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1. List of contributors

Author

Adams, John S., primary, Amrein, Karin, additional, Anderson, Paul H., additional, Arnold, Leggy A., additional, Arora, Juhi, additional, Artusa, Patricio, additional, Ascherio, Alberto, additional, Asmussen, Niels C., additional, Astier, Anne L., additional, Bak, Min Ji, additional, Bauerle, Kevin T., additional, Belorusova, Anna Y., additional, Benkusky, Nancy A., additional, Bernal-Mizrachi, Carlos, additional, Bhattoa, Harjit P., additional, Bikle, Daniel D., additional, Bilezikian, John P., additional, Binkley, Neil C., additional, Bischoff-Ferrari, Heike A., additional, Bishop, Charles W., additional, Blomberg Jensen, Martin, additional, Boisen, Ida Marie, additional, Boucher, Barbara J., additional, Bouillon, Roger, additional, Boyan, Barbara D., additional, Bradford, Dana, additional, Brancatella, Alessandro, additional, Buburuzan, Laura, additional, Burne, Thomas H.J., additional, Buschittari, Damien, additional, Calkins, Hannah, additional, Calvo, Mona S., additional, Camargo, Carlos A., additional, Campbell, Moray J., additional, Cantorna, Margherita T., additional, Cappellani, Daniele, additional, Carlberg, Carsten, additional, Carmeliet, Geert, additional, Cashman, Kevin D., additional, Ceglia, Lisa, additional, Cetani, Filomena, additional, Chang, Wenhan, additional, Cheadle, Charlotte, additional, Chou, Sharon H., additional, Christakos, Sylvia, additional, Christopher, Kenneth B., additional, Chu, Emily Y., additional, Chun, Rene F., additional, Cleal, Jane K., additional, Cobice, Diego F., additional, Cooper, Cyrus, additional, Coort, Susan L.M., additional, Cui, Xiaoying, additional, Curtis, Elizabeth M., additional, Danilenko, Michael, additional, Darling, Andrea L., additional, David Roodman, G., additional, Dawson-Hughes, Bess, additional, de Jongh, Renate, additional, Demay, Marie B., additional, Dennison, Elaine M., additional, Dixon, Katie M., additional, Dong, Bingning, additional, Doroudi, Maryam, additional, Dusso, Adriana, additional, Dvorzhinskiy, Aleksey, additional, Ebeling, Peter R., additional, Erben, Reinhold G., additional, Evelo, Chris T.A., additional, Eyles, Darryl, additional, Feldman, David, additional, Ferrer-Mayorga, Gemma, additional, Fleet, James C., additional, Forcellati, Marianela, additional, Foster, Brian L., additional, Gafni, Rachel I., additional, Gayan-Ramirez, Ghislaine, additional, Giovannucci, Edward, additional, Girgis, Christian M., additional, Glencross, Drew A., additional, Glorieux, Francis H., additional, Gocek, Elzbieta, additional, Goldfarb, David S., additional, Goltzman, David, additional, González-Sancho, José Manuel, additional, Grant, William B., additional, Groves, Natalie J., additional, Gysemans, Conny, additional, Harrison, Stephanie, additional, Harvey, Nicholas C., additional, Haseltine, Katherine, additional, Hawrylowicz, Catherine M., additional, Hayes, Colleen E., additional, Heckel, John E., additional, Hershberger, Pamela A., additional, Hewison, Martin, additional, Högler, Wolfgang, additional, Holick, Michael F., additional, Hollis, Bruce W., additional, Holt, Rune, additional, Hujoel, Philippe P., additional, Hyppönen, Elina, additional, Ismailova, Aiten, additional, Jablonski, Nina G., additional, Jakobsen, Jette, additional, Janssens, Wim, additional, Jeffery, Louisa, additional, Jenkinson, Carl, additional, Jensen, Marie Bagge, additional, Jetten, Anton M., additional, Jiang, Heng, additional, Johnson, Candace S., additional, Jones, Glenville, additional, Jones, Kerry S., additional, Jüppner, Harald, additional, Kalia, Vandana, additional, Kallay, Enikö, additional, Karapalis, Andrew C., additional, Kaufmann, Martin, additional, Kiely, Mairead, additional, Kim, Hanseul, additional, Kim, Tiffany Y., additional, Kojima, Hiroyuki, additional, Kooij, Ireen, additional, Kovacs, Christopher S., additional, Kremer, Richard, additional, Krieger, Kirsten, additional, Kritmetapak, Kittrawee, additional, Krueger, Diane C., additional, Kumar, Rajiv, additional, Kurihara, Noriyoshi, additional, Lane, Joseph M., additional, Lanham-New, Susan A., additional, Latic, Nejla, additional, LeBoff, Meryl S., additional, Lee, Maija B., additional, Lee, Seong Min, additional, Levine, Michael A., additional, Lewis, Richard, additional, Lewis, Rohan M., additional, Li, Wei, additional, Li, Yan Chun, additional, Lincoln, Matthew R., additional, Lips, Paul, additional, Lisse, Thomas S., additional, Liu, Eva S., additional, López de Maturana, Evangelina, additional, Lugg, Sebastian T., additional, Machado, Christopher J., additional, Maes, Karen, additional, Maestro, Miguel A., additional, Malats, Núria, additional, Malloy, Peter J., additional, Manousaki, Despoina, additional, Marcinkowska, Ewa, additional, Marcocci, Claudio, additional, Martens, Pieter-Jan, additional, Martineau, Adrian R., additional, Mason, Rebecca S., additional, Mathieu, Chantal, additional, Mayne, Phoebe, additional, McGrath, John J., additional, Mehta, Mansi, additional, Mellanby, Richard John, additional, Merchant, Nadia, additional, Meyer, Mark B., additional, Miao, Dengshun, additional, Moon, Rebecca J., additional, Mortensen, Li Juel, additional, Motlaghzadeh, Yasaman, additional, Munger, Kassandra L., additional, Muñoz, Alberto, additional, Nakamichi, Yuko, additional, Narvaez, Carmen J., additional, Nikiphorou, Elena, additional, Nonn, Larisa, additional, Pal, Lubna, additional, Parekh, Dhruv, additional, Pettifor, John M., additional, Pike, J. Wesley, additional, Pilz, Stefan, additional, Pittas, Anastassios G., additional, Pludowski, Pawel, additional, Prosser, David E., additional, Pullagura, Sri Ramulu N., additional, Raphael, Joseph, additional, Rauz, Saaeha, additional, Raza, Karim, additional, Real, Francisco X., additional, Reichrath, Jörg, additional, Richards, J. Brent, additional, Rivadeneira, Fernando, additional, Rochel, Natacha, additional, Roizen, Jeffrey D., additional, Ryan, Brittany A., additional, Sarkar, Surojit, additional, Sarmadi, Fatemeh, additional, Schafer, Anne L., additional, Schepelmann, Martin, additional, Schoenmakers, Inez, additional, Schuit, Frans, additional, Schwartz, Zvi, additional, Scott, Kayla M., additional, Sellmeyer, Deborah E., additional, Sempos, Christopher T., additional, Sepiashvili, Lusia, additional, Seshadri, Mukund, additional, Shane, Elizabeth, additional, Shaurova, Tatiana, additional, Shieh, Albert, additional, Shui, Irene, additional, Singh, Ravinder J., additional, Slominski, Andrzej T., additional, Smith, Karl W., additional, St-Arnaud, René, additional, Stein, Emily M., additional, Studzinski, George P., additional, Suda, Tatsuo, additional, Takahashi, Naoyuki, additional, Taylor, Hugh S., additional, Tebben, Peter J., additional, Thacher, Tom D., additional, Thandrayen, Kebashni, additional, Thickett, David R., additional, Tiosano, Dov, additional, Trajanoska, Katerina, additional, Tu, Chia-Ling, additional, Tuckey, Robert C., additional, Tutaworn, Teerapat, additional, Udagawa, Nobuyuki, additional, Uday, Suma, additional, Unnanuntana, Aasis, additional, van Driel, Marjolein, additional, van Leeuwen, Johannes P.T.M., additional, van Schoor, Natasja, additional, Verlinden, Lieve, additional, Vieth, Reinhold, additional, Vimaleswaran, Karina S., additional, Wagner, Carol L., additional, Wallace, Graham R., additional, Weaver, Connie M., additional, Webb, Daniel A., additional, Welsh, JoEllen, additional, White, John H., additional, Whiting, Susan J., additional, Williams, Emma L., additional, Yahyavi, Sam Kafai, additional, Yamamoto, Keiko, additional, Yates, Clayton, additional, Zagorac, Sladjana, additional, Zhang, Rong Mei, additional, Zhao, Hengguang, additional, Zhou, Ang, additional, and Zittermann, Armin, additional

