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Introduction: Endometriosis is a common disabling pain condition in women of childbearing age, frequently showing familial clustering. Nevertheless, little is known about whether familial predispositions influence its severity or presentation. In this study, we investigate disease characteristics in endometriosis patients with a family history (FH) for endometriosis or the comorbidities migraine, depression and early menopause (EMP)., Materials and Methods: We performed an observational case-control study enrolling women with histologically confirmed endometriosis in a tertiary center. Based on surgical findings, patient records and phone interviews, we examined the relations between a FH for endometriosis, migraine, depression or EMP and endometriotic signs and symptoms, such as response to combined hormonal contraceptives (CHC) and analgesics, disease localization, infiltration depth, Enzian- and rASRM-scores., Results: A positive FH for endometriosis, migraine, depression or EMP was reported by 10.2 %, 33.4 %, 32.6 % and 9.9 % of the 344 patients. A positive FH of endometriosis was associated with an increased risk for high rASRM-scores (rASRM 3 + 4: OR 2.74 (95 % CI 1.16-6.49), p = 0.017) and the presence of endometriomas (OR 2.70 (1.22-5.95), p = 0.011). A positive FH for migraine was associated with less response of endometriosis symptoms to CHC (OR 0.469 (0.27-0.82) p = 0.025). Depression in the family was linked to less severe rASRM-scores (rASRM 3 + 4: OR 0.63 (0.39-0.99), p = 0.046) and less endometriomas (OR 0.58 (0.67-0.92), p = 0.02), but increased the risk of both migraine (OR 1.66 (1.01-2.73), p = 0.043) and depression (OR 3.04 (1.89-4.89), p < 0.001) while showing a better response to CHC (OR 2.0 (1.15-3.48, p < 0.001). Patients with EMP in their family reported more current endometriosis symptoms at present (OR 3.72 (1.67-8.30), p = 0.001), more dysmenorrhea (OR 2.13 (1.04-4.35), p = 0.037), more frequent severe dysmenorrhea (OR 2.32 (1.14-4.74), p = 0.019) and suffered significantly more often > 5 days of non-cyclic pain (OR 3.58 (1.72-7.44), p < 0.001)., Conclusions: Around 30% reported a positive FH for migraine or depression. Patients with a positive FH for endometriosis, migraine, depression or EMP differ in symptoms and surgical findings when compared to controls. While a FH for endometriosis is associated with higher rASRM scores and more endometriomas, women with a FH for depression had lower rASRM scores and less endometriomas while responding better to CHC. In contrast, women with a FH for migraine showed less response to CHC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)