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Hormone Replacement Therapy and Obstructive Airway Diseases


Controversy exists as to the role of female reproductive hormones in asthma and COPD and, specifically, the effect of hormone replacement therapy (HRT) on these disorders. The differential incidence of asthma over the menstrual life cycle suggests an effect of female reproductive hormones on asthma; less data are available for COPD. Estrogen and progesterone have protean effects at the cellular level, consistent with potentially harmful and beneficial effects in lung disease. Large epidemiologic studies show an increased risk of development of asthma with the use of HRT but no consistent effects on COPD. Clinical and epidemiologic studies of exacerbations are limited, but suggest either a harmful effect or no effect of HRT on exacerbations of asthma and COPD. HRT appears to increase the risk of development of asthma but is not associated with the loss of lung function characteristic of COPD. Because the development of asthma is rare in postmenopausal women, the absolute increase in risk among women without asthma is modest. Physicians may wish to avoid HRT therapy in patients with difficult to control asthma and COPD. Clinical decisions to start or continue HRT among women without asthma or COPD should be based on the effects of HRT on more common diseases such as cardiovascular disease, breast cancer and osteoporosis, non-vertebral fractures and colon cancer.

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Table I


  1. 1.

    Mannino DM, Homa DM, Akinbami LJ, et al. Surveillance for asthma: United States, 1980–1999. MMWR Morb Mortal Wkly Rep 2002; 47(SS-1): 1–13

  2. 2.

    Petty TL, Weinmann GG. Building a national strategy for the prevention and management of and research in chronic obstructive pulmonary disease. National Heart, Lung, and Blood Institute Workshop Summary. JAMA 1997; 277: 246–53

  3. 3.

    Mannino DM, Homa DM, Akinbami LJ, et al. Chronic obstructive pulmonary disease surveillance: United States, 1971–2000. MMWR Surveill Summ 2002 Aug 2; 51(SS-6): 1–8

  4. 4.

    Self-reported asthma prevalence among adults: United States, 2000. MMWR Morb Mortal Wkly Rep 2001; 50: 682–6

  5. 5.

    Skobeloff EM, Spivey WH, St Clair SS, et al. The influence of age and sex on asthma admissions. JAMA 1992; 268: 3437–40

  6. 6.

    Singh AK, Cydulka RK, Stahmer SA, et al. Sex differences among adults presenting to the emergency department with acute asthma. Arch Intern Med 1999; 159: 1237–43

  7. 7.

    Becklake MR, Kauffmann F. Gender differences in airway behaviour over the human life span. Thorax 1999; 54(12): 1119–38

  8. 8.

    DeMarco R, Locatelli F, Sunyer J, et al. Differences in incidence of reported asthma related to age in men and women: a retrospective analysis of the data of the European Respiratory Health Survey. Am J Respir Crit Care Med 2000; 162: 68–74

  9. 9.

    Kjellman B, Gustafsson PM. Asthma from childhood to adulthood: asthma severity, allergies, sensitization, living conditions, gender influence and social consequences. Respir Med 2000; 94(5): 454–65

  10. 10.

    Gustafsson PM, Kjellman B. Asthma from childhood to adulthood: course and outcome of lung function. Respir Med 2000; 94(5): 466–74

  11. 11.

    Troisi RJ, Speizer FE, Willett WC, et al. Menopause, postmenopausal estrogen preparations, and the risk of adult-onset asthma: a prospective cohort study. Am J Respir Crit Care Med 1995; 152 (4 Pt 1): 1183–8

  12. 12.

    Skobeloff EM, Spivey WH, Silverman R, et al. The effect of the menstrual cycle on asthma presentations in the emergency department. Arch Intern Med 1996; 156: 1837–40

  13. 13.

    Zimmerman JL, Woodruff PG, Clark S, et al. Relation between phase of menstrual cycle and emergency department visits for acute asthma. Am J Respir Crit Care Med 2000; 162: 512–5

  14. 14.

    Beynon HL, Garbett ND, Barnes PJ. Severe premenstrual exacerbations of asthma: effect of intramuscular progesterone. Lancet 1988; II(8607): 370–2

  15. 15.

    Hanley SP. Asthma variation with menstruation. Br J Dis Chest 1981; 75: 306–8

  16. 16.

    Gibbs CJ, Coutts II, Lock R, et al. Premenstrual exacerbation of asthma. Thorax 1984; 39: 833–6

  17. 17.

