Asthma variation with menstruation

doi:10.1016/0007-0971(81)90010-3

British Journal of Diseases of the Chest

Volume 75, Issue 3, July 1981, Pages 306-308

https://doi.org/10.1016/0007-0971(81)90010-3 Get rights and content

Abstract

One hundred and two female asthmatic patients responded to a questionnaire concerning the relationship between their asthma symptoms and the menstrual cycle. Thirty-six subjects stated that their asthma worsened just prior to or at the time of their menses.

Daily monitoring of peak expiratory flow rate (PEFR) showed a significant reduction at the time of menstruation in those who worsened compared with those subjects who were unaffected.

Cycle length was significantly shorter in the group who worsened but the duration of the menses was not significantly different.

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Asthma is a common chronic disease that affects over 300 million people worldwide, resulting in a considerable socio-economic burden.
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Although several mechanisms have been proposed to explain these differences, there are not yet final data available in the literature on the role of gender in the pathogenesis of asthma and different behavior in females.
Some study suggested a more prevalent hyper-responsiveness in women than in men. Nevertheless, in the literature definitive data on a possible different response to drugs used for asthma between males and females are not described.
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Sex steroids effects on guinea pig airway smooth muscle tone and intracellular Ca<sup>2+</sup> basal levels
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To clearly understand androgen protective effects on airway smooth muscle, further research is needed. In contrast, it has been reported that, in women, asthma exacerbations are closely related to life period and this ailment's severity to their hormonal status, i.e., puberty, menstrual cycle, pregnancy or menopause (Bellia and Augugliaro, 2007; Chandler et al., 1997; Hanley, 1981; Juniper et al., 1991). Some studies have demonstrated that asthma is more frequent in boys than in girls, but after puberty it prevails and is more severe in adult women (Bonner, 1984; de Marco et al., 2000; Kjellman and Gustafsson, 2000; Townsend et al., 2012a; Zannolli and Morgese, 1997).
Testosterone (TES), other androgens and female sex steroids induce non-genomic rapid relaxing effects in airway smooth muscle (ASM). In guinea pig ASM, basal tension was relaxed by dehydroepiandrosterone (DHEA) and TES; 17β-estradiol (E2) had a small effect. Blockers of L-type voltage dependent Ca²⁺ channel (L-VDCC, D-600) and store operated Ca²⁺ channel (SOC, 2-APB) also relaxed the basal tone. In tracheal myocytes, DHEA and TES diminished intracellular basal Ca²⁺ concentrations (_b[Ca²⁺]_i) as D-600+2-APB but to a higher extend. TES after D-600+2APB or Pyr3, a blocker of canonical transient receptor potential 3 (TRPC3), further decreased _b[Ca²⁺]_i rendering this response equal to TES alone. With indomethacin, the _b[Ca²⁺]_i decrease induced by the blockade of L-VDCC and TRPC3 was not changed by the addition of TES. PGE₂ or forskolin addition after D600+2-APB, decreased _b[Ca²⁺]_i resembling TES response. An adenylate cyclase inhibitor followed by D-600+2-APB lowered _b[Ca²⁺]_i, TES showed no further effect. Carbachol-induced [Ca²⁺]i increment was reduced by TES or DHEA. 17β-estradiol diminished KCl-induced contraction and, in tracheal myocytes, the voltage-dependent inward Ca²⁺ current. Conclusion: DHEA and TES diminish ASM tone and _b[Ca²⁺]i by blocking L-VDCC and probably a constitutively active TRPC3, and by PGE₂ synthesis. E2 lowers ASM basal tone by blocking only L-VDCC.
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It has been well studied that asthma is linked to gender and it is more frequent in females than in males [7–10]. Furthermore, asthma exacerbations in women are related to life period and its severity to their hormonal status, i.e., puberty, menstrual cycle, pregnancy and menopause [11–15]. Thus, all these evidences point out the role of female sex steroids in airway smooth muscle reactivity.
