<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">akusherstvo</journal-id><journal-title-group><journal-title xml:lang="en">Obstetrics, Gynecology and Reproduction</journal-title><trans-title-group xml:lang="ru"><trans-title>Акушерство, Гинекология и Репродукция</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2313-7347</issn><issn pub-type="epub">2500-3194</issn><publisher><publisher-name>IRBIS LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.17749/2313-7347/ob.gyn.rep.2025.662</article-id><article-id custom-type="elpub" pub-id-type="custom">akusherstvo-2529</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>REVIEW ARTICLES</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>НАУЧНЫЕ ОБЗОРЫ</subject></subj-group></article-categories><title-group><article-title>Progesterone influence on prostate diseases and prospects in preventing and treating benign prostatic hyperplasia</article-title><trans-title-group xml:lang="ru"><trans-title>Влияние прогестерона на заболевания предстательной железы и перспективы его использования для профилактики и лечения доброкачественной гиперплазии предстательной железы</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7954-0437</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Павлова</surname><given-names>З. Ш.</given-names></name><name name-style="western" xml:lang="en"><surname>Pavlova</surname><given-names>Z. Sh.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Павлова Зухра Шариповна - д.м.н. Scopus Author ID: 57208630829.</p><p>119234 Москва, Ломоносовский проспект, д. 27, корп. 10</p></bio><bio xml:lang="en"><p>Zukhra Sh. Pavlova - MD, Dr Sci Med. Scopus Author ID: 57208630829.</p><p>27 bldg. 10, Lomonosovsky Prospect, Moscow 119234 </p></bio><email xlink:type="simple">iam@doctorpavlova.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-8160-5612</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Орлова</surname><given-names>Я. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Orlova</surname><given-names>I. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Орлова Яна Артуровна - д.м.н., проф. Scopus Author ID: 24503460300. WoS ResearcherID: O-3105-2017.</p><p>119234 Москва, Ломоносовский проспект, д. 27, корп. 10</p></bio><bio xml:lang="en"><p>Iana A. Orlova - MD, Dr Sci Med, Prof. Scopus Author ID: 24503460300. WoS ResearcherID: O-3105-2017.</p><p>27 bldg. 10, Lomonosovsky Prospect, Moscow 119234 </p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-4251-7545</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Камалов</surname><given-names>А. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kamalov</surname><given-names>A. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Камалов Армаис Альбертович - д.м.н., проф., академик РАН. WoS ResearcherID: AAO-1396-2020.</p><p>119234 Москва, Ломоносовский проспект, д. 27, корп. 10</p></bio><bio xml:lang="en"><p>Armais A. Kamalov - MD, Dr Sci Med, Prof., Academician of RAS. WoS ResearcherID: AAO-1396-2020.</p><p>27 bldg. 10, Lomonosovsky Prospect, Moscow 119234 </p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Медицинский научно-образовательный институт ФГБОУ ВО «Московский государственный университет имени М.В. Ломоносова»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Medical Scientific-Educational Institute, Lomonosov Moscow State University</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2025</year></pub-date><pub-date pub-type="epub"><day>12</day><month>11</month><year>2025</year></pub-date><volume>19</volume><issue>5</issue><fpage>776</fpage><lpage>787</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Pavlova Z.S., Orlova I.A., Kamalov A.A., 2025</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="ru">Павлова З.Ш., Орлова Я.А., Камалов А.А.</copyright-holder><copyright-holder xml:lang="en">Pavlova Z.S., Orlova I.A., Kamalov A.A.