Estradiol in severe asthma with premenstrual worsening.

OBJECTIVE: To describe the beneficial effects of estradiol in a severely asthmatic woman with premenstrual worsening of asthma. CASE SUMMARY: A 50-year-old white woman, with a 14-year history of severe steroid-dependent asthma and monthly premenstrual worsening of asthma, was randomized to receive estradiol 2 mg or placebo for 6 days during the late luteal phase (days 23-28) of 2 successive menstrual cycles. Despite greater prednisone and inhaled beta-agonist use during the late luteal phase of the placebo cycle, the patient exhibited improved asthma symptoms, pulmonary function, and peak expiratory flows, as well as lower values for biomarkers of airway inflammation during the same time period of the estradiol cycle. DISCUSSION: This subject's response to estradiol was in contrast to results of a randomized, controlled trial involving patients with predominantly mild asthma under excellent control. The discrepant observations for this case versus the majority of subjects in the randomized, controlled study suggest that premenstrual asthma (PMA) and a beneficial response to estradiol may be more likely in women with severe asthma. CONCLUSIONS: The administration of estradiol during the late luteal phase of the menstrual cycle to a woman with severe asthma with PMA was associated with improved asthma symptoms, pulmonary function, and peak expiratory flows, and lower serum eosinophil protein X and urinary leukotriene E(4) biomarker concentrations. Thus, estradiol's potential role in women with severe asthma and PMA may warrant further exploration in this subgroup.

Estradiol in premenstrual asthma: a double-blind, randomized, placebo-controlled, crossover study.

STUDY OBJECTIVES: To characterize asthma symptoms and pulmonary function throughout two menstrual cycles, with and without exogenous estradiol administration, in women with premenstrual asthma, and to determine the effect of estradiol administration on asthma symptoms, pulmonary function, quality of life, and biomarkers of airway inflammation. DESIGN: Double-blind, randomized, placebo-controlled, crossover study. SETTING: Respiratory clinic and clinical research center. SUBJECTS: Twelve women with documented premenstrual asthma (> or = 20% premenstrual worsening of asthma symptoms and/or of peak expiratory flow [PEF] during a 1-month screening phase). INTERVENTION: Each woman received either estradiol 2 mg or placebo orally between cycle days 23 and 28 (i.e., premenstrually, or before the onset of menses) in the first cycle and then crossed over to the other arm in the second cycle. Throughout both cycles, the women recorded daily morning and evening PEF readings and asthma symptoms. MEASUREMENTS AND MAIN RESULTS: Spirometry testing and measurement of serum estradiol and biomarkers of airway inflammation were performed on days 8 (follicular phase), 22 (luteal phase), and 28 (premenstrually) of both the estradiol and placebo cycles. During the two premenstrual visits, the Asthma Quality of Life Questionnaire was administered. No notable differences were observed between the estradiol and placebo cycles in daily PEF recordings or composite asthma symptoms scores. The area under the curve (AUC) for the composite asthma symptoms versus time profile was numerically, but not statistically, lower (denoting less severe symptoms) during the estradiol cycle than during the placebo cycle. Likewise, no significant difference in AUC values for morning PEF or evening PEF was found between the estradiol cycle and the placebo cycle. Despite differences (p<0.05) in day-28 estradiol concentrations for estradiol and placebo cycles, no significant differences were found in forced expiratory volume in 1 second, serum endothelin-1, serum and urine eosinophil protein X, urine leukotriene E4, or quality-of-life scores. CONCLUSION: Exogenously administered estradiol did not have a significant effect in women with premenstrual asthma whose asthma was classified predominantly as mild and under excellent control. As in the case of premenstrual syndrome, the placebo effect may be prominent in premenstrual asthma. Further trials, involving women with more severe asthma under poorer control, are warranted to discern underlying mechanisms for the worsening of asthma in relation to menstruation.