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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) response throughout the menstrual cycle in women with premenstrual asthma (PMA); and to examine the effect of exogenous estradiol administration 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 center. PATIENTS: Seventeen women with mild to moderate asthma, of whom 14 completed the study. INTERVENTIONS: Every morning on awakening during the entire 9-week study, each subject completed visual analog scales for asthma symptomatology (cough, wheezing, breathlessness, chest tightness) and measured and recorded her peak expiratory flow rate (PEFR) 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 [FEV1]), pulmonary response to subcutaneous terbutaline, T lymphocyte beta 2-receptor density (Bmax) and function (cAMP), and estradiol, progesterone, and catecholamine concentrations, both with and without exogenous estradiol administration. MEASUREMENTS AND MAIN RESULTS: At the time of enrollment, only 5 subjects reported premenstrual worsening of asthma symptoms, but all 14 had greater than 20% decrease in PEFR and/or increase in symptoms premenstrually during the study. Significant differences (p < 0.05) existed in asthma symptoms and PEFR between day 13 (highest estradiol concentrations) and day 26 (lowest estradiol concentrations) of the menstrual cycle. Asthma symptoms and dyspnea index scores were significantly improved (p < 0.05) after estradiol administration compared with baseline (premenstrual period without exogenous estrogen). Pulmonary response to terbutaline, beta 2-receptor density and function, and catecholamine concentrations were not significantly altered after estradiol administration, but the trend was toward significant differences (0.05 < p < 0.2) in pulmonary function tests (PEFR, FEV1). CONCLUSIONS: Even asthmatics not previously aware of PMA may experience premenstrual worsening of asthma symptoms and/or PEFR. Estradiol is associated with a significant improvement in asthma symptoms and dyspnea index scores. This ameliorating effect does not appear to be related to beta 2-receptors.