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Beta2-adrenoceptor regulation and function in female asthmatic patients receiving the oral combined contraceptive
K S Tan1, L C McFarlane, B J Lipworth
1Department of Clinical Pharmacology, University of Dundee, Ninewells Hospital and Medical School, Scotland, United Kingdom.
Study Objectives:
Previously it has been shown that there is abnormal hormonal control of beta2-adrenoceptors in asthmatic women. Exogenous progesterone but not estradiol produces paradoxic downregulation and desensitization of beta2-adrenoceptors in asthmatic women when compared with nonasthmatic subjects. This study investigates the effect of the oral combined contraceptive pill (OCP) on beta2-adrenoceptor regulation and function in female asthmatic patients.
Patients:
The study population was comprised of 11 women with stable mild to moderate asthma. The mean age was 25 years; the FEV1 was 89% of predicted, and the forced expiratory flow, mid-expiratory phase (FEF25-75%) was 69% of predicted.
Design:
Patients were evaluated while on (day 20 to 21) and off (day 5 to 7) the OCP during a 28-day calendar period.
Measurements:
Serum sex hormones, lymphocyte beta2-adrenoceptor parameters, and bronchodilator and systemic dose-response curves (DRCs) to albuterol (Salbutamol) (100 to 1,600 microg) were measured at both on and off periods.
Results:
Serum levels of endogenous estradiol and progesterone were both suppressed by the OCP. Baseline FEV1 were not different while patients were on (2.70 L) and off (2.72 L) the OCP. There were no significant differences in lymphocyte beta2-adrenoceptor parameters between the two phases of the cycle. Receptor density (geometric mean Bmax) was 1.78 (on OCP) vs 1.86 (off OCP) fentomole/10(6) cells, maximal cyclic adenosine monophosphate response to isoprenaline was 6.60 (on OCP) vs 7.58 (off OCP) pmol/10(6) cells, and binding affinity was 14.0 (on OCP) and 13.6 (off OCP) pmol/L. Likewise, there were no significant differences in the bronchodilator and systemic DRCs constructed at both phases of the cycle as evaluated: area-under-curve (AUC) FEV1 was 0.53 (on OCP) vs 0.56 (off OCP) L.h; and AUC FEF25-75% was 3,130 (on OCP) vs 3,640 (off OCP) L. Potassium (K) and finger tremor responses were unaltered between the two periods: AUC K was 0.50 (on OCP) vs 0.44 (off OCP) mmol . h/L and AUC tremor was 0.72 (on OCP) vs 0.89 (off OCP) log units.h.
Conclusion:
The OCP did not alter beta2-adrenoceptor regulation and function in stable female asthmatic patients. Further studies are required in patients who have premenstrual asthma.