A Dual Biology: Exogeneous Hormones and Transgender Persons

It’s clear that we have only scratched the surface of how exogenous hormones affect and interact with both our bodies and other pharmaceuticals. But an even bigger gap in our knowledge about how exogenous hormones affect health impacts the most misunderstood and marginalized individuals of all: transgender men and women.
Most medical practitioners don’t understand the unique physiological needs of this population, especially when someone is actively “in transition.” Some relegate the desire to transition to a different biological sex to a simple gender identity issue; others dismiss or ignore it on religious grounds. However, regardless of anyone’s personal standpoint on the situation, the fact is that gender transition creates an overlap between someone’s birth sex (and the presence of the associated hormones, pain pathways, XX or XY chromosomes, etc.) and new sex (with its different balance of hormones, which affect so many basic physiological processes). And because hormones are at play in so many daily bodily functions, we need to understand how exogenous hormones affect not just cisgender (matching biological sex and gender) female bodies but also the bodies of those in transition.
Questions abound. For example, should we prescribe medication based on biological sex as assigned at birth or on the reassigned sex and the hormones being used to aid/sustain the transition? If a person no longer has a penis and testes and is taking estrogen and antiandrogens to transition, should we still prescribe general medications based on the male chromosome model (XY) and according to male dosing? After all, this transgender woman still has XY-chromosomal cells in her liver and kidneys, which are processing and excreting the medicine; how is the estrogen affecting those?
This is a giant gray area, and the research hasn’t come close to catching up to the daily reality. In fact, many providers fail to ask simple questions like, “Which organs do you have?” or “How far along in your transition are you?” Or even “Which types and doses of hormones are you taking?”
Much more study is needed before we can fully understand the holistic effects of exogenous hormones for gender transition. However, what we do know—and what I find extremely compelling—is that taking exogenous hormones puts people at risk for many of the disease patterns of their new sex in addition to those of their former or birth sex.
Transgender women (individuals born with male sex characteristics who are transitioning/have transitioned to female bodies) are more likely to experience female-pattern coronary disease.9 Many trans women take the drug spironolactone (which suppresses androgens like testosterone) as well as “female” hormones like estrogen. The result is an increased risk of deep vein thrombosis, pulmonary embolism, and blood-clotting disorders; these factors are similar, in fact, to the risks of cis women like Katie who are taking oral contraceptives. Therefore, individuals who have clotting disorders, smoke, are obese, or have other risk factors for coronary or microvascular diseases should weigh the benefits of such prescriptions for gender transition against the potential side effects and speak with their providers about how to be sure they’re taking the lowest effective dose of the necessary hormones. Trans women are also at increased risk for both asystole (flatlining) and torsades de pointes (see Chapter 4) and appear to have a decreased incidence of male-pattern heart issues like ventricular fibrillation.
This raises the question, Is it our chromosomes or our hormones that underpin and influence our disease patterns?

