The association between follicle stimulating hormone and glutathione peroxidase activity is dependent on abdominal obesity in postmenopausal women

  • Aleksandra Klisic
  • Jelena Kotur-Stevuljevic
  • Nebojsa Kavaric
  • Milica Martinovic
  • Marija Matic
Original Article

Abstract

Purpose

Menopause is frequently associated with an increase in visceral fat, thus modifying redox status by promoting oxidative damage and decreasing antioxidant defense systems. It is known that at higher concentrations estradiol has some antioxidant properties, while its decline in postmenopause is associated with pro-oxidant effects. However, the role of follicle stimulating hormone (FSH) in antioxidant defense in postmenopausal women is still not well elucidated. Therefore, we aimed to evaluate the potential complex association between visceral obesity, FSH and enzymatic antioxidant defense as measured by glutathione peroxidase (GPx) in postmenopausal women.

Methods

A total of 150 postmenopausal women (mean age 56.6 ± 4.8 years), among them 50 normal weight and 100 overweight/obese, were included. GPx activity, FSH, luteinizing hormone, estradiol, total testosterone, cardiometabolic and anthropometric parameters, were determined.

Results

With increasing tertiles of serum FSH levels, significant increase in GPx activity (P = 0.005) was found. Also, the highest number of overweight/obese subjects were in the group with the lowest FSH values (χ 2 = 14.9, P < 0.001). After multiple linear regression analysis, the relationship between GPx and FSH disappeared, whereas only higher waist circumference (β = −0.218, P = 0.045) predicted lower FSH level (adjusted R 2 = 0.227).

Conclusion

Higher GPx activity is associated with higher FSH level, but abdominal obesity may be the underlying determinant of this relationship.

Keywords

Antioxidant defense Follicle stimulating hormone Obesity Postmenopausal women 

Notes

Acknowledgments

This work was financially supported in part by a grant from the Ministry of Education, Science and Technological Development, Republic of Serbia (Project No. OI 175035-J. Kotur-Stevuljevic).

Compliance with ethical standards

Conflict of interest

The authors declared no conflicts of interest.

Ethical approval

The study protocol was approved by the Ethical Committee of Primary Health Care Center in Podgorica, Montenegro and the research was carried out in compliance with the Declaration of Helsinki.

Informed consent

All the participants provided written informed consent.