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.gynecology.su/jour/article/view/2529">https://www.gynecology.su/jour/article/view/2529</self-uri><abstract><p>The prevalence of prostate diseases primarily benign prostatic hyperplasia (BPH) and prostate cancer (PC) has been progressively increasing with age being related to dramatic change in hormonal balance. Researchers and clinicians adhere to traditional understanding in developing BPH pathogenesis underlying no prominent achievements in the disease prevention and treatment. The ongoing search for gaining insights into the mechanisms behind development of these pathologies lies beyond assessing progesterone as one of the key hormones that plays an crucial role in the prostate gland functioning that has not been studied in this regard for many years. Until now, it is believed that progesterone is an exclusively "female hormone", despite that the first line therapy for BPH relies on using drugs lowering activity of enzyme 5α-reductase involved in testosterone-to-dihydrotestosterone transformation, wherein progesterone serves this function in male body under normal in vivo settings. In fact, such drugs are presented by chemical analogues of progesterone bearing minor changes in its molecule structure. In other words, to correct the pathophysiological aspects, it is necessary to proceed from the physiological basics. Presuming this, international research data available on the pathogenesis of BPH and PC as well as the effectiveness for various approaches to pathognomonic therapeutic approaches to prevent them have been analyzed.</p></abstract><trans-abstract xml:lang="ru"><p>Распространенность заболеваний предстательной железы, прежде всего доброкачественной гиперплазии (ДГПЖ) и рака предстательной железы (РПЖ), прогрессивно увеличивается с возрастом, когда баланс гормонов существенно меняется. Ученые и клиницисты придерживаются традиционных позиций в аспекте патогенеза развития ДГПЖ, и существенных достижений в профилактике и лечении этого заболевания нет. Продолжающиеся поиски в понимании механизмов развития данных патологий не затрагивают один из ключевых гормонов, играющих важную роль в функционировании предстательной железы – прогестерон, который никоим образом не исследовался долгие годы в этой взаимосвязи. До сих пор бытует мнение, что прогестерон – это исключительно «женский гормон», несмотря на то, что первой линией терапии при ДГПЖ являются препараты, снижающие активность фермента 5α-редуктазы, трансформирующих тестостерон в дигидротестостерон, а в условиях нормальной работы организма эту функцию в мужском организме как раз выполняет прогестерон. И указанные препараты, по сути, являются химическими аналогами прогестерона с небольшими изменениями в структуре молекулы. Иначе говоря, чтобы исправить патофизиологические аспекты, нужно исходить из физиологических аспектов. Учитывая эти предпосылки, проведен анализ имеющихся в мировой научной литературе данных, посвященных патогенезу ДГПЖ и РПЖ и эффективности различных патогномоничных терапевтических подходов в профилактике данных заболеваний.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>прогестерон</kwd><kwd>доброкачественная гиперплазия предстательной железы</kwd><kwd>ДГПЖ</kwd><kwd>тестостерон</kwd><kwd>эстрадиол</kwd><kwd>мужчины</kwd></kwd-group><kwd-group xml:lang="en"><kwd>progesterone</kwd><kwd>benign prostatic hyperplasia</kwd><kwd>BPH</kwd><kwd>testosterone</kwd><kwd>estradiol</kwd><kwd>men</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Авторы заявляют об отсутствии финансовой поддержки</funding-statement><funding-statement xml:lang="en">The authors declare no funding</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Cannarella R., Condorelli R.A., Barbagallo F. et al. Endocrinology of the aging prostate: current concepts. Front Endocrinol (Laussane). 