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Estrogen’s Role in Asthma

Also see:
Phospholipases, PUFA, and Inflammation
Unsaturated Fats and Lung Function
Women, Estrogen, and Circulating DHA

Am J Respir Crit Care Med. 1995 Oct;152(4 Pt 1):1183-8.
Menopause, postmenopausal estrogen preparations, and the risk of adult-onset asthma. A prospective cohort study.
Troisi RJ, Speizer FE, Willett WC, Trichopoulos D, Rosner B.
We prospectively evaluated the association of hormone replacement therapy and asthma incidence in a cohort of pre- and postmenopausal women 34 to 68 yr of age. During 582, 135 person-years of follow-up between 1980 and 1990, 726 new cases of asthma were documented. Postmenopausal women who were never users of replacement hormones had a significantly lower age-adjusted risk of asthma than premenopausal women (relative risk = 0.65; 95% confidence interval [CI] = 0.46 to 0.92). Among naturally menopausal women, the age-adjusted relative risk of asthma for ever use of postmenopausal hormones was 1.49 (95% CI = 1.10 to 2.00); for current use of hormones (conjugated estrogens with or without progesterone), 1.50 (95% CI = 0.98 to 2.30); and for past use, 1.52 (95% CI = 1.08 to 2.13), compared with never use of hormones. Ever users of 10 or more years’ duration had twice the age-adjusted risk of asthma compared with women who never used postmenopausal hormones (95% CI = 1.39 to 2.87). Among current users of conjugated estrogens, there was a positive dose-response demonstrated between daily dose and asthma risk (p for trend = 0.007). While confirmatory studies are warranted, these data suggest that estrogen plays a role in the pathophysiology of asthma and that long-term use and/or high doses of postmenopausal hormone therapy increase subsequent risk of asthma.

Am Rev Respir Dis. 1989 Aug;140(2):358-62.
Influence of the menstrual cycle on airway function in asthmatic and normal subjects.
Pauli BD, Reid RL, Munt PW, Wigle RD, Forkert L.
Investigations of premenstrual asthma (PMA) have been based on studies of asthmatics already aware of a deterioration of asthma premenstrually. Little is known, therefore, about relationships between the menstrual cycle and airway function in asthmatics who do not complain of PMA or in normal subjects. We investigated airway function in both of these groups for three or four consecutive menstrual cycles. Daily records of asthma symptoms and peak expiratory flow rates were maintained by 11 asthmatics and 29 normal control subjects. Standard spirometry and serum estradiol and progesterone levels were measured during the follicular, midluteal, and late luteal phases of the menstrual cycle. Airway reactivity to methacholine was tested during the follicular and luteal phases. The normal group showed no significant changes in symptoms, peak flow rates, spirometric parameters, or airway reactivity. Although the asthmatic group also demonstrated no significant changes in spirometry and airway reactivity, asthma symptoms (shortness-of-breath, cough, wheeze, and chest tightness) deteriorated significantly (p less than 0.001) from the follicular to the luteal phase, as did the morning peak flows of the asthmatics (p = 0.045). Airway function and reactivity were not related to hormone levels in either group. This study indicates that asthmatics not previously aware of PMA will record a premenstrual worsening of asthma symptoms and peak expiratory flow rates. These changes are not related to a deterioration in spirometry and airway reactivity or to the absolute levels of circulating progesterone and estradiol.

Lancet. 1988 Aug 13;2(8607):370-2.
Severe premenstrual exacerbations of asthma: effect of intramuscular progesterone.
Beynon HL, Garbett ND, Barnes PJ.
Three patients with severe premenstrual exacerbations of asthma are reported. None had responded to conventional treatment, including high-dose corticosteroids. In all cases there was a striking fall premenstrually in peak flow rate. The addition of intramuscular progesterone (100 mg daily in two cases and 600 mg twice a week in one) to the regimen eliminated the premenstrual dips in peak flow, and daily doses of prednisolone were reduced in the three patients.

Maturitas. 1995 Feb;21(2):153-7.
Sub-clinical worsening of bronchial asthma during estrogen replacement therapy in asthmatic post-menopausal women.
Lieberman D, Kopernik G, Porath A, Lazer S, Heimer D.
BACKGROUND:
Changes in asthma activity, in part related to the female hormonal profile, have been observed during pre-menstrual periods and during pregnancy. Estrogen replacement therapy (ERT) is an accepted routine treatment for post-menopausal women. The effect of ERT on disease activity in post-menopausal asthmatic women has not been investigated in the past and is the subject of the present study.
METHODS:
Fifteen post-menopausal women with mild to moderate asthma completed two 30-day periods in which they measured peak expiratory flow (PEF) at home and filled in a daily diary of asthma-related symptoms. The first monitoring period was pre-ERT and the second was during ERT. In addition spirometry was performed on each woman three times, twice pre-ERT and once during ERT.
RESULTS:
The average daily PEF decreased from 241 (57.9, S.D.) l/min pre-ERT to 226.7 (62.7) l/min during ERT (P < 0.004). Significant differences between the two study periods were also found in morning and evening PEF values. Diurnal variation, measured as the difference between morning and evening PEF values, decreased significantly from 22.3 (26.7) l/min pre-ERT to 17.5 (26.8) l/min during ERT (P < 0.007). The average daily consumption of bronchodilator inhalers increased significantly from 3.7 puffs/day pre-ERT to 4.3 puffs/day during ERT (P < 0.006). Although the differences in spirometry between the two periods did not reach statistical significance, a trend towards a worsening of the obstructive disorder during ERT was observed. However, the general feeling of well-being of the asthmatics did not change during the two periods.
CONCLUSIONS:
During ERT a sub-clinical worsening of disease activity was found in postmenopausal women with mild to moderate asthma. We also detected a decrease in diurnal variation. Our findings should be substantiated by additional studies.

