Vasomotor Symptoms

  • Maria Celeste O. Wender
  • Patrícia Pereira de Oliveira


The menopausal transition can be categorized into several stages, which are accompanied by various changes that may have a significant impact on quality of life. Vasomotor symptoms (VMS) usually appear in the beginning of the menopausal transition and may persist until the end of life. These symptoms are common reasons for seeking medical care and include hot flashes or night sweats which last from 1 to 15 min and may involve sweating, palpitations, nausea, dizziness, chills, pain, or pressure in the head or chest; changes in breathing patterns and heart rate; and sleep disturbances. Although their physiopathology is not well known, it is thought that hot flashes may be caused by increased thermoregulatory responses, which lead to intense sensations of heat and flushing, accompanied by an increase in blood flow. The incidence and intensity of VMS may vary according to clinical factors such as ethnicity, obesity, and mood. Although several hormonal and nonhormonal treatments may be used to treat VMS, their risks and benefits should always be weighed on a case-by-case basis. To further explore this issue, this chapter will review the physiopathology, epidemiology, and treatment of VMS.


Hormone Therapy Standardize Mean Difference Vasomotor Symptom Menopausal Transition Black Cohosh 
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  1. 1.
    Soules MR, Sherman S, Parrott E, Rebar R, Santoro N, Utian W, et al. Executive summary: Stages of Reproductive Aging Workshop (STRAW). Fertil Steril. 2001;76(5):874–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Soules MR, Sherman S, Parrott E, Rebar R, Santoro N, Utian W, et al. Executive summary: Stages of Reproductive Aging Workshop (STRAW). Climacteric. 2001;4(4):267–72.PubMedCrossRefGoogle Scholar
  3. 3.
    Joffe H, Groninger H, Soares CN, Nonacs R, Cohen LS. An open trial of mirtazapine in menopausal women with depression unresponsive to estrogen replacement therapy. J Womens Health Gend Based Med. 2001;10(10):999–1004.PubMedCrossRefGoogle Scholar
  4. 4.
    Thurston RC, Joffe H. Vasomotor symptoms and menopause: findings from the Study of Women’s Health across the Nation. Gynecol Clin North Am. 2011;38(3):489–501.CrossRefGoogle Scholar
  5. 5.
    Deecher DC, Dorries K. Understanding the pathophysiology of vasomotor symptoms (hot flushes and night sweats) that occur in perimenopause, menopause, and postmenopause life stages. Arch Womens Ment Health. 2007;10(6):247–57.PubMedCrossRefGoogle Scholar
  6. 6.
    Santoro N. Symptoms of menopause: hot flushes. Clin Obstet Gynecol. 2008;51(3):539–48.PubMedCrossRefGoogle Scholar
  7. 7.
    Freedman RR. Hot flashes revisited. Menopause. 2000;7(1):3–4.PubMedCrossRefGoogle Scholar
  8. 8.
    Miller EH. Women and insomnia. Clin Cornerstone. 2004;6(Suppl 1B):S8–18.PubMedGoogle Scholar
  9. 9.
    Voda AM. Climacteric hot flash. Maturitas. 1981;3(1):73–90.PubMedCrossRefGoogle Scholar
  10. 10.
    Soares CN. Insomnia in women: an overlooked epidemic? Arch Womens Ment Health. 2005;8(4):205–13.PubMedCrossRefGoogle Scholar
  11. 11.
    Freeman EW, Sammel MD, Sanders RJ. Risk of long-term hot flashes after natural menopause: evidence from the Penn Ovarian Aging Study cohort. Menopause. 2014 [Epub ahead of print]Google Scholar
  12. 12.
    Freedman RR. Hot flashes: behavioral treatments, mechanisms, and relation to sleep. Am J Med. 2005;118(Suppl 12B):124–30.PubMedCrossRefGoogle Scholar
  13. 13.
    Freedman RR, Krell W. Reduced thermoregulatory null zone in postmenopausal women with hot flashes. Am J Obstet Gynecol. 1999;181(1):66–70.PubMedCrossRefGoogle Scholar
  14. 14.
    Freedman RR, Norton D, Woodward S, Cornelissen G. Core body temperature and circadian rhythm of hot flashes in menopausal women. J Clin Endocrinol Metab. 1995;80(8):2354–8.PubMedGoogle Scholar
  15. 15.
    Rebar RW, Spitzer IB. The physiology and measurement of hot flushes. Am J Obstet Gynecol. 1987;156(5):1284–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Berendsen HH. The role of serotonin in hot flushes. Maturitas. 2000;36(3):155–64.PubMedCrossRefGoogle Scholar
  17. 17.