2021;12:554078. https://doi.org/10.3389/fendo.2021.554078.</mixed-citation><mixed-citation xml:lang="en">Cannarella R., Condorelli R.A., Barbagallo F. et al. Endocrinology of the aging prostate: current concepts. Front Endocrinol (Laussane). 2021;12:554078. https://doi.org/10.3389/fendo.2021.554078.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Vuichoud C., Loughlin K.R. Benign prostatic hyperplasia: epidemiology, economics and evaluation. Can J Urol. 2015;22(Suppl 1):1–6.</mixed-citation><mixed-citation xml:lang="en">Vuichoud C., Loughlin K.R. Benign prostatic hyperplasia: epidemiology, economics and evaluation. Can J Urol. 2015;22(Suppl 1):1–6.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30. https://doi.org/10.3322/caac.21332.</mixed-citation><mixed-citation xml:lang="en">Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30. https://doi.org/10.3322/caac.21332.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">De Santis C.E., Siegel R.L., Sauer A.G. et al. Cancer statistics for African Americans, 2016: progress and opportunities in reducing racial disparities. CA Cancer J Clin. 2016;66(4):290–308. https://doi.org/10.3322/caac.21340.</mixed-citation><mixed-citation xml:lang="en">De Santis C.E., Siegel R.L., Sauer A.G. et al. Cancer statistics for African Americans, 2016: progress and opportunities in reducing racial disparities. CA Cancer J Clin. 2016;66(4):290–308. https://doi.org/10.3322/caac.21340.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Rohrmann S., Nelson W.G., Rifai N. et al. Serum estrogen, but not testosterone, levels differ between black and white men in a nationally representative sample of Americans. J Clin Endocrinol Metab. 2007;92(7):2519–25. https://doi.org/10.1210/jc.2007-0028.</mixed-citation><mixed-citation xml:lang="en">Rohrmann S., Nelson W.G., Rifai N. et al. Serum estrogen, but not testosterone, levels differ between black and white men in a nationally representative sample of Americans. J Clin Endocrinol Metab. 2007;92(7):2519–25. https://doi.org/10.1210/jc.2007-0028.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Williams V.L., Awasthi S., Fink A.K. et al. African-American men and prostate cancer-specific mortality: a competing risk analysis of a large institutional cohort, 1989-2015. Cancer Med. 2018;7(5):2160–71. https://doi.org/10.1002/cam4.1451.</mixed-citation><mixed-citation xml:lang="en">Williams V.L., Awasthi S., Fink A.K. et al. African-American men and prostate cancer-specific mortality: a competing risk analysis of a large institutional cohort, 1989-2015. Cancer Med. 2018;7(5):2160–71. https://doi.org/10.1002/cam4.1451.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Каприн А.Д., Алексеев Б.Я., Матвеев В.Б. и др. Рак предстательной железы. Клинические рекомендации. Современная oнкология. 2021;23(2):211–47. https://doi.org/10.26442/18151434.2021.2.200959.</mixed-citation><mixed-citation xml:lang="en">Kaprin A.D., Alekseev B.Ia., Matveev V.B. et al. Prostate cancer. [Rak predstatel'noj zhelezy. Klinicheskie rekomendacii]. Sovremennaya onkologiya. 2021;23(2):211–47. (In Russ.). https://doi.org/10.26442/18151434.2021.2.200959.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Rider J.R., Wilson K.W., Sinnott J.A. et al. Ejaculation frequency and risk of prostate cancer: updated results with an additional decade of follow-up. Eur Urol. 2016;70(6):974–82. https://doi.org/10.1016/j.eururo.2016.03.027.</mixed-citation><mixed-citation xml:lang="en">Rider J.R., Wilson K.W., Sinnott J.A. et al. Ejaculation frequency and risk of prostate cancer: updated results with an additional decade of follow-up. Eur Urol. 2016;70(6):974–82. https://doi.org/10.1016/j.eururo.2016.03.027.