Hyperandrogenemia in polycystic ovary syndrome: exploration of the role of free testosterone and androstenedione in metabolic phenotype.

Elisabeth Lerchbaum,Albrecht Giuliani,Barbara Obermayer-Pietsch,Thomas Rabe,Verena Schwetz,Philipp Eller

doi:10.1371/journal.pone.0108263

Elisabeth Lerchbaum, Albrecht Giuliani + Show 4 more

Open Access

https://doi.org/10.1371/journal.pone.0108263

Copy DOI

Abstract

ObjectiveTo evaluate the association between androstenedione, testosterone, and free testosterone and metabolic disturbances in polycystic ovary syndrome.MethodsWe analyzed the association between androstenedione, testosterone, and free testosterone and metabolic parameters in a cross-sectional study including 706 polycystic ovary syndrome and 140 BMI-matched healthy women. Polycystic ovary syndrome women were categorized into 4 groups: normal androstenedione and normal free testosterone (NA/NFT), elevated androstenedione and normal free testosterone (HA/NFT), normal androstenedione and elevated free testosterone (NA/HFT), elevated androstenedione and free testosterone (HA/HFT).ResultsPolycystic ovary syndrome women with elevated free testosterone levels (HA/HFT and NA/HFT) have an adverse metabolic profile including 2 h glucose, HbA1c, fasting and 2 h insulin, area under the insulin response curve, insulin resistance, insulin sensitivity index (Matsuda), triglycerides, total and high density lipoprotein cholesterol levels compared to NA/NFT (p<0.05 for all age- and BMI-adjusted analyses). In binary logistic regression analysis adjusted for age and BMI, odds ratio for insulin resistance was 2.78 (1.34–5.75, p = 0.006) for polycystic ovary syndrome women with HA/HFT compared to NA/NFT. We found no significantly increased risk of metabolic disorders in polycystic ovary syndrome women with HA/NFT. In multiple linear regression analyses (age- and BMI-adjusted), we found a significant negative association between androstenedione/free testosterone-ratio and area under the insulin response curve, insulin resistance, and total cholesterol/high density lipoprotein cholesterol-ratio and a positive association with Matsuda-index, and high density lipoprotein cholesterol (p<0.05 for all).ConclusionsPolycystic ovary syndrome women with elevated free testosterone levels but not with isolated androstenedione elevation have an adverse metabolic phenotype. Further, a higher androstenedione/free testosterone-ratio was independently associated with a beneficial metabolic profile.

Highlights

Polycystic ovary syndrome (PCOS) is the most common endocrine disease in reproductive-aged women and affects up to 20% of all women when using Rotterdam criteria [1]
Hyperandrogenism was present in 85.6%, menstrual irregularities in 85.5%, and polycystic ovaries (PCO) in 56.8% of PCOS women, respectively
We found hyperandrogenism and menstrual irregularities and PCO in 50.6%, hyperandrogenism and menstrual irregularities in 32.9%, hyperandrogenism and PCO in 6.8%; and menstrual irregularities and PCO in 9.8% of PCOS women, respectively

Summary

Introduction

Polycystic ovary syndrome (PCOS) is the most common endocrine disease in reproductive-aged women and affects up to 20% of all women when using Rotterdam criteria [1]. PCOS women present with hyperandrogenism, oligo- or amenorrhea, and polycystic ovaries (PCO). Metabolic disturbances such as central obesity, insulin resistance (IR), a disturbed glucose metabolism, and the metabolic syndrome (MS) are common findings in women with PCOS [2,3,4,5]. Hyperandrogenism leads to PCO morphology and ovulatory dysfunction in animal models as well as in women with PCOS [8,9]. Those androgens are produced in the ovary as well as in the adrenal gland. Besides its mainly ovarian production, testosterone can be produced by conversion from androstenedione by 17b-hydroxysteroiddehydrogenase type 5 in adipose and other peripheral tissues [10]

Methods

Results

Conclusion