Diabetes mellitus and insulin resistance in mothers, fathers, sisters, and brothers of women with polycystic ovary syndrome: a systematic review and meta-analysis

Yılmaz, Bülent; Vellanki, Priyathama; Ata, Barış; Yildiz, Bülent O.

doi:10.1016/j.fertnstert.2018.04.024

Cited by 39 publications

(28 citation statements)

References 89 publications

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“…Systolic, but not diastolic blood, pressure was significantly higher in male siblings of PCOS probands than in control men [ 5 , 6 ]. Men whose sisters were diagnosed with PCOS had increased levels of 2-h postchallenge glucose, were more insulin-resistant, more frequently met the criteria of metabolic syndrome [ 5 , 7 – 10 ], as well as were characterized by a higher prevalence of type 2 diabetes and impaired glucose tolerance than brothers of unaffected women [ 11 ]. They were also characterized by impaired brachial artery flow-mediated dilatation and this impairment was particularly pronounced in subjects with a family history of diabetes mellitus [ 9 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

The impact of atorvastatin on cardiometabolic risk factors in brothers of women with polycystic ovary syndrome

Krysiak

Szkróbka

2020

Pharmacol. Rep

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Background Women with polycystic ovary syndrome (PCOS) are characterized by increased cardiometabolic risk. The aim of the current study was to compare the impact of atorvastatin on plasma levels of cardiometabolic risk factors between men whose sisters had either PCOS or were unaffected. Methods The study population consisted of two age-, fat-free mass index-, blood pressure- and plasma lipid-matched groups of men with elevated total and LDL cholesterol levels: 20 brothers of PCOS probands (group 1) and 20 brothers of healthy women (group 2). Both groups were then treated with atorvastatin (40 mg daily) for the following 6 months. At the beginning and at the end of the study, we assessed plasma lipid levels, glucose homeostasis markers and levels of dehydroepiandrosterone sulfate, testosterone, bioavailable testosterone, uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine, fibrinogen and 25-hydroxyvitamin D. Results At the beginning of the study, both treatment arms differed in the degree of insulin resistance, calculated bioavailable testosterone, as well as in plasma levels of dehydroepiandrosterone sulfate, uric acid, hsCRP and 25-hydroxyvitamin D. Although atorvastatin reduced total and LDL cholesterol levels, this effect was stronger in group 2 than group 1. In group 2, atorvastatin exerted also a more potent impact on hsCRP, fibrinogen and homocysteine. An unfavorable impact on insulin sensitivity was observed only in group 1; while, statistically significant changes in uric acid and 25-hydroxyvitamin D levels were found only in group 2. Conclusion The obtained results suggest that cardiometabolic effects of atorvastatin are less pronounced in male siblings of PCOS probands than in brothers of unaffected women.

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Section: Introductionmentioning

confidence: 99%

The impact of atorvastatin on cardiometabolic risk factors in brothers of women with polycystic ovary syndrome

Krysiak

Szkróbka

2020

Pharmacol. Rep

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“…We are not aware of previous studies regarding AGD in boys born of mothers with PCOS. However, previous studies regarding the male phenotype of PCOS reported that brothers of women with PCOS had higher levels of dehydroepiandrosterone sulfate and higher risk of dyslipidemia and insulin resistance compared to controls (Legro et al, 2002;Yilmaz et al, 2018). Furthermore, a recent study reported that PCOS offspring (boys and girls) had increased levels of inflammatory biomarkers, suggesting increased chronic low-grade inflammation (Daan et al, 2016).…”

Section: Discussionmentioning

confidence: 98%

Anogenital distance in children born of mothers with polycystic ovary syndrome: the Odense Child Cohort