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Pernar C.H., Ebot E.M., Wilson K.M., Mucci L.A. The epidemiology of prostate cancer. Cold Spring Harb Perspect Med. 2018;8(12):a030361. https://doi.org/10.1101/cshperspect.a030361.</mixed-citation><mixed-citation xml:lang="en">Pernar C.H., Ebot E.M., Wilson K.M., Mucci L.A. The epidemiology of prostate cancer. Cold Spring Harb Perspect Med. 2018;8(12):a030361. https://doi.org/10.1101/cshperspect.a030361.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Дедов И.И., Мельниченко Г.А., Фадеев В.Ф. Руководство по эндокринологии. M.: ГЭОТАР-Медиа, 2007. 432 с.</mixed-citation><mixed-citation xml:lang="en">Dedov I.I., Melnichenko G.A., Fadeev V.F. Guide to endocrinology. [Rukovodstvo po endokrinologii]. Moscow: GEOTAR-Media, 2007. 432 p. (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Зильбер А.П. Синдромы сонного апноэ: клиническая физиология, лечение, профилактика. Петрозаводск: Изд-во Петрозаводского университета, 1994. 184 с.</mixed-citation><mixed-citation xml:lang="en">Zilber A.P. Sleep apnea syndromes: clinical physiology, treatment, prevention. [Sindromy sonnogo apnoe: klinicheskaya fiziologiya, lechenie, profilaktika]. Petrozavodsk: Izd-vo Petrozavodskogo universiteta, 1994. 184 р. (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Al-Shboul O.A., Mustafa A.G., Omar A.A. et al. Effect of progesterone on nitric oxide/cyclic guanosine monophosphate signaling and contraction in gastric smooth muscle cells. Biomed Rep. 2018;9(6):511–6. https://doi.org/10.3892/br.2019.1251.</mixed-citation><mixed-citation xml:lang="en">Al-Shboul O.A., Mustafa A.G., Omar A.A. et al. Effect of progesterone on nitric oxide/cyclic guanosine monophosphate signaling and contraction in gastric smooth muscle cells. Biomed Rep. 2018;9(6):511–6. https://doi.org/10.3892/br.2019.1251.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Alqudah M., Al-Shboul O., Al Dwairi A. et al. Progesterone inhibitory role on gastrointestinal motility. Physiol Res. 2022;71(2):193–8. https://doi.org/10.33549/physiolres.934824.</mixed-citation><mixed-citation xml:lang="en">Alqudah M., Al-Shboul O., Al Dwairi A. et al. Progesterone inhibitory role on gastrointestinal motility. Physiol Res. 2022;71(2):193–8. https://doi.org/10.33549/physiolres.934824.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Shackleton C., Malunowicz E. Apparent pregnene hydroxylation deﬁciency (APDH): seekingthe parentage of an orphan metabolome. Steroids. 2003;68(9):707–17. https://doi.org/10.1016/s0039-128x(03)00115-6.</mixed-citation><mixed-citation xml:lang="en">Shackleton C., Malunowicz E. Apparent pregnene hydroxylation deﬁciency (APDH): seekingthe parentage of an orphan metabolome. Steroids. 2003;68(9):707–17. https://doi.org/10.1016/s0039-128x(03)00115-6.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Oettel M., Mukhopadhyay A.K. Progesterone: the forgotten hormone in man. Aging Male. 2004;7(3):236–57. https://doi.org/10.1080/13685530400004199.</mixed-citation><mixed-citation xml:lang="en">Oettel M., Mukhopadhyay A.K. Progesterone: the forgotten hormone in man. Aging Male. 2004;7(3):236–57. https://doi.org/10.1080/13685530400004199.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Федотчева Т.А. Клиническое применение прогестинов и механизмы их действия: настоящее и будущее (обзор). Современные технологии в медицине. 2021;13(1):93–108. https://doi.org/10.17691/stm2021.13.1.11.</mixed-citation><mixed-citation xml:lang="en">Fedotcheva T.A. Clinical use of progestins and their mechanisms of action: present and future (review). [Klinicheskoe primenenie progestinov i mekhanizmy ih dejstviya: nastoyashchee i budushchee (obzor)]. Sovremennye tekhnologii v medicine. 2021;13(1):93–108. (In Russ.). https://doi.org/10.17691/stm2021.13.1.11.