Skip to main content
Springer Nature Link
Log in

A macrophage activation marker chitotriosidase in women with PCOS: does low-grade chronic inflammation in PCOS relate to PCOS itself or obesity?

  • Reproductive Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Objective

Polycystic ovary syndrome (PCOS) is described as a low-grade chronic inflammatory state where the macrophage infiltration increased in visceral fat play the major role. The aim of this study was to assess chitotriosidase (ChT) activity (an activated macrophage marker) in women with PCOS and controls and to evaluate its correlation with anthropometric and biochemical parameters.

Study design

Seventy-nine women with PCOS and 60 healthy controls were included in the study. PCOS and controls were divided into two subgroups according to body mass indexes (BMIs) as normoweight (<25 kg/m2) and overweight (≥25 kg/m2). ChT activity, biochemical (free testosterone, luteinizing hormone, insulin resistance index, etc.) and clinical parameters [BMI, waist-to-hip ratio, modified Ferriman–Gallwey scores (mFG)] were analyzed according to groups.

Results

Serum ChT activity was significantly (p < 0.001) higher in women with PCOS than controls (normoweight, 87.1 ± 90.1 vs. 18.4 ± 9.0 nmol/ml/h; overweight, 92.0 ± 96.7 vs. 17.9 ± 12.1 nmol/ml/h PCOS and controls, respectively). No statistically significant difference was noted between ChT activity of normoweight and overweight PCOS subgroups. A positive correlation was found between ChT activity and PCOS status (r 0.598, p < 0.001), mFG scores (r 0.525, p < 0.001), free testosterone (r 0.402, p 0.001) and total testosterone (r 0.168, p 0.048) for the combined groups (PCOS + controls). In multivariant linear regression analysis participants’ PCOS status (presence or absence) and LH levels were the main predictors of ChT activity in the whole study population (p 0.002 and p 0.041, respectively).

Conclusion

ChT activity elevates in PCOS independent of obesity. Our findings support the concept of PCOS is a state of low-grade chronic inflammation where the macrophages could play the major role. Hyperandrogenism might also be related to this inflammatory state and can be a subject of further trials.

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

Access this article

Log in via an institution

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 includes VAT (Canada)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. March WA, Moore VM, Wilson KJ, Phillips DIW, Norman RJ, Davies MJ (2010) The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod 25:544–551

    Article  PubMed  Google Scholar 

  2. Goodarzi MO, Dumesic DA, Chazenbalk G, Azziz R (2011) Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol 7:219–231

    Article  PubMed  CAS  Google Scholar 

  3. Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel SF (2009) The androgen excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril 91:456–488

    Article  PubMed  Google Scholar 

  4. Norman RJ, Dewailly D, Legro RS, Hickey TE (2007) Polycystic ovary syndrome. Lancet 370:685–697

    Article  PubMed  CAS  Google Scholar 

  5. Katsikis I, Karkanaki A, Misichronis G, Delkos D, Kandaraki EA, Panidis D (2011) Phenotype expression, body mass index and insulin resistance in relation to LH levels in women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod 156(2):181–185

    Article  CAS  Google Scholar 

  6. Doi SAR, Towers PA, Scott CJ, Al-Shoumer KAS (2005) PCOS: an ovarian disorder that leads to dysregulation in the hypothalamic–pituitary–adrenal axis? Eur J Obstet Gynecol Reprod 118:4–16

    Article  CAS  Google Scholar 

  7. Baptiste CG, Battista M-C, Trottier A, Baillargeon J-P (2010) Insulin and hyperandrogenism in women with polycystic ovary syndrome. J Steroid Biochem Mol Biol 122:42–52

    Article  PubMed  CAS  Google Scholar 

  8. Dunaif A (1997) Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 18:774–800

    Article  PubMed  CAS  Google Scholar 

  9. Gilling-Smith C, Story H, Rogers S (1997) Evidence for a primary abnormality of theca cell steroidogenesis in the polycystic ovary syndrome. Clin Endocrinol 47:93–99

    Article  CAS  Google Scholar 

  10. Kelly CJ, Lyall H, Petrie JR, Gould GW, Connell JM, Sattar N (2001) Low grade chronic inflammation in women with polycystic ovarian syndrome. J Clin Endocrinol Metab 86:2453–2455

