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Developmental Programming of Polycystic Ovary Syndrome: Role of Prenatal Androgen Excess

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Diabetes in Women

Part of the book series: Contemporary Diabetes ((CDI))

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrine/metabolic disorder in women, characterized by hyperandrogenism, chronic anovulation, and/or polycystic ovaries in association with android fat distribution and insulin resistance/hyperinsulinism. The etiology of PCOS remains elusive but there is increasing evidence that the phenotypic traits of the syndrome may be programmed in utero by androgen excess.

Thus, female primates, exposed to androgen excess during fetal life, exhibit the reproductive and metabolic features of PCOS in adulthood. Women with congenital 21-hydroxylase deficiency and congenital adrenal virilizing tumors develop features characteristic of PCOS during adult life, despite the normalization of androgen excess after birth. Rare cases of women with congenital sex hormone-binding globulin (SHBG) and P450 aromatase deficiency may also develop some of the features of PCOS in adulthood.

The potential sources of gestational hyperandrogenism to account for the developmental programming of PCOS in humans are not clearly understood. However, maternal and/or fetal hyperandrogenism, in association with reduced placental SHBG and/or aromatase activity, can provide a plausible mechanism and this, in part, may be genetically determined. Indeed, genetic association studies have indicated that common 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 genetic variants may provide the genetic link to prenatal androgenization in human PCOS.

It appears, therefore, that prenatal androgenization of the female fetus, induced by genetic factors and environmental signals, or by the interaction of both, may program the differentiating target tissues toward the development of PCOS in adult life.

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Tsatsoulis, A. (2009). Developmental Programming of Polycystic Ovary Syndrome: Role of Prenatal Androgen Excess. In: Tsatsoulis, A., Wyckoff, J., Brown, F. (eds) Diabetes in Women. Contemporary Diabetes. Humana Press. https://doi.org/10.1007/978-1-60327-250-6_5

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