Measurement of selected androgens using liquid chromatography-tandem mass spectrometry in reproductive-age women with Type 1 diabetes
Author(s)
Type
Journal Article
Abstract
STUDY QUESTION
What information does androgen profiling using liquid chromatography tandem mass spectrometry (LC–MS/MS) provide in reproductive-age women with Type 1 diabetes (T1D)?
SUMMARY ANSWER
In T1D women, androstenedione proved most useful of the measured androgens in differentiating subgroups based on clinical phenotypes of hyperandrogenism (HA) and polycystic ovary syndrome (PCOS).
WHAT IS KNOWN ALREADY
The prevalence of HA and PCOS are increased in women with T1D. These observations are based on measurement of serum androgens using immunoassays, to-date no studies using LC–MS/MS have been reported in reproductive-age women with T1D.
STUDY DESIGN, SIZE, DURATION
This was a cross-sectional study with recruitment of three groups of reproductive-age women: women with T1D (n = 87), non-diabetic women with (N = 97) and without PCOS (N = 101).
PARTICIPANTS/MATERIALS, SETTING, METHODS
Using LC–MS/MS, we aimed to characterize androgen profiles and PCOS status in women with T1D, and interpret findings in relation to cohorts of non-diabetic women with and without PCOS.
MAIN RESULTS AND THE ROLE OF CHANCE
Compared to non-diabetic women, dehydroepiandrosterone/dehydroepiandrosterone sulphate (DHEA/DHEAS) ratio was lower (P < 0.05) in women with T1D. Testosterone levels were greater in T1D women with clinical HA and anovulation compared to those without clinical HA and with regular cycles, while androstenedione levels were greater in T1D women with HA and anovulation compared to those with HA and regular cycles and also those without HA and with regular cycles (P < 0.05 for all). Compared to T1D women without PCOS, the 18% of T1D women who had PCOS were younger with lower BMI, an older age of menarche, and were more likely to have a positive family history of PCOS (P < 0.05 for all). Androgen levels did not differ between women with T1D and PCOS compared to BMI-matched non-diabetic women with PCOS, but androstenedione levels were greater in T1D women with PCOS compared to obese women with PCOS (P < 0.05).
LIMITATIONS, REASONS FOR CAUTION
Relatively small subgroups of patients were studied, reducing the power to detect small differences. Free testosterone levels were not measured using equilibrium dialysis, and were not calculated – commonly used formulae have not been validated in T1D.
WIDER IMPLICATIONS OF THE FINDINGS
Androstenedione is a sensitive biochemical marker of clinical hyperandrogenism and PCOS in T1D. T1D women with PCOS are leaner than those without PCOS but are more likely to have a family history of PCOS. Women with T1D and PCOS have a similar biochemical phenotype to lean non-diabetic women with PCOS but differ from obese women with PCOS. The mechanisms underlying PCOS in T1D and its clinical significance require further investigation.
STUDY FUNDING/COMPETING INTEREST(S)
The study was part-funded by the Meath Foundation. The authors have no competing interests.
What information does androgen profiling using liquid chromatography tandem mass spectrometry (LC–MS/MS) provide in reproductive-age women with Type 1 diabetes (T1D)?
SUMMARY ANSWER
In T1D women, androstenedione proved most useful of the measured androgens in differentiating subgroups based on clinical phenotypes of hyperandrogenism (HA) and polycystic ovary syndrome (PCOS).
WHAT IS KNOWN ALREADY
The prevalence of HA and PCOS are increased in women with T1D. These observations are based on measurement of serum androgens using immunoassays, to-date no studies using LC–MS/MS have been reported in reproductive-age women with T1D.
STUDY DESIGN, SIZE, DURATION
This was a cross-sectional study with recruitment of three groups of reproductive-age women: women with T1D (n = 87), non-diabetic women with (N = 97) and without PCOS (N = 101).
PARTICIPANTS/MATERIALS, SETTING, METHODS
Using LC–MS/MS, we aimed to characterize androgen profiles and PCOS status in women with T1D, and interpret findings in relation to cohorts of non-diabetic women with and without PCOS.
MAIN RESULTS AND THE ROLE OF CHANCE
Compared to non-diabetic women, dehydroepiandrosterone/dehydroepiandrosterone sulphate (DHEA/DHEAS) ratio was lower (P < 0.05) in women with T1D. Testosterone levels were greater in T1D women with clinical HA and anovulation compared to those without clinical HA and with regular cycles, while androstenedione levels were greater in T1D women with HA and anovulation compared to those with HA and regular cycles and also those without HA and with regular cycles (P < 0.05 for all). Compared to T1D women without PCOS, the 18% of T1D women who had PCOS were younger with lower BMI, an older age of menarche, and were more likely to have a positive family history of PCOS (P < 0.05 for all). Androgen levels did not differ between women with T1D and PCOS compared to BMI-matched non-diabetic women with PCOS, but androstenedione levels were greater in T1D women with PCOS compared to obese women with PCOS (P < 0.05).
LIMITATIONS, REASONS FOR CAUTION
Relatively small subgroups of patients were studied, reducing the power to detect small differences. Free testosterone levels were not measured using equilibrium dialysis, and were not calculated – commonly used formulae have not been validated in T1D.
WIDER IMPLICATIONS OF THE FINDINGS
Androstenedione is a sensitive biochemical marker of clinical hyperandrogenism and PCOS in T1D. T1D women with PCOS are leaner than those without PCOS but are more likely to have a family history of PCOS. Women with T1D and PCOS have a similar biochemical phenotype to lean non-diabetic women with PCOS but differ from obese women with PCOS. The mechanisms underlying PCOS in T1D and its clinical significance require further investigation.
STUDY FUNDING/COMPETING INTEREST(S)
The study was part-funded by the Meath Foundation. The authors have no competing interests.
Date Issued
2018-09-01
Date Acceptance
2018-06-26
Citation
Human Reproduction, 2018, 33 (9), pp.1727-1734
ISSN
0268-1161
Publisher
Oxford University Press
Start Page
1727
End Page
1734
Journal / Book Title
Human Reproduction
Volume
33
Issue
9
Copyright Statement
© The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/30020477
PII: 5055524
Subjects
ACCURACY
androgens
androstenedione
ANDROSTENEDIONE
ASSAY
BINDING
biomarkers
DEHYDROEPIANDROSTERONE
FREE TESTOSTERONE
hyperandrogenism
HYPERANDROGENISM
Life Sciences & Biomedicine
liquid chromatography-mass spectrometry
METABOLIC PHENOTYPE
Obstetrics & Gynecology
polycystic ovary syndrome
POLYCYSTIC-OVARY-SYNDROME
PREVALENCE
Reproductive Biology
Science & Technology
Type 1 diabetes
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2018-07-18