Published
2024
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7. Menopausal hormone therapy and women's health: An umbrella review

Author

Zhang, Guo-Qiang, Chen, Jin-Liang, Luo, Ying, Mathur, Maya B., Anagnostis, Panagiotis, Nurmatov, Ulugbek, Talibov, Madar, Zhang, Jing, Hawrylowicz, Catherine M., Lumsden, Mary Ann, Critchley, Hilary, Sheikh, Aziz, Lundbäck, Bo, Lässer, Cecilia, Kankaanranta, Hannu, Lee, Siew Hwa, and Nwaru, Bright I.

Subjects
Women -- Health aspects, Hormone therapy -- Patient outcomes -- Complications and side effects, Menopause -- Patient outcomes -- Complications and side effects, Biological sciences
Abstract

Background There remains uncertainty about the impact of menopausal hormone therapy (MHT) on women's health. A systematic, comprehensive assessment of the effects on multiple outcomes is lacking. We conducted an umbrella review to comprehensively summarize evidence on the benefits and harms of MHT across diverse health outcomes. Methods and findings We searched MEDLINE, EMBASE, and 10 other databases from inception to November 26, 2017, updated on December 17, 2020, to identify systematic reviews or meta-analyses of randomized controlled trials (RCTs) and observational studies investigating effects of MHT, including estrogen-alone therapy (ET) and estrogen plus progestin therapy (EPT), in perimenopausal or postmenopausal women in all countries and settings. All health outcomes in previous systematic reviews were included, including menopausal symptoms, surrogate endpoints, biomarkers, various morbidity outcomes, and mortality. Two investigators independently extracted data and assessed methodological quality of systematic reviews using the updated 16-item AMSTAR 2 instrument. Random-effects robust variance estimation was used to combine effect estimates, and 95% prediction intervals (PIs) were calculated whenever possible. We used the term MHT to encompass ET and EPT, and results are presented for MHT for each outcome, unless otherwise indicated. Sixty systematic reviews were included, involving 102 meta-analyses of RCTs and 38 of observational studies, with 102 unique outcomes. The overall quality of included systematic reviews was moderate to poor. In meta-analyses of RCTs, MHT was beneficial for vasomotor symptoms (frequency: 9 trials, 1,104 women, risk ratio [RR] 0.43, 95% CI 0.33 to 0.57, p < 0.001; severity: 7 trials, 503 women, RR 0.29, 95% CI 0.17 to 0.50, p = 0.002) and all fracture (30 trials, 43,188 women, RR 0.72, 95% CI 0.62 to 0.84, p = 0.002, 95% PI 0.58 to 0.87), as well as vaginal atrophy (intravaginal ET), sexual function, vertebral and nonvertebral fracture, diabetes mellitus, cardiovascular mortality (ET), and colorectal cancer (EPT), but harmful for stroke (17 trials, 37,272 women, RR 1.17, 95% CI 1.05 to 1.29, p = 0.027) and venous thromboembolism (23 trials, 42,292 women, RR 1.60, 95% CI 0.99 to 2.58, p = 0.052, 95% PI 1.03 to 2.99), as well as cardiovascular disease incidence and recurrence, cerebrovascular disease, nonfatal stroke, deep vein thrombosis, gallbladder disease requiring surgery, and lung cancer mortality (EPT). In meta-analyses of observational studies, MHT was associated with decreased risks of cataract, glioma, and esophageal, gastric, and colorectal cancer, but increased risks of pulmonary embolism, cholelithiasis, asthma, meningioma, and thyroid, breast, and ovarian cancer. ET and EPT had opposite effects for endometrial cancer, endometrial hyperplasia, and Alzheimer disease. The major limitations include the inability to address the varying effects of MHT by type, dose, formulation, duration of use, route of administration, and age of initiation and to take into account the quality of individual studies included in the systematic reviews. The study protocol is publicly available on PROSPERO (CRD42017083412). Conclusions MHT has a complex balance of benefits and harms on multiple health outcomes. Some effects differ qualitatively between ET and EPT. The quality of available evidence is only moderate to poor., Author(s): Guo-Qiang Zhang 1,*, Jin-Liang Chen 2, Ying Luo 3, Maya B. Mathur 4, Panagiotis Anagnostis 5, Ulugbek Nurmatov 6, Madar Talibov 7, Jing Zhang 8, Catherine M. Hawrylowicz 9, [...]

Published
2021
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9. List of Contributors

