Abstract
Recent works have shown a dual side of estrogens, and research on the relationship between oxidative stress and menopausal status remains unclear and has produced controversial results. In this work, we aimed to evaluate by sensitive methods the oxidant and antioxidant changes that develop after natural menopause. Thirty premenopausal and 28 naturally postmenopausal women volunteered for this study. Blood was collected and plasma used. 17-OH estradiol levels in plasma were estimated. Plasma levels of advanced oxidation protein products (AOPP), lipid peroxidation products (such as hydroperoxides and malondialdehyde (MDA)), and nitrites were measured, and total radical antioxidant parameter testing was performed to determine the oxidant and antioxidant profiles, respectively. Estrogen levels were significantly increased (p < 0.02) in premenopausal women (54.28 ± 9.34 pg/mL) as compared with postmenopausal women (18.10 ± 1.49 pg/mL). Postmenopausal women had lower levels of lipid hydroperoxide oxidation (p < 0.0001), lipid hydroperoxide levels evaluated by the area under the curve (AUC; 1,366,000 ± 179,400 AUC; p < 0.01), and hydroperoxides as measured by the ferrous oxidation-xylenol orange method (31.48 ± 2.7 μM; p < 0.0001). The MDA levels did not differ between pre- and postmenopausal women whether measured by thiobarbituric acid-reactive substances or high-performance liquid chromatography assays. No differences in AOPP and nitrite levels were observed between pre- and postmenopausal women. Postmenopausal women also exhibited a higher total radical antioxidant level (0.89 ± 0.08 μM Trolox; p < 0.0001). Postmenopausal women demonstrated lower levels of oxidative damage and a higher antioxidant capacity than premenopausal women.
Similar content being viewed by others
References
Arteaga E, Rojas A, Villaseca P, Bianchi M, Arteaga A, Durán D (1998) In vitro effect of estradiol, progesterone, testosterone, and of combined estradiol/progestins on low density lipoprotein (LDL) oxidation in postmenopausal women. Menopause 5(1):16–23
Ayres S, Abplanalp W, Liu JH, Subbiah MTR (1998) Mechanisms involved in the protective effect of estradiol-17β on lipid peroxidation and DNA damage. Am J Physiol 274(37):1002–1008
Beckman KB, Ames BN (1998) The free radical theory of aging matures. Physiol Rev 78(2):547–581
Bednarek-Tupikowska G, Tupikowski K, Bidzińska B et al (2004) Serum lipid peroxides and total antioxidant status in postmenopausal women on hormone replacement therapy. Gynecol Endocrinol 19(2):57–63
Bednarek-Tupikowska G, Tworowska U, Jedrychowska I, Radomska B, Tupikowski K, Bidzinska-Speichert B, Milewicz A (2006) Effects of oestradiol and oestroprogestin on erythrocyte antioxidative enzyme system activity in postmenopausal women. Clin Endocrinol 64:463–468
Borrás C, Sastre J, García-Sala D, Lloret A, Pallardó FV, Vinã J (2003) Mitochondria from females exhibit higher antioxidant gene expression and lower oxidative damage than males. Free Radic Biol Med 34(5):546–552
Borrás C, Gambini J, López-Grueso R, Pallardó FV, Viña J (2010) Direct antioxidant and protective effect of estradiol on isolated mitochondria. Biochim Biophys Acta 1802:205–211
Casado MF, Cecchini AL, Simão ANC, Oliveira RD, Cecchini R (2007) Free radical mediated pre-hemolytic injury in human red blood cells subjected to lead acetate as evaluated by chemiluminescence. Food Chem Toxicol 45:945–952
Chirico S (1994) High-performance liquid chromatography-based thiobarbituric acid tests. Methods Enzymol 234:314–318
Colado-Simão AN, Suzukawa AA, Casado MF, Oliveira RD, Cecchini R (2006) Genistein abrogates pre-hemolytic and oxidative stress damage induced by 2,2′-Azobis (Amidinopropane). Life Sci 78(11):1202–1210
Costa CM, Santos RCC, Lima ES (2006) Simple automated procedure for thiol measurement in human serum samples. J Bras Patol Med Lab 42(5):345–350
Cunha NV, de Abreu SB, Panis C et al (2010) Cox-2 inhibition attenuates cardiovascular and inflammatory aspects in monosodium glutamate-induced obese rats. Life Sci 87(11–12):375–381
Darabi M, Ani M, Movahedian A, Zarean E, Panjehpour M, Rabbani M (2010) Effect of hormone replacement therapy on total serum anti-oxidant potential and oxidized LDL/ß2-glycoprotein I complexes in postmenopausal women. Endocr J 57(12):1029–1034
