Skip to main content

Advertisement

Log in

Free androgen index and Irisin in polycystic ovary syndrome

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Purpose

PCOS is associated with hyperandrogenism and insulin resistance (IR). Recent studies have shown that circulating Irisin levels increase in PCOS women. However, no report has demonstrated a relationship between Irisin and hyperandrogenism in PCOS women. The purpose of the study was to compare interrelationship between Irisin or androgen excess with IR in PCOS and normal subjects.

Methods

166 PCOS and 103 control women were prospectively studied. Euglycemic- hyperinsulinemic clamps were preformed to assess their insulin sensitivity, which was expressed as M value. Circulating Irisin was determined by ELISA kit. Circulating androgens were measured using ultrasensitive assays.

Results

PCOS women with high FAI had significantly higher BMI, FAT%, TC, DHEA-S and HOMA-IR, and significantly lower levels of M values and SHBG than PCOS women with low FAI or the controls. Pearson correlations showed that in the entire population, FAI correlated positively with BMI, WHR, FAT%, blood pressure, TG, DHEA-S, LH/FSH, AUCinsulin, HOMA-IR and Irisin, and negatively with M values. In multiple stepwise regression analysis, only FAT%, DHEA-S and LH/FSH were independent related factors with FAI.

Conclusion

The elevated Irisin levels in PCOS women were associated with androgen excess. Circulating Irisin is a primary predictor of hyperandrogenism, MetS and IR in PCOS women.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

PCOS:

Polycystic ovary syndrome

BMI:

Body mass index

FAT%:

The percentage of fat in vivo

TC:

Total cholesterol

DHEA-S:

Dehydroepiandrostenedione sulfate

HOMA-IR:

Homeostasis model assessment of insulin resistance

SHBG:

Sex hormone binding globulin

WHR:

Waist-to-hip ratio

TG:

Triglyceride

LH:

Luteinizing hormone

FSH:

Follicle- stimulating hormone

AUCinsulin :

The area under the curve for insulin

FAI:

Free androgen index

References

  1. Diamanti-Kandarakis E, Kouli CR, Bergiele AT, Filandra FA, Tsianateli TC, Spina GG, Zapanti ED, Bartzis MI (1999) A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. J Clin Endocrinol Metab 84:4006–4011

    Article  CAS  PubMed  Google Scholar 

  2. Markopoulos MC, Valsamakis G, Kouskouni E, Boutsiadis A, Papassotiriou I, Creatsas G, Mastorakos G (2012) Study of carbohydrate metabolism indices and adipocytokine profile and their relationship with androgens in polycystic ovary syndrome after menopause. Eur J Endocrinol 168:83–90

    Article  PubMed  Google Scholar 

  3. Ehrmann DA, Liljenquist DR, Kasza K, Azziz R, Legro RS, Ghazzi MN, PCOS/Troglitazone Study Group (2006) Prevalence and predictors of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab 91:48–53

    Article  CAS  PubMed  Google Scholar 

  4. Norman RJ, Wu R, Stankiewicz MT (2004) Polycystic ovary syndrome. Med J 180:132–137

    Google Scholar 

  5. Rincon J, Holmäng A, Wahlström EO, Lönnroth P, Björntorp P, Zierath JR, Wallberg-Henriksson H (1996) Mechanisms behind insulin resistance in rat skeletal muscle after oophorectomy and additional testosterone treatment. Diabetes 45:615–621

    Article  CAS  PubMed  Google Scholar 

  6. Corbould A (2007) Chronic testosterone treatment induces selective insulin resistance in subcutaneous adipocytes of women. J Endocrinol 192:585–594

    Article  CAS  PubMed  Google Scholar 

  7. Qu J, Wang Y, Wu X, Gao L, Hou L, Erkkola R (2009) Insulin resistance directly contributes to androgenic potential within ovarian theca cells. Fertil Steril 91:1990–1997

    Article  CAS  PubMed  Google Scholar 

  8. Barber TM, Wass JA, McCarthy MI, Franks S (2007) Metabolic characteristics of women with polycystic ovaries and oligoamenorrhoea but normal androgen levels: implications for the management of polycystic ovary syndrome. Clin Endocrinol 66:513–517

    CAS  Google Scholar 

  9. Cohen B, Novick D, Rubinstein M (1996) Modulation of insulin activities by leptin. Science 274:1185–1188

    Article  CAS  PubMed  Google Scholar 

  10. Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M (2005) Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science 307:426–430

