The Circadian Variation in Anti-Müllerian Hormone in Patients with Polycystic Ovary Syndrome Differs Significantly from Normally Ovulating Women

Leif Bungum,Aleksander Giwercman,Mona Bungum,Florencia Franssohn,Peter Humaidan,Samuel Kim

doi:10.1371/journal.pone.0068223

Leif Bungum, Aleksander Giwercman + Show 4 more

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https://doi.org/10.1371/journal.pone.0068223

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Journal: PloS one	Publication Date: Sep 4, 2013
Citations: 70	License type: CC BY 4.0

Affiliation: Lund University, Skåne University Hospital

Abstract

ObectiveTo improve the biologic understanding of the Polycystic Ovarian Syndrome (PCOS) condition by examining the circadian variation and relationship between Anti Müllerian Hormone (AMH), gonadotropins and ovarian steroids in PCOS patients compared to normally ovulating and menstruating women. By comparing the pattern of co-variation between AMH and Luteinizing Hormone, two compounds closely linked to hyperandrogenism and anovulation in PCOS, the involvement of the Hypothalamic-Pituitary-Ovarian axis in PCOS pathology could be elucidated.PatientsEight normal-weighted young, anovulatory PCOS-women as study group and ten normal menstruating and ovulating women as controls.InterventionsObservational prospective study of the circadian variation in AMH, gonadotropins, sex steroids and androgens in a study and a control group. A circadian profile was performed in each study and control subject during a 24-h period by blood sampling every second hour, starting at 8:00 a.m. and continuing until 8:00 a.m. the following day.Result(s)Significant differences in hormonal levels were found between the groups, with higher concentrations of AMH, LH and androgens in the PCOS group and lower amounts of FSH and progesterone. A distinct difference in the circadian variation pattern of AMH and LH between PCOS patients and normal controls was seen, with PCOS patients presenting a uniform pattern in serum levels of AMH and LH throughout the study period, without significant nadir late-night values as was seen in the control group. In PCOS women, a significant positive association between LH/ FSH and testosterone was found opposite to controls.Main outcome measuresCircadian variation in Anti-Müllerian Hormone, gonadotropins and ovarian steroids and the covariation between them.ConclusionA significant difference in the circadian secretion of LH and AMH in PCOS women compared to normally ovulating women indicate an increased GnRH pulse, creating high and constant LH serum concentrations. A significant co-variation between LH and AMH may suggest LH as a factor involved in the control of AMH secretion.

Highlights

Polycystic ovary syndrome (PCOS), anovulation and clinical or biochemical hyperandrogenism, are phenotypically heterogenic endocrine disorders, affecting women of reproductive age with a prevalence of 6–10% [1]
A significant difference in the circadian secretion of Luteinizing Hormone (LH) and Anti Mullerian Hormone (AMH) in PCOS women compared to normally ovulating women indicate an increased Gonadotropin Releasing Hormone (GnRH) pulse, creating high and constant LH serum concentrations
A significant covariation between LH and AMH may suggest LH as a factor involved in the control of AMH secretion

Summary

Introduction

Polycystic ovary syndrome (PCOS), anovulation and clinical or biochemical hyperandrogenism, are phenotypically heterogenic endocrine disorders, affecting women of reproductive age with a prevalence of 6–10% [1]. Insulin has been reported to increase LH secretion secondary to altered GnRH-neurone activity in both animals and in normally menstruating women [11], but this issue is debated due to surveys of insulin-infusion in PCOS-women not confirming this effect [12,13,14,15]. If present, both mechanisms would promote an increase in the androgen synthesis [16,17] which may further deteriorate the regulation of the folliculogenesis

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