docruДоктор.РуTitle1727-23782713-2994ООО "ГК "РУСМЕДИКАЛ"10.31550/1727-2378-2023-22-5-69-74docru-205Research ArticleГИНЕКОЛОГИЯGYNECOLOGYМенопаузальная гормональная терапия и течение COVID-19Menopausal Hormone Therapy and the Course of COVID-19https://orcid.org/0000-0002-2995-5228АверьяноваМ. В.AveryanovaM. V.

Марина Владимировна Аверьянова, аспирант, врач — акушер-гинеколог

отделение гинекологической эндокринологии

117997;  ул. Академика Опарина, д. 4; Москва

117997; 4 Academician Oparin Str.; Moscow

m_averyanova@oparina4.ruhttps://orcid.org/0000-0002-7430-1207ЯкушевскаяО. В.YakushevskayaO. V.

Оксана Владимировна Якушевская, к. м. н., научный сотрудник

отделение гинекологической эндокринологии

117997; ул. Академика Опарина, д. 4; Москва

117997; 4 Academician Oparin Str.; Moscow

aluckyone777@gmail.comhttps://orcid.org/0000-0003-2864-066XЮреневаС. В.YurenevaS. V.

Светлана Владимировна Юренева,  д. м. н., профессор, заместитель директора по научной работе, профессор кафедры

Институт онкогинекологии и маммологии; кафедра акушерства и гинекологии

117997;  ул. Академика Опарина, д. 4; Москва

117997; 4 Academician Oparin Str.; Moscow

syureneva@gmail.comФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии имени академика В.И. Кулакова» Министерства здравоохранения Российской ФедерацииРоссияV.I. Kulakov National Medical Scientific Centre of Obstetrics, Gynecology and Perinatal MedicineRussian Federation202318022025225ГИНЕКОЛОГИЯ6974Copyright © Аверьянова М.В., Якушевская О.В., Юренева С.В., 20252025Аверьянова М.В., Якушевская О.В., Юренева С.В.Averyanova M.V., Yakushevskaya O.V., Yureneva S.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://docru.elpub.ru/jour/article/view/205   Цель исследования

   Цель исследования: оценить симптомы и тяжесть течения коронавирусной инфекции, вызываемой вирусом SARS-CoV-2, у пациенток в пери- и постменопаузе на фоне менопаузальной гормональной терапии (МГТ) различных форм (пероральной и трансдермальной) и при ее отсутствии.

   Дизайн

   Дизайн: ретроспективное когортное исследование.

   Материалы и методы

   Материалы и методы. В исследование были включены 93 пациентки в пери- и постменопаузе, перенесшие инфекцию, вызываемую вирусом SARS-CoV-2, в разных условиях: на фоне пероральной МГТ (первая группа, n = 22), трансдермальной МГТ (вторая группа, n = 22) с применением стандартных и низких доз препаратов в обеих группах и без МГТ (третья группа, или группа сравнения, n = 49). Проводился опрос пациенток о симптомах, длительности, тяжести течения и терапии COVID-19.

   Результаты

   Результаты. Длительность заболевания COVID-19, а также частота различных симптомов болезни (кашель, боль в горле, тошнота, диарея, астения, боли в мышцах, головная боль и др.) у пациенток, не использовавших МГТ и применявших пероральную либо трансдермальную МГТ, статистически значимо не различались (p > 0,05). При объединении пациенток с пероральной и трансдермальной МГТ в одну группу и сравнении ее с группой без МГТ обнаружено, что тяжелое течение COVID-19 статистически значимо чаще (p = 0,03) встречалось у женщин, не применявших МГТ.

   Заключение

   Заключение. Поиск путей терапии острой коронавирусной инфекции, вызываемой SARS-CoV-2, до сих пор актуален, на решение этой задачи направлены усилия научно-исследовательских лабораторий по всему миру. В публикуемом исследовании женщины, применявшие МГТ, реже имели тяжелое течение коронавирусной инфекции, чем пациентки безМГТ. Требуются дополнительные исследования для поиска защитных механизмов половых стероидов в отношении коронавирусной инфекции, чтобы в дальнейшем медицинские работники были готовы локализовать данную инфекцию и справиться с ней как можно скорее.