    Article  CAS  PubMed  Google Scholar 

  11. Esteve E, Ricart W, Fernandez-Real JM (2009) Adipocytokines and insulin resistance: the possible role of lipocalin-2, retinol binding protein-4, and adiponectin. Diabetes Care 32(Suppl 2):S362–S367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Boström EA, Choi JH, Long JZ, Kajimura S, Zingaretti MC, Vind BF, Tu H, Cinti S, Højlund K, Gygi SP, Spiegelman BM (2012) A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481:463–468

    Article  PubMed  PubMed Central  Google Scholar 

  13. Liu JJ, Wong MD, Toy WC, Tan CS, Liu S, Ng XW, Tavintharan S, Sum CF, Lim SC (2003) Lower circulating irisin is associated with type 2 diabetes mellitus. J Diabetes Complicat 27:365–369

    Article  Google Scholar 

  14. Choi YK, Kim MK, Bae KH, Seo HA, Jeong JY, Lee WK, Kim JG, Lee IK, Park KG (2013) Serum irisin levels in new-onset type 2 diabetes. Diabetes Res Clin Pract 100:96–101

    Article  CAS  PubMed  Google Scholar 

  15. Huh JY, Panagiotou G, Mougios V, Brinkoetter M, Vamvini MT, Schneider BE, Mantzoros CS (2012) FNDC5 and irisin in humans: I. Predictors of circulating concentrations in serum and plasma and II. mRNA expression and circulating concentrations in response to weight loss and exercise. Metabolism 61:1725–1738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Stengel A, Hofmann T, Goebel-Stengel M, Elbelt U, Kobelt P, Klapp BF (2013) Circulating levels of irisin in patients with anorexia nervosa and different stages of obesity: correlation with body mass index. Peptides 39:125–130

    Article  CAS  PubMed  Google Scholar 

  17. Moreno-Navarrete JM, Ortega F, Serrano M, Guerra E, Pardo G, Tinahones F, Ricart W, Fernández-Real JM (2013) Irisin is expressed and produced by human muscle and adipose tissue in association with obesity and insulin resistance. J Clin Endocrinol Metab 98:E769–E778

    Article  CAS  PubMed  Google Scholar 

  18. Park KH, Zaichenko L, Brinkoetter M, Thakkar B, Sahin-Efe A, Joung KE, Tsoukas MA, Geladari EV, Huh JY, Dincer F, Davis CR, Crowell JA, Mantzoros CS (2013) Circulating irisin in relation to insulin resistance and the metabolic syndrome. J Clin Endocrinol Metab 98:4899–4907

    Article  CAS  PubMed  Google Scholar 

  19. Li M, Yang M, Zhou X, Fang X, Hu W, Zhu W, Wang C, Liu D, Li S, Liu H, Yang G, Li L (2015) Elevated circulating levels of irisin and the effect of metformin treatment in women with polycystic ovary syndrome. J Clin Endocrinol Metab 100:1485–1493

    Article  CAS  PubMed  Google Scholar 

  20. Chen MJ, Chiu HM, Chen CL, Yang WS, Yang YS, Ho HN (2010) Hyperandrogenemia is independently associated with elevated alanine aminotransferase activity in young women with polycystic ovary syndrome. J Clin Endocrinol Metab 95:3332–3341

    Article  CAS  PubMed  Google Scholar 

  21. Rotterdam ESHRE/ASRM-Sponsored PCOS 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

    Article  Google Scholar 

  22. The Chinese Diabetes Society (2014) Recommendations of MS according to the Chinese Diabetes Society. Chin J Diabetes 12:156–161

    Google Scholar 

  23. Legro RS, Arslanian SA, Ehrmann DA, Hoeger KM, Murad MH, Pasquali R, Welt CK (2013) Endocrine Society Diagnosis and treatment of polycystic ovary syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 98:4565–4592

    Article  CAS  PubMed  Google Scholar 

  24. Albareda M, Rodríguez-Espinosa J, Murugo M, de Leiva A, Corcoy R (2000) Assessment of insulin sensitivity and β-cell function from measurements in the fasting state and during an oral glucose tolerance test. Diabetologia 43:1507–1511

    Article  CAS  PubMed  Google Scholar 

  25. Allison DB, Paultre F, Maggio C, MezzitisN P-SF (1995) The use of areas under curves in diabetes research. Diabetes Care 18:245–250