Author

Adams, John S., primary, Adams, Judith E., additional, Alsalem, Jawaher A., additional, Anderson, Paul H., additional, Andreopoulou, Panagiota, additional, Angellotti, Edith, additional, Arnold, Leggy A., additional, Atkins, Gerald J., additional, Barbáchano, Antonio, additional, Bassuk, Shari S., additional, Beaudin, Sarah, additional, Belorusova, Anna Y., additional, Benkusky, Nancy A., additional, Bernal-Mizrachi, Carlos, additional, Bhan, Ishir, additional, Bhattoa, Harjit P., additional, Bikle, Daniel D., additional, Bilezikian, John P., additional, Binkley, Neil C., additional, Bischoff-Ferrari, Heike A., additional, Bishop, Charles W., additional, Boisen, Ida M., additional, Bonelli, Fabrizio, additional, Boskey, Adele L., additional, Boucher, Barbara J., additional, Bouillon, Roger, additional, Bouttier, Manuella, additional, Boyan, Barbara D., additional, Bruce, Danny, additional, Buburuzan, Laura, additional, Burghardt, Andrew J., additional, Burne, Thomas H.J., additional, Calvo, Mona S., additional, Camargo Jr., Carlos A., additional, Cannata-Andia, Jorge B., additional, Cantorna, Margherita T., additional, Carlberg, Carsten, additional, Carmeliet, Geert, additional, Carpenter, Thomas O., additional, Carter, Graham D., additional, Cashman, Kevin D., additional, Ceglia, Lisa, additional, Christakos, Sylvia, additional, Christopher, Kenneth B., additional, Chun, Rene F., additional, Coe, Fredric L., additional, Coffman, Frederick, additional, Compston, Juliet, additional, Cooper, Cyrus, additional, Curtis, Elizabeth M., additional, Cusano, Natalie E., additional, Danilenko, Michael, additional, David Roodman, G., additional, Dawson-Hughes, Bess, additional, De Clercq, Pierre, additional, DeLuca, Hector F., additional, Demaret, Julie, additional, Demay, Marie B., additional, Dempster, David W., additional, Dennison, Elaine M., additional, Dhawan, Puneet, additional, Dimitrov, Vassil, additional, Dixon, Katie M., additional, Doroudi, Maryam, additional, Doyle, Shevaun M., additional, Dusso, Adriana S., additional, Dvorzhinskiy, Aleksey, additional, Ebeling, Peter R., additional, Eisman, John A., additional, Emkey, Gregory R., additional, Epstein Jr., Ervin H., additional, Epstein, Sol, additional, Eyles, Darryl, additional, Favus, Murray J., additional, Feldman, David, additional, Ferrer-Mayorga, Gemma, additional, Findlay, David M., additional, Fleet, James C., additional, Foster, Brian L., additional, Franceschi, Renny T., additional, Fraser, David R., additional, Furst, Jessica M., additional, Gafni, Rachel I., additional, Giovannucci, Edward, additional, Girgis, Christian M., additional, Gleason, James L., additional, Glorieux, Francis H., additional, Gocek, Elzbieta, additional, Goltzman, David, additional, González-Sancho, José Manuel, additional, Graeff-Armas, Laura A., additional, Grant, William B., additional, Groves, Natalie J., additional, Gysemans, Conny, additional, Hansen, Lasse Bøllehuus, additional, Harvey, Nicholas C., additional, Hawrylowicz, Catherine M., additional, Hayes, Colleen E., additional, Heaney, Robert P., additional, Hendy, Geoffrey N., additional, Hershberger, Pamela A., additional, Hewison, Martin, additional, Holick, Michael F., additional, Hollis, Bruce W., additional, Hujoel, Philippe P., additional, Hyppönen, Elina, additional, Insogna, Karl L., additional, Jablonski, Nina G., additional, Jensen, Martin Blomberg, additional, Jolliffe, David A., additional, Jones, Glenville, additional, Jones, Kerry S., additional, Jüppner, Harald, additional, Kallay, Enikö, additional, Karaplis, Andrew C., additional, Kaufmann, Martin, additional, Kiely, Mairead, additional, Kim, Tiffany Y., additional, Konrad, Martin, additional, Kovacs, Christopher S., additional, Kremer, Richard, additional, Krug, Roland, additional, Kumar, Rajiv, additional, Kurihara, Noriyoshi, additional, Laing, Emma, additional, Lane, Joseph M., additional, Larner, Dean P., additional, Larriba, María Jesús, additional, Laverny, Gilles, additional, Le Roy, Nathalie, additional, Lee, Seong M., additional, Levine, Michael