Dorjgochoo T, Gao YT, Chow WH et al (2011) Obesity, age, and oxidative stress in middle-aged and older women. Antioxidants Redox Signal 14(12):2453–2460
Felty Q, Xiong WC, Sun D et al (2005) Estrogen-induced mitochondrial reactive oxygen species as signal-transducing messengers. Biochemistry 44:6900–6909
Feng J, Bussière F, Hekimi S (2001) Mitochondrial electron transport is a key determinant of life span in Caenorhabditis elegans. Dev Cell 1:633–644
Fussell CK, Udasin RG, Smith PJS, Gallo MA, Laskin JD (2011) Catechol metabolites of endogenous estrogens induce redox cycling and generate reactive oxygen species in breast epithelial cells. Carcinogenesis (0): 1–9
Gago-Dominguez M, Jiang X, Castelao JE (2007) Lipid peroxidation, oxidative stress genes and dietary factors in breast cancer protection: a hypothesis. Breast Cancer Res 9:201
Gallagher JC, Levine JP (2008) Preventing osteoporosis in symptomatic postmenopausal women. Menopause 18(1):109–118
Gambacciani M, Ciaponi M, Cappagli B et al (1997) Body weight, body fat distribution, and hormonal replacement therapy in early postmenopausal women. J Clin Endocrinol Metab 82:414–417
Gast GCM, Pop VJM, Samsioe GN, Grobbee DE, Nilsson PM, Keyzer JJ, van Gent CJMW, van der Schouw YT (2011) Vasomotor menopausal symptoms are associated with increased risk of coronary heart disease. Menopause 18(2):146–151
Gay CA, Gebicki JM (2002) Perchloricacid enhances sensitivity and reproducibility of the ferric–xylenolorange peroxide assay. Anal Biochem 304:42–46
Ghiselli A, Serafini M, Maiani G, Azzini E, Ferro-Luzzi A (1995) A fluorescence-based method for measuring total plasma antioxidant capability. Free Radic Biol Med 18:29–36
Giddabasappa A, Bauler M, Yepuru M, Chaum E, Dalton JT, Eswaraka J (2010) 17-β estradiol protects ARPE-19 cells from oxidative stress through estrogen receptor-β. Invest Ophthalmol Vis Sci 51(10):5278–5287
Gokkusu C, Tata G, Ademoğlu E, Tamer S (2010) The benefits of hormone replacement therapy on plasma and platelet antioxidant status and fatty acid composition in healthy postmenopausal women. Platelets 21(6):439–444
Gonzales-Flecha B, Llesuy S, Boveris A (1991) Hydroperoxide-initiated chemiluminescence: an assay for oxidative stress in biopsies of heart, liver, and muscle. Free Radic Biol Med 10(2):93–100
Halliwell B (2007) Oxidative stress and cancer: have we moved forward? Biochem J 401:1–11
Halliwell B, Gutteridge JMC (2007) Free radicals in biology and medicine: oxygen is a toxic gas—an introduction to oxygen toxicity and reactive species, 4th edn. Oxford University, New York, pp 1–28
Hays J, Ockene JK, Brunner RL et al (2003) Effects of estrogen plus progestin on health-related quality of life. N Engl J Med 348(19):1839–1854
Kanda N, Watanabe S (2003) 17b-estradiol inhibits oxidative stress-induced apoptosis in keratinocytes by promoting Bcl-2 expression. J Invest Dermatol 121:1500–1509
Karatas F, Karatepe M, Baysar A (2002) Determination of free malondialdehyde in human serum by high-performance liquid chromatography. An Biochem 311:76–79
Lozovoy MA, Simão AN, Panis C, Rotter MA, Reiche EM, Morimoto HK, Lavado E, Cecchini R, Dichi I (2011) Oxidative stress is associated with liver damage, inflammatory status, and corticosteroid therapy in patients with systemic lupus erythematosus. Lupus 20(12):1250–1259
Nathan L, Chaudhuri G (1998) Antioxidant and prooxidant actions of estrogens: potential physiological and clinical implications. Semin Reprod Endocrinol 16:309–314
Numakawa Y, Matsumoto T, Yokomaku D, Taguchi T, Niki E, Hatanaka H, Kunugi H, Numakawa T (2007) 17β-estradiol protects cortical neurons against oxidative stress-induced cell death through reduction in the activity of mitogen-activated protein kinase and in the accumulation of intracellular calcium. Endocrinol 148(2):627–637
Okoh V, Deoraj A, Roy D (2011) Estrogen-induced reactive oxygen species-mediated signalings contribute to breast cancer. Biochim Biophys Acta 1815:115–133
Oliveira FJA, Cecchini R (2008) Oxidative stress of liver in hamsters infected with Leishmania (L.) chagasi. J Parasitol 6(5):1067–1072
Panis C, Herrera ACSA, Victorino VJ et al (2011a) Oxidative stress and hematological profiles of advanced breast cancer patients subjected to paclitaxel or doxorubicin chemotherapy. Breast Cancer Res Treat. doi:10.1007/s10549-011-1693-x