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Graham J.D., Clarcke C.L. Physiological action of progesterone in target tissues. Endocr Rev. 1997;18(4):502–19. https://doi.org/10.1210/edrv.18.4.0308.</mixed-citation><mixed-citation xml:lang="en">Graham J.D., Clarcke C.L. Physiological action of progesterone in target tissues. Endocr Rev. 1997;18(4):502–19. https://doi.org/10.1210/edrv.18.4.0308.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Kuhl H. Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric. 2005;8 Suppl 1:3–63. https://doi.org/10.1080/13697130500148875.</mixed-citation><mixed-citation xml:lang="en">Kuhl H. Pharmacology of estrogens and progestogens: influence of different routes of administration. Climacteric. 2005;8 Suppl 1:3–63. https://doi.org/10.1080/13697130500148875.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Якушевская О.В. Современные подходы к назначению прогестерона в практике акушера-гинеколога. Эффективная фармакотерапия. Акушерство и гинекология. 2012;(4):12–6.</mixed-citation><mixed-citation xml:lang="en">Yakushevskaya O.V. Modern approaches to the appointment of progesterone in the practice of an obstetrician-gynecologist. [Sovremennye podhody k naznacheniyu progesterona v praktike akushera-ginekologa]. Effektivnaya farmakoterapiya. Akusherstvo i ginekologiya. 2012;(4):12–6. (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Baranizadeh K., Mahboobian M.M., Amiri I. et al. Effects of progesterone nanoparticles on the sperm capacitation and acrosome reaction in asthenozoospermia men. Andrologia. 2022;54(1):e14258. https://doi.org/10.1111/and.14258.</mixed-citation><mixed-citation xml:lang="en">Baranizadeh K., Mahboobian M.M., Amiri I. et al. Effects of progesterone nanoparticles on the sperm capacitation and acrosome reaction in asthenozoospermia men. Andrologia. 2022;54(1):e14258. https://doi.org/10.1111/and.14258.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Sutter-Dub M. Rapid non-genomic and genomic responses to progestogens, estrogens, and glucocorticoids in the endocrine pancreatic B cell, the adipocyte and other cell types. Steroids. 2002;67(2):77–93. https://doi.org/10.1016/s0039-128x(01)00142-8.</mixed-citation><mixed-citation xml:lang="en">Sutter-Dub M. Rapid non-genomic and genomic responses to progestogens, estrogens, and glucocorticoids in the endocrine pancreatic B cell, the adipocyte and other cell types. Steroids. 2002;67(2):77–93. https://doi.org/10.1016/s0039-128x(01)00142-8.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Ghandehari S., Matusov Y., Pepkowitz S. 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. https://doi.org/10.1016/j.chest.2021.02.024.</mixed-citation><mixed-citation xml:lang="en">Ghandehari S., Matusov Y., Pepkowitz S. 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. https://doi.org/10.1016/j.chest.2021.02.024.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Beltrame A., Salguero P., Rossi E. et al. Immunometabolic mechanisms underlying the severity of COVID-19. Viral Immunol. 2022;13:1–10. https://doi.org/10.3389/fimmu.2022.834851.</mixed-citation><mixed-citation xml:lang="en">Beltrame A., Salguero P., Rossi E. et al. Immunometabolic mechanisms underlying the severity of COVID-19. Viral Immunol. 2022;13:1–10. https://doi.org/10.3389/fimmu.2022.834851.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Mauvais-Jarvis F., Klein S.L., Levin E.R. Estradiol, progesterone, immunomodulation, and COVID-19 outcomes. Endocrinology. 2020;161(9):bqaa127. https://doi.org/10.1210/endocr/bqaa127.</mixed-citation><mixed-citation xml:lang="en">Mauvais-Jarvis F., Klein S.L., Levin E.R. Estradiol, progesterone, immunomodulation, and COVID-19 outcomes. Endocrinology. 2020;161(9):bqaa127. https://doi.org/10.1210/endocr/bqaa127.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Physicians desk reference. Montvale N.J.: Thomson P.D.R., 2006. 