    Article  CAS  PubMed  Google Scholar 

  26. Jia Y, Yuan L, Hu W, Luo Y, Suo L, Yang M, Chen S, Wang Y, Liu H, Yang G, Li L (2014) Zinc-finger BED domain-containing 3 (Zbed3) is a novel secreted protein associated with insulin resistance in humans. J Intern Med 275:522–533

    Article  CAS  PubMed  Google Scholar 

  27. Yang M, Liu R, Li S, Luo Y, Zhang Y, Zhang L, Liu D, Wang Y, Xiong Z, Boden G, Chen S, Li L, Yang G (2013) Zinc-alpha2-glycoprotein is associated with insulin resistance in humans and is regulated by hyperglycemia, hyperinsulinemia, or liraglutide administration: cross-sectional and interventional studies in normal subjects, insulin- resistant subjects, and subjects with newly diagnosed diabetes. Diabetes Care 36:1074–1082

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Ibáñez L, Ong KK, López-Bermejo A, Dunger DB, de Zegher F (2014) Hyperinsulinaemic androgen excess in adolescent girls. Nat Rev Endocrinol 10:499–508

    Article  PubMed  Google Scholar 

  29. Liu JJ, Wong MD, Toy WC, Tan CS, Liu S, Ng XW, Tavintharan S, Sum CF, Lim SC (2013) Lower circulating irisin is associated with type 2 diabetes mellitus. J Diabetes Complicat 27:365–369

    Article  PubMed  Google Scholar 

  30. Chang CL, Huang SY, Soong YK, Cheng PJ, Wang CJ, Liang IT (2014) Circulating irisin and glucose-dependent insulinotropic peptide are associated with the development of polycystic ovary syndrome. J Clin Endocrinol Metab 99:E2539–E2548

    Article  CAS  PubMed  Google Scholar 

  31. Blank SK, Helm KD, Mccartney CR, Marshall JC (2008) Polycystic ovary syndrome in adolescence. Ann N Y Acad Sci 1135:76–84

    Article  CAS  PubMed  Google Scholar 

  32. Patel SM, Ratcliffe SJ, Reilly MP, Weinstein R, Bhasin S, Blackman MR, Cauley JA, Sutton-Tyrrell K, Robbins J, Fried LP, Cappola AR (2009) Higher serum testosterone concentration in older women is associated with insulin resistance, metabolic syndrome, and cardiovascular disease. J Clin Endocrinol Metab 94:4776–4784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Corbould A (2008) Effects of androgens on insulin action in women: is androgen excess a component of female metabolic syndrome? Diabetes Metab Res Rev 24:520–532

    Article  CAS  PubMed  Google Scholar 

  34. Laaksonen DE, Niskanen L, Punnonen K, Nyyssönen K, Tuomainen TP, Valkonen VP, Salonen JT (2005) The metabolic syndrome and smoking in relation to hypogonadism in middleaged men: a prospective cohort study. J Clin Endocrinol Metab 90:712–719

    Article  CAS  PubMed  Google Scholar 

  35. Völzke H, Aumann N, Krebs A, Nauck M, Steveling A, Lerch MM, Rosskopf D, Wallaschofski H (2010) Hepatic steatosis is associated with low serum testosterone and high serum DHEAS levels in men. Int J Androl 33:45–53

    Article  PubMed  Google Scholar 

  36. Muller M, Grobbee DE, den Tonkelaar I, Lamberts SW, van der Schouw YT (2005) Endogenous sex hormones and metabolic syndrome in aging men. J Clin Endocrinol Metab 90:2618–2623

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to L. Gao.

Ethics declarations

Funding

This work was supported by research grants from the Doctoral Fund of Ministry of Education of China (20105503110003).

Conflict of interest

The authors declare that they have no conflict of interest in prepared manuscript.

Ethical approval

The study was conducted in accordance with the Declaration of Helsinki. The study was approved by the human research ethics committee of Chongqing Medical University (Ethical review of scientific research No. 68, approved time: August 15th, 2014). And have been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

H. Li, X. Xu have contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, H., Xu, X., Wang, X. et al. Free androgen index and Irisin in polycystic ovary syndrome. J Endocrinol Invest 39, 549–556 (2016). https://doi.org/10.1007/s40618-015-0403-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40618-015-0403-7

Keywords

Navigation