    Meldrum DR, Erlik Y, Lu JK, Judd HL. Objectively recorded hot flushes in patients with pituitary insufficiency. J Clin Endocrinol Metab. 1981;52(4):684–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Tataryn IV, Lomax P, Bajorek JG, Chesarek W, Meldrum DR, Judd HL. Postmenopausal hot flushes: a disorder of thermoregulation. Maturitas. 1980;2(2):101–7.PubMedCrossRefGoogle Scholar
  19. 19.
    Thurston RC, Christie IC, Matthews KA. Hot flashes and cardiac vagal control: a link to cardiovascular risk? Menopause. 2010;17(3):456–61.PubMedCentralPubMedGoogle Scholar
  20. 20.
    Sowers MR, Wilson AL, Karvonen-Gutierrez CA, Kardia SR. Sex steroid hormone pathway genes and health-related measures in women of 4 races/ethnicities: the Study of Women’s Health Across the Nation (SWAN). Am J Med. 2006;119(9 Suppl 1):S103–10.PubMedCrossRefGoogle Scholar
  21. 21.
    Thurston RC, Sowers MR, Sutton-Tyrrell K, Everson-Rose SA, Lewis TT, Edmundowicz D, et al. Abdominal adiposity and hot flashes among midlife women. Menopause. 2008;15(3):429–34.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Thurston RC, Sowers MR, Sternfeld B, Gold EB, Bromberger J, Chang Y, et al. Gains in body fat and vasomotor symptom reporting over the menopausal transition: the study of women’s health across the nation. Am J Epidemiol. 2009;170(6):766–74.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Gold EB, Block G, Crawford S, Lachance L, FitzGerald G, Miracle H, et al. Lifestyle and demographic factors in relation to vasomotor symptoms: baseline results from the Study of Women’s Health Across the Nation. Am J Epidemiol. 2004;159(12):1189–99.PubMedCrossRefGoogle Scholar
  24. 24.
    Gold EB, Leung K, Crawford SL, Huang MH, Waetjen LE, Greendale GA. Phytoestrogen and fiber intakes in relation to incident vasomotor symptoms: results from the Study of Women’s Health Across the Nation. Menopause. 2013;20(3):305–14.PubMedCentralPubMedGoogle Scholar
  25. 25.
    Gold EB, Colvin A, Avis N, Bromberger J, Greendale GA, Powell L, et al. Longitudinal analysis of the association between vasomotor symptoms and race/ethnicity across the menopausal transition: study of women’s health across the nation. Am J Public Health. 2006;96(7):1226–35.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Gibson C, Matthews K, Thurston R. Daily physical activity and hot flashes in the Study of Women’s Health Across the Nation (SWAN) Flashes Study. Fertil Steril. 2014;101(4):1110–6.PubMedCrossRefGoogle Scholar
  27. 27.
    Bromberger JT, Meyer PM, Kravitz HM, Sommer B, Cordal A, Powell L, et al. Psychologic distress and natural menopause: a multiethnic community study. Am J Public Health. 2001;91(9):1435–42.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Freeman EW, Sammel MD, Lin H, Gracia CR, Kapoor S, Ferdousi T. The role of anxiety and hormonal changes in menopausal hot flashes. Menopause. 2005;12(3):258–66.PubMedCrossRefGoogle Scholar
  29. 29.
    Hunter MS, Gupta P, Chedraui P, Blumel JE, Tserotas K, Aguirre W, et al. The International Menopause Study of Climate, Altitude, Temperature (IMS-CAT) and vasomotor symptoms. Climacteric. 2013;16(1):8–16.PubMedCrossRefGoogle Scholar
  30. 30.
    Kravitz HM, Ganz PA, Bromberger J, Powell LH, Sutton-Tyrrell K, Meyer PM. Sleep difficulty in women at midlife: a community survey of sleep and the menopausal transition. Menopause. 2003;10(1):19–28.PubMedGoogle Scholar
  31. 31.
    Joffe H, White DP, Crawford SL, McCurnin KE, Economou N, Connors S, et al. Adverse effects of induced hot flashes on objectively recorded and subjectively reported sleep: results of a gonadotropin-releasing hormone agonist experimental protocol. Menopause. 2013;20(9):905–14.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Greendale GA, Wight RG, Huang MH, Avis N, Gold EB, Joffe H, et al. Menopause-associated symptoms and cognitive performance: results from the study of women’s health across the nation. Am J Epidemiol. 2010;171(11):1214–24.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Weber MT, Rubin LH, Maki PM. Cognition in perimenopause: the effect of transition stage. Menopause. 2013;20(5):511–7.PubMedGoogle Scholar
  34. 34.
    Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288(3):321–33.PubMedCrossRefGoogle Scholar
  35. 35.
    Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) research group. JAMA. 1998;280(7):605–13.PubMedCrossRefGoogle Scholar
  36. 36.
    Grady D, Herrington D, Bittner V, Blumenthal R, Davidson M, Hlatky M, et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA. 2002;288(1):49–57.PubMedCrossRefGoogle Scholar
  37. 37.
    Thurston RC, Sutton-Tyrrell K, Everson-Rose SA, Hess R, Powell LH, Matthews KA. Hot flashes and carotid intima media thickness among midlife women. Menopause. 2011;18(4):352–8.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Thurston RC, Sutton-Tyrrell K, Everson-Rose SA, Hess R, Matthews KA. Hot flashes and subclinical cardiovascular disease: findings from the Study of Women’s Health Across the Nation Heart Study. Circulation. 2008;118(12):1234–40.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Maclennan AH, Broadbent JL, Lester S, Moore V. Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes. Cochrane Database Syst Rev. 2004; (4):CD002978.Google Scholar
  40. 40.
    Villaseca P. Non-estrogen conventional and phytochemical treatments for vasomotor symptoms: what needs to be known for practice. Climacteric. 2012;15(2):115–24.PubMedCrossRefGoogle Scholar
  41. 41.
    Newton KM, Reed SD, LaCroix AZ, Grothaus LC, Ehrlich K, Guiltinan J. Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: a randomized trial. Ann Intern Med. 2006;145(12):869–79.PubMedCrossRefGoogle Scholar
  42. 42.
    de Villiers TJ, Gass ML, Haines CJ, Hall JE, Lobo RA, Pierroz DD, et al. Global consensus statement on menopausal hormone therapy. Climacteric. 2013;16(2):203–4.PubMedCrossRefGoogle Scholar
  43. 43.
    North American Menopause Society. The 2012 hormone therapy position statement of: The North American Menopause Society. Menopause. 2012;19(3):257–71.Google Scholar
  44. 44.
    Schierbeck LL, Rejnmark L, Tofteng CL, Stilgren L, Eiken P, Mosekilde L, et al. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial. BMJ. 2012;345:e6409.PubMedCrossRefGoogle Scholar
  45. 45.
    Sturdee DW, Pines A, International Menopause Society Writing G, Archer DF, Baber RJ, Barlow D, et al. Updated IMS recommendations on postmenopausal hormone therapy and preventive strategies for midlife health. Climacteric. 2011;14(3):302–20.PubMedCrossRefGoogle Scholar
  46. 46.
    Fichera M, Rinaldi N, Tarascio M, Taschetta S, Caldaci LM, Catavorello A, et al. Indications and contraindications of hormone replacement therapy in menopause. Minerva Ginecol. 2013;65(3):331–44.PubMedGoogle Scholar
  47. 47.
    Wender MCO, Freitas F, De Castro JAS, Caran JZ, De Oliveira PP. Climatério. In: Freitas FM CH, Rivoire WA, Passos EP, editors. Rotinas em ginecologia. 6th ed. Porto Alegre: Artmed; 2011. p. 700–22.Google Scholar
  48. 48.
    Nelson HD, Vesco KK, Haney E, Fu R, Nedrow A, Miller J, et al. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA. 2006;295(17):2057–71.PubMedCrossRefGoogle Scholar
  49. 49.
    Nelken RS, Ozel BZ, Leegant AR, Felix JC, Mishell Jr DR. Randomized trial of estradiol vaginal ring versus oral oxybutynin for the treatment of overactive bladder. Menopause. 2011;18(9):962–6.PubMedCrossRefGoogle Scholar
  50. 50.
    Anderson GL, Judd HL, Kaunitz AM, Barad DH, Beresford SA, Pettinger M, et al. Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: the Women’s Health Initiative randomized trial. JAMA. 2003;290(13):1739–48.PubMedCrossRefGoogle Scholar
  51. 51.
    Greiser CM, Greiser EM, Doren M. Menopausal hormone therapy and risk of lung cancer-systematic review and meta-analysis. Maturitas. 2010;65(3):198–204.PubMedCrossRefGoogle Scholar
  52. 52.
    Oh SW, Myung SK, Park JY, Lym YL, Ju W. Hormone therapy and risk of lung cancer: a meta-analysis. J Womens Health (Larchmt). 2010;19(2):279–88.CrossRefGoogle Scholar
  53. 53.
