Studies in both transgender and cisgender women receiving transdermal estradiol have shown little to no increased VTE risk. For example, Ott and colleagues found no incidence of VTE in transgender women receiving only transdermal estradiol in combination with cyperterone acetate and finasteride after an average follow-up of 64.2 months. However, transdermal patch-administered estradiol is uncommon in the United States because it has decreased efficacy when combined with the common antiandrogen spironolactone. Therefore, it may be necessary to use multiple patches to appropriately suppress testosterone production.

In another recent review, Shatzel and colleagues outlined key guidelines for managing thrombotic risk in transgender women undergoing estrogen therapy, including:

  • Estrogen supplementation may increase the rate of VTE. VTE incidence appears to be highest with oral estrogen supplementation and during the first year after starting supplementation. It appears to be lowest with transdermal estrogen administration. Therefore, this should be the first line of therapy for individuals at high risk for thrombosis.
  • The rate of stroke may increase. Some studies indicate that women receiving HRT may experience increased risk of stroke. However, data are limited and inconclusive on the risk for arterial vascular events in this patient population. Therefore, it is recommended that cardiovascular risk factors, such as smoking, hypertension, and dyslipidemia, be well controlled.
  • Additional factors may increase risk for thrombosis. Potential other risk factors include age, provoking factors such as major surgery or immobilization, cancer, history of thrombosis, smoking, thrombophilia, and obesity. Similar to recommendations for women beginning a birth control regimen, routine testing for thrombophilia is not recommended in transgender women preparing to initiate HRT. In patients with multiple risk factors, transdermal estrogen should be considered because of the lower thrombotic risks associated with this mode of delivery.
  • Use of prophylactic anticoagulants in individuals with high risk for thrombosis is not recommended. Although aspirin may offer benefits for secondary VTE prophylaxis, insufficient evidence exists on its routine use in transgender women.
  • HRT should be paused 2 weeks prior to gender-affirming surgery. This practice is common for managing thrombotic risk in transgender women, but no prospective studies have been conducted. HRT may be resumed after the patient regains mobility. Postoperative thromboprophylaxis is recommended during hospitalization.

If thrombosis does occur, estrogen therapy can be continued. In a statement to Hematology Advisor, Joseph Shatzel, MD, assistant professor at Oregon Health & Science University in Portland, offered the following advice: “Many providers are uncomfortable continuing HRT in the event of a VTE; however, there is data to suggest this is safe if done with concurrent anticoagulation [as long as no contraindications exist]. [Transgender women] who happen to have a VTE event while on HRT can stay on the estrogen as long as they take anticoagulation concurrently.” He noted that he and his colleagues preferred apixaban 5 mg administered twice daily.

Dr Shatzel stated that the biggest challenge for most physicians managing thrombotic risk in transgender patients is a lack of experience and clear guidelines. The data on transgender women receiving estrogen therapy are minimal, and few alternative therapies exist.

Despite the lack of randomized controlled trials and clear guidelines on HRT in transgender women, case reports, retrospective studies, and recent prospective studies have begun laying a foundation for improving thrombotic risk management in transgender women. With careful provider supervision and risk management, HRT for transgender women appears to be safe, but more long-term and prospective studies are needed.

References

1. Shatzel JJ, Connelly KJ, DeLoughery TG. Thrombotic issues in transgender medicine: A review. Am J Hematol. 2017;92(2):204-8. doi: 10.1002/ajh.24593

2. Weinand JD, Safer JD. Hormone therapy in transgender adults is safe with provider supervision; A review of hormone therapy sequelae for transgender individuals. J Clin Transl Endocrinol. 2015;2(2):55-60. doi: 10.1016/j.jcte.2015.02.003

3. Khan J, Schmidt RL, Spittal MJ, Goldstein Z, Smock KJ, Greene DN. Venous thrombotic risk in transgender women undergoing estrogen therapy: A systematic review and metaanalysis. Clin Chem. 2019;65(1):57-66. doi: 10.1373/clinchem.2018.288316

4. Getahun D, Nash R, Flanders WD, et al. Cross-sex hormones and acute cardiovascular events in transgender persons. Ann Intern Med. 2018;169(4):205. doi: 10.7326/M17-2785

5. Ott J, Kaufmann U, Bentz E-K, Huber JC, Tempfer CB. Incidence of thrombophilia and venous thrombosis in transsexuals under cross-sex hormone therapy. Fertil Steril. 2010;93(4):1267-72. doi: 10.1016/j.fertnstert.2008.12.017

6. Gava G, Cerpolini S, Martelli V, Battista G, Seracchioli R, Meriggiola MC. Cyproterone acetate vs leuprolide acetate in combination with transdermal oestradiol in transwomen: a comparison of safety and effectiveness. Clin Endocrinol (Oxf). 2016;85(2):239-46. doi: 10.1111/cen.13050

7. Gooren LJ, Giltay EJ, Bunck MC. Long-term treatment of transsexuals with cross-sex hormones: extensive personal experience. J Clin Endocrinol Metab. 2008;93(1):19-25. doi: 10.1210/jc.2007-1809

8. Arnold JD, Sarkodie EP, Coleman ME, Goldstein DA. Incidence of venous thromboembolism in transgender women receiving oral estradiol. J Sex Med. 2016;13(11):1773-7. doi: 10.1016/j.jsxm.2016.09.001

9. Wierckx K, Elaut E, Declercq E, et al. Prevalence of cardiovascular disease and cancer during cross-sex hormone therapy in a large cohort of trans persons: a case–control study. Eur J Endocrinol. 2013;169(4):471-8. doi: 10.1530/EJE-13-0493.

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This article originally appeared on Hematology Advisor