scholarly journals Review: Fetal Programming of Polycystic Ovary Syndrome by Androgen Excess — Evidence from Experimental, Clinical and Genetic Association Studies

2014 ◽  
Vol 6 (2) ◽  
pp. 129-130
Author(s):  
N Xita ◽  
A Tsatsoulis
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Genetic Association ◽  
Fetal Programming ◽  
Polycystic Ovary ◽  
Association Studies ◽  
Adult Life ◽  
Genetic Association Studies ◽  
Androgen Excess ◽  
Ovary Syndrome ◽  
21 Hydroxylase Deficiency

ABSTRACT Objective Polycystic ovary syndrome (PCOS) is a common endocrine disorder of premenopausal women, characterized by hyperandrogenism, polycystic ovaries, and chronic anovulation along with insulin resistance and abdominal obesity as frequent metabolic traits. Although, PCOS manifests clinically during adolescence, emerging data suggest that the natural history of PCOS may originate in intrauterine life. Evidence Acquisition Evidence from experimental, clinical, and genetic research supporting the hypothesis for the fetal origins of PCOS has been analyzed. Evidence Synthesis Female primates, exposed in utero to androgen excess, exhibit the phenotypic features of PCOS during adult life. Clinical observations also support a potential fetal origin of PCOS. Women with fetal androgen excess disorders, including congenital 21-hydroxylase deficiency and congenital adrenal virilizing tumors, develop features characteristic of PCOS during adulthood despite the normalization of androgen excess after birth. The potential mechanisms of fetal androgen excess leading to a PCOS phenotype in humans are not clearly understood. However, maternal and/or fetal hyperandrogenism can provide a plausible mechanism for fetal programming of PCOS, and this, in part, may be genetically determined. Thus, genetic association studies have indicated that common polymorphic variants of genes determining androgen activity or genes that influence the availability of androgens to target tissues are associated with PCOS and increased androgen levels. These genomic variants may provide the genetic link to prenatal androgenization in human PCOS. Conclusion Prenatal androgenization of the female fetus induced by genetic and environmental factors, or the interaction of both, may program differentiating target tissues toward the development of PCOS phenotype in adult life.

scholarly journals Mechanisms Involved in Intrauterine Growth Restriction in Patients With Polycystic Ovary Syndrome: Primary and Secondary Prevention of Metabolic Syndrome and Cancer Risk in the Adult Life of Offspring

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A741-A742
Author(s):  
Domingo Mugnolo ◽  
Erica Giraldo ◽  
Maria Perez Lana ◽  
Susana Beatriz Campeni
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Polycystic Ovary Syndrome ◽  
Fetal Programming ◽  
Intrauterine Growth Restriction ◽  
Polycystic Ovary ◽  
Adult Life ◽  
Ovary Syndrome ◽  
Intrauterine Growth ◽  
Increased Risk

Abstract Polycystic ovary syndrome (PCOS) is one of the most common hormonal disorders that affects between 5- 10% of women of reproductive age. It is currently considered a complex and multifactorial disease with metabolic, cardiovascular implications and represents per se an increased cancer risk. PATIENTS with PCOS routinely have menstrual disorders, hyperandrogenism, infertility and reproductive complications such as recurrent abortions, gestational diabetes, intrauterine growth restriction, pregnancy induced hypertension that give rise to underweight newborns and condition metabolic diseases to adult life and increased risk of cancer, especially breast and endometrial cancer. Insulin resistance and hyperandrogenism are the most important etiopathogenic factors in PCOS. On the other hand, subjects exposed to an adverse microenvironment in the intrauterine stage develop compensating responses to survive, a process called fetal programming. Prenatal exposure to androgens and/or insulin resistance may act as fetal programming factors and cause restriction of intrauterine growth, obesity and insulin resistance in offspring. Newborn may have an increased risk of metabolic syndrome, increased incidence of hypertensive, type 2 diabetes, heart disease and cerebrovascular disease. Prevention of these complications will be achieved if women with Polycystic Ovary Syndrome are treated appropriately throughout their lives, but especially before and during their pregnancy. Only in this way can the risk of them be reduced, representing a better quality and greater life expectancy.

scholarly journals Fetal programming of polycystic ovary syndrome: Effects of androgen exposure on prenatal ovarian development

2021 ◽  
Vol 207 ◽  
pp. 105830
Author(s):  
Maya Barsky ◽  
Jamie Merkison ◽  
Pardis Hosseinzadeh ◽  
Liubin Yang ◽  
Janet Bruno-Gaston ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Fetal Programming ◽  
Ovarian Development ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Androgen Exposure

scholarly journals Family-Based Quantitative Trait Meta-Analysis Implicates Rare Noncoding Variants in DENND1A in Polycystic Ovary Syndrome