    Shames RS, Heilbron DC, Janson SL, et al. Clinical differences among women with and without self-reported perimenstrual asthma. Ann Allergy Asthma Immunol 1998; 81: 65–72

  18. 18.

    Tan KS, McFarlane LC, Lipworth BJ. Modulation of airway reactivity and peak flow variability in asthmatics receiving the oral contraceptive pill. Am J Respir Crit Care Med 1997; 155(4): 1273–7

  19. 19.

    Horan JD, Lederman JJ. Possible asthmogenic effect of oral contraceptives. Can Med Assoc J 1968; 99: 130–1

  20. 20.

    Forbes L, Jarvis D, Burney P. Do hormonal contraceptives influence asthma severity? Eur Respir J 1999; 14: 1028–33

  21. 21.

    Lange P, Parner J, Prescott E, et al. Exogenous female sex steriod hormones and risk of asthma and asthma-like symptoms: a cross sectional study of the general population. Thorax 2001; 56: 613–6

  22. 22.

    Forbes L. Do exogenous oestrogens and progesterone influence asthma? Thorax 1999; 54(3): 265–7

  23. 23.

    Weinmann GG, Zacur H, Fish JE. Absence of changes in airway responsiveness during the menstrual cycle. J Allergy Clin Immunol 1987; 79: 634–8

  24. 24.

    Pauli BD, Reid RL, Munt PW, et al. Influence of the menstrual cycle on airway function in asthmatic and normal subjects. Am Rev Respir Dis 1989; 140(2): 358–62

  25. 25.

    Juniper EF, Kline PA, Roberts RS, et al. Airway responsiveness to methacholine during the natural menstrual cycle and the effect of oral contraceptives. Am Rev Respir Dis 1987; 135(5): 1039–42

  26. 26.

    Cushley MJ, Holgate ST. Adenosine-induced bronchoconstriction in asthma: role of mast cell-mediator release. J Allergy Clin Immunol 1985; 75: 272–8

  27. 27.

    Chandler MH, Schuldheisz S, Phillips BA, et al. Premenstrual asthma: the effect of estrogen on symptoms, pulmonary function, and beta 2-receptors. Pharmacotherapy 1997; 17(2): 224–34

  28. 28.

    Anonymous. British Thoracic Society guidelines for the management of chronic obstructive pulmonary disease. The COPD Guidelines Group of the Standards of Care Committee of the British Thoracic Society. Thorax 1997; 52Suppl. 5: S1–S28

  29. 29.

    Vollmer WM, Enright PL, Pedula KL, et al. Race and gender differences in the effects of smoking on lung function. Chest 2000; 117: 764–72

  30. 30.

    Vollmer WM, Johnson LR, McCament LE, et al. Longitudinal versus cross-sectional estimation of lung function decline: further insights. Stat Med 1988; 7: 685–96

  31. 31.

    Xu X, Dockery DW, Ware JH, et al. Effects of cigarette smoking on rate of loss of pulmonary function in adults: a longitudinal assessment. Am Rev Respir Dis 1992; 146: 1345–8

  32. 32.

    Sherrill DL, Lebowitz MD, Knudson RJ, et al. Longitudinal methods for describing the relationship between pulmonary function, respiratory symptoms and smoking in elderly subjects: the Tuscon Study. Eur Respir J 1993; 6: 342–8

  33. 33.

    Xu X, Weiss ST, Riijcken B, et al. Smoking, changes in smoking habits, and rate of decline in FEV1: new insight into gender differences. Eur Respir J 1994; 7: 1056–61

  34. 34.

    Lange P, Groth S, Nyboe GJ, et al. Effects of smoking and changes in smoking habits on the decline of FEV1. Eur Respir J 1989; 2: 811–6

  35. 35.

    Prescott E, Bjerg AM, Andersen PK, et al. Gender difference in smoking effects on lung function and risk of hospitalization for COPD: results from a Danish longitudinal population study. Eur Respir J 1997; 10(4): 822–7

  36. 36.

    Macklem P. Mechanical factors determining maximum bronchoconstriction. Eur Respir J Suppl 1989; 2: 516–9

  37. 37.

    Lai-Fook SJ, Beck KC, Sutcliff AM, et al. Effect of edema and height on bronchial diameter and shape in excised dog lung. Respir Physiol 1984; 55: 223–37

  38. 38.

    Yager D, Butler JP, Bastacky J, et al. Amplification of airway constriction due to liquid filling of airway interstices. J Appl Physiol 1989; 66: 2873–84

  39. 39.