   Aim

   Aim: To assess the symptoms and severity of the coronavirus infection caused by the SARS-CoV-2 virus in peri- and postmenopausal patients on the background of various types of MHT (oral and transdermal) and in its absence.

   Design

   Design: a retrospective, cohort study.

   Materials and methods

   Materials and methods. The study included 93 postmenopausal patients who had an infection caused by the SARS-CoV-2 virus, against the background of oral MHT - group 1, transdermal MHT - group 2 at standard and low doses, without MHT - group 3 comparison. A survey of patients was conducted, including information about the symptoms, severity of the course and ongoing therapy for COVID-19.

   Results

   Results. Duration of COVID-19 illness, as well as the frequency of various symptoms of the disease in patients (cough, rhinitis, sore throat, weakness, muscle pain, fever, diarrhea, nausea, headaches) not using MHT and using various forms of MHT (oral and transdermal) did not differ significantly. When patients using oral and transdermal MHT were combined into one group and compared with the group not taking MHT, it was found that severe COVID-19 was significantly more common in the group not taking MHT.

   Conclusions

   Conclusions. In our study, individuals who took MHT had a significantly significantly milder course of coronavirus infection compared to women who did not use MHT. More research is needed to find protective mechanisms of sex steroids against coronavirus infection in order to continue to be ready to localize and manage this infection as soon as possible.