A., additional, Lewis, Richard, additional, Lips, Paul, additional, Lisse, Thomas S., additional, Liu, Eva S., additional, Liu, Philip T., additional, Li, Yan, additional, Li, Yan Chun, additional, MacKrell, James G., additional, Mady, Leila J., additional, Majumdar, Sharmila, additional, Makishima, Makoto, additional, Malloy, Peter J., additional, Mann, Elizabeth H., additional, Manson, JoAnn E., additional, Martineau, Adrian R., additional, Mason, Rebecca S., additional, Mathieu, Chantal, additional, Matsumoto, Toshio, additional, Matthews, Donald G., additional, McGrath, John J., additional, Metzger, Daniel, additional, Meyer, Mark B., additional, Miao, Denshun, additional, Mizwicki, Mathew T., additional, Moon, Rebecca J., additional, Morris, Howard A., additional, Mortensen, Li J., additional, Muñoz, Alberto, additional, Nakamichi, Yuko, additional, Narvaez, Carmen J., additional, Nashold, Faye E., additional, Naveh-Many, Tally, additional, Nielson, Carrie M., additional, Norman, Anthony W., additional, Nys, Yves, additional, Onal, Melda, additional, Pal, Lubna, additional, Patterson, Kristine Y., additional, Pauwels, Steven, additional, Pehrsson, Pamela R., additional, Petkovich, Martin, additional, Pettifor, John M., additional, Pfeffer, Paul E., additional, Phillips, Katherine M., additional, Pike, J. Wesley, additional, Pilz, Stefan, additional, Pittas, Anastassios G., additional, Pludowski, Pawel, additional, Prosser, David E., additional, Pullagura, Sri Ramulu N., additional, Quarles, L. Darryl, additional, Rajagopal, Rithwick, additional, Ransohoff, Katherine J., additional, Rauz, Saaeha, additional, Rebolledo, Brian J., additional, Reichrath, Jörg, additional, Rieger, Sandra, additional, Riek, Amy E., additional, Rochel, Natacha, additional, Roizen, Jeffrey D., additional, Roseland, Janet M., additional, Rosen, Cliff, additional, Rybchyn, Mark S., additional, Saitoh, Hiroshi, additional, Salehi-Tabar, Reyhaneh, additional, Schafer, Anne L., additional, Schlingmann, Karl P., additional, Schoenmakers, Inez, additional, Schwartz, Zvi, additional, Scott, Kayla, additional, Sempos, Christopher T., additional, Sepiashvili, Lusia, additional, Seshadri, Mukund, additional, Shane, Elizabeth, additional, Shaurova, Tatiana, additional, Shui, Irene, additional, Silver, Justin, additional, Singh, Ravinder J., additional, Skingle, Linda, additional, St-Arnaud, René, additional, Starr, Jessica, additional, Stayrook, Keith R., additional, Stein, Emily M., additional, Stites, Ryan E., additional, Studzinski, George P., additional, Suda, Tatsuo, additional, Takahashi, Fumiaki, additional, Takahashi, Naoyuki, additional, Tang, Jean Y., additional, Taylor, Christine L., additional, Taylor, Hugh S., additional, Tebben, Peter J., additional, Thacher, Thomas D., additional, Thadhani, Ravi, additional, Thandrayen, Kebashni, additional, Thys-Jacobs, Susan, additional, Tiosano, Dov, additional, Toni, Roberto, additional, Towler, Dwight A., additional, Trump, Donald L., additional, Udagawa, Nobuyuki, additional, Uitterlinden, André G., additional, Unnanuntana, Aasis, additional, van de Peppel, Jeroen, additional, van der Eerden, Bram C.J., additional, van Driel, Marjolein, additional, van Leeuwen, Johannes P.T.M., additional, van Schoor, Natasja, additional, Vanherwegen, An-Sofie, additional, Vazirnia, Aria, additional, Verlinden, Lieve, additional, Verstuyf, Annemieke, additional, Vieth, Reinhold, additional, Wagner, Carol L., additional, Wallace, Graham R., additional, Weaver, Connie, additional, Welsh, JoEllen, additional, White, John H., additional, Whiting, Susan J., additional, Whyte, Michael P., additional, Wysolmerski, John J., additional, Yamada, Sachiko, additional, Yu, Olivia B., additional, Zavala, Kathryn, additional, Zechner, Christoph, additional, Zeytinoglu, Meltem, additional, and Zhao, Hengguang, additional

Published
2018
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14. T Cells in Allergic Disease

Author

Hawrylowicz, Catherine M., Corrigan, Christopher, Faith, Alex, Pawankar, Ruby, editor, Holgate, Stephen T., editor, and Rosenwasser, Lanny J., editor

