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A 35 year old non-smoking woman was referred to hospital for advice regarding poorly controlled atopic asthma. Despite good compliance with fluticasone 2 mg/day, a long acting β2 agonist, anticholinergic agent, nebulised bronchodilators plus theophylline, she experienced persistent symptoms necessitating frequent courses of oral corticosteroids. It became apparent that her asthma control deteriorated before menstruation—a pattern which was not influenced by premenstrual or continuous oral corticosteroids. Trials with various combined oral contraceptive pills failed to improve asthma control. Some improvement was observed with 6 months of treatment with a gonadorelin analogue (goserelin); although premenstrual symptoms did persist, exacerbations were less marked resulting in a significant reduction in oral corticosteroid use. Gonadorelin analogues produce an initial phase of stimulation followed by downregulation of gonadotrophin releasing hormone receptors, thereby reducing the release of gonadotrophins and subsequent inhibition of oestrogen production. On discontinuation of goserelin (contraindicated for use longer than 6 months) symptomatic asthma recurred, requiring repeated monthly courses of oral corticosteroids. Following discussion with the patient and her gynaecologist, it was decided that, given the cyclical severity of symptoms, the need for frequent oral corticosteroids, and partial success with a gonadorelin analogue, definitive surgical treatment should be considered.
Four years after initial referral a bilateral oophorectomy and subtotal hysterectomy was performed without complication and an oestrogen alone hormone replacement was implanted. In the year following surgery the patient had a single exacerbation of asthma that coincided with the end of the effectiveness of her oestrogen implant (with consequent rise in gonadotrophin levels due to lack of suppression by oestrogen). She was subsequently commenced on regular oestrogen only hormone replacement therapy to good effect. One year after surgery the patient has discontinued alternate day oral prednisolone, is asymptomatic, and maintained on 250 μg/day fluticasone combined with salmeterol.
This unusual case highlights the importance of enquiring about the possible temporal relationship between worsening asthma control and the menstrual cycle. Premenstrual exacerbations of asthma are well recognised and do not always respond to more aggressive anti-inflammatory treatment. Some success has been observed with the institution of oral oestrogen and intramuscular progesterone administration.1,2 We believe this to be one of the first documented cases of difficult asthma where marked improvement in asthma control has been achieved after a beneficial therapeutic trial of a gonadorelin analogue, followed by bilateral oophorectomy and subtotal hysterectomy plus oestrogen replacement. An initial improvement in asthma control was observed when gonadotrophin levels were low (as a result of the gonadorelin analogue) and a deterioration occurred when gonadotrophin levels were likely to have been rising (towards the end of the effectiveness of the oestrogen implant). This, in turn, suggests that high (or rapidly increasing) gonadotrophin levels, rather than oestrogen/progesterone, were implicated in adversely affecting asthma activity.
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