CoChat
Sign Up
Cited by 110Ovarian function and disordersDiabetes, Cardiovascular Risks, and LipoproteinsHormonal and reproductive studies

Hyperandrogenemia in Polycystic Ovary Syndrome: Exploration of the Role of Free Testosterone and Androstenedione in Metabolic Phenotype

Open access
Lerchbaum, Elisabeth, Schwetz, Verena, Rabe, Thomas, Giuliani, Albrecht, Obermayer-Pietsch, Barbara·2014·PLoS ONE
DOI 10.1371/journal.pone.0108263PMC PMC4195601
Open this paper in CoChat — free accountOpen PDF

Abstract

OBJECTIVE: To evaluate the association between androstenedione, testosterone, and free testosterone and metabolic disturbances in polycystic ovary syndrome. METHODS: We 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). RESULTS: Polycystic 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). CONCLUSIONS: Polycystic 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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0108263

Cites

6 of 6 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Obesity in men decreases SHBG and total T but free T remains stable; obesity in women decreases SHBG and increases free T.

    “In contrast to obese men, in whom SHBG and total T concentrations decrease but free T remains stable, obesity in women causes, next to a decrease in SHBG, a higher free T [182, 239].”

    From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [239]

    The Discussion (page not provided) reports higher free testosterone in abdominally obese women and a positive association between free testosterone and obesity. The Results table shows lower SHBG in some groups with elevated free testosterone, but does not establish that obesity causes the decrease. The paper does not address the claimed pattern in men. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 33

