Interpretation
We have provided a new insight that adenomyosis can trigger abdominal pain during pregnancy. Fibroids cause abdominal pain in up to 28% of cases during pregnancy,(12) but whether the same physiologic changes occur in adenomyosis during pregnancy is not well understood. The pathophysiology underlying pain mechanism in fibroids is degeneration, which occurs predominantly during the second and early third trimesters.(18),(19) It is generally diagnosed by confirming the presence of pain directly over the fibroid correlating with ultrasound examination findings, and further accurate diagnosis can be made with MRI.(20, 21) The degeneration of fibroids is often accompanied by enhanced inflammation and an increase in CRP levels,(12),(13) which decrease with the amelioration of pain, usually within two weeks.(12),(20) However, whether this phenomenon is linked to adverse perinatal outcomes has not been conclusive.(22) Considering the similarity between fibroids and adenomyosis, the timing of pain onset that we reported in this study and the past reports of degeneration of adenomyosis during pregnancy indicate that the pain followed by the enhanced inflammatory response observed in our cohort mimics the degeneration of fibroids.(11, 23, 24) Nevertheless, it seems unquestionable that some proportion of women with adenomyosis develop pain during pregnancy.
A recent meta-analysis showed that women with adenomyosis had an increased likelihood of PE (odds ratio [OR]: 4.35; 95% confidence interval [CI], 1.07–17.72; p <0.05), although the pathophysiology underlying this result is unknown.(5) In our study, the adenomyosis pain onset was associated with the onset of PE, which intriguingly was more conspicuous in patients with elevated CRP levels. Interestingly, the median time from the maximum CRP level to the onset of PE was 15 days, and the CRP level decreased in the days before PE development. Several mouse models of PE have been reported that were induced by inflammatory cytokines.(25-28) Although CRP cannot be used as a marker for predicting the onset of PE, circulating CRP is reported to be elevated in some groups of women, such as those with periodontal disease or obesity, before the onset of PE. (29-31) Although the number of cases is limited, considering that the maximum CRP preceded the onset of PE in our cohort and that previous reports show an association with inflammation and the onset of PE, enhanced inflammation at the utero-placental unit may be the key factor to induce the onset of PE in women with adenomyosis pain.