    Umland EM. Treatment strategies for reducing the burden of menopause-associated vasomotor symptoms. J Manag Care Pharm. 2008;14(3 Suppl):14–9.PubMedGoogle Scholar
  54. 54.
    Kenemans P, Bundred NJ, Foidart JM, Kubista E, von Schoultz B, Sismondi P, et al. Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double-blind, randomised, non-inferiority trial. Lancet Oncol. 2009;10(2):135–46.PubMedCrossRefGoogle Scholar
  55. 55.
    Wolff EF, He Y, Black DM, Brinton EA, Budoff MJ, Cedars MI, et al. Self-reported menopausal symptoms, coronary artery calcification, and carotid intima-media thickness in recently menopausal women screened for the Kronos early estrogen prevention study (KEEPS). Fertil Steril. 2013;99(5):1385–91.PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. JAMA. 1995;273(3):199–208.CrossRefGoogle Scholar
  57. 57.
    Smith NL, Wiley JR, Legault C, Rice KM, Heckbert SR, Psaty BM, et al. Effect of progestogen and progestogen type on hemostasis measures in postmenopausal women: the Postmenopausal Estrogen/Progestin Intervention (PEPI) study. Menopause. 2008;15(6):1145–50.PubMedCrossRefGoogle Scholar
  58. 58.
    Formoso G, Perrone E, Maltoni S, Balduzzi S, D’Amico R, Bassi C, et al. Short and long term effects of tibolone in postmenopausal women. Cochrane Database Syst Rev; 2012;(2):CD008536.Google Scholar
  59. 59.
    Cummings SR, Ettinger B, Delmas PD, Kenemans P, Stathopoulos V, Verweij P, et al. The effects of tibolone in older postmenopausal women. N Engl J Med. 2008;359(7):697–708.PubMedCentralPubMedCrossRefGoogle Scholar
  60. 60.
    Palacios S. Advances in hormone replacement therapy: making the menopause manageable. BMC Womens Health. 2008;8:22.PubMedCentralPubMedCrossRefGoogle Scholar
  61. 61.
    Thacker HL. Assessing risks and benefits of nonhormonal treatments for vasomotor symptoms in perimenopausal and postmenopausal women. J Womens Health (Larchmt). 2011;20(7):1007–16.CrossRefGoogle Scholar
  62. 62.
    Stearns V. Clinical update: new treatments for hot flushes. Lancet. 2007;369(9579):2062–4.PubMedCrossRefGoogle Scholar
  63. 63.
    Stearns V, Slack R, Greep N, Henry-Tilman R, Osborne M, Bunnell C, et al. Paroxetine is an effective treatment for hot flashes: results from a prospective randomized clinical trial. J Clin Oncol. 2005;23(28):6919–30.PubMedCrossRefGoogle Scholar
  64. 64.
    Kelly CM, Juurlink DN, Gomes T, Duong-Hua M, Pritchard KI, Austin PC, et al. Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study. BMJ. 2010;340:c693.PubMedCentralPubMedCrossRefGoogle Scholar
  65. 65.
    FDA. FDA approves the first non-hormonal treatment for hot flashes associated with menopause 2013 [Oct 7 2013]. Available from:
  66. 66.
    Archer DF, Seidman L, Constantine GD, Pickar JH, Olivier S. A double-blind, randomly assigned, placebo-controlled study of desvenlafaxine efficacy and safety for the treatment of vasomotor symptoms associated with menopause. Am J Obstet Gynecol. 2009;200(2):172.e1–10.Google Scholar
  67. 67.
    Loprinzi CL, Kugler JW, Sloan JA, Mailliard JA, LaVasseur BI, Barton DL, et al. Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial. Lancet. 2000;356(9247):2059–63.PubMedCrossRefGoogle Scholar
  68. 68.
    Speroff L, Gass M, Constantine G, Olivier S, Study I. Efficacy and tolerability of desvenlafaxine succinate treatment for menopausal vasomotor symptoms: a randomized controlled trial. Obstet Gynecol. 2008;111(1):77–87.PubMedCrossRefGoogle Scholar
  69. 69.
    Archer DF, Pinkerton JV, Guico-Pabia CJ, Hwang E, Cheng RF, Study I. Cardiovascular, cerebrovascular, and hepatic safety of desvenlafaxine for 1 year in women with vasomotor symptoms associated with menopause. Menopause. 2013;20(1):47–56.PubMedGoogle Scholar
  70. 70.
    Kerwin JP, Gordon PR, Senf JH. The variable response of women with menopausal hot flashes when treated with sertraline. Menopause. 2007;14(5):841–5.PubMedCrossRefGoogle Scholar
  71. 71.