    Article  PubMed  CAS  Google Scholar 

  11. Puder JJ, Varga S, Kraenzlin M, De Geyter C, Keller U, Muller B (2005) Central fat excess in polycystic ovary syndrome: relation to low-grade inflammation and insulin resistance. J Clin Endocrinol Metab 90:6014–6021

    Article  PubMed  CAS  Google Scholar 

  12. Repaci A, Gambineri A, Pasquali R (2011) The role of low-grade inflammation in the polycystic ovary syndrome. Mol Cell Endocrinol 335:30–41

    Article  PubMed  CAS  Google Scholar 

  13. Barber TM, McCarthy MI, Wass JAH, Franks S (2006) Obesity and polycystic ovary syndrome. Clin Endocrinol 65:137–145

    Article  CAS  Google Scholar 

  14. Kirchengast S, Huber J (2001) Body composition characteristics and body fat distribution in lean women with polycystic ovary syndrome. Hum Reprod 16:1255–1260

    Article  PubMed  CAS  Google Scholar 

  15. Carmina E, Bucchieri S, Esposito A et al (2007) Abdominal fat quantity and distribution in women with polycystic ovary syndrome and extent of its relation to insulin resistance. J Clin Endocrinol Metab 92:2500–2505

    Article  PubMed  CAS  Google Scholar 

  16. Yildirim B, Sabir N, Kaleli B (2003) Relation of intra-abdominal fat distribution to metabolic disorders in nonobese patients with polycystic ovary syndrome. Fertil Steril 79(6):1358–1364

    Article  PubMed  Google Scholar 

  17. Glintborg D, Andersen M (2010) An update on the pathogenesis, inflammation, and metabolism in hirsutism and polycystic ovary syndrome. Gynecol Endocrinol 26:281–296

    Article  PubMed  CAS  Google Scholar 

  18. Cascella T, Palomba S, De Sio I, Manguso F, Giallauria F, De Simone B, Tafuri D, Lombardi G, Colao A, Orio F (2008) Visceral fat is associated with cardiovascular risk in women with polycystic ovary syndrome. Hum Reprod 23:153–159

    Article  PubMed  CAS  Google Scholar 

  19. Cancello R, Cle′ment K (2006) Is obesity an inflammatory illness? Role of low-grade inflammation and macrophage infiltration in human white adipose tissue. BJOG 113:1141–1147

    Article  PubMed  CAS  Google Scholar 

  20. Zeyda M, Stulnig TM (2007) Adipose tissue macrophages Immunology. Immunol Lett 112:61–67

    Article  PubMed  CAS  Google Scholar 

  21. Strissel KJ, Stancheva Z, Miyoshi H et al (2007) Adipocyte death, adipose tissue remodeling, and obesity complications. Diabetes 56:2910–2918

    Article  PubMed  CAS  Google Scholar 

  22. Heilbronn LK, Campbell LV (2008) Adipose tissue macrophages. Low grade inflammation and insulin resistance in human obesity. Cur Pharm Des 14:1225–1230

    Article  CAS  Google Scholar 

  23. Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E, Wang S, Fortier M, Greenberg AS, Obin MS (2005) Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 46:2347–2355

    Article  PubMed  CAS  Google Scholar 

  24. Hollak CE, van Weely S, van Oers MH, Aerts JM (1994) Marked elevation of plasma chitotriosidase activity. A novel hallmark of Gaucher disease. J Clin Invest 93:1288–1292

    Article  PubMed  CAS  Google Scholar 

  25. Boot RG, Renkema GH, Strijland A, van Zonneveld AJ, Aerts JM (1995) Cloning of a cDNA encoding chitotriosidase, a human chitinase produced by macrophages. J Biol Chem 270:26252–26256

    Article  PubMed  CAS  Google Scholar 

  26. Malaguarnera L (2006) Chitotriosidase: the yin and yang. Cell Mol Life Sci 63:3018–3029

    Article  PubMed  CAS  Google Scholar 

  27. The Rotterdam ESHRE/ASRM-Sponsored PCOS Conference Workshop Group (2004) Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 81:19–25

    Google Scholar 

  28. Ferriman D, Gallwey JD (1961) Clinical assessment of body hair growth in women. J Clin Endocrinol Metab 21:1440–1447

    Article  PubMed  CAS  Google Scholar 

  29. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419

    Article  PubMed  CAS  Google Scholar 

  30. Legro RS, Castracane VD, Kauffman RP (2004) Detecting insulin resistance in polycystic ovary syndrome: purposes and pitfalls. Obstet Gynecol Surv 59:141–154

