Deep Infiltrating Endometriosis Influence of Endometriosis and Progestin Therapy on the Course of COVID Infection: A Prospective Study at a University Endometriosis Center in Germany
Morva Tahmasbi Rad （ Department of Obstetrics and Gynecology, University of Frankfurt, Frankfurt am Main, Germany ）
Lisa Marie Wilhelm （ Department of Obstetrics and Gynecology, University of Frankfurt, Frankfurt am Main, Germany ）
Denis Brachmann （ Department of Obstetrics and Gynecology, University of Frankfurt, Frankfurt am Main, Germany ）
Sven Becker （ Department of Obstetrics and Gynecology, University of Frankfurt, Frankfurt am Main, Germany ）
Sophie Simon （ Department of Obstetrics and Gynecology, University of Frankfurt, Frankfurt am Main, Germany ）
https://doi.org/10.37155/3060-8708-0302-3Abstract
Objective: Endometriosis is a chronic immune-related inflammatory disease. As progestin therapy modulates estrogen and progesterone pathways it may also influence antiviral immune response. This study aimed to evaluate the impact of deep infiltrating endometriosis (DIE) and progestin therapy on the clinical course of SARS-CoV-2 infection. Methods: This prospective, single-center cohort study included 30 women with confirmed deep infiltrating endometriosis (DIE). Clinical data and standardized questionnaires were used to assess SARS-CoV-2 infection status, symptom severity, duration of PCR positivity, vaccination status, and endometriosis symptoms. Patients were stratified according to progestin therapy use versus no hormonal treatment. Results: Seventeen women (56.7%) were receiving progestin therapy, while 13 (43.3%) did not. The mean age was 34.0 ± 7.2 years, with no significant baseline differences between the groups. All patients contracted SARS-CoV-2. The mean time to PCR negativity was significantly longer in the progestin group (10.76 ± 4.1 vs. 8.00 ± 2.2 days; p = 0.026). Moderate COVID-19 symptoms were more frequent among progestin users (47.1% vs. 7.7%; p = 0.042), whereas mild disease predominated in non-users (92.3%). No hospitalizations or thromboembolic events were observed. Endometriosis-related symptoms remained stable following both SARS-CoV-2 infection and vaccination. Conclusion: In women with DIE, progestin therapy was associated with prolonged viral clearance and a higher frequency of moderate COVID-19 symptoms. Although causality cannot be established in this small cohort, the findings suggest a potential interaction between hormonal therapy and the immune response to SARS-CoV-2. As current evidence in this area remains scarce, these preliminary observations provide a basis for future larger, adequately powered prospective studies aimed at elucidating the immunological mechanisms underlying these associations and determining their clinical relevance.
Keywords
Deep Infiltrating Endometriosis (DIE); COVID; ProgestinFull Text
PDFReferences
[2] Giudice LC, Kao LC. Endometriosis. Lancet. 2004;364(9447):1789-99.
[3] Berbic M, Fraser IS. Immunology of normal and abnormal menstruation. Womens Health (Lond). 2013;9(4):387-95.
[4] Symons LK, Miller JE, Kay VR, Marks RM, Liblik K, Koti M, et al. The Immunopathophysiology of Endometriosis. Trends Mol Med. 2018;24(9):748-62.
[5] Shen HH, Zhang T, Yang HL, Lai ZZ, Zhou WJ, Mei J, et al. Ovarian hormones-autophagy-immunity axis in menstruation and endometriosis. Theranostics. 2021;11(7):3512-26.
[6] Bulun SE. Endometriosis. N Engl J Med. 2009;360(3):268-79.
[7] Donnez J, Taylor RN, Taylor HS. Partial suppression of estradiol: a new strategy in endometriosis management? Fertil Steril. 2017;107(3):568-70.
[8] Vercellini P, Somigliana E, Viganò P, Abbiati A, Barbara G, Crosignani PG. Endometriosis: current therapies and new pharmacological developments. Drugs. 2009;69(6):649-75.
[9] Strowitzki T, Marr J, Gerlinger C, Faustmann T, Seitz C. Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial. Hum Reprod. 2010;25(3):633-41.
[10] Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. Jama. 2020;323(13):1239-42.
[11] Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506.
[12] Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol. 2016;16(10):626-38.