Published
2009
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19. Double-blind randomised placebo-controlled trial of bolus-dose vitamin D3 supplementation in adults with asthma (ViDiAs)

Author

Martineau, Adrian R, MacLaughlin, Beverley D, Hooper, Richard L, Barnes, Neil C, Jolliffe, David A, Greiller, Claire L, Kilpin, Kate, McLaughlin, David, Fletcher, Gareth, Mein, Charles A, Hoti, Mimoza, Walton, Robert, Grigg, Jonathan, Timms, Peter M, Rajakulasingam, Raj K, Bhowmik, Angshu, Rowe, Marion, Venton, Timothy R, Choudhury, Aklak B, Simcock, David E, Sadique, Zia, Monteiro, William R, Corrigan, Christopher J, Hawrylowicz, Catherine M, and Griffiths, Christopher J

Published
2015
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23. Menopausal hormone therapy and women's health : An umbrella review

Author

Zhang, Guo Qiang, Chen, Jin Liang, Luo, Ying, Mathur, Maya B., Anagnostis, Panagiotis, Nurmatov, Ulugbek, Talibov, Madar, Zhang, Jing, Hawrylowicz, Catherine M., Lumsden, Mary Ann, Critchley, Hilary, Sheikh, Aziz, Lundbäck, Bo, Lässer, Cecilia, Kankaanranta, Hannu, Lee, Siew Hwa, Nwaru, Bright I., Tampere University, Clinical Medicine, and Seinäjoen keskussairaala VA

Subjects
3123 Gynaecology and paediatrics, 3121 Internal medicine
Abstract

Background There remains uncertainty about the impact of menopausal hormone therapy (MHT) on women's health. A systematic, comprehensive assessment of the effects on multiple outcomes is lacking. We conducted an umbrella review to comprehensively summarize evidence on the benefits and harms of MHT across diverse health outcomes. Methods and findings We searched MEDLINE, EMBASE, and 10 other databases from inception to November 26, 2017, updated on December 17, 2020, to identify systematic reviews or meta-analyses of randomized controlled trials (RCTs) and observational studies investigating effects of MHT, including estrogen-alone therapy (ET) and estrogen plus progestin therapy (EPT), in perimenopausal or postmenopausal women in all countries and settings. All health outcomes in previous systematic reviews were included, including menopausal symptoms, surrogate endpoints, biomarkers, various morbidity outcomes, and mortality. Two investigators independently extracted data and assessed methodological quality of systematic reviews using the updated 16-item AMSTAR 2 instrument. Random-effects robust variance estimation was used to combine effect estimates, and 95% prediction intervals (PIs) were calculated whenever possible. We used the term MHT to encompass ET and EPT, and results are presented for MHT for each outcome, unless otherwise indicated. Sixty systematic reviews were included, involving 102 meta-analyses of RCTs and 38 of observational studies, with 102 unique outcomes. The overall quality of included systematic reviews was moderate to poor. In meta-analyses of RCTs, MHT was beneficial for vasomotor symptoms (frequency: 9 trials, 1,104 women, risk ratio [RR] 0.43, 95% CI 0.33 to 0.57, p < 0.001; severity: 7 trials, 503 women, RR 0.29, 95% CI 0.17 to 0.50, p = 0.002) and all fracture (30 trials, 43,188 women, RR 0.72, 95% CI 0.62 to 0.84, p = 0.002, 95% PI 0.58 to 0.87), as well as vaginal atrophy (intravaginal ET), sexual function, vertebral and nonvertebral fracture, diabetes mellitus, cardiovascular mortality (ET), and colorectal cancer (EPT), but harmful for stroke (17 trials, 37,272 women, RR 1.17, 95% CI 1.05 to 1.29, p = 0.027) and venous thromboembolism (23 trials, 42,292 women, RR 1.60, 95% CI 0.99 to 2.58, p = 0.052, 95% PI 1.03 to 2.99), as well as cardiovascular disease incidence and recurrence, cerebrovascular disease, nonfatal stroke, deep vein thrombosis, gallbladder disease requiring surgery, and lung cancer mortality (EPT). In meta-analyses of observational studies, MHT was associated with decreased risks of cataract, glioma, and esophageal, gastric, and colorectal cancer, but increased risks of pulmonary embolism, cholelithiasis, asthma, meningioma, and thyroid, breast, and ovarian cancer. ET and EPT had opposite effects for endometrial cancer, endometrial hyperplasia, and Alzheimer disease. The major limitations include the inability to address the varying effects of MHT by type, dose, formulation, duration of use, route of administration, and age of initiation and to take into account the quality of individual studies included in the systematic reviews. The study protocol is publicly available on PROSPERO (CRD42017083412). Conclusions MHT has a complex balance of benefits and harms on multiple health outcomes. Some effects differ qualitatively between ET and EPT. The quality of available evidence is only moderate to poor. publishedVersion

Published
2021

30. Ligation of TLR9 induced on human IL-10-secreting Tregs by 1[alpha],25-dihydroxyvitamin D3 abrogates regulatory function

Author

Urry, Zoe, Xystrakis, Emmanuel, Richards, David F., McDonald, Joanne, Sattar, Zahid, Cousins, David J., Corrigan, Christopher J., Hickman, Emma, Brown, Zarin, and Hawrylowicz, Catherine M.

