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Polycystic ovary syndrome and mitochondrial dysfunction.

ABSTRACT: Polycystic ovary syndrome (PCOS) is a prevalent hormonal disorder of premenopausal women worldwide and is characterized by reproductive, endocrine, and metabolic abnormalities. The clinical manifestations of PCOS include oligomenorrhea or amenorrhea, hyperandrogenism, ovarian polycystic changes, and infertility. Women with PCOS are at an increased risk of suffering from type 2 diabetes; me\tabolic syndrome; cardiovascular events, such as hypertension, dyslipidemia; gynecological diseases, including infertility, endometrial dysplasia, endometrial cancer, and ovarian malignant tumors; pregnancy complications, such as premature birth, low birthweight, and eclampsia; and emotional and mental disorders in the future. Although numerous studies have focused on PCOS, the underlying pathophysiological mechanisms of this disease remain unclear. Mitochondria play a key role in energy production, and mitochondrial dysfunction at the cellular level can affect systemic metabolic balance. The recent wide acceptance of functional mitochondrial disorders as a correlated factor of numerous diseases has led to the presupposition that abnormal mitochondrial metabolic markers are associated with PCOS. Studies conducted in the past few years have confirmed that increased oxidative stress is associated with the progression and related complications of PCOS and have proven the relationship between other mitochondrial dysfunctions and PCOS. Thus, this review aims to summarize and discuss previous and recent findings concerning the relationship between mitochondrial dysfunction and PCOS.

SUBMITTER: Zhang J

PROVIDER: S-EPMC6698037 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Polycystic ovary syndrome and mitochondrial dysfunction.

Zhang Jingshun J Bao Yigang Y Zhou Xu X Zheng Lianwen L

Reproductive biology and endocrinology : RB&E 20190816 1

Polycystic ovary syndrome (PCOS) is a prevalent hormonal disorder of premenopausal women worldwide and is characterized by reproductive, endocrine, and metabolic abnormalities. The clinical manifestations of PCOS include oligomenorrhea or amenorrhea, hyperandrogenism, ovarian polycystic changes, and infertility. Women with PCOS are at an increased risk of suffering from type 2 diabetes; me\tabolic syndrome; cardiovascular events, such as hypertension, dyslipidemia; gynecological diseases, includ ...[more]

PMID: 31420039

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Project description:Study questionIs the severity of menstrual cyclicity related to hyperinsulinemia and dysglycemia in women with hyperandrogenic polycystic ovary syndrome (PCOS)?Summary answerHyperandrogenic PCOS women with amenorrhea, compared to those with oligomenorrhea or eumenorrhea, had a greater risk of post-challenge hyperinsulinemia, which may explain their higher prevalence of dysglycemia.What is known alreadyPCOS is associated with metabolic dysregulation including insulin resistance (IR) and hyperinsulinemia, risk factors for type 2 diabetes mellitus (T2DM) and other vascular-metabolic morbidities. Although the severity of menstrual cyclicity is associated with IR in PCOS, it is unclear whether, and to what extent, it is related to hyperinsulinemia and glycemic abnormalities.Study design, size, durationWe prospectively compared the degree of menstrual cyclicity with the presence of dysglycemia (elevated 1-h plasma glucose ≥155 mg/dl; abnormal glucose tolerance [AGT], including prediabetes and T2DM; and AUC for glucose [G-AUC]) or dynamic state hyperinsulinemia (peak insulin levels either at 1 or 2 h of the oral glucose tolerance test (oGTT) and AUC for insulin [I-AUC]) in 333 hyperandrogenic PCOS women.Participants/materials, setting, methodsIn a tertiary care setting, hyperandrogenic PCOS participants with ovulatory eumenorrhea (Ov-Eumeno, n = 25), anovulatory eumenorrhea (Anov-Eumeno, n = 33), oligomenorrhea (Oligo, n = 150) and amenorrhea (Ameno, n = 125) underwent comprehensive phenotyping and a 2-h 75 g oGTT.Main results and the role of chanceMean BMI was greater among Ameno women than among Oligo, Anov-Eumeno or Ov-Eumeno women. Adjusting for BMI, the Ameno group demonstrated higher mean 1- and 2-h insulin and glucose, peak insulin and I-AUC and G-AUC, and either had a higher, or tended toward having a higher, prevalence of elevated 1-h glucose level and prevalence of AGT than the Oligo, Anov-Eumeno or Ov-Eumeno groups. In logistic regression, adjusting for BMI, Ameno women were more likely to have: AGT than Oligo women (odds ratio [OR]: 2.3; 95% CI: 1.3 to 4.2); elevated 1-h glucose (OR: 10.2; CI: 1.3-79.7) than those with Ov-Eumeno; and both AGT (OR: 1.7; CI: 1.1-2.6) and elevated 1-h glucose (OR: 1.8; CI: 1.1-2.8) than those with Anov-Eumeno or Ov-Eumeno when combined. Race/ethnicity, age, waist-to-hip ratio, fasting insulin and glucose, and biochemical or clinical measures of hyperandrogenism were similar across the four menstrual categories.Limitations, reasons for cautionOur study was limited by its cross-sectional nature and by studying women affected by PCOS as defined by the Androgen Excess & PCOS Society criteria (i.e. Rotterdam Phenotypes A, B and C) who were identified in the clinical setting. Consequently, extrapolation of the present data to other PCOS phenotypes (e.g. PCOS Phenotype D) should be made with caution.Wider implications of the findingsIn hyperandrogenic PCOS phenotypes, a history of amenorrhea, compared to oligomenorrhea or eumenorrhea, suggests a more severe cardiometabolic risk, including a higher degree of hyperinsulinemia and greater prevalence of glycemic abnormalities. These findings may assist in refining the treatment and screening guidelines for glycemic abnormalities in PCOS.Study funding/competing interest(s)This work was supported in part by grants R01-DK073632 and R01-HD29364 from the NIH and an endowment of the Helping Hand of Los Angeles, Inc. (to R.A.). M.D.P. has no competing interests to declare. U.E. is an investor in Concentric Analgesics, Inc. R.A. serves as a consultant for Spruce Biosciences and Fortress Biotech and an advisor for Aurora Forge.Trial registration numberN/A.

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Polycystic ovary syndrome and mitochondrial dysfunction.

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Polycystic ovary syndrome and mitochondrial dysfunction.

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