    Article  PubMed  Google Scholar 

  31. Escobar-Morreale HF, San Millán JL (2007) Abdominal adiposity and the polycystic ovary syndrome. Trends Endocrinol Metab 18:266–272

    Article  PubMed  CAS  Google Scholar 

  32. Lord J, Thomas R, Fox B, Acharya U, Wilkin T (2006) The central issue? Visceral fat is a good marker of insulin resistance and metabolic disturbance in women with polycystic ovary syndrome. BJOG 113:817–824

    Article  PubMed  CAS  Google Scholar 

  33. Gesta S, Tseng YH, Kahn CR (2007) Developmental origin of fat: tracking obesity to its source. Cell 131:242–256

    Article  PubMed  CAS  Google Scholar 

  34. González F, Rote NS, Minium J, Weaver AM, Kirwan JP (2010) Elevated circulating levels of macrophage migration inhibitory factor in polycystic ovary syndrome. Cytokine 51:240–244

    Article  PubMed  Google Scholar 

  35. Gonzalez F, Thusu K, Abdel-Rahman E, Prabhala A, Tomani M, Dandona P (1999) Elevated serum levels of tumor necrosis factor alpha in normal-weight women with polycystic ovary syndrome. Metabolism 48:437–441

    Article  PubMed  CAS  Google Scholar 

  36. Escobar-Morreale HF, Luque-Ramırez M, Gonzalez F (2011) Circulating inflammatory markers in polycystic ovary syndrome: a systematic review and metaanalysis. Fertil Steril 95:1048–1058

    Article  PubMed  CAS  Google Scholar 

  37. González F, Rote NS, Minium J, Kirwan JP (2006) Reactive oxygen species-induced oxidative stress in the development of insulin resistance and hyperandrogenism in polycystic ovary syndrome. J Clin Endocrinol Metab 91:334–336

    Google Scholar 

  38. González F, Rote NS, Minium J, Kirwan JP (2006) Increased activation of nuclear factor jB triggers inflammation and insulin resistance in polycystic ovary syndrome. J Clin Endocrinol Metab 91:1508–1512

    Article  PubMed  Google Scholar 

  39. Diamanti-Kandarakis E, Paterakis T, Alexandraki K, Piperi C, Aessopus A, Katsikis I, Katsilambros N, Kraetsas G, Panidis D (2006) Indices of low- grade chronic inflammation in polycystic ovary syndrome and beneficial effect of metformin. Hum Reprod 21:1426–1431

    Article  PubMed  CAS  Google Scholar 

  40. Cortón M, Botella-Carretero JI, Benguría A, Villuendas G, Zaballos A, San Milla′n JL, Escobar-Morreale HF, Peral B (2007) Differential gene expression profile in omental adipose tissue in women with polycystic ovary syndrome. J Clin Endocrinol Metab 92(1):328–337

    Article  PubMed  Google Scholar 

  41. Möhlig M, Spranger J, Ristow M, Pfeiffer AF, Schill T, Schlösser HW, Moltz L, Brabant G, Schöfl C (2006) Predictors of abnormal glucose metabolism in women with polycystic ovary syndrome. Eur J Endocrinol 154:295–301

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

We declare that we have no conflict of interest.

Author information

Authors and Affiliations

  1. Obstetrics and Gynecology Department, Gulhane Military Medical Faculty, 06018, Etlik, Ankara, Turkey

    Ibrahim Alanbay, Cihangir Mutlu Ercan, Hakan Coksuer & Mustafa Ozturk

  2. Obstetrics and Gynecology Department, Akdeniz University Medical Faculty, 07059, Antalya, Turkey

    Mehmet Sakinci

  3. Department of Clinical Biochemistry, Gulhane Military Medical Faculty, 06018, Etlik, Ankara, Turkey

    Serkan Tapan

Authors
  1. Ibrahim Alanbay
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Cihangir Mutlu Ercan
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Mehmet Sakinci
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Hakan Coksuer
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Mustafa Ozturk
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Serkan Tapan
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to Mehmet Sakinci.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Alanbay, I., Ercan, C.M., Sakinci, M. et al. A macrophage activation marker chitotriosidase in women with PCOS: does low-grade chronic inflammation in PCOS relate to PCOS itself or obesity?. Arch Gynecol Obstet 286, 1065–1071 (2012). https://doi.org/10.1007/s00404-012-2425-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-012-2425-0

Keywords