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Atopy includes hay fever (allergic rhinitis), asthma, and eczema (atopic dermatitis/urticaria). It's a type of allergy with certain hallmark featuresEarly onset.High allergen-specific circulating IgE antibody is better associated with allergic asthma while skin prick response (wheal size) with allergic rhinitis.Presumed genetic predisposition.SummaryAsthma prevalence is higher in boys compared to girls but higher in women compared to men.Menstrual cycle stage influences asthma symptoms. In particular, symptoms such as shortness of breath tend to be lowest with peak circulating progesterone levels.Early menarche (first period) and HRT (Hormone Replacement Therapy) are associated with higher asthma.No clear pattern with contraception.A problem with many studies is they don't explicitly assess IgE or skin prick responses nor do they always confirm early-onset. Rather they rely on self-reporting of symptoms so atopy assessment is loose to say the least.Explicit mechanistic link between estrogen, progesterone and lung function is still missing in human studies but epidemiology suggests a plausible link. Link with eczema (atopic dermatitis/urticaria) is as yet even more feeble.Asthma prevalence is higher in boys compared to girls but higher in women compared to menThese are well-substantiated age associations (1, 2, 3, 4, 5, 6, 7, 8, 9; figure below from 9 adapted from data in 10).Epidemiology suggests that menstrual cycle stage influences asthma symptomsEmergency room visits for bouts of acute asthma differ with menstrual cycle stage.Asthma exacerbations were more frequent during the preovulatory menstrual phase (days 5 to 11).While they were lowest with highest progesterone levels (based on an idealized menstrual cycle).Includes two independent prospective studies on 288 women (12) and 792 women (13).These studies have several advantages over previous studiesProspective, i.e., minimized recall bias.More women than in previous studies, also recruited at many more sites, i.e., minimized demographic bias (for e.g., reference 12 included 64 Emergency Departments in 22 US states and 2 Canadian provinces).Consecutive enrollment, i.e., as and when women presented to emergency department with acute asthma.These results were different from earlier questionnaire-based retrospective studies where 30 to 40% women reported symptom worsening immediately or prior to menstruation.Weaknesses of these studiesSelf-reporting of asthma and menstrual histories.Estradiol and progesterone levels weren't measured.So link between menstrual cycle stage and severity of asthma appears robust. However, the association is much more complicated rather than simply linear. Certain, not all, symptoms worsen at certain stages of the menstrual cycle. A questionnaire-based study on 3926 women (14) assessed various asthma symptoms vis-a-vis menstrual cycle stage.They analyzed symptoms of shortness of breath, wheeze and cough among both healthy and asthmatic women.'incidence of wheeze was lowest on days 14 to 16, coinciding with peak estrogen, LH [Luteinizing Hormone] and FSH [Follicle Stimulating Hormone].OTOH, 'shortness of breath incidence was strikingly low in the late luteal phase, the time when progesterone peaks'.Cough did not fit into any neat, predictable pattern.While specialists haven't yet explicitly connected the link, high progesterone levels (the luteal phase of the menstrual cycle) coincide with improved lung function measures such as lung volume and peak flow (15, 16, 17, 18, 19, 20). In other words, a plausible mechanistic link between female sex hormone level and lung function.Early menarche (first period) is associated with higher asthmaEarlier menarche, higher the risk of allergic rhinitis (hay fever) (21), especially in childless women (22).The flips side of the association also holds true as in later the menarche (>13 years of age), lower the risk of new-onset allergic rhinitis (hay fever) (32).As for asthma, a meta-analysis (31) of 7 independent studies (24, 25, 26, 27, 28, 29, 30) observed a clear 37% increased risk of asthma in girls with early menarche.The most detailed assessment among these studies identified poorer lung function, greater likelihood of wheeze, multiple asthma symptoms and higher asthma score in women who had menarche at <10 years of age (30).The first ever twin cohort study also observed association between early menarche and increased asthma risk (32).Since menarche's a surrogate marker for puberty, it implies a role for increased female sex hormone levels in lung immune function dysregulations such as asthma and allergic rhinitis.Postmenopausal HRT (Hormone Replacement Therapy) is associated with higher asthma (33, 34, 35).Risk is highest for women using conjugated estrogen (36) and who are non-smoking (37) or for those who have low BMI (Body Mass Index) (38, 39). 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