Therapy with estrogens is frequently used in menopausal women and as hormonal contraception. Because of its thrombotic effects, long term estrogen administration used in hormonal replacement therapy (HRT) and contraception could represent a health hazard. In this regard, 17β-aminoestrogens such as aminoestrol, butolame and pentolame have shown promising HRT potential, because they have a weak agonist estrogenic action and antithrombotic activity. Additionally, estrogens play a protective role in airway smooth muscle, but the effect of 17β-aminoestrogens on the airway smooth muscle has not been tested yet. In guinea pig tracheal smooth muscle pentolame and butolame induced hyperresponsiveness to histamine (His), carbachol (Cch) and KCl. Interestingly, aminoestrol did not show this effect at the highest concentration studied, it even lowered the contraction induced by Cch. The hyperresponsiveness induced by pentolame to His was abolished by nifedipine. In single tracheal myocytes, KCl induced an increment in the intracellular Ca²⁺ concentration [Ca²⁺]_i, pentolame also showed an increase in [Ca²⁺]_i and the addition of KCl in the plateau of this rise further significantly augmented the [Ca²⁺]_i response. Additionally, in patch clamp experiments pentolame increased the L-type Ca²⁺ currents. Thus, 17β-aminoestrogens such as pentolame and butolame, but not aminoestrol, activate L-type Ca²⁺ channel to induced hyperresponsiveness to Cch, His and KCl in guinea pig tracheal smooth muscle. Due to its lack of effect on airways and to its anticoagulant characteristics, aminoestrol seems to be the best alternative in the HRT among the 17β-aminoestrogens studied.
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2013, Pulmonary Pharmacology and Therapeutics
A growing body of clinical and experimental evidence indicates that female sex hormones, particularly estrogen, have significant effects on normal airway function as well as on respiratory disorders, such as asthma. These effects are very complex and are exerted at several levels, directly on airway reactivity or indirectly through regulation of the immune and inflammatory responses in the lung. They can have relevant clinical implications not only according to the phases of the reproductive life in women, but also in relation to the therapeutical administration of estrogen, as in the case of menopausal hormone therapy. Clinical evidence suggests that administration of estrogen to menopausal women is associated with increased rates of newly diagnosed asthma. Conversely, functional studies show that estrogen can improve objective indexes of respiratory functionality.
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Important differences between men and women with asthma have been demonstrated, with women describing more symptoms and worse asthma-related quality of life (QOL) despite having similar or better pulmonary function. While current guidelines focus heavily on assessing asthma control, they lack information about whether sex-specific approaches to asthma assessment should be considered. We sought to determine if sex differences in asthma control or symptom profiles exist in the well-characterized population of participants in the American Lung Association Asthma Clinical Research Centers (ALA-ACRC) trials.
We reviewed baseline data from four trials published by the ALA-ACRC to evaluate individual item responses to three standardized asthma questionnaires: the Juniper Asthma Control Questionnaire (ACQ), the multi-attribute Asthma Symptom Utility Index (ASUI), and Juniper Mini Asthma Quality of Life Questionnaire (mini-AQLQ).
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Although perimenstrual asthma (PMA) has been associated with severe and difficult-to-control asthma, it remains poorly characterized and understood. The objectives of this study were to identify clinical, demographic, and inflammatory factors associated with PMA and to assess the association of PMA with asthma severity and control.
Women with asthma recruited to the National Heart, Lung, and Blood Institute Severe Asthma Research Program who reported PMA symptoms on a screening questionnaire were analyzed in relation to basic demographics, clinical questionnaire data, immunoinflammatory markers, and physiologic parameters. Univariate comparisons between PMA and non-PMA groups were performed. A severity-adjusted model predicting PMA was created. Additional models addressed the role of PMA in asthma control.
Self-identified PMA was reported in 17% of the subjects (n = 92) and associated with higher BMI, lower FVC % predicted, and higher gastroesophageal reflux disease rates. Fifty-two percent of the PMA group met criteria for severe asthma compared with 30% of the non-PMA group. In multivariable analyses controlling for severity, aspirin sensitivity and lower FVC % predicted were associated with the presence of PMA. Furthermore, after controlling for severity and confounders, PMA remained associated with more asthma symptoms and urgent health-care utilization.
PMA is common in women with severe asthma and associated with poorly controlled disease. Aspirin sensitivity and lower FVC % predicted are associated with PMA after adjusting for multiple factors, suggesting that alterations in prostaglandins may contribute to this phenotype.

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Short communicationAsthma variation with menstruation

Abstract

Lancet

J. psychosom. Res.

Short communication
Asthma variation with menstruation