Cross-sex Hormones and Acute Cardiovascular Events in Transgender Persons
      				:
      			
   A Cohort Study

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Abstract

Background:

Venous thromboembolism (VTE), ischemic stroke, and myocardial infarction in transgender persons may be related to hormone use.

Objective:

To examine the incidence of these events in a cohort of transgender persons.

Design:

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.

Setting:

Kaiser Permanente in Georgia and northern and southern California.

Patients:

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.

Measurements:

VTE, ischemic stroke, and myocardial infarction events ascertained from diagnostic codes through the end of 2016 in transgender and reference cohorts.

Results:

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.

Limitation:

Inability to determine which transgender members received hormones elsewhere.

Conclusion:

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.

Related collections

Most cited references 23

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Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society* Clinical Practice Guideline

Wylie Hembree, Peggy Cohen-Kettenis, Louis J.G. Gooren … (2017)

To update the "Endocrine Treatment of Transsexual Persons: An Endocrine Society Clinical Practice Guideline," published by the Endocrine Society in 2009.

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Hormonal therapy and sex reassignment: a systematic review and meta-analysis of quality of life and psychosocial outcomes.

Victor Montori, Susana Garcia, Rebecca Mullan … (2010)

To assess the prognosis of individuals with gender identity disorder (GID) receiving hormonal therapy as a part of sex reassignment in terms of quality of life and other self-reported psychosocial outcomes. We searched electronic databases, bibliography of included studies and expert files. All study designs were included with no language restrictions. Reviewers working independently and in pairs selected studies using predetermined inclusion and exclusion criteria, extracted outcome and quality data. We used a random-effects meta-analysis to pool proportions and estimate the 95% confidence intervals (CIs). We estimated the proportion of between-study heterogeneity not attributable to chance using the I(2) statistic. We identified 28 eligible studies. These studies enrolled 1833 participants with GID (1093 male-to-female, 801 female-to-male) who underwent sex reassignment that included hormonal therapies. All the studies were observational and most lacked controls. Pooling across studies shows that after sex reassignment, 80% of individuals with GID reported significant improvement in gender dysphoria (95% CI = 68-89%; 8 studies; I(2) = 82%); 78% reported significant improvement in psychological symptoms (95% CI = 56-94%; 7 studies; I(2) = 86%); 80% reported significant improvement in quality of life (95% CI = 72-88%; 16 studies; I(2) = 78%); and 72% reported significant improvement in sexual function (95% CI = 60-81%; 15 studies; I(2) = 78%). Very low quality evidence suggests that sex reassignment that includes hormonal interventions in individuals with GID likely improves gender dysphoria, psychological functioning and comorbidities, sexual function and overall quality of life.

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Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study.

Marianne Canonico, Emmanuel Oger, Geneviève Plu-Bureau … (2007)

Oral estrogen therapy increases the risk of venous thromboembolism (VTE) in postmenopausal women. Transdermal estrogen may be safer. However, currently available data have limited the ability to investigate the wide variety of types of progestogen. We performed a multicenter case-control study of VTE among postmenopausal women 45 to 70 years of age between 1999 and 2005 in France. We recruited 271 consecutive cases with a first documented episode of idiopathic VTE (208 hospital cases, 63 outpatient cases) and 610 controls (426 hospital controls, 184 community controls) matched for center, age, and admission date. After adjustment for potential confounding factors, odds ratios (ORs) for VTE in current users of oral and transdermal estrogen compared with nonusers were 4.2 (95% CI, 1.5 to 11.6) and 0.9 (95% CI, 0.4 to 2.1), respectively. There was no significant association of VTE with micronized progesterone and pregnane derivatives (OR, 0.7; 95% CI, 0.3 to 1.9 and OR, 0.9; 95% CI, 0.4 to 2.3, respectively). In contrast, norpregnane derivatives were associated with a 4-fold-increased VTE risk (OR, 3.9; 95% CI, 1.5 to 10.0). Oral but not transdermal estrogen is associated with an increased VTE risk. In addition, our data suggest that norpregnane derivatives may be thrombogenic, whereas micronized progesterone and pregnane derivatives appear safe with respect to thrombotic risk. If confirmed, these findings could benefit women in the management of their menopausal symptoms with respect to the VTE risk associated with oral estrogen and use of progestogens.

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Author and article information

Journal

Journal ID (nlm-journal-id): 0372351

Journal ID (pubmed-jr-id): 596

Journal ID (nlm-ta): Ann Intern Med

Journal ID (iso-abbrev): Ann. Intern. Med.

Title: Annals of internal medicine

ISSN (Print): 0003-4819

ISSN (Electronic): 1539-3704

Publication date Nihms-submitted: 28 June 2019

Publication date (Electronic): 10 July 2018

Publication date (Print): 21 August 2018

Publication date PMC-release: 17 July 2019

Volume: 169

Issue: 4

Pages: 205-213

Affiliations

Kaiser Permanente Southern California, Pasadena, California (D.G., T.A.B., V.P.Q.); Emory University, Atlanta, Georgia (R.N., W.D.F., T.L.L., M.G.); Kaiser Permanente Los Angeles Medical Center, Los Angeles, California (T.C.B.); Kaiser Permanente Georgia, Atlanta, Georgia (L.C., B.R.); Kaiser Permanente Northern California, Oakland, California (E.H., A.M., M.J.S., J.S.); Kaiser Permanente Mid-Atlantic States, Rockville, Maryland (D.R.); Icahn School of Medicine at Mount Sinai, New York, New York (J.S.); and Emory University School of Medicine and Atlanta VA Medical Center, Atlanta, Georgia (V.T.).

Author notes

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. Tang-pricha, 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.

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 Pl, 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.

Corresponding Author: Michael Goodman, MD, MPH, Department of Epidemiology, Emory University School of Public Health, 1518 Clifton Road Northeast, CNR 3021, Atlanta, GA 30322; mgoodm2@ 123456emory.edu .

Article

Accession ID: PMC6636681 Pmcid ID: PMC6636681 Pmc-uid ID: 6636681 Manuscript ID: nihpa1030323

DOI: 10.7326/M17-2785

PMC ID: 6636681

PubMed ID: 29987313

SO-VID: 6c9d7bed-64c4-4c00-bb90-3241257e95d1

Cross-sex Hormones and Acute Cardiovascular Events in Transgender Persons : A Cohort Study

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Abstract

Background:

Objective:

Design:

Setting:

Patients:

Measurements:

Results:

Limitation:

Conclusion:

Related collections

Sex hormones and lung development

Most cited references 23

Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society* Clinical Practice Guideline

Hormonal therapy and sex reassignment: a systematic review and meta-analysis of quality of life and psychosocial outcomes.

Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study.

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