On the flip side, transgender men (individuals born with female sex characteristics who are transitioning/have transitioned to male bodies) are at increased risk for male-pattern diseases when they start taking exogenous testosterone. Potential complications include high blood pressure, elevated cholesterol, and diabetes, as well as mental and emotional side effects like aggression and neurotic behaviors. While these potential side effects may not adversely affect someone who is young and healthy, if you’re someone who already suffers from hypertension, high cholesterol, elevated triglycerides, or circulatory issues, it’s important to understand what adding testosterone to the mix might precipitate.
Studies have also found that trans men undergo several changes to mood and brain function as a result of taking exogenous testosterone. Brain scans have found increased connectivity between the temporoparietal junction (involved in own-body perception) and other brain areas, which has the effect of increasing the “fight or flight” response.10 Mood changes, such as increased aggression and neurotic behaviors, have also been observed. Overall brain volume also increased with testosterone use—particularly in the hypothalamus, which (among other tasks) monitors hormone secretions.11 Therefore, individuals who suffer from compulsive disorders, anxiety, previous hormonal imbalances, and mood disorders should be cautious when introducing testosterone; it may be necessary to increase or adjust existing mediations to ameliorate the effects of the hormone therapy.
For me and for other physicians who work with transgender individuals, risks like these merit a high level of attention. While studies are starting to emerge about the effects of hormones for gender affirmation on transgender persons’ brains and bodies, whenever you start adapting your body’s mechanisms with exogeneous hormones, new and often unforeseen issues can arise. While gender affirmation via hormones is generally considered safe, and while the benefits for most transgender individuals far outweigh the risks, this process should always be undertaken under a doctor’s supervision.
Unfortunately, this isn’t always what happens. While the medical environment is becoming friendlier to transgender persons, many who don’t have the support of family or community still attempt to transition on their own, using hormone “kits” available on the internet. These medications may be altered or diluted by unscrupulous sellers or may simply not be the right brand, dose, or combination for specific individuals and their unique health concerns. I understand that, for those without adequate social support, insurance, funds, or other resources, transitioning without medical supervision often feels like the only way; for many, the reality of depression, self-harm, or even suicidal thoughts is too much to bear, despite the dangers of self-directed transition. However, as a doctor, I feel compelled to reiterate that the risk of unforeseen complications throughout the process of gender reassignment is already great in a multitude of areas, and it increases exponentially when steps are undertaken without medical supervision.
This isn’t meant to instill any fear around gender transition or to discourage people from affirming their gender; in fact, quite the opposite. It’s simply important to be aware of and vigilantly monitor the effects and changes that exogenous hormones precipitate. Also, because we have so little information about what happens when someone uses gender-altering hormones long-term, it’s important if you’re in transition (or if someone you love is in that process) to work closely with providers you trust on a long-term basis to make sure you identify and minimize any issues as soon as they arise.
It’s also important to note that transgender people are far more likely than any other population group to be subject to implicit bias, so whether you’re considering gender reassignment, currently in transition, or fully transitioned, it’s vitally important to find doctors’ offices, hospitals, and care facilities at which you feel comfortable, respected, and secure. As you’ve learned throughout this book, physicians need the right information in order to provide the right care; it’s therefore often necessary to share details like birth sex, gender identity, current hormone prescriptions and doses, and which organs are still present (if you’ve undergone sex reassignment surgery) with one or more providers in the course of both routine and emergency care. For example, if you are a transgender male but still have your uterus and ovaries, you’re still at risk for things like ovarian cysts and uterine fibroids. If you need to go to the hospital for abdominal pain, it’s important for your providers to know this so they can more accurately diagnose your condition. It may also be necessary in certain situations for you to be seen unclothed. Therefore, it’s essential to identify in advance where you want to receive care, and from whom, and to work to build a relationship of trust with your providers. If you don’t feel that you are being treated equally with other patients for any reason, find another doctor or facility. Period.
A good resource for trans-friendly (as well as LGBTQ-friendly) providers is the GLMA: Health Professionals Advancing LGBTQ Equality network (formerly the Gay and Lesbian Medical Association). It has an extensive online directory of doctors and other providers as well as resources for physicians.


  • Talal Alzahrani et al., “Cardiovascular Disease Risk Factors and Myocardial Infarction in the Transgender Population,” Circulation: Cardiovascular Quality and Outcomes 12 (2019): e005597. doi.org/10.1161/CIRCOUTCOMES.119.005597; Louis J. Gooren, Katrien Wierckx, and Erik J. Giltay, “Cardiovascular Disease in Transsexual Persons Treated with Cross-Sex Hormones: Reversal of the Traditional Sex Difference in Cardiovascular Disease Pattern,” European Journal of Endocrinology 170, no. 6 (2014): 809–819. doi: https://doi.org/10.1530/EJE-14-0011.
  • Sarah M. Burke et al., “Testosterone Effects on the Brain in Transgender Men,” Cerebral Cortex 28, no. 5 (2018): 1582–1596, https://doi.org/10.1093/cercor/bhx054.
  • Hilleke E. Hulshoff Pol et al., “Changing Your Sex Changes Your Brain: Influences of Testosterone and Estrogen on Adult Human Brain Structure,” European Journal of Endocrinology 155 (2006): S107–S114. doi:10.1530/eje.1.02248.


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