understanding of how these factors influence sex-specific differences in metabolic disease susceptibility.
Linkage and association of variants in the dopamine receptor 2 gene (DRD2) with polycystic ovary syndrome
2023, Journal of Ovarian Research

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Hyperandrogenic anovulation (PCOS): A unique disorder of insulin action associated with an increased risk of non-insulin-dependent diabetes mellitus

Fertil Steril

Metabolism

Rec Prog Horm Res

J Biol Chem

J Biol Chem

J Biol Chem

Cellular Signaling

J Biol Chem

Cell

J Biol Chem

J Biol Chem

Metabolism

Characterization of groups of hyperandrogenic women with acanthosis nigricans impaired glucose tolerance and/or hyperinsulinemia

J Clin Endocrinol Metab

Profound peripheral insulin resistance independent of obesity in the polycystic ovary syndrome

Diabetes

Evidence for distinctive and instrinsic defects in insulin action in the polycystic ovary syndrome

Diabetes

Prevalence of diabetes impaired glucose tolerance and plasma glucose levels in U.S. population aged 20–74 yr

Diabetes

Diabetes in identical twins. A study of 200 pairs

Diabetologia

Pathogenesis of type 2 (non-insulin-dependent) diabetes mellitus: candidates for a signal transmitter defect causing insulin resistance of the skeletal muscle

Diabetologia

Insulin resistance and noninsulin-dependent diabetes mellitus: which horse is pulling the cart?

Diabetes/Metabolism Reviews

Mutations in the insulin receptor gene

Endocr Rev

Gene for non-insulin-dependent diabetes mellitus (maturity-onset diabetes of the young subtype) is linked to DNA polymorphism on human chromosome 20q

Human glucokinase gene: isolation characterization and identification of two missense mutations linked to early-onset non-insulin dependent (type 2) diabetes mellitus