Darios Getahun, MD, PhD, MPH; Rebecca Nash, MPH; W. Dana Flanders, MD, MPH, DSc; Tisha C. Baird, MD; Tracy A. Becerra-Culqui, PhD; Lee Cromwell, MS; Enid Hunkeler, MA; Timothy L. Lash, PhD; Andrea Millman, MA; Virginia P. Quinn, PhD; Brandi Robinson, MPH; Douglas Roblin, PhD; Michael J. Silverberg, PhD; Joshua Safer, MD; Jennifer Slovis, MD; Vin Tangpricha, MD, PhD; Michael Goodman, MD, MPH
Acknowledgment: This work would not be possible without continuous support and advice from the Stakeholder Advisory Group, which included representatives of the transgender community and health care providers and researchers who work with transgender persons. The authors thank Dr. Lemuel Arnold, Dr. Nancy Baisch, Dr. John Blosnich, Dr. George Brown, Dr. Robin Dea, Ms. Cheryl Courtney-Evans, Dr. Shawn Giammattei, Ms. Monica Helms, Ms. Cadence Valentine, Mr. Willy Wilkinson, Ms. Savannah Winter, and Mr. Evan Young for their valuable input and willingness to collaborate.
Grant Support: By contract AD-12-11-4532 from PCORI and grant R21HD076387 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Disclosures: Ms. Nash, Ms. Millman, and Dr. Goodman report a contract from PCORI and grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development during the conduct of the study. Dr. Becerra-Culqui and Ms. Cromwell report grants from PCORI during the conduct of the study. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-2785.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol and statistical code: Available from Dr. Goodman (e-mail, firstname.lastname@example.org). Data set: Not available.
Corresponding Author: Michael Goodman, MD, MPH, Department of Epidemiology, Emory University School of Public Health, 1518 Clifton Road Northeast, CNR 3021, Atlanta, GA 30322; e-mail, email@example.com.
Current Author Addresses: Drs. Getahun, Becerra-Culqui, and Quinn: Kaiser Permanente Southern California, Department of Research and Evaluation, 100 South Los Robles Avenue, Pasadena, CA 91101.
Ms. Nash and Drs. Flanders and Lash: Emory University Department of Epidemiology, 1518 Clifton Road Northeast, Atlanta, GA 30322.
Dr. Baird: Department of Endocrinology, Kaiser Permanente Los Angeles Medical Center, 4950 West Sunset Boulevard, Los Angeles, CA 90027.
Ms. Cromwell and Ms. Robinson: Kaiser Permanente of Georgia, Center for Research and Evaluation, 3495 Piedmont Road Northeast, Atlanta, GA 30305.
Ms. Hunkeler, Ms. Millman, and Dr. Silverberg: Kaiser Permanente Northern California, Division of Research, 2000 Broadway, Oakland, CA 94612.
Dr. Roblin: Mid-Atlantic Permanente Research Institute, 2101 East Jefferson Street, 3W, Rockville, MD 20852.
Dr. Safer: Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY 10029.
Dr. Slovis: Kaiser Permanente Northern California, Oakland Medical Center, 3779 Piedmont Avenue, Oakland, CA 94611.
Dr. Tangpricha: Emory University School of Medicine, 101 Woodruff Circle Northeast, Atlanta GA 30322.
Dr. Goodman: Department of Epidemiology, Emory University School of Public Health, 1518 Clifton Road Northeast, CNR 3021, Atlanta, GA 30322.
Author Contributions: Conception and design: D. Getahun, T.A. Becerra-Culqui, E. Hunkeler, V.P. Quinn, D. Roblin, V. Tangpricha, M. Goodman.
Analysis and interpretation of the data: D. Getahun, R. Nash, W.D. Flanders, T.C. Baird, E. Hunkeler, T.L. Lash, V.P. Quinn, D. Roblin, M.J. Silverberg, J. Slovis, V. Tangpricha, M. Goodman.