менопаузальная гормональная терапияCOVID-19коронавирусная инфекцияиммунная системаэстрогеныMenopausal hormone therapyCOVID-19coronavirus infectionimmune systemestrogensАвторы заявляют об отсутствии внешнего финансирования при проведении исследованияThis study was not supported by any external sources of fundingReferencesCucinotta D., Vanelli M. WHO Declares COVID-19 a Pandemic. Acta Biomed. 2020; 91(1): 157–60. DOI: 10.23750/abm.v91i1.9397Cucinotta D., Vanelli M. WHO Declares COVID-19 a Pandemic. Acta Biomed. 2020; 91(1): 157–60. DOI: 10.23750/abm.v91i1.9397Msemburi W., Karlinsky A., Knutson V., Aleshin-Guendel S. et al. The WHO estimates of excess mortality associated with the COVID-19 pandemic. Nature. 2023; 613(7942): 130–7. Epub. 2022 Dec. 14. DOI: 10.1038/s41586-022-05522-2Msemburi W., Karlinsky A., Knutson V., Aleshin-Guendel S. et al. The WHO estimates of excess mortality associated with the COVID-19 pandemic. Nature. 2023; 613(7942): 130–7. Epub. 2022 Dec. 14. DOI: 10.1038/s41586-022-05522-2Mauvais-Jarvis F., Klein S.L., Levin E.R. Estradiol, Progesterone, Immunomodulation, and COVID-19 Outcomes. Endocrinology. 2020; 161(9): bqaa127. DOI: 10.1210/endocr/bqaa127Mauvais-Jarvis F., Klein S.L., Levin E.R. Estradiol, Progesterone, Immunomodulation, and COVID-19 Outcomes. Endocrinology. 2020; 161(9): bqaa127. DOI: 10.1210/endocr/bqaa127Liu Y., Li H., Peng Y., Gao L. et al. Impacts of pregnancy and menopause on COVID-19 severity: A systematic review and meta-analysis of 4.6 million women. QJM. 2023; hcad106. DOI: 10.1093/qjmed/hcad106Liu Y., Li H., Peng Y., Gao L. et al. Impacts of pregnancy and menopause on COVID-19 severity: A systematic review and meta-analysis of 4.6 million women. QJM. 2023; hcad106. DOI: 10.1093/qjmed/hcad106Sund M., Fonseca-Rodríguez O., Josefsson A., Welen K. et al. 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. DOI: 10.1136/bmjopen-2021-053032Sund M., Fonseca-Rodríguez O., Josefsson A., Welen K. et al. 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. DOI: 10.1136/bmjopen-2021-053032Garg R., Agrawal P., Gautam A., Pursnani N. et al. COVID-19 Outcomes in Postmenopausal and Perimenopausal Females: Is Estrogen Hormone Attributing to Gender Differences? J. Midlife Health. 2020; 11(4): 250–6. Epub. 2021 Jan. 21. DOI: 10.4103/jmh.jmh_287_20Garg R., Agrawal P., Gautam A., Pursnani N. et al. COVID-19 Outcomes in Postmenopausal and Perimenopausal Females: Is Estrogen Hormone Attributing to Gender Differences? J. Midlife Health. 2020; 11(4): 250–6. Epub. 2021 Jan. 21. DOI: 10.4103/jmh.jmh_287_20Agrawal U., Bedston S., McCowan C., Oke J. et al. Severe COVID-19 outcomes after full vaccination of primary schedule and initial boosters: pooled analysis of national prospective cohort studies of 30 million individuals in England, Northern Ireland, Scotland, and Wales. Lancet. 2022; 400(10360): 1305–20. DOI: 10.1016/S0140-6736(22)01656-7Agrawal U., Bedston S., McCowan C., Oke J. et al. Severe COVID-19 outcomes after full vaccination of primary schedule and initial boosters: pooled analysis of national prospective cohort studies of 30 million individuals in England, Northern Ireland, Scotland, and Wales. Lancet. 2022; 400(10360): 1305–20. DOI: 10.1016/S0140-6736(22)01656-7Zheng Z., Peng F., Xu B., Zhao J. et al. Risk factors of critical & mortal COVID-19 cases : A systematic literature review and meta-analysis. Meta-Analysis J. Infect. 2020; 81(2): e16–25. DOI: 10.1016/j.jinf.2020.04.021Zheng Z., Peng F., Xu B., Zhao J. et al. Risk factors of critical & mortal COVID-19 cases : A systematic literature review and meta-analysis. Meta-Analysis J. Infect. 2020; 81(2): e16–25. DOI: 10.1016/j.jinf.2020.04.021Galbadage T., Peterson B.M., Wang J.S., Jayasekara A. Molecular Mechanisms Lead to Sex-Specific COVID-19 Prognosis and Targeted Therapies. Front. Med. (Lausanne). 