[13] Pivonello R, Auriemma RS, Pivonello C, Isidori AM, Corona G, Colao A, et al. Sex Disparities in COVID-19 Severity and Outcome: Are Men Weaker or Women Stronger? Neuroendocrinology. 2021;111(11):1066-85.
[14] Seeland U, Coluzzi F, Simmaco M, Mura C, Bourne PE, Heiland M, et al. Evidence for treatment with estradiol for women with SARS-CoV-2 infection. BMC Med. 2020;18(1):369.
[15] Sund M, Fonseca-Rodríguez O, Josefsson A, Welen K, Fors Connolly AM. Association between pharmaceutical modulation of oestrogen in postmenopausal women in Sweden and death due to COVID-19: a cohort study. BMJ Open. 2022;12(2):e053032.
[16] Feng Y, Ling Y, Bai T, Xie Y, Huang J, Li J, et al. COVID-19 with Different Severities: A Multicenter Study of Clinical Features. Am J Respir Crit Care Med. 2020;201(11):1380-8.
[17] Tahamtan A, Ardebili A. Real-time RT-PCR in COVID-19 detection: issues affecting the results. Expert Rev Mol Diagn. 2020;20(5):453-4.
[18] Becker K, Heinemann K, Imthurn B, Marions L, Moehner S, Gerlinger C, et al. Real world data on symptomology and diagnostic approaches of 27,840 women living with endometriosis. Sci Rep. 2021;11(1):20404.
[19] De Corte P, Klinghardt M, von Stockum S, Heinemann K. Time to Diagnose Endometriosis: Current Status, Challenges and Regional Characteristics-A Systematic Literature Review. Bjog. 2025;132(2):118-30.
[20] Schilling J, Lehfeld AS, Schumacher D, Ullrich A, Diercke M, Buda S, et al. Disease severity of the first COVID-19 wave in Germany using reporting data from the national notification system. J Health Monit. 2021;5(Suppl 11):2-19.
[21]Grant MC, Geoghegan L, Arbyn M, Mohammed Z, McGuinness L, Clarke EL, et al. The prevalence of symptoms in 24,410 adults infected by the novel coronavirus (SARS-CoV-2; COVID-19): A systematic review and meta-analysis of 148 studies from 9 countries. PLoS One. 2020;15(6):e0234765.
[22] Eser F, Kayaaslan B, Güner R, Hasanoğlu I, Kaya Kalem A, Aypak A, et al. The Effect of prolonged PCR Positivity on patient Outcomes and Determination of Isolation period in COVID-19 patients. Int J Clin Pract. 2021;75(5):e14025.
[23] Alvergne A, Woon EV, Male V. Effect of COVID-19 vaccination on the timing and flow of menstrual periods in two cohorts. Front Reprod Health. 2022;4:952976.
[24] Ghandehari S, Matusov Y, Pepkowitz S, Stein D, Kaderi T, Narayanan D, et al. Progesterone in Addition to Standard of Care vs Standard of Care Alone in the Treatment of Men Hospitalized With Moderate to Severe COVID-19: A Randomized, Controlled Pilot Trial. Chest. 2021;160(1):74-84.
[25] Ramírez-de-Arellano A, Gutiérrez-Franco J, Sierra-Diaz E, Pereira-Suárez AL. The role of estradiol in the immune response against COVID-19. Hormones (Athens). 2021;20(4):657-67.
[26] Costeira R, Lee KA, Murray B, Christiansen C, Castillo-Fernandez J, Ni Lochlainn M, et al. Estrogen and COVID-19 symptoms: Associations in women from the COVID Symptom Study. PLoS One. 2021;16(9):e0257051.
[27] Ramanadhan S, Hansen K, Henderson JT, Cohen MA, Paynter R, Edelman A. Risk of thromboembolism in patients with COVID-19 who are using hormonal contraception. Cochrane Database Syst Rev. 2023;5(5):Cd014908.
[28] Spencer JI, Mezquita G, Shakir F. The ongoing impact of the Covid-19 pandemic on endometriosis patients: A survey of 1,089 UK patients. Facts Views Vis Obgyn. 2022;14(3):257-64.
[29] Vallée A, Arutkin M, Ceccaldi PF, Feki A, Ayoubi JM. Long COVID and endometriosis: a systematic review and meta-analysis. BMC Womens Health. 2025;25(1):229.
Copyright ©
Publishing time:2026-06-30
This work is licensed under a Creative Commons Attribution 4.0 International License