References

  1. 1.
    Carr MC (2003) The emergence of the metabolic syndrome with menopause. J Clin Endocrinol Metab 88:2404–2411. doi: 10.1210/jc.2003-030242 CrossRefPubMedGoogle Scholar
  2. 2.
    Kim C, Randolph JF, Golden SH, Labrie F, Kong S, Nan B et al (2015) Weight loss increases follicle stimulating hormone in overweight postmenopausal women. Obesity (Silver Spring) 23:228–233. doi: 10.1002/oby.20917 CrossRefGoogle Scholar
  3. 3.
    Freeman EW, Sammel MD, Lin H, Gracia CR (2010) Obesity and reproductive hormone levels in the transition to menopause. Menopause 17:718–726. doi: 10.1097/gme.0b013e3181cec85d CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Randolph JF Jr, Zheng H, Sowers MR, Crandall C, Crawford S, Gold EB et al (2011) Change in follicle-stimulating hormone and estradiol across the menopausal transition: effect of age at the final menstrual period. J Clin Endocrinol Metab 96:746–754. doi: 10.1210/jc.2010-1746 CrossRefPubMedGoogle Scholar
  5. 5.
    Halawaty S, ElKattan E, Azab H, ElGhamry N, Al-Inany H (2010) Effect of obesity on parameters of ovarian reserve in premenopausal women. J Obstet Gynaecol Can 32:687–690. doi: 10.1016/S1701-2163(16)34573-X CrossRefPubMedGoogle Scholar
  6. 6.
    Yaylali GF, Tekekoglu S, Akin F (2010) Sexual dysfunction in obese and overweight women. Int J Impot Res 22:220–226. doi: 10.1038/ijir.2010.7 CrossRefPubMedGoogle Scholar
  7. 7.
    Lovejoy JC, Champagne CM, de Jonge L, Xie H, Smith SR (2008) Increased visceral fat and decreased energy expenditure during the menopausal transition. Int J Obes (Lond) 32:949–958. doi: 10.1038/ijo.2008.25 CrossRefGoogle Scholar
  8. 8.
    Wisse BE, Kim F, Schwartz MW (2007) Physiology. An integrative view of obesity. Science 318:928–929. doi: 10.1126/science.1148032 CrossRefPubMedGoogle Scholar
  9. 9.
    Lubrano C, Valacchi G, Specchia P, Gnessi L, Rubanenko EP, Shuginina EA et al (2015) Integrated haematological profiles of redox status, lipid, and inflammatory protein biomarkers in benign obesity and unhealthy obesity with metabolic syndrome. Oxid Med Cell Longev 2015:490613. doi: 10.1155/2015/490613 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Dröge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82:47–95. doi: 10.1152/physrev.00018.2001 CrossRefPubMedGoogle Scholar
  11. 11.
    Doshi SB, Agarwal A (2013) The role of oxidative stress in menopause. J Midlife Health 4:140–146. doi: 10.4103/0976-7800.118990 PubMedPubMedCentralGoogle Scholar
  12. 12.
    Serviddio G, Loverro G, Vicino M, Prigigallo F, Grattagliano I, Altomare E et al (2002) Modulation of endometrial redox balance during the menstrual cycle: relation with sex hormones. J Clin Endocrinol Metab 87:2843–2848. doi: 10.1210/jcem.87.6.8543 CrossRefPubMedGoogle Scholar
  13. 13.
    Pejić S, Todorović A, Stojiljković V, Gavrilović L, Popović N, Pajović SB (2015) Antioxidant status in women with uterine leiomyoma: relation with sex hormones. An Acad Bras Cienc 87:1771–1782. doi: 10.1590/0001-3765201520130416 CrossRefPubMedGoogle Scholar
  14. 14.
    Ogunro PS, Bolarinde AA, Owa OO, Salawu AA, Oshodi AA (2014) Antioxidant status and reproductive hormones in women during reproductive, perimenopausal and postmenopausal phase of life. Afr J Med Med Sci 43:49–57PubMedGoogle Scholar
  15. 15.
    Borekci B, Ingec M, Kumtepe Y, Karaca M, Koc F, Salman S et al (2009) Effect of estrogen, progesterone, LH and FSH on oxidant and antioxidant parameters in rat uterine tissue. Int J Fertil Steril 3:119–128Google Scholar
  16. 16.
    Tsai-Turton M, Luderer U (2006) Opposing effects of glutathione depletion and follicle-stimulating hormone on reactive oxygen species and apoptosis in cultured preovulatory rat follicles. Endocrinology 147:1224–1236. doi: 10.1210/en.2005-1281 CrossRefPubMedGoogle Scholar
  17. 17.
    Schisterman EF, Gaskins AJ, Mumford SL, Browne RW, Yeung E, Trevisan M (2010) Influence of endogenous reproductive hormones on F2-isoprostane levels in premenopausal women: the BioCycle Study. Am J Epidemiol 172:430–439. doi: 10.1093/aje/kwq131 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Savini I, Catani MV, Evangelista D, Gasperi V, Avigliano L (2013) Obesity-associated oxidative stress: strategies finalized to improve redox state. Int J Mol Sci 14:10497–10538. doi: 10.3390/ijms140510497 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    American Diabetes Association (2013) Standards of medical care in diabetes 2013. Diabetes Care 36(Suppl 1):S11–S66. doi: 10.2337/dc13-S011 CrossRefGoogle Scholar
  20. 20.
    World Medical Association declaration of Helsinki (1997) Recommendations guiding physicians in biomedical research involving human subjects. JAMA 277:925–926. doi: 10.1001/jama.1997.03540350075038 CrossRefGoogle Scholar
  21. 21.
