Genetic Variants Associated with Hyperandrogenemia in PCOS Pathophysiology

Polycystic ovary syndrome is a multifactorial endocrine disorder whose pathophysiology baffles many researchers till today. This syndrome is typically characterized by anovulatory cycles and infertility, altered gonadotropin levels, obesity, and bulky multifollicular ovaries on ultrasound. Hyperandrogenism and insulin resistance are hallmark features of its complex pathophysiology. Hyperandrogenemia is a salient feature of PCOS and a major contributor to cosmetic anomalies including hirsutism, acne, and male pattern alopecia in affected women. Increased androgen levels may be intrinsic or aggravated by preexisting insulin resistance in women with PCOS. Studies have reported augmented ovarian steroidogenesis patterns attributed mainly to theca cell hypertrophy and altered expression of key enzymes in the steroidogenic pathway. Candidate gene studies have been performed in order to delineate the association of polymorphisms in genes, which encode enzymes in the intricate cascade of steroidogenesis or modulate the levels and action of circulating androgens, with risk of PCOS development and its related traits. However, inconsistent findings have impacted the emergence of a unanimously accepted genetic marker for PCOS susceptibility. In the current review, we have summarized the influence of polymorphisms in important androgen related genes in governing genetic predisposition to PCOS and its related metabolic and reproductive traits.

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Anti-Müllerian hormone gene polymorphism is associated with androgen levels in Chinese polycystic ovary syndrome patients with insulin resistance

Journal of Assisted Reproduction and Genetics ◽

10.1007/s10815-015-0641-9 ◽

2016 ◽

Vol 33 (2) ◽

pp. 199-205 ◽

Cited By ~ 5

Author(s):

Meng-Xue Zheng ◽

Yan Li ◽

Rong Hu ◽

Fei-Miao Wang ◽

Xiao-Mei Zhang ◽

...

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Gene Polymorphism ◽

Polycystic Ovary ◽

Ovary Syndrome ◽

Androgen Levels

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No changes of peripheral insulin resistance in polycystic ovary syndrome after long-term reduction of endogenous androgens with leuprolide

Acta Endocrinologica ◽

10.1530/eje.0.1330718 ◽

1995 ◽

Vol 133 (6) ◽

pp. 718-722 ◽

Cited By ~ 7

Author(s):

Antonino Lasco ◽

Domenico Cucinotta ◽

Alfonso Gigante ◽

Giulia Denuzzo ◽

Marilena Pedulla ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Obese Women ◽

Ovary Syndrome ◽

Control Subjects ◽

Peripheral Insulin Resistance ◽

Androgen Levels

Lasco A, Cucinotta D, Gigante A, Denuzzo G, Pedulla M, Trifiletti A, Frisina N. No changes of peripheral insulin resistance in polycystic ovary syndrome after long-term reduction of endogenous androgens with leuprolide. Eur J Endocrinol 1995;133:718–22. ISSN 0804–4643 The aim of this study was to investigate the relationship between plasma insulin levels, peripheral insulin sensitivity and androgen secretion in ten patients with polycystic ovary syndrome and in six obese women as compared with six normal-weight control subjects. During a euglycemic–hyperinsulinemic clamp no significant change of testosterone, androstenedione or dehydroepiandrosterone sulfate plasma levels was observed in the two groups of patients or in the control subjects; insulin sensitivity was clearly reduced and was similar in polycystic ovary patients and in obese women, in spite of the different plasma androgen levels. A long-term (5 months) androgen suppression with the gonadotropin-releasing hormone agonist leuprolide was not able to improve significantly the insulin sensitivity. These results demonstrate that the short-term hyperinsulinemia achieved with the clamp technique does not affect androgen secretion and that insulin resistance, measured with the same technique, is not influenced by long-term suppression of plasma androgen levels in polycystic ovary syndrome. A Lasco, Via Faustina e Tertullo 19, 98100 Messina, Italy

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