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. 1997 Jul;52(7):608–611. doi: 10.1136/thx.52.7.608

Loss of normal cyclical beta 2 adrenoceptor regulation and increased premenstrual responsiveness to adenosine monophosphate in stable female asthmatic patients

K S Tan, L C McFarlane, B J Lipworth
PMCID: PMC1758601  PMID: 9246131

Abstract

BACKGROUND: A study was undertaken to investigate the influence of the menstrual cycle on airway responsiveness and beta 2 adrenoceptor function in female asthmatic patients. It has previously been shown that normal women exhibit cyclical changes in beta 2 adrenoceptor function with an increase in beta 2 adrenoceptor density in the luteal phase during the premenstrual period. METHODS: Fifteen women with stable, well controlled asthma (mean forced expiratory volume in one second (FEV1) 2.971 (93.8% predicted)) were evaluated. Measurements were made at the follicular phase (days 1-6) and the luteal phase (days 21-24) of the menstrual cycle. Airway responsiveness was assessed using adenosine 5'-monophosphate (AMP) and expressed as PC20 AMP. Beta 2 adrenoceptor function was evaluated by measuring lymphocyte beta 2 adrenoceptor parameters and constructing dose-response curves to salbutamol (100-1600 micrograms). The levels of female sex hormones were also measured at both phases of the cycle. RESULTS: There were significant increases in serum levels of both oestradiol (2.2-fold, p < 0.001) and progesterone (7.2-fold, p < 0.05) between the follicular and luteal phases. Geometric mean PC20 AMP was 19.0 mg/ml and 7.6 mg/ml during the follicular and luteal phases, respectively (p < 0.05), a 2.51-fold difference (95% CI 1.19 to 5.30) amounting to 1.33 doubling doses of AMP. There was no change in lymphocyte beta 2 adrenoceptor parameters or in airway beta 2 adrenoceptor responses to salbutamol between the two phases. CONCLUSIONS: Despite an appropriate rise in female sex hormones during the luteal period, beta 2 adrenoceptor regulation in female asthmatic subjects shows a loss of the normal cyclical pattern. In addition, there were cyclical changes in airway responsiveness to AMP which was highest during the premenstrual period. Thus, drugs such as theophylline which block adenosine receptors warrant investigation in premenstrual asthma. 




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Selected References

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  1. Beynon H. L., Garbett N. D., Barnes P. J. Severe premenstrual exacerbations of asthma: effect of intramuscular progesterone. Lancet. 1988 Aug 13;2(8607):370–372. doi: 10.1016/s0140-6736(88)92837-1. [DOI] [PubMed] [Google Scholar]
  2. Cushley M. J., Holgate S. T. Adenosine-induced bronchoconstriction in asthma: role of mast cell-mediator release. J Allergy Clin Immunol. 1985 Feb;75(2):272–278. doi: 10.1016/0091-6749(85)90057-0. [DOI] [PubMed] [Google Scholar]
  3. Foster P. S., Goldie R. G., Paterson J. W. Effect of steroids on beta-adrenoceptor-mediated relaxation of pig bronchus. Br J Pharmacol. 1983 Feb;78(2):441–445. doi: 10.1111/j.1476-5381.1983.tb09409.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gibbs C. J., Coutts I. I., Lock R., Finnegan O. C., White R. J. Premenstrual exacerbation of asthma. Thorax. 1984 Nov;39(11):833–836. doi: 10.1136/thx.39.11.833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Grove A., Lipworth B. J. Bronchodilator subsensitivity to salbutamol after twice daily salmeterol in asthmatic patients. Lancet. 1995 Jul 22;346(8969):201–206. doi: 10.1016/s0140-6736(95)91265-7. [DOI] [PubMed] [Google Scholar]
  6. Hanley S. P. Asthma variation with menstruation. Br J Dis Chest. 1981 Jul;75(3):306–308. doi: 10.1016/0007-0971(81)90010-3. [DOI] [PubMed] [Google Scholar]
  7. Juniper E. F., Frith P. A., Dunnett C., Cockcroft D. W., Hargreave F. E. Reproducibility and comparison of responses to inhaled histamine and methacholine. Thorax. 1978 Dec;33(6):705–710. doi: 10.1136/thx.33.6.705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kalogeromitros D., Katsarou A., Armenaka M., Rigopoulos D., Zapanti M., Stratigos I. Influence of the menstrual cycle on skin-prick test reactions to histamine, morphine and allergen. Clin Exp Allergy. 1995 May;25(5):461–466. doi: 10.1111/j.1365-2222.1995.tb01078.x. [DOI] [PubMed] [Google Scholar]
  9. Richards R., Simpson S. F., Renwick A. G., Holgate S. T. Inhalation rate of sodium cromoglycate determines plasma pharmacokinetics and protection against AMP-induced bronchoconstriction in asthma. Eur Respir J. 1988 Dec;1(10):896–901. [PubMed] [Google Scholar]
  10. Tan K. S., McFarlane L. C., Coutie W. J., Lipworth B. J. Effects of exogenous female sex-steroid hormones on lymphocyte beta 2-adrenoceptors in normal females. Br J Clin Pharmacol. 1996 May;41(5):414–416. doi: 10.1046/j.1365-2125.1996.331/1.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Troisi R. J., Speizer F. E., Willett W. C., Trichopoulos D., Rosner B. Menopause, postmenopausal estrogen preparations, and the risk of adult-onset asthma. A prospective cohort study. Am J Respir Crit Care Med. 1995 Oct;152(4 Pt 1):1183–1188. doi: 10.1164/ajrccm.152.4.7551368. [DOI] [PubMed] [Google Scholar]
  12. Weinmann G. G., Zacur H., Fish J. E. Absence of changes in airway responsiveness during the menstrual cycle. J Allergy Clin Immunol. 1987 Apr;79(4):634–638. doi: 10.1016/s0091-6749(87)80160-4. [DOI] [PubMed] [Google Scholar]
  13. Wheeldon N. M., Newnham D. M., Coutie W. J., Peters J. A., McDevitt D. G., Lipworth B. J. Influence of sex-steroid hormones on the regulation of lymphocyte beta 2-adrenoceptors during the menstrual cycle. Br J Clin Pharmacol. 1994 Jun;37(6):583–588. doi: 10.1111/j.1365-2125.1994.tb04308.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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