Research critical in the transgender population

The transgender community is a growing and underserved population estimated to reach over 25 million worldwide [1]. A transgender person is an individual who experiences gender dysphoria. That means their gender, which is defined as socially constructed roles, expressions and identity, doesn't align with their biological attributes (sex) assigned at birth.

This population may receive gender-affirming hormone therapy, such as synthetic estrogens, testosterone and anti-androgens. However, these therapies may increase their risk of developing  cardiovascular disease [2].

Despite the growing transgender population and the increased use of  gender-affirming hormone therapy, there is little research, outside of HIV prevalence, in this demographic. In fact, transgender persons face significant health care disparities and suffer from higher rates of depression, suicide and substance-abuse disorders [3].

There is a great diversity in the gender affirming therapies given because the formulation and dose of these synthetic hormones depend on the  transition goals of  the individuals. As a result,  research studies with conclusive results that consider this variability are limited by a lack of proper data collection and stratification. Additionally, how this hormone therapy is delivered, for example orally or non-orally, may be partly responsible for the variability in research outcomes. This prevents adequate quantification of the health risks these therapies may pose.

For example, use of oral estrogen therapy (whether for contraceptive or postmenopausal use) in cis women (biological females) increases cardiovascular risk compared to non-oral routes [4]. As a result of these findings in biological women, transgender women (male to female transition) older than 45 are prescribed non-oral forms of estrogen to minimize risk [5].

Health-care protocols for transgender women have been modelled after research done in cis-women populations. Yet, very little research has been done to prove these models apply to the transgender population. This makes clinical concerns about the risks of using gender-affirming hormone therapy in patients with cardiovascular and chronic kidney disease very real.

The only way to put these concerns to rest is to include transgender individuals in research studies. Studies that report on hormone formulations, administration route, duration of exposure and other hormone variables will help advance clinical understandings and protocols.

Keila Turino Miranda is a fourth-year  Honors Pharmacology student from the University of Alberta. She is a current Trainee within the Libin Cardiovascular Institute under the supervision of Dr. Sofia Ahmed, MD, and Dr. Sandi Dumanski, MD. She is in the process of submitting a systematic review and meta-analysis looking into cardiovascular risk and route of estrogen administration in transgender women. Additionally, Keila co-led an international workshop titled “Transgender Health: Personal, Research and Clinical perspectives” with over 100 registrants. More recently, she collaborated with Hypertension Canada on a two-day seminar series titled “Hypertension Across the Lifespan” to advocate for the advancement of CV care.

References

1. Reisner, SL, Poteat, T, Keatley, J, et al. Global health burden and needs of transgender populations: a review. Lancet. 2016;388(10042):412-436. doi:10.1016/s0140-6736(16)00684-x.
2. Alzahrani, T., Nguyen, T., Ryan, A., Dwairy, A., Mccaffrey, J., Yunus, R., . . . Reiner, J. (2019). Cardiovascular Disease Risk Factors and Myocardial Infarction in the Transgender Population. Circulation: Cardiovascular Quality and Outcomes, 12(4). doi:10.1161/circoutcomes.119.005597
3. Reback, C. J., Clark, K., Holloway, I. W., & Fletcher, J. B. (2018). Health Disparities, Risk Behaviors and Healthcare Utilization Among Transgender Women in Los Angeles County: A Comparison from 1998–1999 to 2015–2016. AIDS and Behavior, 22(8), 2524-2533. doi:10.1007/s10461-018-2165-7
4. Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, et al; Women's Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hys- terectomy: the Women's Health Initiative randomized controlled trial. JAMA. 2004;291:1701-12. [PMID: 15082697]
5. Velzen, D. M., Paldino, A., Klaver, M., Nota, N. M., Defreyne, J., Hovingh, G. K., . . . Heijer, M. D. (2019). Cardiometabolic Effects of Testosterone in Transmen and Estrogen Plus Cyproterone Acetate in Transwomen. The Journal of Clinical Endocrinology & Metabolism, 104(6), 1937-1947. doi:10.1210/jc.2018-02138