60th ed. 3529 p.</mixed-citation><mixed-citation xml:lang="en">Physicians desk reference. Montvale N.J.: Thomson P.D.R., 2006. 60th ed. 3529 p.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Garg D., Ng S.S.M., Baig K.M. et al. Progesterone-mediated non-classical signaling. Trends Endocrinol Metab. 2017;28(9):656–68. https://doi.org/10.1016/j.tem.2017.05.006.</mixed-citation><mixed-citation xml:lang="en">Garg D., Ng S.S.M., Baig K.M. et al. Progesterone-mediated non-classical signaling. Trends Endocrinol Metab. 2017;28(9):656–68. https://doi.org/10.1016/j.tem.2017.05.006.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Wetendorf M., DeMayo F.J. Progesterone receptor signaling in the initiation of pregnancy and preservation of a healthy uterus. Int J Dev Biol. 2014;58(2–4):95–106. https://doi.org/10.1387/ijdb.140069mw.</mixed-citation><mixed-citation xml:lang="en">Wetendorf M., DeMayo F.J. Progesterone receptor signaling in the initiation of pregnancy and preservation of a healthy uterus. Int J Dev Biol. 2014;58(2–4):95–106. https://doi.org/10.1387/ijdb.140069mw.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Valadez-Cosmes P., Vázquez-Martínez E.R., Cerbon M., Camacho-Arroyo I. Membrane progesterone receptors in reproduction and cancer. Mol Cell Endocrinol. 2016;434:166–75. https://doi.org/10.1016/j.mce.2016.06.027.</mixed-citation><mixed-citation xml:lang="en">Valadez-Cosmes P., Vázquez-Martínez E.R., Cerbon M., Camacho-Arroyo I. Membrane progesterone receptors in reproduction and cancer. Mol Cell Endocrinol. 2016;434:166–75. https://doi.org/10.1016/j.mce.2016.06.027.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Kolatorova L., Vitku J., Suchopar J. et al. Progesterone: a steroid with wide range of effects in physiology as well as human medicine. Int J Mol Sci. 2022;23(14):7989. https://doi.org/10.3390/ijms23147989.</mixed-citation><mixed-citation xml:lang="en">Kolatorova L., Vitku J., Suchopar J. et al. Progesterone: a steroid with wide range of effects in physiology as well as human medicine. Int J Mol Sci. 2022;23(14):7989. https://doi.org/10.3390/ijms23147989.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Haseroth K., Christ M., Falkenstein E., Wehling M. Aldosterone- and progesterone-membrane-binding proteins: new concepts of nongenomic steroid action. Curr Protein Pept Sci. 2000;1(4):385–401. https://doi.org/10.2174/1389203003381270.</mixed-citation><mixed-citation xml:lang="en">Haseroth K., Christ M., Falkenstein E., Wehling M. Aldosterone- and progesterone-membrane-binding proteins: new concepts of nongenomic steroid action. Curr Protein Pept Sci. 2000;1(4):385–401. https://doi.org/10.2174/1389203003381270.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Falkenstein E., Heck M., Gerdes D. et al. Specific progesterone binding to a membrane protein and related nongenomic effects on Ca2+-fluxes in sperm. Endocrinology. 1999;140(12):5999–6002. https://doi.org/10.1210/endo.140.12.7304.</mixed-citation><mixed-citation xml:lang="en">Falkenstein E., Heck M., Gerdes D. et al. Specific progesterone binding to a membrane protein and related nongenomic effects on Ca2+-fluxes in sperm. Endocrinology. 1999;140(12):5999–6002. https://doi.org/10.1210/endo.140.12.7304.</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Falkenstein E., Tillmann H.C., Christ M. et al. Multiple actions of steroid hormones-a focus on rapid, nongenomic effects. Pharmacol Rev. 2000;52(4):513–56. https://doi.org/10.1016/S0031-6997(24)01468-6.</mixed-citation><mixed-citation xml:lang="en">Falkenstein E., Tillmann H.C., Christ M. et al. Multiple actions of steroid hormones-a focus on rapid, nongenomic effects. Pharmacol Rev. 2000;52(4):513–56. https://doi.org/10.1016/S0031-6997(24)01468-6.