    Liu MC, Hubbard WC, Proud D, et al. Immediate and late inflammatory response to ragweed antigen challenge of the peripheral airways in asthmatics: cellular, mediator and permeability changes. Am Rev Respir Dis 1991; 144: 51–8

  40. 40.

    Peebles RS, Wagner EM, Liu MC, et al. Allergen-induced changes in airway responsiveness are not related to indices of airway edema. J Allergy Clin Immunol 2001; 107: 805–11

  41. 41.

    Minucci S, Di Matteo L, Chieffi P, et al. 17 beta-estradiol effects on mast cell number and spermatogonial mitotic index in the testis of the frog, Rana esculenta. J Exp Zool 1997; 278(2): 93–100

  42. 42.

    Wilhelm M, King B, Silverman AJ, et al. Gonadal steroids regulate the number and activational state of mast cells in the medial habenula. Endocrinology 2000; 141(3): 1178–86

  43. 43.

    Zhao XJ, McKerr G, Dong Z, et al. Expression of oestrogen and progesterone receptors by mast cells alone, but not lymphocytes, macrophages or other immune cells in human upper airways. Thorax 2001; 56(3): 205–11

  44. 44.

    Hamano N, Terada N, Maesako K, et al. Effect of sex hormones on eosinophilic inflammation in nasal mucosa. Allergy Asthma Proc 1998; 19(5): 263–9

  45. 45.

    Moawad AH, River LP, Kilpatrick SJ. The effect of estrogen and progesterone on beta-adrenergic receptor activity in rabbit lung tissue. Am J Obstet Gynecol 1982; 144(5): 608–13

  46. 46.

    Tan KS, McFarlane LC, Coutie WJ, et al. Effects of exogenous female sex-steroid hormones on lymphocyte beta 2- adrenoceptors in normal females. Br J Clin Pharmacol 1996; 41(5): 414–6

  47. 47.

    Tan KS, McFarlane LC, Lipworth BJ. Effect of exogenous female sex-steroid hormones on beta 2-adrenoceptors in healthy males. Eur J Clin Pharmacol 1997; 52(4): 281–3

  48. 48.

    Abdul-Karim RW, Marshall LD, Nesbitt Jr RE. Influence of estradiol-17 beta on the acetylcholine content of the lung in the rabbit neonate. Am J Obstet Gynecol 1970; 107(4): 641–4

  49. 49.

    Degano B, Prevost MC, Berger P, et al. Estradiol decreases the acetylcholine-elicited airway reactivity in ovariectomized rats through an increase in epitheilal acetylcholinesterase activity. Am J Respir Crit Care Med 2001; 164: 1849–54

  50. 50.

    Abdul-Karim RW, Drucker M, Jacobs RD. The influence of estradiol-17 beta on cholinesterase activity in the lung. Am J Obstet Gynecol 1970; 108(7): 1098–101

  51. 51.

    Kirsch EA, Yuhanna IS, Chen Z, et al. Estrogen acutely stimulates endothelial nitric oxide synthase in H441 human airway epithelial cells. Am J Respir Cell Mol Biol 1999; 20: 658–66

  52. 52.

    MacRitchie AN, Jun SS, Chen Z, et al. Estrogen upregulates endothelial nitric oxide synthase gene expression in fetal pulmonary endothelium. Circ Res 1997; 81: 355–62

  53. 53.

    Kharitonov SA, Logan-Sinclair RB, Busset CM, et al. Peak expiratory nitric oxide differences in men and women: relation to the menstrual cycle. Br Heart J 1994; 72: 243–5

  54. 54.

    Barr RG, Somers SC, Grodstein F, et al. Prospective cohort study of hormone replacement therapy and risk of asthma or chronic obstructive pulmonary disease among postmenopausal women [abstract]. Chest 2000; 118 Suppl.: 76S

  55. 55.

    Lieberman D, Kopernik G, Porath A, et al. Influence of estrogen replacement therapy on airway reactivity. Respiration 1995; 62: 205–8

  56. 56.

    Collins LC, Pieris A. Bronchospasm secondary to replacement estrogen therapy. Chest 1993; 104: 1300–2

  57. 57.

    Myers JR, Sherman CB. Should supplemental estrogens be used as steroid-sparing agents in asthmatic women? Chest 1994; 106(1): 318–9

  58. 58.

    Barr RG, Somers SC, Grodstein F, et al. Hormone replacement therapy and asthma exacerbations among postmenopausal women [abstract]. Chest 2001; 120 Suppl.: 171S

  59. 59.

