The disease course in microscopic colitis may be influenced by hormonal factors | BMC Gastroenterology

In the present study intake of oral contraceptives or HRT did not have any significant impact on the disease course. In contrast, smoking and celiac disease increased the risk for more active disease, something that had been observed before at least for smoking [15,16,17]. The factors BMI, age at diagnosis or childbirth were not associated with the disease course. Among the conditions affecting the hormone balance endometriosis and IVF were not associated while oophorectomy seems to have a protective effect.

The lack of association with oral contraceptives or HRT could indicate that there is no actual effect. The p-values are far from significant. Furthermore, the risk ratios are contradictory. It is not possible to draw any conclusions from the results in the present study. However, a previous study from 2013 found that more patients than controls had been exposed to oral contraceptives but fewer to current MHT, but without any effect on disease activity [12]. This is in line with our observed risk ratios. A latter and larger study from 2018 studied the risk for disease onset in relation to use of hormone replacement therapy and found it to be highest in patients on current therapy [13]. The finding that oral contraceptives, but not menopausal hormone therapy (MHT), appear to have an impact may seem contradictory at first. However, this discrepancy might be explained by the longer duration of contraceptive use, which typically begins earlier in life. The earlier initiation and prolonged exposure to contraceptives may have played a significant role in influencing the observed outcomes.

The association with smoking was not unexpected. The effect on disease course by smoking has already been proven [15, 16]. However, the association between celiac disease and more active disease has not, to the best of our knowledge, been presented before. Microscopic colitis and celiac disease share the same genetical predisposition, something that could contribute to this phenomenon [18]. Patients with CC have HLA DQ2 to a larger extent than patients with LC and they also have a more severe disease course. It could be that patients with HLA DQ2 risk both to develop celiac disease and a at the same time a more active disease, but this remains to be proven.

Among the other factors influencing the hormone balance, i.e., endometriosis, IVF and oophorectomy a negative association was apparent for the latter. This is in accordance with the hypothesis that the hormone balance could have an impact. A reduction of hormonal influence could consequently influence the disease course towards a more quiescent state,

The study from Burke et al. reported an increased risk for MC per se by hormone substitution. In that study the hazard ratio of MC was 2.33 for ever use of estrogen, 2.12 for combined estrogen and progestin preparations, and 1.42 for progestin concerning MHT [13]. Consequently, a varying effect of different hormone preparations must be taken into consideration.

When it comes to the other factors that could influence the hormone levels no significant results were observed. Endometriosis was reported among 33 (8.6%) of the participants. This is in line with the reported prevalence in the background population, i.e., 10% [19]. As many as 135 patients (35.2%) stated that they had undergone bilateral oophorectomy. Since this percentage is higher than anticipated the patient files in Malmö, Lund and Linköping were double checked and it seems as if the number is correct. Regardless of this, in view of the fact that it is a retrospective study, we don’t know whether the patients had been operated before or after menopause and we don’t know if all operations really were bilateral. In view of these circumstances the outcome must be interpreted with caution.

One strength of the present study is that the patients exposed to certain medicines or conditions were compared with individuals from the same cohort simultaneously and with the same questions. However, the present study also has some limitations. As all study participants had MC, it was not possible to estimate the risk for disease onset. The fact that we do not have access to the timing of medication and different hormone affecting conditions make any estimation on the effect on disease onset impossible why the present study is focused on the disease course. In many cases the time span from medication and/or surgery until the questionnaire was distributed was long. Consequently, some patients could not remember how long time they had been treated with contraceptives or MHT, moreover, some did not know the exact names of their medicines hampering further analyses. Accordingly, the risk of recall bias is given in this retrospective study design. The treatments administered vary considerably, and as a result, the impact of different hormonal therapies on hormonal balance also differs accordingly. Furthermore, the number of participants is small why sampling errors could occur.

In conclusion, this study could confirm the previously known association with smoking but also with celiac disease but also revealed a negative association with oophorectomy, while the results for oral contraceptives and HRT were insignificant. The observation that oophorectomy could influence the disease course indicates that the hormonal levels could still have an effect on MC despite the lack of significant impacts of oral contraceptives and MHT in the present study. These findings highlight the need to consider the varying effects of different hormonal factors on the disease course. Further research is warranted to explore this phenomenon in greater detail.