</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Simoncini T., Genazzani A.R. Non-genomic actions of sex steroid hormones. Eur J Endocrinol. 2003;148(3):281–92. https://doi.org/10.1530/eje.0.1480281.</mixed-citation><mixed-citation xml:lang="en">Simoncini T., Genazzani A.R. Non-genomic actions of sex steroid hormones. Eur J Endocrinol. 2003;148(3):281–92. https://doi.org/10.1530/eje.0.1480281.</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Conneely O.M., Lydon J.P. Progesterone receptors in reproduction: functional impact of the A and B isoforms. Steroids. 2000;65(10–11):571–7. https://doi.org/10.1016/s0039-128x(00)00115-x.</mixed-citation><mixed-citation xml:lang="en">Conneely O.M., Lydon J.P. Progesterone receptors in reproduction: functional impact of the A and B isoforms. Steroids. 2000;65(10–11):571–7. https://doi.org/10.1016/s0039-128x(00)00115-x.</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Cassidenti D.L., Paulson R.J., Serafini P. et al. Effects of sex steroids on skin 5 alpha-reductase activity in vitro. Obstet Gynecol. 1991;78(1):103–7.</mixed-citation><mixed-citation xml:lang="en">Cassidenti D.L., Paulson R.J., Serafini P. et al. Effects of sex steroids on skin 5 alpha-reductase activity in vitro. Obstet Gynecol. 1991;78(1):103–7.</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Hou Z., Huang S., Mei Z. et al. Inhibiting 3βHSD1 to eliminate the oncogenic effects of progesterone in prostate cancer. Cell Rep Med. 2022;3(3):100561. https://doi.org/10.1016/j.xcrm.2022.100561.</mixed-citation><mixed-citation xml:lang="en">Hou Z., Huang S., Mei Z. et al. Inhibiting 3βHSD1 to eliminate the oncogenic effects of progesterone in prostate cancer. Cell Rep Med. 2022;3(3):100561. https://doi.org/10.1016/j.xcrm.2022.100561.</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Chen G., Shi J.-X., Qi M. et al. Effects of progesterone on intestinal inflammatory response, mucosa structure alterations, and apoptosis following traumatic brain injury in male rats. J Surg Res. 2008;147(1):92–8. https://doi.org/10.1016/j.jss.2007.05.029.</mixed-citation><mixed-citation xml:lang="en">Chen G., Shi J.-X., Qi M. et al. Effects of progesterone on intestinal inflammatory response, mucosa structure alterations, and apoptosis following traumatic brain injury in male rats. J Surg Res. 2008;147(1):92–8. https://doi.org/10.1016/j.jss.2007.05.029.</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Nalli A.D., Kumar D.P., Mahavadi S. et al. Hypercontractility of intestinal longitudinal smooth muscle induced by cytokines is mediated by the nuclear factor-κB/AMP-activated kinase/myosin light chain kinase pathway. J Pharmacol Exp Therap. 2014;350(1):89–98. https://doi.org/10.1124/jpet.113.212522.</mixed-citation><mixed-citation xml:lang="en">Nalli A.D., Kumar D.P., Mahavadi S. et al. Hypercontractility of intestinal longitudinal smooth muscle induced by cytokines is mediated by the nuclear factor-κB/AMP-activated kinase/myosin light chain kinase pathway. J Pharmacol Exp Therap. 2014;350(1):89–98. https://doi.org/10.1124/jpet.113.212522.</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Pang Y., Dong J., Thomas P. Progesterone increases nitric oxide synthesis in human vascular endothelial cells through activation of membrane progesterone receptor-α. Am J Physiol Endocrinol Metab. 2015;308(10):E899–E911. https://doi.org/10.1152/ajpendo.00527.2014.</mixed-citation><mixed-citation xml:lang="en">Pang Y., Dong J., Thomas P. Progesterone increases nitric oxide synthesis in human vascular endothelial cells through activation of membrane progesterone receptor-α. Am J Physiol Endocrinol Metab. 2015;308(10):E899–E911. https://doi.org/10.1152/ajpendo.00527.2014.</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Andriole G.L., Humphrey P., Ray P. et al. Effect of the dual 5alpha-reductase inhibitor dutasteride on markers of tumor regression in prostate cancer. J Urol. 2004;172(3):915–9. https://doi.org/10.1097/01.ju.0000136430.37245.b9.