Risk for Venous Thromboembolism in Transgender Patients Undergoing Cross-Sex Hormone Treatment: A Systematic Review
Vasanth S. Kotamarti, M.D., Megan Gray, M.D, Paschalia Mountziaris, M.D., Ph.D., Joseph A. Ricci, M.D., Ashit Patel, M.B.Ch.B, F.A.C.S..
Albany Medical Center, Albany, NY, USA.
Purpose: Surgical treatment of gender dysphoria is a rapidly growing area of interest in Plastic Surgery. Cross-sex hormone treatment is an established component of management and is required by World Professional Association for Transgender Health guidelines prior to surgical interventions. The impact of hormone replacement therapy in gender congruent individuals on hemostatic outcomes is well-established. Unfortunately, comprehensive understanding of its effects on venous thromboembolism (VTE) risk in the transgender population is lacking.
Methods: A systematic review of the Pubmed, Google Scholar, and EBSCO databases was performed in October 2018. Studies assessing thromboembolic events in transgender patients undergoing cross-sex hormone treatment were included. Review articles, case reports, and studies lacking descriptions of hormone therapies were excluded. Data regarding demographics, hormone therapy, and venous thromboembolism incidence were collected and pooled for analysis. Statistical analysis was performed using a Student’s t-test.
Results: Of 2,948 initial titles, 51 articles were read in their entirety, and 23 were included for pooled analysis. All studies were retrospective in nature. In total, 9,180 transgender patients (6,068 male-to-female and 3,112 female-to-male) underwent cross-sex hormone therapy. Hormone therapies in male-to-female (MTF) patients most commonly consisted of oral or transdermal estrogen formulations with-or-without progestogens. The majority of female-to-male (FTM) patients received intramuscular or oral testosterone. Weighted VTE rates of 2.5% in male-to-female patients (50.6 per 10,000 person-years) and 0.87% (20.7 per 10,000 person-years) in female-to-male patients were observed. When compared to previously published rates in cis-gender patients undergoing hormone replacement therapy, MTF patients did not have a significantly risk for VTE (p=0.953) while FTM patients had significantly lower risk for VTE (p >0.001). Additionally, the data demonstrated a trend towards higher VTE risk in male-to-female patients undergoing oral estrogen treatment compared to transdermal estrogen.
Conclusions: Hormone therapy in transgender patients is essential to promote a physiologic state aligned with gender identity. However its potential effects on thrombotic complications must be assessed prior to surgical interventions. Transgender patients may undergo invasive surgeries requiring periods of immobilization in order to complete their transitions. Our analysis suggests that MTF patients undergoing cross-sex hormone therapy are at similar risk for VTE to cis-gender individuals undergoing hormone replacement therapy, and FTM patients may have lower risk. Surgical planning regarding perioperative and postoperative VTE prophylaxis or cessation of hormone therapy should take into account each patient’s Caprini risk assessment and the nature of each intervention.
| First Author | Title | N (total) | N (MTF) | N (FTM) | VTE (MTF) | VTE (FTM) |
| Draman et al. 2018 | Hormone Consumption among Mak Nyahs in Kuantan Town: A Preliminary Survey | 35 | 35 | 0 | 2.9% | |
| Gaither et al. 2018 | Postoperative complications following primary penile inversion vaginoplasty among 330 male-to-female transgender patients | 330 | 330 | 0 | 0 | |
| Getahun et al. 2018 | Cross-sex Hormones and Acute Cardiovascular Events in Transgender Persons: A Cohort Study | 4960 | 2842 | 2118 | 2.1% | 1.1% |
| Salgado et al. 2018 | Primary Sigmoid Vaginoplasty in Transwomen: Technique and Outcomes | 12 | 12 | 0 | 16.7% | |
| Arnold et al. 2016 | Incidence of Venous Thromboembolism in Transgender Women Receiving Oral Estradiol | 676 | 676 | 0 | 0.15% | - |
| Cameron et al. 2016 | Transgender Subcutaneous Mastectomy for Gender Affirmation: A Single Surgeon’s 5-Year Experience | 97 | 0 | 97 | [[Unsupported Character - Codename ­]]- | 0 |
| Leinung et al. 2013 | Endocrine treatment of transsexual persons: extensive personal experience | 242 | 192 | 50 | 2.6% | - |
| Wierckx et al. 2013 | Prevalence of cardiovascular disease and cancer during cross-sex hormone therapy in a large cohort of trans persons: a case-control study | 352 | 214 | 138 | 5.1% | 0 |
| Seal et al. 2012 | Predictive markers for mammoplasty and a comparison of side effect profiles in transwomen taking various hormonal regimens | 330 | 330 | 0 | 1.2% | |
| Wierckx et al. 2012 | Long-term evaluation of cross-sex hormone treatment in transsexual persons | 100 | 50 | 50 | 2.0% | 0 |
| Ott et al. 2010 | Incidence of thrombophilia and venous thrombosis in transsexuals under cross-sex hormone therapy | 251 | 162 | 89 | 0 | 0 |
| Weyers et al. 2006 | Two-stage versus one-stage sex reassignment surgery in female-to-male transsexual individuals | 105 | 0 | 105 | 0.95% | |
| Dittrich et al. 2005 | Endocrine treatment of male-to-female transsexuals using gonadotropin-releasing hormone agonist | 60 | 60 | 0 | 1.7% | - |
| Ergeneli et al. 1999 | Vaginectomy and laparoscopically assisted vaginal hysterectomy as adjunctive surgery for female-to-male transsexual reassignment: preliminary report | 8 | 0 | 8 | 25% | |
| Schlatterer et al. 1998 | A follow-up study for estimating the effectiveness of a cross-gender hormone substitution therapy on transsexual patients | 88 | 46 | 42 | 6.5% | 0 |
| van Kesteren et al. 1997 | Mortality and morbidity in transsexual subjects treated with cross-sex hormones | 1109 | 816 | 293 | 5.5% | 0.34% |
| Asscheman et al. 1989 | Mortality and morbidity in transsexual patients with cross-gender hormone treatment | 425 | 303 | 122 | 6.3% | 0 |
| Total | 9180 | 6068 | 3112 | 2.5% | 0.87% |
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