Using a Cox regression model incorporating co-variables such as age, parity, rASRM scores, total cyst volumes, and the immunostaining levels of HMGB1, TLR4, RAGE, p-p65, PCNA, IL-33 and OPN, we found that the severity of dysmenorrhea in women with endometriosis was significantly associated with the extent of lesional fibrosis (p = 0.019) and lesional HMGB1 staining levels (p = 0.026). This evidence concerns the gene SPP1 and endometriosis.