Chest. 1993 Oct;104(4):1300-2.
Bronchospasm secondary to replacement estrogen therapy.
Collins LC, Peiris A.
A postmenopausal woman with severe obstructive airways disease and bronchospasm developed increased airflow limitation with the reintroduction of estrogen therapy for osteoporosis. Discontinuation of the estrogen caused symptomatic improvement and decreased her corticosteroid requirement. Readministration of estrogen caused recrudescence of her symptoms and a decline in her peak expiratory flow rate and spirometric data, which reversed with withdrawal of the estrogen therapy. Bronchospasm during the luteal phase of the menstrual cycle is well known, but exacerbation of reactive airways disease with the administration of exogenous estrogen has not previously been reported; however, with the increasing practice of reintroducing estrogen in postmenopausal women to reduce the risk of symptomatic osteoporosis, other susceptible women may suffer clinically significant deterioration of their underlying pulmonary disease.

Pediatr Allergy Immunol. 1997 Nov;8(4):200-4.
Is asthma an endocrine disease?
Wjst M, Dold S.
The prevalence of pediatric asthma has increased in many parts of the world. This increase started more than 30 years ago and is particularly obvious in studies which document the onset of asthma in native populations when they change to a “Western” lifestyle. Besides a genetic influence, numerous environmental factors have been described for the development of asthma. Genetic factors are unlikely to explain the sharp increase within the short time period and also allergen and pollution exposure or any specific infection does not actually seem to be the main cause for this phenomenon. Another factor, however, that fits well into the geographical and temporal background of the asthma epidemic is the mother’s oral contraceptive use. We therefore review the epidemiological association with later asthma in the children, give a summary of estrogen effects on immune function and develop a preliminary theory how oral contraception could influence later pregnancy.

J Microbiol Immunol Infect. 1998 Sep;31(3):197-9.
Premenstrual asthma: report of a case with hormonal studies.
Lam SM, Huang SC.
We report a 39-year-old female non-smoker who has history of asthma since the age of 29 and history of allergic rhinitis at age 13. No symptomatic characteristics of premenstrual tension were reported. Forced expiratory peak flow rate (PEFR) readings showed striking falls 24 hours before menses, with the peak flows dropping from a baseline of 350 L/min to 200 L/min. The patient received 10 mg prednisolone daily which was increased to 40 mg prednisolone in the menstrual week in an attempt to maintain a normal peak flow. Daily peak flow readings and every other day hormonal studies of progesterone and estrogen both demonstrated a positive correlation between the serum progesterone and the peak flow readings. The addition of intramuscular progesterone (75 mg daily) to the bronchodilators eliminated the premenstrual dips in peak flow, and daily doses of prednisolone were reduced to 5-10 mg. We suggest that a rapid fall in serum progesterone may play an important role in the pathogenesis of premenstrual asthma.

Ann Allergy Asthma Immunol. 1998 Sep;81(3):243-6.
Exacerbation of premenstrual asthma caused by an oral contraceptive.
Derimanov GS, Oppenheimer J.
BACKGROUND:
The relationship between sex hormones and asthma has not been clarified. Studies have suggested a potential beneficial effect of exogenous sex hormones and/or contraceptive pills on asthma in premenopausal females whereas the data for postmenopausal females are inconsistent.
CASE REPORT:
A 33-year-old woman suffering from asthma with premenstrual exacerbations had a stable course until she began taking oral contraceptives. At that time she experienced clinical deterioration of her asthma associated with decline of pulmonary function tests. No other precipitating factors were identified. After discontinuing the contraceptives, her condition returned to baseline.
CONCLUSION:
We found only two reports of worsening of asthma related to hormonal therapy (estrogen in one case, contraceptive pills in the other) in premenopausal women. Our report, together with these observations, suggests that in some premenopausal women exogenous sex hormones and/or contraceptive pills may, contrary to expected, produce exacerbation of asthma.
PIP:
Although the mechanism of premenstrual asthma has not been established, hormonal variations during the menstrual cycle are believed to play an important role. About 30-40% of female asthmatics report worsening of asthma symptoms during the premenstrual and/or menstrual period. This article presents a case in which oral contraceptives (OCs) appeared to precipitate an asthma attack. The patient, a 33-year-old White US woman, first developed asthma at age 27 years. The strongest trigger to her asthma attacks was her menstrual period. All periods were associated with a worsening of asthma, typically extending from 1 week before to 2-3 days after the onset of menstrual bleeding. Subsequently, the patient’s asthma was stabilized by continuous inhaled steroids. However, clinical deterioration of asthma and a decline of pulmonary function occurred immediately after the woman initiated OC use. There was a rapid stabilization in clinical status once OC use was discontinued. Although the weight of scientific evidence points to a possible beneficial effect of OCs or exogenous sex hormones on premenstrual asthma, this case suggests there may be a subset of women in whom sex hormones exacerbate asthma.

Compr Ther. 2001 Spring;27(1):65-71.
Menstrual cycle effects on common medical conditions.
Case AM, Reid RL.
Menstrual cycle-related exacerbation of common medical conditions such as migraine, epilepsy, asthma, irritable bowel syndrome, and diabetes, is a well-recognized phenomenon. Accurate documentation of symptoms on a menstrual calendar allows identification of women with cyclic alterations in disease activity.

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