  1. [1]Yildiz BO, Bozdag G, Yapici Z, Esinler I, Yarali H (2012) Prevalence, phenotype and cardiometabolic risk of polycystic ovary syndrome under different diagnostic criteria. Hum Reprod 27: 3067– 3073. 22777527
  2. [3]Wehr E, Gruber HJ, Giuliani A, Möller A, Pieber TR, et al (2011) The lipid accumulation product is associated with impaired glucose tolerance in PCOS women. J Clin Endocrinol Metab 96: E986– 990. 21470992
  3. [4]Lerchbaum E, Schwetz V, Giuliani A, Obermayer-Pietsch B (2013) Hypertriglyceridemic waist is associated with impaired glucose tolerance in polycystic ovary syndrome. Nutr Metab Cardiovasc Dis 23: e15– 16. 23218173
  4. [6]Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, et al (2006) Criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an androgen excess society guideline. J Clin Endocrinol Metab 91: 4237– 4245. 16940456
  5. [7]Wehr E, Möller R, Horejsi R, Giuliani A, Kopera D, et al (2009) Subcutaneous Adipose Tissue Topography and Metabolic Disturbances in Polycystic Ovary Syndrome. Wien Klin Wochenschr 121: 262– 269. 19562283
  6. [8]Jonard S, Dewailly D (2004) The follicular excess in polycystic ovaries, due to intra-ovarian hyperandrogenism, may be the main culprit for the follicular arrest. Hum Reprod Update 10: 107– 117. 15073141
  7. [9]Chen MJ, Yang WS, Chen CL, Wu MY, Yang YS, et al (2008) The relationship between anti-Mullerian hormone, androgen and insulin resistance on the number of antral follicles in women with polycystic ovary syndrome. Hum Reprod 23: 952– 957. 18256110
  8. [10]Quinkler M, Sinha B, Tomlinson JW, Bujalska IJ, Stewart PM, et al (2004) Androgen generation in adipose tissue in women with simple obesity–a site-specific role for 17beta-hydroxysteroid dehydrogenase type 5. J Endocrinol 183: 331– 342. 15531721
  9. [11]Legro RS, Arslanian SA, Ehrmann DA, Hoeger KM, Murad MH, et al (2013) Diagnosis and Treatment of Polycystic Ovary Syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 98: 4565– 4592. 24151290 PMC5399492
  10. [12]O'Reilly MW, Taylor AE, Crabtree NJ, Hughes BA, Capper F, et al (2014) Hyperandrogenemia predicts metabolic phenotype in polycystic ovary syndrome: the utility of serum androstenedione. J Clin Endocrinol Metab 99: 1027– 1036. 24423344 PMC3955250
  11. [13]Asagami T, Holmes TH, Reaven G (2008) Differential effects of insulin sensitivity on androgens in obese women with polycystic ovary syndrome or normal ovulation. Metabolism 57: 1355– 1360. 18803938 PMC2573867
  12. [14]Misichronis G, Georgopoulos NA, Marioli DJ, Armeni AK, Katsikis I, et al (2012) The influence of obesity on androstenedione to testosterone ratio in women with polycystic ovary syndrome (PCOS) and hyperandrogenemia. Gynecol Endocrinol 28: 249– 252. 21970600
  13. [15]The Rotterdam ESHRE/ASRM-Sponsored consensus workshop group (2004) Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 19: 41– 47. 14688154
  14. [16]Lerchbaum E, Schwetz V, Giuliani A, Pieber TR, Obermayer-Pietsch B (2012) Opposing effects of DHEAS and free testosterone on metabolic phenotype in women with polycystic ovary syndrome. Fertil Steril 98: 1318– 1325. 22835450
  15. [17]Lerchbaum E, Gruber HJ, Schwetz V, Giuliani A, Möller R, et al (2011) Fatty liver index in polycystic ovary syndrome. Eur J Endocrinol 165: 935– 943. 21937505
  16. [18]Lerchbaum E, Giuliani A, Gruber H, Pieber TR, Obermayer-Pietsch B (2012) Adult-type hypolactasia and calcium intake in polycystic ovary syndrome. Clin Endocrinol (Oxf) 77: 834– 843. 22233423
  17. [20]Matsuda M, DeFronzo RA (1999) Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22: 1462– 1470. 10480510
  18. [21]Abdul-Ghani MA, Matsuda M, Balas B, DeFronzo RA (2007) Muscle and liver insulin resistance indexes derived from the oral glucose tolerance test. Diabetes Care 30: 89– 94. 17192339
  19. [22]American Diabetes Association (2013) Standards of Medical Care in Diabetes - 2013. Diabetes Care 36: S11– 66. 23264422 PMC3537269
  20. [24]Doi SA, Al-Zaid M, Towers PA, Scott CJ, Al-Shoumer KA (2006) Steroidogenic alterations and adrenal androgen excess in PCOS. Steroids 71: 751– 759. 16781743
  21. [26]Guido M, Romualdi D, Suriano R, Giuliani M, Costantini B, et al (2004) Effect of pioglitazone treatment on the adrenal androgen response to corticotrophin in obese patients with polycystic ovary syndrome. Hum Reprod 19: 534– 539. 14998947
  22. [27]Rittmaster RS, Deshwal N, Lehman L (1993) The role of adrenal hyperandrogenism, insulin resistance, and obesity in the pathogenesis of polycystic ovarian syndrome. J Clin Endocrinol Metab 76: 1295– 1300. 8388405
  23. [28]Bernasconi D, Del Monte P, Meozzi M, Randazzo M, Marugo A, et al (1996) The impact of obesity on hormonal parameters in hirsute and nonhirsute women. Metabolism 45: 72– 75. 8544780
  24. [29]Ivandić A, Prpić-Krizevac I, Sucić M, Jurić M (1998) Hyperinsulinemia and sex hormones in healthy premenopausal women: relative contribution of obesity, obesity type, and duration of obesity. Metabolism 47: 13– 19. 9440471
  25. [30]Carmina E, Lobo RA (2007) Prevalence and metabolic characteristics of adrenal androgen excess in hyperandrogenic women with different phenotypes. J Endocrinol Invest 30: 111– 116. 17392600
  26. [31]Buffington CK, Givens JR, Kitabchi AE (1991) Opposing actions of dehydroepiandrosterone and testosterone on insulin sensitivity. In vivo and in vitro studies of hyperandrogenic females. Diabetes 40: 693– 700. 1828239
  27. [32]Brennan K, Huang A, Azziz R (2009) Dehydroepiandrosterone sulfate and insulin resistance in patients with polycystic ovary syndrome. Fertil Steril 91: 1848– 1852. 18439591 PMC2691796
  28. [33]Köşüş N, Köşüş A, Kamalak Z, Hızlı D, O Turhan N (2012) Impact of adrenal versus ovarian androgen ratio on signs and symptoms of polycystic ovarian syndrome. Gynecol Endocrinol 28: 611– 614. 22296561
  29. [34]Fulghesu A, Magnini R, Portoghese E, Angioni S, Minerba L, et al (2010) Obesity-related lipid profile and altered insulin incretion in adolescents with polycystic ovary syndrome. J Adolesc Health 46: 474– 481. 20413084
  30. [35]Valkenburg O, Steegers-Theunissen RP, Smedts HP, Dallinga-Thie GM, Fauser BC, et al (2008) A more atherogenic serum lipoprotein profile is present in women with polycystic ovary syndrome: a case-control study. J Clin Endocrinol Metab 93: 470– 476. 18056772
  31. [36]Essah PA, Nestler JE, Carmina E (2008) Differences in dyslipidemia between American and Italian women with polycystic ovary syndrome. J Endocrinol Invest 31: 35– 41. 18296903
  32. [38]Legro RS, Brzyski RG, Diamond MP, Coutifaris C, Schlaff WD, et al (2014) Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med 371: 119– 129. 25006718 PMC4175743
  33. [39]De Frène V, Vansteelandt S, T'Sjoen G, Gerris J, Somers S, et al.. (2014) A retrospective study of the pregnancy, delivery and neonatal outcome in overweight versus normal weight women with polycystic ovary syndrome. Hum Reprod: [Epub ahead of print]. 24963163

Cited by

Sorted by citations

Authors
Lerchbaum, E., Schwetz, V., Rabe, T., Giuliani, A., & Obermayer-Pietsch, B.
Affiliations
Medical University of Graz (AT)
Corresponding author
Lerchbaum, Elisabeth
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2014-10-13
Volume
9
Issue
10
Pages
e108263
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0108263
PMC
PMC4195601
OpenAlex
W2024582127
Cited by
110
References
6
Citations by year
2026: 2 · 2025: 7 · 2024: 5 · 2023: 17 · 2022: 12 · 2021: 16 · 2020: 13 · 2019: 10 · 2018: 10 · 2017: 7 · 2016: 7 · 2015: 3 · 2012: 1
FWCI
6.88
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Keywords
polycystic ovary syndrome, hyperandrogenemia, free testosterone, androstenedione, insulin resistance, insulin sensitivity, Matsuda index, dyslipidemia, hypertriglyceridemia, hyperglycemia, metabolic phenotypes
MeSH terms
Adolescent, Adult, Androstenedione, Blood Glucose, Cross-Sectional Studies, Fasting, Female, Humans, Insulin, Middle Aged, Polycystic Ovary Syndrome, Testosterone, Body Mass Index, Hyperandrogenism, Young Adult

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review