Subjects
Cellular signal transduction -- Research, Interleukin-10 -- Health aspects, Interleukin-10 -- Research, Cell receptors -- Research, Cell receptors -- Genetic aspects, Cell receptors -- Physiological aspects, Cancer -- Research, Oncology, Experimental
Abstract

Signaling through the TLR family of molecular pattern recognition receptors has been implicated in the induction of innate and adaptive immune responses. A role for TLR signaling in the maintenance and/or regulation of Treg function has been proposed, however its functional relevance remains unclear. Here we have shown that TLR9 is highly expressed by human Treg secreting the antiinflammatory cytokine IL-10 induced following stimulation of blood and tissue [CD3.sup.+] T cells in the presence of 1[alpha],25-dihydroxyvitamin D3 (1[alpha]25VitD3), the active form of Vitamin D, with or without the glucocorticoid dexamethasone. By contrast, TLR9 was not highly expressed by naturally occurring [CD4.sup.+][CD25.sup.+] Treg or by Th1 and Th2 effector cells. Induction of TLR9, but not other TLRs, was IL-10 dependent and primarily regulated by 1[alpha]25VitD3 in vitro. Furthermore, ingestion of calcitriol (1[alpha]25VitD3) by human volunteers led to an increase of both IL-10 and TLR9 expression by [CD3.sup.+][CD4.sup.+] T cells analyzed directly ex vivo. Stimulation of 1[alpha]25VitD3-induced IL-10-secreting Treg with TLR9 agonists, CpG oligonucleotides, resulted in decreased IL-10 and IFN-[gamma] synthesis and a concurrent loss of regulatory function, but, unexpectedly, increased IL-4 synthesis. We therefore suggest that TLR9 could be used to monitor and potentially modulate the function of 1[alpha]25VitD3-induced IL-10-secreting Treg in vivo, and that this has implications in cancer therapy and vaccine design., Introduction The TLRs represent a family of evolutionarily conserved receptors, which recognize pathogen-associated molecular patterns (PAMPs) and certain host molecules. Ten TLRs (TLR1-10) have been identified in humans to date. [...]

Published
2009

31. Menopausal hormone therapy and women’s health: an umbrella review of systematic reviews and meta-analyses of randomized controlled trials and observational epidemiological studies

Author

Guo-Qiang, Zhang, primary, Jin-Liang, Chen, additional, Luo, Ying, additional, Mathur, Maya B., additional, Anagnostis, Panagiotis, additional, Nurmatov, Ulugbek, additional, Talibov, Madar, additional, Zhang, Jing, additional, Hawrylowicz, Catherine M., additional, Lumsden, Mary Ann, additional, Critchley, Hilary, additional, Sheikh, Aziz, additional, Bo, Lundbäck, additional, Cecilia, Lässer, additional, Kankaanranta, Hannu, additional, Lee, Siew Hwa, additional, and Nwaru, Bright I., additional

Published
2021
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32. Hormone replacement therapy and asthma onset in menopausal women: National cohort study

Author

Shah, Syed A., primary, Tibble, Holly, additional, Pillinger, Rebecca, additional, McLean, Susannah, additional, Ryan, Dermot, additional, Critchley, Hilary, additional, Price, David, additional, Hawrylowicz, Catherine M., additional, Simpson, Colin R., additional, Soyiri, Ireneous N., additional, Appiagyei, Francis, additional, Sheikh, Aziz, additional, and Nwaru, Bright I., additional

Published
2021
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40. List of contributors

