PREMENSTRUAL ASTHMA - THE EFFECT OF ESTROGEN ON SYMPTOMS, PULMONARY-FUNCTION, AND BETA(2)-RECEPTORS

Study Objectives. To characterize asthma symptoms, pulmonary function, and responsiveness to beta(2)-agonist stimulation, and in vitro beta( 2)-receptor density and cyclic adenosine 3',5'-monophosphate (cAMP) re sponse throughout the menstrual cycle in women with premenstrual asthm a (PMA); and to examine the effect of exogenous estradiol administrati on on asthma symptoms, pulmonary function and responsiveness, and beta (2)-receptor density and function in these women. Design. Open-label, longitudinal, 9-week study. Setting. A university clinical research ce nter. Patients. Seventeen women with mild to moderate asthma, of whom 14 completed the study. Interventions. Every morning on awakening duri ng the entire 9-week study each subject completed visual analog scales for asthma symptomatology (cough, wheezing, breathlessness, chest tig htness) and measured and recorded her peak expiratory flow rate (PEER) with a peak flow meter. Also measured at various times throughout the menstrual cycle were dyspnea index scores, pulmonary function (PEFR, forced expiratory volume in 1 sec [FEV(1)]), pulmonary response to sub cutaneous terbutaline, T lymphocyte beta(2)-receptor density (B-max) a nd function (cAMP), and estradiol, progesterone, and catecholamine con centrations, both with and without exogenous estradiol administration. Measurements and Main Results. At the time of enrollment, only 5 subj ects reported premenstrual worsening of asthma symptoms, but all 14 ha d greater than 20% decrease in PEER and/or increase in symptoms premen strually during the study. Significant differences (p<0.05) existed in asthma symptoms and PEER between day 13 (highest estradiol concentrat ions) and day 26 (lowest estradiol concentrations) of the menstrual cy cle. Asthma symptoms and dyspnea index scores were significantly impro ved (p<0.05) after estradiol administration compared with baseline (pr emenstrual period without exogenous estrogen). Pulmonary response to t erbutaline, beta(2)-receptor density and function, and catecholamine c oncentrations were not significantly altered after estradiol administr ation, but the trend was toward significant differences (0.05<p<0.2) i n pulmonary function tests (PEER, FEV(1)). Conclusions. Even asthmatic s not previously aware of PMA may experience premenstrual worsening of asthma symptoms and/or PEER. Estradiol is associated with a significa nt improvement in asthma symptoms and dyspnea index scores. This ameli orating effect does not appear to be related to beta(2)-receptors.