</mixed-citation><mixed-citation xml:lang="en">Andriole G.L., Humphrey P., Ray P. et al. Effect of the dual 5alpha-reductase inhibitor dutasteride on markers of tumor regression in prostate cancer. J Urol. 2004;172(3):915–9. https://doi.org/10.1097/01.ju.0000136430.37245.b9.</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Clark R.V., Hermann D.J., Cunningham G.R. et al. Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor. J Clin Endocrinol Metab. 2004;89(5):2179–84. https://doi.org/10.1210/jc.2003-030330.</mixed-citation><mixed-citation xml:lang="en">Clark R.V., Hermann D.J., Cunningham G.R. et al. Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor. J Clin Endocrinol Metab. 2004;89(5):2179–84. https://doi.org/10.1210/jc.2003-030330.</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">McConnell J.D., Wilson J.D., George F.W. et al. Finasteride, an inhibitor of 5 alpha-reductase, suppresses prostatic dihydrotestosterone in men with benign prostatic hyperplasia. J Clin Endocrinol Metab. 1992;74(3):505–8. https://doi.org/10.1210/jcem.74.3.1371291.</mixed-citation><mixed-citation xml:lang="en">McConnell J.D., Wilson J.D., George F.W. et al. Finasteride, an inhibitor of 5 alpha-reductase, suppresses prostatic dihydrotestosterone in men with benign prostatic hyperplasia. J Clin Endocrinol Metab. 1992;74(3):505–8. https://doi.org/10.1210/jcem.74.3.1371291.</mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">Span P.N., Voller M.C., Smals A.G. et al Selectivity of finasteride as an in vivo inhibitor of 5alpha-reductase isozyme enzymatic activity in the human prostate. J Urol. 1999;161(1):332–7.</mixed-citation><mixed-citation xml:lang="en">Span P.N., Voller M.C., Smals A.G. et al Selectivity of finasteride as an in vivo inhibitor of 5alpha-reductase isozyme enzymatic activity in the human prostate. J Urol. 1999;161(1):332–7.</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</label><citation-alternatives><mixed-citation xml:lang="ru">Wu Y., Godoy A., Azzouni F. et al. Prostate cancer cells differ in testosterone accumulation, dihydrotestosterone conversion, and androgen receptor signaling response to steroid 5α-reductase inhibitors. Prostate. 2013;73(13):1470–82. https://doi.org/10.1002/pros.22694.</mixed-citation><mixed-citation xml:lang="en">Wu Y., Godoy A., Azzouni F. et al. Prostate cancer cells differ in testosterone accumulation, dihydrotestosterone conversion, and androgen receptor signaling response to steroid 5α-reductase inhibitors. Prostate. 2013;73(13):1470–82. https://doi.org/10.1002/pros.22694.</mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">Lazier C.B., Thomas L.N., Douglas R.C. et al. Dutasteride, the dual 5alpha-reductase inhibitor, inhibits androgen action and promotes cell death in the LNCaP prostate cancer cell line. Prostate. 2004;58(2):130–44. https://doi.org/10.1002/pros.10340.</mixed-citation><mixed-citation xml:lang="en">Lazier C.B., Thomas L.N., Douglas R.C. et al. Dutasteride, the dual 5alpha-reductase inhibitor, inhibits androgen action and promotes cell death in the LNCaP prostate cancer cell line. Prostate. 2004;58(2):130–44. https://doi.org/10.1002/pros.10340.</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru">Wu Y., Chhipa R.R., Zhang H., Ip C. The antiandrogenic effect of finasteride against a mutant androgen receptor. Cancer Biol Ther. 2011;11(10):902–9. https://doi.org/10.4161/cbt.11.10.15187.</mixed-citation><mixed-citation xml:lang="en">Wu Y., Chhipa R.R., Zhang H., Ip C. The antiandrogenic effect of finasteride against a mutant androgen receptor. Cancer Biol Ther. 2011;11(10):902–9. https://doi.org/10.4161/cbt.11.10.15187.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