2019 ◽  
Vol 104 (9) ◽  
pp. 3835-3850 ◽  
Author(s):  
Matthew Dapas ◽  
Ryan Sisk ◽  
Richard S Legro ◽  
Margrit Urbanek ◽  
Andrea Dunaif ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Quantitative Trait ◽  
Rare Variants ◽  
Polycystic Ovary ◽  
Association Studies ◽  
Meta Analysis ◽  
Premenopausal Women ◽  
Endocrine Disorders ◽  
Genome Wide Association Studies ◽  
Ovary Syndrome

AbstractContextPolycystic ovary syndrome (PCOS) is among the most common endocrine disorders of premenopausal women, affecting 5% to15% of this population depending on the diagnostic criteria applied. It is characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. PCOS is highly heritable, but only a small proportion of this heritability can be accounted for by the common genetic susceptibility variants identified to date.ObjectiveThe objective of this study was to test whether rare genetic variants contribute to PCOS pathogenesis.Design, Patients, and MethodsWe performed whole-genome sequencing on DNA from 261 individuals from 62 families with one or more daughters with PCOS. We tested for associations of rare variants with PCOS and its concomitant hormonal traits using a quantitative trait meta-analysis.ResultsWe found rare variants in DENND1A (P = 5.31 × 10−5, adjusted P = 0.039) that were significantly associated with reproductive and metabolic traits in PCOS families.ConclusionsCommon variants in DENND1A have previously been associated with PCOS diagnosis in genome-wide association studies. Subsequent studies indicated that DENND1A is an important regulator of human ovarian androgen biosynthesis. Our findings provide additional evidence that DENND1A plays a central role in PCOS and suggest that rare noncoding variants contribute to disease pathogenesis.

scholarly journals Association of CYP3A7*1C and Serum Dehydroepiandrosterone Sulfate Levels in Women with Polycystic Ovary Syndrome

2008 ◽  
Vol 93 (7) ◽  
pp. 2909-2912 ◽  
Author(s):  
Mark O. Goodarzi ◽  
Ning Xu ◽  
Ricardo Azziz
Keyword(s):  
Los Angeles ◽  
Polycystic Ovary Syndrome ◽  
White Women ◽  
Polycystic Ovary ◽  
Medical Center ◽  
Free Testosterone ◽  
Total Testosterone ◽  
Adrenal Androgen ◽  
Androgen Excess ◽  
Ovary Syndrome

Abstract Context: Adrenal androgen excess is common in polycystic ovary syndrome (PCOS) and appears to be heritable. CYP3A7 metabolizes dehydroepiandrosterone and its sulfate (DHEAS). A promoter variant, CYP3A7*1C, which results in persistent expression in adults, was associated with reduced DHEAS levels in a previous study, which led us to consider CYP3A7*1C as a modulator of adrenal androgen excess in patients with PCOS. Objective: The objective was to replicate the association between CYP3A7*1C and reduced DHEAS levels in PCOS patients and assess its possible role in modulating testosterone levels. Design: Women with and without PCOS were genotyped for CYP3A7*1C, and this variant was tested for association with DHEAS and total and free testosterone. Setting: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; controls were recruited from the surrounding community. Genotyping took place at Cedars-Sinai Medical Center (Los Angeles, CA). Participants: A total of 287 white women with PCOS and 187 controls were studied. Main Measurements: CYP3A7*1C genotype, PCOS risk, and androgen levels were measured. Results: PCOS subjects who carried the CYP3A7*1C variant had lower levels of serum DHEAS and total testosterone (P = 0.0006 and 0.046, respectively). The variant was not associated with PCOS risk. Conclusion: This study replicated prior work of the association of CYP3A7*1C and decreased DHEAS in a different population of young PCOS women, providing further genetic evidence that CYP3A7 plays a potential role in modulation of DHEAS levels. Adult expression of CYP3A7 may modify the PCOS phenotype by ameliorating adrenal androgen excess.

scholarly journals Epidemiology, diagnosis and management of hirsutism: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society

2011 ◽  
Vol 18 (2) ◽  
pp. 146-170 ◽  
Author(s):  
H.F. Escobar-Morreale ◽  
E. Carmina ◽  
D. Dewailly ◽  
A. Gambineri ◽  
F. Kelestimur ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Consensus Statement ◽  
Polycystic Ovary ◽  
Androgen Excess ◽  
Ovary Syndrome ◽  
Diagnosis And Management

scholarly journals POSITION STATEMENT: Glucose Intolerance in Polycystic Ovary Syndrome—A Position Statement of the Androgen Excess Society

2007 ◽  
Vol 92 (12) ◽  
pp. 4546-4556 ◽  
Author(s):  
Kelsey E. S. Salley ◽  
Edmond P. Wickham ◽  
Kai I. Cheang ◽  
Paulina A. Essah ◽  
Nicole W. Karjane ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Glucose Intolerance ◽  
Polycystic Ovary ◽  
Position Statement ◽  
Androgen Excess ◽  
Ovary Syndrome
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