    Gordon PR, Kerwin JP, Boesen KG, Senf J. Sertraline to treat hot flashes: a randomized controlled, double-blind, crossover trial in a general population. Menopause. 2006;13(4):568–75.PubMedCrossRefGoogle Scholar
  72. 72.
    Kimmick GG, Lovato J, McQuellon R, Robinson E, Muss HB. Randomized, double-blind, placebo-controlled, crossover study of sertraline (Zoloft) for the treatment of hot flashes in women with early stage breast cancer taking tamoxifen. Breast J. 2006;12(2):114–22.PubMedCrossRefGoogle Scholar
  73. 73.
    Freeman EW, Guthrie KA, Caan B, Sternfeld B, Cohen LS, Joffe H, et al. Efficacy of escitalopram for hot flashes in healthy menopausal women: a randomized controlled trial. JAMA. 2011;305(3):267–74.PubMedCentralPubMedCrossRefGoogle Scholar
  74. 74.
    Pandya KJ, Morrow GR, Roscoe JA, Zhao H, Hickok JT, Pajon E, et al. Gabapentin for hot flashes in 420 women with breast cancer: a randomised double-blind placebo-controlled trial. Lancet. 2005;366(9488):818–24.PubMedCentralPubMedCrossRefGoogle Scholar
  75. 75.
    Guttuso Jr T, Kurlan R, McDermott MP, Kieburtz K. Gabapentin’s effects on hot flashes in postmenopausal women: a randomized controlled trial. Obstet Gynecol. 2003;101(2):337–45.PubMedCrossRefGoogle Scholar
  76. 76.
    Yadav M, Volkar J. Potential role of gabapentin and extended-release gabapentin in the management of menopausal hot flashes. Int J Gen Med. 2013;6:657–64.PubMedCentralPubMedCrossRefGoogle Scholar
  77. 77.
    Butt DA, Lock M, Lewis JE, Ross S, Moineddin R. Gabapentin for the treatment of menopausal hot flashes: a randomized controlled trial. Menopause. 2008;15(2):310–8.PubMedCrossRefGoogle Scholar
  78. 78.
    Pandya KJ, Raubertas RF, Flynn PJ, Hynes HE, Rosenbluth RJ, Kirshner JJ, et al. Oral clonidine in postmenopausal patients with breast cancer experiencing tamoxifen-induced hot flashes: a University of Rochester Cancer Center Community Clinical Oncology Program study. Ann Intern Med. 2000;132(10):788–93.PubMedCrossRefGoogle Scholar
  79. 79.
    L’Esperance S, Frenette S, Dionne A, Dionne JY. Comite de l’evolution des pratiques en o. Pharmacological and non-hormonal treatment of hot flashes in breast cancer survivors: CEPO review and recommendations. Support Care Cancer. 2013;21(5):1461–74.PubMedCrossRefGoogle Scholar
  80. 80.
    Geller SE, Shulman LP, van Breemen RB, Banuvar S, Zhou Y, Epstein G, et al. Safety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomized controlled trial. Menopause. 2009;16(6):1156–66.PubMedCentralPubMedCrossRefGoogle Scholar
  81. 81.
    Cramer H, Lauche R, Langhorst J, Dobos G. Effectiveness of yoga for menopausal symptoms: a systematic review and meta-analysis of randomized controlled trials. Evid Based Complement Alternat Med. 2012;2012:863905.PubMedCentralPubMedCrossRefGoogle Scholar
  82. 82.
    Daley AJ, Stokes-Lampard HJ, Macarthur C. Exercise to reduce vasomotor and other menopausal symptoms: a review. Maturitas. 2009;63(3):176–80.PubMedCrossRefGoogle Scholar
  83. 83.
    Lipov EG, Joshi JR, Xie H, Slavin KV. Updated findings on the effects of stellate-ganglion block on hot flushes and night awakenings. Lancet Oncol. 2008;9(9):819–20.PubMedCrossRefGoogle Scholar
  84. 84.
    Haest K, Kumar A, Van Calster B, Leunen K, Smeets A, Amant F, et al. Stellate ganglion block for the management of hot flashes and sleep disturbances in breast cancer survivors: an uncontrolled experimental study with 24 weeks of follow-up. Ann Oncol. 2012;23(6):1449–54.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Maria Celeste O. Wender
    • 1
  • Patrícia Pereira de Oliveira
    • 2
  1. 1.Department of Obstetrics and GynecologyMenopause Clinic of Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande do SulPorto AlegreBrazil
  2. 2.Department of MedicineUniversity UnochapecóChapecóBrazil

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