et al. 2019

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STUDY QUESTION Are higher testosterone levels during pregnancy in women with polycystic ovary syndrome (PCOS) associated with longer offspring anogenital distance (AGD)? SUMMARY ANSWER AGD was similar in 3-month-old children born of mothers with PCOS compared to controls. WHAT IS KNOWN ALREADY AGD is considered a marker of prenatal androgenization. STUDY DESIGN, SIZE, DURATION Maternal testosterone levels were measured by mass spectrometry at Gestational Week 28 in 1127 women. Maternal diagnosis of PCOS before pregnancy was defined according to Rotterdam criteria. Offspring measures included AGD from anus to posterior fourchette (AGDaf) and clitoris (AGDac) in girls and to scrotum (AGDas) and penis (AGDap) and penile width in boys and body composition (weight and BMI SD scores) at age 3 months. PARTICIPANTS/MATERIALS, SETTING, METHODS The study was part of the prospective study, Odense Child Cohort (OCC), and included mothers with PCOS (n = 139) and controls (n = 1422). The control population included women with regular menstrual cycles (<35 days) before conception and no signs of androgen excess (hirsutism and/or acne). MAIN RESULTS AND THE ROLE OF CHANCE AGD measures were comparable in offspring of women with PCOS compared to controls (all P > 0.2) despite significantly higher maternal levels of total testosterone (mean: 2.4 versus 2.0 nmol/l) and free testosterone (mean: 0.005 versus 0.004 nmol/l) in women with PCOS versus controls (both P < 0.001). In women with PCOS, maternal testosterone was an independent positive predictor of offspring AGDas and AGDap in boys. Maternal testosterone levels did not predict AGD in girls born of mothers with PCOS or in boys or girls born of women in the control group. LIMITATIONS, REASONS FOR CAUTION The diagnosis of PCOS was based on retrospective information and questionnaires during pregnancy. Women participating in OCC were more ethnically homogenous, leaner, more educated and less likely to smoke compared to the background population. Our study findings, therefore, need to be reproduced in prospective study cohorts with PCOS, in more obese study populations and in women of other ethnicities. WIDER IMPLICATIONS OF THE FINDINGS Our finding of the same AGD in girls born of mothers with PCOS compared to controls expands previous results of studies reporting longer AGD in adult women with PCOS. Our results suggest that longer AGD in adult women with PCOS could be the result of increased testosterone levels in puberty, perhaps in combination with weight gain. STUDY FUNDING/COMPETING INTEREST(S) Financial grants for the study were provided by the Danish Foundation for Scientific Innovation and Technology (09-067180), Ronald McDonald Children Foundation, Odense University Hospital, the Region of Southern Denmark, the Municipality of Odense, the Mental Health Service of the Region of Southern Denmark, The Danish Council for Strategic Research, Program Commission on Health, Food and Welfare (2101-08-0058), Odense Patient data Explorative Network, Novo Nordisk Foundation (grant no. NNF15OC00017734), the Danish Council for Independent Research and the Foundation for research collaboration between Rigshospitalet and Odense University Hospital and the Health Foundation (Helsefonden). There is no conflict of interest of any author that could be perceived as prejudicing the impartiality of the research reported.

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“…PCOS clusters within families and having a first degree relative suffering from PCOS conveys a 25% risk of either developing the full blown clinical picture or having a 25% risk of sharing characteristics of the syndrome amongst siblings to other siblings (6, 7). Similar results were obtained in several twin studies showing higher rates of concordance in PCOS characteristics between monozygotic twin sisters compared to dizygotic twins (8).…”

Section: Genetics Of Pcosmentioning

confidence: 99%

Follicle Stimulating Hormone Receptor (FSHR) Polymorphisms and Polycystic Ovary Syndrome (PCOS)

Laven

2019

Front. Endocrinol.

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Polycystic ovary syndrome (PCOS) is the commonest endocrine abnormality in women of reproductive age typically presenting with chronic oligo- or anovulation, clinical, or biochemical hyperandrogenism and polycystic ovarian morphology (PCOM). Restoring mono-ovulation is the ultimate goal of ovulation induction and most women do respond to ovulation inducing agents causing their Follicle-stimulating hormone (FSH) levels to rise. Familial clustering and the results from twin studies strongly support an underlying genetic basis for PCOS. Recent Genome wide association studies (GWAS) have identified several genetic variants being genome wide significantly associated with PCOS. Amongst those are variants in or near the Luteinizing hormone (LH) and FSH receptor genes as well as a variant in the FSH-β gene. The aim of this review is to summarize the available evidence as to whether single nucleotide polymorphisms are able to modify the PCOS phenotype or whether they constitute a risk factor for the syndrome. Data on the role of FSHR polymorphisms in PCOS are conflicting. It seems that in large Chinese studies FSHR polymorphisms are not associated with either PCOS risk or with PCOS treatment outcome. However, in large scale studies in Caucasians these polymorphisms seem to influence the risk of having PCOS. Moreover, these studies also showed that some polymorphisms might affect some clinical features of PCOS as well as treatment outcome. Although most research has focussed on the role of FSHR polymorphisms there seems to be also some evidence showing that single nucleotide polymorphisms (SNPs) in the LHCG-Receptor as well as those in FSH-β gene might also alter the phenotype of PCOS. In conclusion most studies confirm that FSHR polymorphisms do alter the phenotype of PCOS in that they either alter the response to exogenous FSH or hat they increase the risk of having PCOS.

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Diabetes mellitus and insulin resistance in mothers, fathers, sisters, and brothers of women with polycystic ovary syndrome: a systematic review and meta-analysis

Abstract: PROSPERO 2016 CRD42016048551.

Cited by 39 publications

References 89 publications

The impact of atorvastatin on cardiometabolic risk factors in brothers of women with polycystic ovary syndrome

The impact of atorvastatin on cardiometabolic risk factors in brothers of women with polycystic ovary syndrome

Anogenital distance in children born of mothers with polycystic ovary syndrome: the Odense Child Cohort

Follicle Stimulating Hormone Receptor (FSHR) Polymorphisms and Polycystic Ovary Syndrome (PCOS)

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