Drafting of the article: R. Nash, T.A. Becerra-Culqui, V.P. Quinn, D. Roblin, M.J. Silverberg, J. Safer, J. Slovis, V. Tangpricha, M. Goodman.
Critical revision for important intellectual content: D. Getahun, T.A. Becerra-Culqui, E. Hunkeler, T.L. Lash, V.P. Quinn, D. Roblin, M.J. Silverberg, J. Slovis, V. Tangpricha, M. Goodman.
Final approval of the article: D. Getahun, R. Nash, W.D. Flanders, T.C. Baird, T.A. Becerra-Culqui, L. Cromwell, E. Hunkeler, T.L. Lash, A. Millman, V.P. Quinn, B. Robinson, D. Roblin, M.J. Silverberg, J. Safer, J. Slovis, V. Tangpricha, M. Goodman.
Provision of study materials or patients: E. Hunkeler, V.P. Quinn, B. Robinson, M.J. Silverberg.
Statistical expertise: W.D. Flanders.
Obtaining of funding: E. Hunkeler, V.P. Quinn, D. Roblin, V. Tangpricha, M. Goodman.
Administrative, technical, or logistic support: D. Getahun, T.A. Becerra-Culqui, L. Cromwell, E. Hunkeler, V.P. Quinn, B. Robinson, M. Goodman.
Collection and assembly of data: D. Getahun, T.C. Baird, T.A. Becerra-Culqui, L. Cromwell, E. Hunkeler, A. Millman, V.P. Quinn, M.J. Silverberg, J. Slovis, V. Tangpricha, M. Goodman.
Venous thromboembolism (VTE), ischemic stroke, and myocardial infarction in transgender persons may be related to hormone use.
To examine the incidence of these events in a cohort of transgender persons.
Electronic medical record–based cohort study of transgender members of integrated health care systems who had an index date (first evidence of transgender status) from 2006 through 2014. Ten male and 10 female cisgender enrollees were matched to each transgender participant by year of birth, race/ethnicity, study site, and index date enrollment.
Kaiser Permanente in Georgia and northern and southern California.
2842 transfeminine and 2118 transmasculine members with a mean follow-up of 4.0 and 3.6 years, respectively, matched to 48 686 cisgender men and 48 775 cisgender women.
VTE, ischemic stroke, and myocardial infarction events ascertained from diagnostic codes through the end of 2016 in transgender and reference cohorts.
Transfeminine participants had a higher incidence of VTE, with 2- and 8-year risk differences of 4.1 (95% CI, 1.6 to 6.7) and 16.7 (CI, 6.4 to 27.5) per 1000 persons relative to cisgender men and 3.4 (CI, 1.1 to 5.6) and 13.7 (CI, 4.1 to 22.7) relative to cisgender women. The overall analyses for ischemic stroke and myocardial infarction demonstrated similar incidence across groups. More pronounced differences for VTE and ischemic stroke were observed among transfeminine participants who initiated hormone therapy during follow-up. The evidence was insufficient to allow conclusions regarding risk among transmasculine participants.
Inability to determine which transgender members received hormones elsewhere.
The patterns of increases in VTE and ischemic stroke rates among transfeminine persons are not consistent with those observed in cisgender women. These results may indicate the need for long-term vigilance in identifying vascular side effects of cross-sex estrogen.
Patient-Centered Outcomes Research Institute and Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Getahun D, Nash R, Flanders WD, Baird TC, Becerra-Culqui TA, Cromwell L, et al. Cross-sex Hormones and Acute Cardiovascular Events in Transgender Persons: A Cohort Study. Ann Intern Med. [Epub ahead of print 10 July 2018]169:205–213. doi: 10.7326/M17-2785
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Published: Ann Intern Med. 2018;169(4):205-213.
Published at www.annals.org on 10 July 2018
Endocrine and Metabolism.
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