Sir,

I read with interest the paper by Sanghvi et al1 ‘Uveitis and the Menstrual Cycle’. The authors studied a group of patients that presented with new or recurrent episodes of acute anterior uveitis to determine the relationship between their incidences and the menstrual cycle. They found an increased incidence of these episodes during the postovulatory phase of the menstrual cycle. I have to commend the authors for their effort and their valuable and genuinely interesting findings. I have, however, a query and some comments to make.

The authors included patients on combined oral contraceptives and excluded those with irregular menstrual cycles and those who are postmenopausal, pregnant, or lactating. It was not mentioned, however, whether any of their patients were on immunomodulatory medications such as corticosteroids or other immunosuppressive or cytotoxic drugs for coexistent autoimmune diseases or if these patients were also excluded. Those on intermittent or on-demand therapy such as asthma sufferers were particularly important group to exclude since they tend to have their episodes in the premenstrual period, as quoted in the paper, and the administration of steroids around that period could certainly have affected the distribution of the incidence of their uveitis episodes.

The results, however, were extremely interesting. The authors found a significant increase in the incidence of acute anterior uveitis during the postovulatory phase and premenstrual period of the menstrual cycle. They postulated that this is mainly related to the rapid withdrawal of the protective anti-inflammatory effect of either oestrogen or progesterone or both in the late luteal phase. Although I agree with the authors that it is difficult to decide which hormone might be responsible, I would like to suggest that this anti-inflammatory effect is most probably related to the influence of oestrogen rather than progesterone, especially as the majority of the study patients experienced the inflammatory episodes during the late postovulatory phase of the cycle when normally oestrogen drops and progesterone peaks. Also, Salem2 recently reviewed the role of oestrogen in immune response and demonstrated that several studies have provided evidence to the modulatory effect of oestrogen on the CD4-T cells subpopulation designated TH1 and TH2. Oestrogen was found to inhibit the production of TH1 proinflammatory cytokines such as IL-12, TNF-α, and IFN-γ but to stimulate the production of TH2 anti-inflammatory cytokines such as IL-10, IL-4, and TGF-β. Both increased aqueous IL-123 and decreased IL-104 have been linked to the development and severity of anterior uveitis and increased serum IFN-γ has been associated with serious visual loss.5

The interesting findings of the study are relevant to a great number of female patients suffering from uveitis and point forward to several potential areas of research. One can hypothesise that some of these patients who suffer incessant recurrences might have relatively lower oestrogen or progesterone levels that, perhaps, render them more vulnerable to recurrent inflammation. A possible beneficial effect would then be achieved in these patients by prescribing them, unless contraindicated, some form of hormonal supplement. Also, although the study excluded postmenopausal patients, it can be extrapolated that hormonal replacement therapy may be a useful therapeutic addition in these patients, especially in cases with recalcitrant and potentially sight-threatening recurrences. These hormones have been suggested to have anti-inflammatory effect through reducing E-selectin,6 a proinflammatory mediator involved in some types of uveitis.7, 8 I am sure many would agree that some patients would be better off taking these hormones, if at all possible, instead of immunosuppressive or cytotoxic drugs. Only future studies can prove or refute these hypotheses.