Author

Adams, John S., Amrein, Karin, Anderson, Paul H., Arnold, Leggy A., Arora, Juhi, Artusa, Patricio, Ascherio, Alberto, Asmussen, Niels C., Astier, Anne L., Bak, Min Ji, Bauerle, Kevin T., Belorusova, Anna Y., Benkusky, Nancy A., Bernal-Mizrachi, Carlos, Bhattoa, Harjit P., Bikle, Daniel D., Bilezikian, John P., Binkley, Neil C., Bischoff-Ferrari, Heike A., Bishop, Charles W., Blomberg Jensen, Martin, Boisen, Ida Marie, Boucher, Barbara J., Bouillon, Roger, Boyan, Barbara D., Bradford, Dana, Brancatella, Alessandro, Buburuzan, Laura, Burne, Thomas H.J., Buschittari, Damien, Calkins, Hannah, Calvo, Mona S., Camargo, Carlos A., Jr., Campbell, Moray J., Cantorna, Margherita T., Cappellani, Daniele, Carlberg, Carsten, Carmeliet, Geert, Cashman, Kevin D., Ceglia, Lisa, Cetani, Filomena, Chang, Wenhan, Cheadle, Charlotte, Chou, Sharon H., Christakos, Sylvia, Christopher, Kenneth B., Chu, Emily Y., Chun, Rene F., Cleal, Jane K., Cobice, Diego F., Cooper, Cyrus, Coort, Susan L.M., Cui, Xiaoying, Curtis, Elizabeth M., Danilenko, Michael, Darling, Andrea L., David Roodman, G., Dawson-Hughes, Bess, de Jongh, Renate, Demay, Marie B., Dennison, Elaine M., Dixon, Katie M., Dong, Bingning, Doroudi, Maryam, Dusso, Adriana, Dvorzhinskiy, Aleksey, Ebeling, Peter R., Erben, Reinhold G., Evelo, Chris T.A., Eyles, Darryl, Feldman, David, Ferrer-Mayorga, Gemma, Fleet, James C., Forcellati, Marianela, Foster, Brian L., Gafni, Rachel I., Gayan-Ramirez, Ghislaine, Giovannucci, Edward, Girgis, Christian M., Glencross, Drew A., Glorieux, Francis H., Gocek, Elzbieta, Goldfarb, David S., Goltzman, David, González-Sancho, José Manuel, Grant, William B., Groves, Natalie J., Gysemans, Conny, Harrison, Stephanie, Harvey, Nicholas C., Haseltine, Katherine, Hawrylowicz, Catherine M., Hayes, Colleen E., Heckel, John E., Hershberger, Pamela A., Hewison, Martin, Högler, Wolfgang, Holick, Michael F., Hollis, Bruce W., Holt, Rune, Hujoel, Philippe P., Hyppönen, Elina, Ismailova, Aiten, Jablonski, Nina G., Jakobsen, Jette, Janssens, Wim, Jeffery, Louisa, Jenkinson, Carl, Jensen, Marie Bagge, Jetten, Anton M., Jiang, Heng, Johnson, Candace S., Jones, Glenville, Jones, Kerry S., Jüppner, Harald, Kalia, Vandana, Kallay, Enikö, Karapalis, Andrew C., Kaufmann, Martin, Kiely, Mairead, Kim, Hanseul, Kim, Tiffany Y., Kojima, Hiroyuki, Kooij, Ireen, Kovacs, Christopher S., Kremer, Richard, Krieger, Kirsten, Kritmetapak, Kittrawee, Krueger, Diane C., Kumar, Rajiv, Kurihara, Noriyoshi, Lane, Joseph M., Lanham-New, Susan A., Latic, Nejla, LeBoff, Meryl S., Lee, Maija B., Lee, Seong Min, Levine, Michael A., Lewis, Richard, Lewis, Rohan M., Li, Wei, Li, Yan Chun, Lincoln, Matthew R., Lips, Paul, Lisse, Thomas S., Liu, Eva S., López de Maturana, Evangelina, Lugg, Sebastian T., Machado, Christopher J., Maes, Karen, Maestro, Miguel A., Malats, Núria, Malloy, Peter J., Manousaki, Despoina, Marcinkowska, Ewa, Marcocci, Claudio, Martens, Pieter-Jan, Martineau, Adrian R., Mason, Rebecca S., Mathieu, Chantal, Mayne, Phoebe, McGrath, John J., Mehta, Mansi, Mellanby, Richard John, Merchant, Nadia, Meyer, Mark B., Miao, Dengshun, Moon, Rebecca J., Mortensen, Li Juel, Motlaghzadeh, Yasaman, Munger, Kassandra L., Muñoz, Alberto, Nakamichi, Yuko, Narvaez, Carmen J., Nikiphorou, Elena, Nonn, Larisa, Pal, Lubna, Parekh, Dhruv, Pettifor, John M., Pike, J. Wesley, Pilz, Stefan, Pittas, Anastassios G., Pludowski, Pawel, Prosser, David E., Pullagura, Sri Ramulu N., Raphael, Joseph, Rauz, Saaeha, Raza, Karim, Real, Francisco X., Reichrath, Jörg, Richards, J. Brent, Rivadeneira, Fernando, Rochel, Natacha, Roizen, Jeffrey D., Ryan, Brittany A., Sarkar, Surojit, Sarmadi, Fatemeh, Schafer, Anne L., Schepelmann, Martin, Schoenmakers, Inez, Schuit, Frans, Schwartz, Zvi, Scott, Kayla M., Sellmeyer, Deborah E., Sempos, Christopher T., Sepiashvili, Lusia, Seshadri, Mukund, Shane, Elizabeth, Shaurova, Tatiana, Shieh, Albert, Shui, Irene, Singh, Ravinder J., Slominski, Andrzej T., Smith, Karl W., St-Arnaud, René, Stein, Emily M., Studzinski, George P., Suda, Tatsuo, Takahashi, Naoyuki, Taylor, Hugh S., Tebben, Peter J., Thacher, Tom D., Thandrayen, Kebashni, Thickett, David R., Tiosano, Dov, Trajanoska, Katerina, Tu, Chia-Ling, Tuckey, Robert C., Tutaworn, Teerapat, Udagawa, Nobuyuki, Uday, Suma, Unnanuntana, Aasis, van Driel, Marjolein, van Leeuwen, Johannes P.T.M., van Schoor, Natasja, Verlinden, Lieve, Vieth, Reinhold, Vimaleswaran, Karina S., Wagner, Carol L., Wallace, Graham R., Weaver, Connie M., Webb, Daniel A., Welsh, JoEllen, White, John H., Whiting, Susan J., Williams, Emma L., Yahyavi, Sam Kafai, Yamamoto, Keiko, Yates, Clayton, Zagorac, Sladjana, Zhang, Rong Mei, Zhao, Hengguang, Zhou, Ang, and Zittermann, Armin

Published
2023
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41. Hormonal contraception and the risk of severe asthma exacerbation: 17-year population-based cohort study

Author

Nwaru, Bright I, primary, Tibble, Holly, additional, Shah, Syed A, additional, Pillinger, Rebecca, additional, McLean, Susannah, additional, Ryan, Dermot P, additional, Critchley, Hilary, additional, Price, David B, additional, Hawrylowicz, Catherine M, additional, Simpson, Colin R, additional, Soyiri, Ireneous N, additional, Appiagyei, Francis, additional, and Sheikh, Aziz, additional

Published
2020
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43. Does use of hormonal contraceptives impact on exacerbations and control in reproductive-age women with asthma? A 17-year population-based cohort study

Author

Shah, Syed Ahmar, primary, Tibble, Holly, additional, Pillinger, Rebecca, additional, Mclean, Susannah, additional, Ryan, Dermot, additional, Critchley, Hilary, additional, Price, David, additional, Hawrylowicz, Catherine M, additional, Simpson, Colin R, additional, Soyiri, Ireneous N, additional, Appiagyei, Francis, additional, Sheikh, Aziz, additional, and Nwaru, Bright, additional

Published
2020
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47. Urban particulate matter stimulation of human dendritic cells enhances priming of naive CD8 T lymphocytes

Author

Pfeffer, Paul E., Ho, Tzer R., Mann, Elizabeth H., Kelly, Frank J., Sehlstedt, Maria, Pourazar, Jamshid, Dove, Rosamund E., Sandstrom, Thomas, Mudway, Ian S., and Hawrylowicz, Catherine M.