2020; 7: 589060. DOI: 10.3389/fmed.2020.589060Galbadage T., Peterson B.M., Wang J.S., Jayasekara A. Molecular Mechanisms Lead to Sex-Specific COVID-19 Prognosis and Targeted Therapies. Front. Med. (Lausanne). 2020; 7: 589060. DOI: 10.3389/fmed.2020.589060Costeira R., Lee K.A., Murray B., Christiansen C. et al. Estrogen and COVID-19 symptoms: Associations in women from the COVID Symptom Study. PLoS One. 2021; 16(9): e0257051. DOI: 10.1371/journal.pone.0257051Costeira R., Lee K.A., Murray B., Christiansen C. et al. Estrogen and COVID-19 symptoms: Associations in women from the COVID Symptom Study. PLoS One. 2021; 16(9): e0257051. DOI: 10.1371/journal.pone.0257051Yoshida Y., Chu S., Zu Y., Fox S. et al.; N3C consortium. Effect of menopausal hormone therapy on COVID-19 severe outcomes in women — A population-based study of the US National COVID Cohort Collaborative (N3C) data. Maturitas. 2023; 170: 39–41. Epub. 2022 Nov. 4. DOI: 10.1016/j.maturitas.2022.10.005Yoshida Y., Chu S., Zu Y., Fox S. et al.; N3C consortium. Effect of menopausal hormone therapy on COVID-19 severe outcomes in women — A population-based study of the US National COVID Cohort Collaborative (N3C) data. Maturitas. 2023; 170: 39–41. Epub. 2022 Nov. 4. DOI: 10.1016/j.maturitas.2022.10.005Seeland U., Coluzzi F., Simmaco M., Mura C. et al. Evidence for treatment with estradiol for women with SARS-CoV-2 infection. BMC Med. 2020; 18(1): 369. DOI: 10.1186/s12916-020-01851-zSeeland U., Coluzzi F., Simmaco M., Mura C. et al. Evidence for treatment with estradiol for women with SARS-CoV-2 infection. BMC Med. 2020; 18(1): 369. DOI: 10.1186/s12916-020-01851-zSakulpaisal M., Sothornwit J., Somboonporn W. The effects of exogenous estrogen in women with SAR-CoV-2 infection : a systematic review and meta-analysis. Hum. Reprod. 2023; 38(6): 1111–23. DOI: 10.1093/humrep/dead074Sakulpaisal M., Sothornwit J., Somboonporn W. The effects of exogenous estrogen in women with SAR-CoV-2 infection : a systematic review and meta-analysis. Hum. Reprod. 2023; 38(6): 1111–23. DOI: 10.1093/humrep/dead074Averyanova M., Vishnyakova P., Yureneva S., Yakushevskaya O. et al. Sex hormones and immune system: Menopausal hormone therapy in the context of COVID-19 pandemic. Front. Immunol. 2022; 13: 928171. DOI: 10.3389/fimmu.2022.928171Averyanova M., Vishnyakova P., Yureneva S., Yakushevskaya O. et al. Sex hormones and immune system: Menopausal hormone therapy in the context of COVID-19 pandemic. Front. Immunol. 2022; 13: 928171. DOI: 10.3389/fimmu.2022.928171Авдеев С.Н., Адамян Л.В., Алексеева Е.И., Багненко С.Ф. и др. Профилактика, диагностика и лечение новой коронавирусной инфекции (COVID-19) : Временные методические рекомендации. Москва; 2022. 248 с. URL: static-0.minzdrav.gov.ru/system/attachments/attaches/000/060/193/original/BMP_COVID-19_V16.pdf (дата обращения — 14. 07. 2023).Avdeev S.N., Adamyan L.V., Alekseeva E.I., Bagnenko S.F. et al. Prevention, diagnosis and management of the novel coronavirus infection (COVID-19). Temporary guidelines. (in Russian). URL: static-0.minzdrav.gov.ru/system/attachments/attaches/000/060/193/original/BMP_COVID-19_V16.pdfGallo Marin B., Aghagoli G., Lavine K., Yang L. et al. Predictors of COVID-19 severity : A literature review. Rev. Med. Virol. 2021; 31(1): 1–10. DOI: 10.1002/rmv.2146. Epub. 2020 Jul. 30.Gallo Marin B., Aghagoli G., Lavine K., Yang L. et al. Predictors of COVID-19 severity : A literature review. Rev. Med. Virol. 2021; 31(1): 1–10. DOI: 10.1002/rmv.2146. Epub. 2020 Jul. 30.Gargaglioni L.H., Marques D.A. Let's talk about sex in the context of COVID-19. J. Appl. Physiol. (1985). 