    Alberti KGMM, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA et al (2009) Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120:1640–1645. doi: 10.1161/CIRCULATIONAHA.109.192644 CrossRefPubMedGoogle Scholar
  22. 22.
    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419CrossRefPubMedGoogle Scholar
  23. 23.
    Gunzler WA, Kremers H, Flohe L (1974) An improved coupled test procedure for glutathione peroxidase in blood. Z Klin Chem Klin Biochem 12:444–448PubMedGoogle Scholar
  24. 24.
    Michalakis K, Mintziori G, Kaprara A, Tarlatzis BC, Goulis DG (2013) The complex interaction between obesity, metabolic syndrome and reproductive axis: a narrative review. Metabolism 62:457–478. doi: 10.1016/j.metabol.2012.08.012 CrossRefPubMedGoogle Scholar
  25. 25.
    Wang N, Kuang L, Han B, Li Q, Chen Y, Zhu C et al (2015) Follicle-stimulating hormone associates with prediabetes and diabetes in postmenopausal women. Acta Diabetol. doi: 10.1007/s00592-015-0769-1 PubMedCentralGoogle Scholar
  26. 26.
    Stefanska A, Ponikowska I, Cwiklinska-Jurkowska M, Sypniewska G (2014) Association of FSH with metabolic syndrome in postmenopausal women: a comparison with CRP, adiponectin and leptin. Biomark Med 8:921–930. doi: 10.2217/bmm.14.49 CrossRefPubMedGoogle Scholar
  27. 27.
    Stefanska A, Sypniewska G, Ponikowska I, Cwiklinska-Jurkowska M (2012) Association of follicle-stimulating hormone and sex hormone binding globulin with the metabolic syndrome in postmenopausal women. Clin Biochem 45:703–706. doi: 10.1016/j.clinbiochem.2012.03.011 CrossRefPubMedGoogle Scholar
  28. 28.
    Matsuda M, Shimomura I (2013) Increased oxidative stress in obesity: implications for metabolic syndrome, diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer. Obes Res Clin Pract 7:330–341. doi: 10.1016/j.orcp.2013.05.004 CrossRefGoogle Scholar
  29. 29.
    Gutierrez-Lopez L, Garcia-Sanchez JR, MdeJ Rincon-Viquez, Lara-Padilla E, Sierra-Vargas MP, Olivares-Corichi IM (2012) Hypocaloric diet and regular moderate aerobic exercise is an effective strategy to reduce anthropometric parameters and oxidative stress in obese patients. Obes Facts 5:12–22. doi: 10.1159/000336526 CrossRefPubMedGoogle Scholar
  30. 30.
    Brown LA, Kerr CJ, Whiting P, Finer N, McEneny J, Ashton T (2009) Oxidant stress in healthy normal-weight, overweight, and obese individuals. Obesity 17:460–466. doi: 10.1038/oby.2008.590 CrossRefPubMedGoogle Scholar
  31. 31.
    Stefanović A, Kotur-Stevuljević J, Spasić S, Bogavac-Stanojević N, Bujisić N (2008) The influence of obesity on the oxidative stress status and the concentration of leptin in type 2 diabetes mellitus patients. Diabetes Res Clin Pract 79:156–163. doi: 10.1016/j.diabres.2007.07.019 CrossRefPubMedGoogle Scholar
  32. 32.
    Massafra C, Buonocore G, Gioia D, Sargentini I (1996) Changes in the erythrocyte antioxidant enzyme system during transdermal estradiol therapy for secondary amenorrhea. Gynecol Endocrinol 10:1–4. doi: 10.3109/09513599609027982 CrossRefGoogle Scholar
  33. 33.
    Massafra C, Buonocore G, Gioia D, Sargentini I, Farina G (1997) Effects of estradiol and medroxyprogesterone acetate treatment on erythrocyte antioxidant enzyme activities and malondialdehyde plasma levels in amenorrhoeic women. J Clin Endocrinol Metab 82:173–175. doi: 10.1210/jcem.82.1.3688#sthash.fHO1phI3.dpuf PubMedGoogle Scholar
  34. 34.
    Bednarek-Tupikowska G, Bohdanowicz-Pawlak A, Bidzinska B, Milewicz A, Antonowicz-Juchniewicz J, Andrzejak R (2001) Serum lipid peroxide levels and erythrocyte glutathione peroxidase and superoxide dismutase activity in premenopausal and postmenopausal women. Gynecol Endocrinol 15:298–303. doi: 10.1080/gye.15.4.298.303 CrossRefPubMedGoogle Scholar
  35. 35.
    Massafra C, Gioia D, De Felice C, Picciolini E, De Leo V, Bonifazi M et al (2000) Effects of estrogens and androgens on erythrocyte antioxidant superoxide dismutase, catalase and glutathione peroxidase activities during the menstrual cycle. J Endocrinol 167:447–452. doi: 10.1677/joe.0.1670447 CrossRefPubMedGoogle Scholar
  36. 36.
    Mumford SL, Browne RW, Schliep KC, Schmelzer J, Plowden TC, Michels KA et al (2016) Serum antioxidants are associated with serum reproductive hormones and ovulation among healthy women. J Nutr 146:98–106. doi: 10.3945/jn.115.217620 CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Aleksandra Klisic
    • 1
  • Jelena Kotur-Stevuljevic
    • 2
  • Nebojsa Kavaric
    • 1
  • Milica Martinovic
    • 3
  • Marija Matic
    • 4
  1. 1.Primary Health Care CenterPodgoricaMontenegro
  2. 2.Department for Medical Biochemistry, Faculty of PharmacyUniversity of BelgradeBelgradeSerbia
  3. 3.Department for Pathophysiology and Laboratory Medicine, Medical FacultyUniversity of MontenegroPodgoricaMontenegro
  4. 4.Faculty of Medicine, Institute of Medical and Clinical BiochemistryUniversity of BelgradeBelgradeSerbia

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