LOSS OF NORMAL CYCLICAL BETA(2) ADRENOCEPTOR REGULATION AND INCREASEDPREMENSTRUAL RESPONSIVENESS TO ADENOSINE-MONOPHOSPHATE IN STABLE FEMALE ASTHMATIC-PATIENTS

Background - A study was undertaken to investigate the influence of th e menstrual cycle on airway responsiveness and beta(2) adrenoceptor fu nction in female asthmatic patients. It has previously been shown that normal women exhibit cyclical changes in beta(2) adrenoceptor functio n 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 (F EV1) 2.971 (93.8% predicted)) were evaluated. Measurements were made a t the follicular phase (days 1-6) and the luteal phase (days 21-24) of the menstrual cycle. Airway responsiveness was assessed using adenosi ne 5'-monophosphate (AMP) and expressed as PC20 AMP. Beta(2) adrenocep tor function was evaluated by measuring lymphocyte beta(2) adrenocepto r parameters and constructing dose-response curves to salbutamol (100- 1600 mu g). The levels of female sex hormones were also measured at bo th 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. Geometri c 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 c hange in lymphocyte beta(2) adrenoceptor parameters or in airway beta( 2) adrenoceptor responses to salbutamol between the two phases. Conclu sions - Despite an appropriate rise in female sex hormones during the luteal period, beta(2) adrenoceptor regulation in female asthmatic sub jects shows a loss of the normal cyclical pattern. In addition, there were cyclical changes in airway responsiveness to AMP which was highes t during the premenstrual period. Thus, drugs such as theophylline whi ch block adenosine receptors warrant investigation in premenstrual ast hma.