2020; 128(6): 1533–8. DOI: 10.1152/japplphysiol.00335.2020Gargaglioni L.H., Marques D.A. Let's talk about sex in the context of COVID-19. J. Appl. Physiol. (1985). 2020; 128(6): 1533–8. DOI: 10.1152/japplphysiol.00335.2020Rachoń D., Myśliwska J., Suchecka-Rachoń K., Wieckiewicz J. et al. Effects of oestrogen deprivation on interleukin-6 production by peripheral blood mononuclear cells of postmenopausal women. J. Endocrinol. 2002; 172(2): 387–95. DOI: 10.1677/joe.0.1720387Rachoń D., Myśliwska J., Suchecka-Rachoń K., Wieckiewicz J. et al. Effects of oestrogen deprivation on interleukin-6 production by peripheral blood mononuclear cells of postmenopausal women. J. Endocrinol. 2002; 172(2): 387–95. DOI: 10.1677/joe.0.1720387Abdi F., Mobedi H., Mosaffa N., Dolatian M. et al. Effects of hormone replacement therapy on immunological factors in the postmenopausal period. Climacteric. 2016; 19(3): 234–9. DOI: 10.3109/13697137.2016.1164136Abdi F., Mobedi H., Mosaffa N., Dolatian M. et al. Effects of hormone replacement therapy on immunological factors in the postmenopausal period. Climacteric. 2016; 19(3): 234–9. DOI: 10.3109/13697137.2016.1164136Kumru S., Godekmerdan A., Yilmaz B. Immune effects of surgical menopause and estrogen replacement therapy in peri-menopausal women. J. Reprod. Immunol. 2004; 63(1): 31–8. DOI: 10.1016/j.jri.2004.02.001Kumru S., Godekmerdan A., Yilmaz B. Immune effects of surgical menopause and estrogen replacement therapy in peri-menopausal women. J. Reprod. Immunol. 2004; 63(1): 31–8. DOI: 10.1016/j.jri.2004.02.001Аверьянова М.В., Юренева С.В., Киселёва В.В., Якушевская О.В. и др. Менопаузальная гормональная терапия: влияние на параметры иммунной системы. Акушерство и гинекология. 2023; 4: 68–77. – Averyanova M.V., Yureneva S.V., Kiseleva V.V., Yakushevskaya O.V. et al. Impact of menopausal hormone therapy on immune system parameters. Obstetrics and Gynecology. 2023; 4: 68–77. (in Russian). DOI: 10.18565/aig.2023.59Averyanova M.V., Yureneva S.V., Kiseleva V.V., Yakushevskaya O.V. et al. Impact of menopausal hormone therapy on immune system parameters. Obstetrics and Gynecology. 2023; 4: 68–77. (in Russian). DOI: 10.18565/aig.2023.59Fruzzetti F., Cagnacci A., Primiero F., De Leo V. et al. Contraception during Coronavirus-Covid 19 pandemia. Recommendations of the Board of the Italian Society of Contraception. Eur. J. Contracept. Reprod. Health Care. 2020; 25(3): 231–2. DOI: 10.1080/13625187.2020.1766016Fruzzetti F., Cagnacci A., Primiero F., De Leo V. et al. Contraception during Coronavirus-Covid 19 pandemia. Recommendations of the Board of the Italian Society of Contraception. Eur. J. Contracept. Reprod. Health Care. 2020; 25(3): 231–2. DOI: 10.1080/13625187.2020.1766016Ramírez I., De la Viuda E., Baquedano L., Coronado P. et al. Managing thromboembolic risk with menopausal hormone therapy and hormonal contraception in the COVID-19 pandemic: Recommendations from the Spanish Menopause Society, Sociedad Española de Ginecología y Obstetricia and Sociedad Española de Trombosis y Hemostasia. Maturitas. 2020; 137: 57–62. DOI: 10.1016/j.maturitas.2020.04.019Ramírez I., De la Viuda E., Baquedano L., Coronado P. et al. Managing thromboembolic risk with menopausal hormone therapy and hormonal contraception in the COVID-19 pandemic: Recommendations from the Spanish Menopause Society, Sociedad Española de Ginecología y Obstetricia and Sociedad Española de Trombosis y Hemostasia. Maturitas. 2020; 137: 57–62. DOI: 10.1016/j.maturitas.2020.04.019Traish A.M. Sex steroids and COVID-19 mortality in women. Trends Endocrinol. Metab. 2021; 32(8): 533–6. DOI: 10.1016/j.tem.2021.04.006Traish A.M. Sex steroids and COVID-19 mortality in women. Trends Endocrinol. Metab. 2021; 32(8): 533–6. DOI: 10.1016/j.tem.2021.04.006

The authors declare that there are no conflicts of interest present.