Subjects
particulate matter, Receptors, CCR7, Membrane Glycoproteins, granzyme, Immunology in the medical area, Immunoglobulins, Original Articles, Dendritic Cells, CD8-Positive T-Lymphocytes, Healthy Volunteers, CD8(+) T lymphocyte, lung, granulocyte-macrophage colony-stimulating factor, Antigens, CD, Immunologi inom det medicinska området, Humans, Original Article, dendritic cells, CD8+ T lymphocyte, Cells, Cultured, granulocyte–macrophage colony‐stimulating factor, Cell Proliferation
Abstract

Summary Epidemiological studies have consistently shown associations between elevated concentrations of urban particulate matter (UPM) air pollution and exacerbations of asthma and chronic obstructive pulmonary disease, which are both associated with viral respiratory infections. The effects of UPM on dendritic cell (DC) ‐stimulated CD4 T lymphocytes have been investigated previously, but little work has focused on CD8 T‐lymphocyte responses despite their importance in anti‐viral immunity. To address this, we examined the effects of UPM on DC‐stimulated naive CD8 T‐cell responses. Expression of the maturation/activation markers CD83, CCR7, CD40 and MHC class I on human myeloid DCs (mDCs) was characterized by flow cytometry after stimulation with UPM in vitro in the presence/absence of granulocyte–macrophage colony‐stimulating factor (GM‐CSF). The capacity of these mDCs to stimulate naive CD8 T‐lymphocyte responses in allogeneic co‐culture was then assessed by measuring T‐cell cytokine secretion using cytometric bead array, and proliferation and frequency of interferon‐γ (IFN‐γ)‐producing T lymphocytes by flow cytometry. Treatment of mDCs with UPM increased expression of CD83 and CCR7, but not MHC class I. In allogeneic co‐cultures, UPM treatment of mDCs enhanced CD8 T‐cell proliferation and the frequency of IFN‐γ + cells. The secretion of tumour necrosis factor‐α, interleukin‐13, Granzyme A and Granzyme B were also increased. GM‐CSF alone, and in concert with UPM, enhanced many of these T‐cell functions. The PM‐induced increase in Granzyme A was confirmed in a human experimental diesel exposure study. These data demonstrate that UPM treatment of mDCs enhances priming of naive CD8 T lymphocytes and increases production of pro‐inflammatory cytokines. Such UPM‐induced stimulation of CD8 cells may potentiate T‐lymphocyte cytotoxic responses upon concurrent airway infection, increasing bystander damage to the airways.

Published
2017
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50. Vitamin D (1,25(OH)2D3) induces α-1-antitrypsin synthesis by CD4+ T cells, which is required for 1,25(OH)2D3-driven IL-10

Author

Dimeloe, Sarah, Rice, Louise V., Chen, Hebe, Cheadle, Charlotte, Raynes, John, Pfeffer, Paul, Lavender, Paul, Richards, David F., Nyon, Mun Peak, Mcdonnell, James M., Kemper, Claudia, Gooptu, Bibek, and Hawrylowicz, Catherine M.

Subjects
Immune regulation, α-1-Antitrypsin, IL-10, Complement, C3a
Abstract

Studies to identify novel immune-regulatory functions of active vitamin D (1,25(OH)2D3) in human CD4+ T cells revealed that 1,25(OH)2D3 potently induced expression of the gene SERPINA1, encoding the anti-protease α-1-antitrypsin. We confirmed α-1-antitrypsin protein expression by 1,25(OH)2D3-treated CD4+ T cells, but not in CD8+ T cells or monocytes. α-1-antitrypsin promotes anti-inflammatory IL-10 synthesis in other immune cell populations. We therefore investigated its immune-regulatory effects in CD4+ T cells. Plasma-derived α-1-antitrypsin drove IL-10synthesis by CD4+ T cells, which was not dependent on anti-protease activity, but appeared to require a serum binding factor, since this could not be achieved with recombinant protein. α-1-antitrypsin is reported to bindcomplement components, which regulate T cell function. A role for this interaction was therefore probed. Plasmaderived, but not recombinant α-1-antitrypsin contained C3a. Surface Plasmon Resonance and MicroscaleThermophoresis demonstrated α-1-antitrypsin binding to C3a. Addition of C3a to CD4+ T cells cultured with recombinant α-1-antitrypsin restored induction of IL-10, whereas neutralisation of C3a abrogated IL-10 induced by plasma-derived α-1-antitrypsin. To interrogate an endogenous role for the α-1-antitrypsin-C3a axis in 1,25(OH)2D3-driven CD4+ T cell IL-10 synthesis, we treated cells from healthy or α-1-antitrypsin-deficient individuals (which transcribe SERPINA1 but do not secrete protein) with 1,25(OH)2D3. A significant correlation was identified betweenSERPINA1 and IL10 gene expression in healthy donor CD4+ T cells, which was absent in cells from α-1-antitrypsindeficient individuals. Therefore, α-1-antitrypsin is required for 1,25(OH)2D3-induced IL-10 expression in CD4+ T cells, interacting with C3a to drive IL-10 expression.

Published
2019
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