Panis C, Mazzuco TL, Costa CZF et al (2011b) Trypanosoma cruzi: effect of the absence of 5-lipoxygenase (5-LO)-derived leukotrienes on levels of cytokines, nitric oxide and iNOS expression in cardiac tissue in the acute phase of infection in mice. Exp Parasitol 127:58–65
Pansini F, Cervellati C, Guariento A et al (2008) Oxidative stress, body fat composition, and endocrine status in pre- and postmenopausal women. Menopause 15(1):112–118
Peres PS, Terra VA, Guarnier FA, Cecchini R, Cecchini AL (2011) Photoaging and chronological aging profile: understanding oxidation of the skin. J Photochem Photobiol B Biol 103:93–97
Pollycove R, Frederick Naftolin MD, Simon JA (2011) The evolutionary origin and significance of menopause. Menopause 18(3):336–342
Potischman N, Swanson CA, Siiteri P, Hoover RN (1996) Reversal of relation between body mass and endogenous estrogen concentrations with menopausal status. J Natl Cancer Inst 88(11):756–758
Russo J, Lareef MH, Balogh G, Guo S, Russo IH (2003) Estrogen and its metabolites are carcinogenic agents in human breast epithelial cells. J Steroid Biochem Mol Biol 87:1–25
Schriner SE, Linford NJ, Martin GM et al (2005) Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308:1909–1911
Sherman AM, Shumaker SA, Sharp P (2003) No effect of HRT on health-related quality of life in postmenopausal women with heart disease. Minerva Ginecol 55(6):511–517
Shumaker SA, Legault C et al (2003) Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women The Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA 289:2651–2662
Signorelli SS, Neri S, Sciacchitano S, Di Pino L et al (2006) Behaviour of some indicators of oxidative stress in postmenopausal and fertile women. Maturitas 53:77–82
Sipe HJ, Jordan SJ, Hanna PM, Mason RP (1994) The metabolism of 17 beta-estradiol by lactoperoxidase: a possible source of oxidative stress in breast cancer. Carcinogenesis 15(11):2637–2643
Soules MR, Sherman S, Parrott E et al (2001) Stages of Reproductive Aging Workshop (STRAW). Fertil Steril 76(5):874–878
Sowers MF, McConnell D, Jannausch ML et al (2008) Estrogen metabolites and their relation to isoprostanes as a measure of oxidative stress. Clin Endocrinol (Oxf) 68(5):806–813
Tagawa N, Yuda R, Kubota S, Wakabayashi M, Yamaguchi Y, Kiyonaga D, Mori N, Minamitani E, Masuzaki H, Kobayashi Y (2009) 17b-estradiol inhibits 11b-hydroxysteroid dehydrogenase type 1 activity in rodent adipocytes. J Endocrinol 202:131–139
Thurston RC, Sutton-Tyrrell K, Everson-Rose SA, Hess R, Powell LH, Matthews KA (2011) Hot flashes and carotid intima media thickness among midlife women. Menopause 18(4):352–358
Trevisan M, Browne R, Ram M, Muti P, Freudenheim J, Carosella AM, Armstrong D (2001) Correlates of markers of oxidative status in the general population. Am J Epidemiol 154(4):348–356
Unfer TC, Conterato GMM, Silva JCN, Duarte MMMF, Emanuelli T (2006) Influence of hormone replacement therapy on blood antioxidant enzymes in menopausal women. Clinica Chimica Acta 369:73–77
Urata Y, Ihara Y, Murata H, Goto S, Koji T, Yodoi J, Inoue S, Kondo T (2006) 17β-estradiol protects against oxidative stress-induced cell death through the glutathione/glutaredoxin-dependent redox regulation of Akt in myocardiac H9c2 cells. J Biol Chem 281(19):13092–13102
Woodard GA, Brooks MM, Barinas-Mitchell E, Mackey RH, Matthews KA, Sutton-Tyrrell K (2011) Lipids, menopause, and early atherosclerosis in Study of Women’s Health Across the Nation Heart women. Menopause 18(4):376–384
Yager JD (2000) Endogenous estrogens as carcinogens through metabolic activation. JNCI Monogr 27:67–73
Zwart LL, Meerman JHN, Commandeur JNM, Vermeulen NP (1999) Biomarkers of free radical damage applications in experimental animals and in humans. Free Radic Biol Med 26:202–226
Acknowledgments
The authors would like to thank Jesus Antônio Vargas for excellent technical assistance and all of the participating women for making the study possible. This work was supported by Coordination of Improvement of Higher Education (CAPES), National Council of Scientific and Technological Development (CNPq), and Araucaria Foundation.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Victorino, V.J., Panis, C., Campos, F.C. et al. Decreased oxidant profile and increased antioxidant capacity in naturally postmenopausal women. AGE 35, 1411–1421 (2013). https://doi.org/10.1007/s11357-012-9431-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11357-012-9431-9