treat premenstrual asthma with ICS and LABA

This patient has premenstrual asthma (PMA). While there are no evidence-based treatment algorithms for PMA, usual strategies for the management of asthma should be initiated first, so adding a long-acting β2-agonist to this patient with poorly controlled asthma who is maintained on an inhaled corticosteroid and a leukotriene receptor antagonist would be consistent with established asthma guidelines (choice A is correct). Some have advocated perimenstrual adjustment of medications in patients with PMA, including one randomized double-blind cross-over study that showed that long-acting β2-agonists given during the second half of the menstrual cycle prevented premenstrual exacerbations in most patients.

PMA refers to worsening of asthma symptoms prior to or during the first days of menstruation. About 20% of women report worsening of asthma control in the premenstrual phase, though this number is likely an underestimate because menstrual histories are not consistently taken. Asthma flares vary from mild to severe, with reports of PMA related to increases in asthma-related ED visits, hospitalizations, ICU admissions, intubations, and near-fatal and fatal events. Patients commonly report dysmenorrhea as well as premenstrual bloating and swelling. Characteristics of patients with PMA demonstrate heterogeneity; however, in general, patients are older, have a higher BMI, and more frequently have aspirin-exacerbated respiratory disease (choice B is incorrect).

The mechanism of PMA is poorly understood. Fluctuations in female sex hormones during the menstrual cycle would seem to play a central role, though at present there is insufficient evidence for causality. Just prior to the onset of menses, in the late luteal phase, both progesterone and estrogen rapidly decline. Progesterone has been shown to attenuate the contraction of isolated airway smooth muscle, potentiate the relaxation induced by β2-agonists, and reduce microvascular leakage, while stimulation of estrogen receptors in asthmatic airway smooth muscle downregulates airway hyperresponsiveness. These findings would suggest that a sudden drop in these hormones may contribute to airway hyperresponsiveness, which has been noted during the late luteal phase; however, to date, the association of sex hormone levels and PMA remains obscure.

Studies looking at the effect of exogenous hormones on PMA are inconsistent and are mostly observational, with small sample sizes. Hormonal therapy involving different combinations of estrogen and progesterone has yielded conflicting results. While a reduction in the number of exacerbations is reported by many, some note a worsening of symptoms as well as increased asthma incidence. Case reports suggest gonadotropin-releasing hormone analogues may also be considered in these patients. A trial of endogenous hormones may be reasonable, if evidenced-based treatment proves ineffective, though large randomized controlled trials are needed to determine the role for hormone therapy for PMA (choice C is incorrect).

Salpingo-oophorectomy may be considered for patients with life-threatening asthma exacerbations associated with menstruation who do not respond to medical therapy, though that is not the case with this patient (choice D is incorrect).

Interestingly, this patient is on a leukotriene receptor antagonist. Elevated levels of leukotriene C4 have been reported in PMA patients, with one small series showing a protective effect of a leukotriene receptor antagonist. Others, however, have found no clear differences in leukotriene C4 levels in women with and without PMA.