Abstract
BackgroundAndrosterone glucuronide (ADTG) concentrations have been suggested as a marker of the effects of androgens at the target tissue level. As the mechanism for hyperandrogenemia in obese and nonobese polycystic ovary syndrome (PCOS) may differ, this study compared the different androgen parameters in non-obese compared to obese women with PCOS, and in normal subjects.MethodsEleven non-obese and 14 obese women with PCOS were recruited and compared to 11 control women without PCOS. Total testosterone, dehydroepiandrosterone sulphate (DHEAS), ADTG, and androstenedione were analysed using gold standard tandem mass spectrometry, and the free androgen index (FAI) was calculated.ResultsTotal testosterone, ADTG and androstendione levels did not differ between non-obese (body mass index (BMI) ≤25 kg/m2) and obese PCOS (BMI >25 kg/m2) but all were significantly higher than for controls (p < 0.01). The ADTG to DHEAS ratio was significantly elevated 39 ± 6 (p < 0.01) in obese PCOS in comparison to non-obese PCOS and controls (28 ± 5 and 29 ± 4, respectively). The free androgen index (FAI) and insulin resistance (HOMA-IR) were significantly higher in obese PCOS compared to non-obese PCOS and controls (p < 0.01). DHEAS was significantly higher in the non-obese versus obese PCOS (p < 0.01). All androgen parameters were significantly lower and sex hormone binding globulin (SHBG) significantly higher in normal subjects compared to those with obese and non-obese PCOS.ConclusionsThe ADTG:DHEAS ratio was significantly elevated in obese PCOS compared to non-obese PCOS and controls suggesting that this may be a novel biomarker discriminatory for obese PCOS subjects, perhaps being driven by higher hepatic 5α reductase activity increasing ADTG formation in these women.
Highlights
Androsterone glucuronide (ADTG) concentrations have been suggested as a marker of the effects of androgens at the target tissue level
ADTG has been measured by immunoassay that may be inaccurate due to cross-reactivity with other androgen metabolites such as dehydroepiandrosterone sulphate (DHEAS) [12, 13], circumvented by tandem mass spectrometry
This study showed that using state of the art measurement that the ADTG:DHEAS ratio was significantly elevated in obese polycystic ovary syndrome (PCOS) compared to non-obese PCOS and to controls subjects, whilst the latter two groups did not differ, suggesting that this may be a novel biomarker and discriminatory for PCOS in obesity
Summary
Androsterone glucuronide (ADTG) concentrations have been suggested as a marker of the effects of androgens at the target tissue level. With the advent of liquid chromatography tandem mass spectroscopy the accurate measurement of low serum levels of androgens, their precursors and their metabolites is possible, allowing the role of androgens in PCOS to be studied with sufficient sensitivity and specificity [5]. Cho et al BMC Endocrine Disorders (2017) 17:26 reflects adrenal androgen secretion from hepatic 5αreductase activity, and to a lesser extent peripheral 5αreductase activity, that converts dehydroepiandrosterone sulphate (DHEAS) to ADTG [7, 8]. ADTG has been reported to be a more reliable marker for the effects of androgen at the target tissue level and studies have shown that ADTG is significantly elevated in hirsute compared to non-hirsute women with PCOS [9,10,11]. ADTG has been measured by immunoassay that may be inaccurate due to cross-reactivity with other androgen metabolites such as DHEAS [12, 13], circumvented by tandem mass spectrometry
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