    Lieberman D, Kopernik G, Porath A, et al. Sub-clinical worsening of bronchial asthma during estrogen replacement therapy in asthmatic post-menopausal women. Maturitas 1995; 21(2): 153–7

  60. 60.

    Hepburn MJ, Dooley DP, Morris MJ. The effects of estrogen replacement therapy on airway function in postmenopausal, asthmatic women. Arch Intern Med 2001; 161: 2717–20

  61. 61.

    Kos-Kudla B, Ostrowska Z, Marek B, et al. Effects of hormone replacement therapy on endocrine and spirometric parameters in asthmatic postmenopausal women. Gynecol Endocrinol 2001; 15(4): 304–11

  62. 62.

    Kos-Kudla B, Ostrowska Z, Marek B, et al. Hormone replacement therapy in postmenopausal asthmatic women. J Clin Pharm Ther 2000; 25: 461–6

  63. 63.

    Carlson CL, Cushman M, Enright PL, et al. Hormone replacement therapy is associated with higher FEV1 in elderly women. Am J Respir Crit Care Med 2001; 163: 423–8

  64. 64.

    Barr RG, Herbstman J, Speizer FE, et al. Validation of self-reported chronic obstructive pulmonary disease in a cohort study of nurses. Am J Epidemiol 2002; 155: 965–71

  65. 65.

    Barr RG, Somers SC, Grodstein F, et al. Postmenopausal hormone use and COPD exacerbations [abstract]. Am J Respir Crit Care Med 2002; 165 Suppl.: B5

  66. 66.

    USPSTF. Preventive Services Task Force. Guide to clinical preventive services: report of the US Preventive Services Task Force. 2nd ed. Baltimore (MD): Lippincott Williams & Wilkins, 1996

  67. 67.

    Hodis HN, Mack WJ, Lobo RA, et al. for the Estrogen in the Prevention of Artherosclerosis Trial Research Group. Estrogen in the prevention of artheros-clerosis: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 2001; 135: 939–53

  68. 68.

    Hulley S, Grady D, Bush T, et al. for the Heart and Estrogen/progestin Replacement Study (HERS) Research Group. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA 1998; 280: 605–13

  69. 69.

    Rossouw JE, Anderson GL, Prentice RL, 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: 321–33

  70. 70.

    Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52 705 women with breast cancer and 108 411 women without breast cancer. Lancet 1997; 350: 1047–59

  71. 71.

    The Writing Group for the PEPI. Effects of hormone therapy on bone mineral density: results from the postmenopausal estrogen/progestin interventions (PEPI) trial. JAMA 1996; 276: 1389–96

  72. 72.

    Torgerson DJ, Bell-Syer SEM. Hormone replacement therapy and prevention of nonvertebral fractures: a meta-analysis of randomized trials. JAMA 2001; 285: 2891–7

  73. 73.

    Laatikainen AK, Kroger HPJ, Tukiainen HO, et al. Bone mineral density in perimenopausal women with asthma: a population-based cross-sectional study. Am J Respir Crit Care Med 1999; 159: 1179–85

  74. 74.

    Lau EM, Li M, Woo J, et al. Bone mineral density and body composition in patients with airflow obstruction: the role of inhaled steroid therapy, disease and lifestyle. Clin Exp Allergy 1998; 28(9): 1066–71

  75. 75.

    Herrington DM, Howard TD, Hawkins GA, et al. Estrogen-receptor polymorphisms and effects of estrogen replacement on high-density lipoprotein cholesterol in women with coronary disease. N Engl J Med 2002; 346: 967–74

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Dr Barr was supported by a Robert Wood Johnson Generalist Physician Faculty Scholar Award and grant HL-07427 and AI-052338 from the National Institutes of Health. Dr Camargo was supported, in part, by grant HL-63841 and AI-052338 from the National Institutes of Health. The authors gratefully acknowledge the assistance of Brenda Taveras with manuscript preparation.

The authors have no conflicts of interest that are directly relevant to the content of this manuscript.

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Correspondence to Dr R. Graham Barr.

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Barr, R.G., Camargo, C.A. Hormone Replacement Therapy and Obstructive Airway Diseases. Treat Respir Med 3, 1–7 (2004).

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  • Asthma
  • Hormone Replacement Therapy
  • Emergency Department Visit
  • Estrogen Replacement Therapy
  • Physician Diagnosis