Offspring born to women with PCOS
Disturbances during intrauterine life have been implicated in the origin of PCOS and may modify the endocrine and metabolic function of a child born to a PCOS mother independently of genetic inheritance and sex. Daughters of women with PCOS show 4 components of the syndrome (ovarian dysfunction, neuroendocrine dysfunction, hyperandrogenism, and hyperinsulinemia) that appear in a sequential pattern during infancy, childhood and puberty increasing the chance for developing PCOS during adulthood. Sons born to PCOS mothers show few reproductive but important metabolic disturbances. These metabolic features, both in girls and boys, have early cardiovascular effects that may put these children at risk for later cardiovascular disease. Recent combined animal/human models have been able to identify common markers that will help us elucidate the precise mechanisms involved in the transgenerational transmission of this syndrome and provide possible therapies to prevent it.
Polycystic ovary syndrome (PCOS) is a highly prevalent (5–10%) endocrine-metabolic dysfunction in adult women, characterized by chronic anovulation, hyperandrogenism and polycystic ovarian morphology..In an attempt to understand the sequence of appearance of the pathophysiological components of PCOS, 13 years ago our group designed a strategy that involved the assessment of daughters born to PCOS mothers at different stages of development.
Evidence we propose that there are 4 components that are evident in daughters of women with PCOS as they mature:
Ovarian Dysfunction: AMH and ovarian volumes have been found systematically higher in PCOS daughters from very early stages onwards This is the first feature that can be recognized in PCOSd and is a very consistent marker in all of our studies. Very importantly AMH levels may be driving LH levels up as recently shown in a mouse model linking this component with the following one, neuroendocrine dysfunction.
Neuroendocrine dysfunction: In adolescents with PCOS, increased LH has been described as an early feature in the establishment of the syndrome. Accordingly, in our studies, PCOS daughters exhibited elevated peak LH levels after leuprolide administration during early postnatal life and in late puberty.
Hyperandrogenism: PCOSd exhibit higher basal and peak testosterone levels in Tanner stages 4 and 5 compared to control girls.
Hyperinsulinemia: The fourth component is a higher insulin response in the oral glucose tolerance test, which may reflect metabolic disruption, which is one of the main determinants of the severity of PCOS expression.
Several markers of metabolic and reproductive disruption have been described in the offspring of PCOS patients.
Journal of Clinical Research and Bioethics
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