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Transfem Trail Guide 4: It's In Your Blood — The Hematology of Feminizing HRT
2025-10-18
I love and loathe testosterone. Add a little testosterone into the mix and suddenly you’ll gain strength, muscle mass, thick chest hair, and enough body odor to put even the sweatiest offensive lineman to shame. With testosterone, you’ll recover faster (Collado-Boira et al., 2021) and build stronger bones (Tracz et al., 2006). You won’t even need to exercise all that much to bask in the benefits of the main male sex hormone (Bhasin et al., 2003). But slather me in Androgel, and I’ll be bedridden and depressed within the week. Male to female transition is a uniquely personal process, and for many that transition includes hormone replacement or surgical interventions. These transformations are beautiful and complicated, but they come with enough warning labels and cautionary tales to make even the State of California proud. Are the benefits worth the downsides? 1000% yes. But it’s worth knowing what something like feminizing hormone replacement therapy can do to the body outside of redistributing fat or reversing male-pattern baldness. Feminizing HRT typically has two main goals: decrease testosterone and increase estrogen.* Both testosterone and estrogen are steroid hormones that play a substantial role in tissue growth and development. Although testosterone and estrogen are in many respects different versions of the same molecule, testosterone tends to be a more potent anabolic hormone than estrogen particularly in areas that directly impact physical fitness. I imagine it like the difference between a bottle of Clorox and a bottle of Clorox with bleach. Both will clean a moldy tub, but one of them will do it a bit quicker, a bit more effectively, and with an aggression that will strip paint and stain clothes. <b>It’s In Your Blood</b> Testosterone supercharges muscle growth, bone formation, and red blood cell creation. Taking testosterone away slows those processes down. Muscles rebuild more slowly. Bones may break down quicker than they rebuild. Red blood cell count slides from cis male to cis female ranges. Each of these effects can hamper aerobic ability. Each poses a new challenge for someone training to be their fastest and happiest selves. Red blood cell creation is one of the key places that testosterone plays a role in someone’s ability to run and run fast. Red blood cells are the oxygen carrying cells in the blood. The more red blood cells you have, the more oxygen your body can deliver to your muscles allowing them to work faster for longer. Once your muscles begin asking for oxygen more quickly than your blood can deliver it, you start a metabolic countdown, and if things don’t change soon, you’ll be lying on the side of the road gasping for air. Thus, a fair bit of your ability to run fast for long periods of time comes down to the amount of oxygen your blood can effectively deliver to the working muscles. The oxygen delivery system has been an obsession of exercise physiologists for decades. They place a lot of value on the body's ability to breathe in and maximally use oxygen (known as VO2max). Someone’s VO2max correlates very strongly with their performance across distances and disciplines, and the main determining factors for someone’s VO2max are how much blood their heart can pump and how much oxygen that blood can carry. In other words, VO2max is made up primarily by your cardiac output and your red blood cell count. So how does testosterone help encourage the body to make more red blood cells? And how can you or I limit the decrease in the amount of red blood cells that comes with blocking testosterone? <b>Allow Me to Dazzle You With <i>Science</i></b> Red blood cell production typically begins in the kidneys. Yes, the same organ that manages how much you pee also senses blood oxygen content. When you begin to run low on oxygen in your blood (hypoxia) a couple of very specific cells in your kidneys sense that change and set off what essentially amounts to a biological Rube Goldberg machine of protein creation. After a few hours of balls, levers, and springs, the machine reaches its climax and releases erythropoietin (EPO) into the bloodstream. EPO finds its way through the blood, around the body, and eventually into the bone marrow. Within the marrow, EPO begins another cascade of protein creation that tells the stem cells in bone marrow to grow new red blood cells. These cells consume iron and create hemoglobin—the oxygen carrying bit of the red blood cells. After a week or two, the new red blood cells enter the bloodstream increasing your body’s ability to shuttle oxygen. Testosterone accelerates and enables this process in at least two ways. First, testosterone directly stimulates the kidney’s oxygen sensing cells and tells them to make more EPO (Semenza, 2023). This stimulus to the kidneys increases circulating EPO levels which in turn push bone marrow to produce more red blood cells (Bachman et al., 2014). This is part of the reason males tend to have higher red blood cell counts and hematocrits (ratio of red blood cells to whole blood) than females or androgen-depleted men (Gagliano-Juca et al., 2018). Second, testosterone suppresses a molecule called hepcidin (Beggs et al., 2014). One of hepcidin’s main roles in the body is to bind to iron. In that way, it’s pretty much a gym bro. It sits around all day waiting for a chance to wrap its fingers around some iron and get swol. But gym bros and hepcidin have something else in common…an even greater love for testosterone. Why pump iron when you can bathe yourself in testosterone instead? When in the presence of testosterone, hepcidin production slows. With less iron-hungry hepcidin, more iron frees up for use in making new red blood cells. This is part of why trans women may develop low hematocrit—which is typically an indicator of anemia—during the initial months of feminizing HRT (Antun et al., 2020). <b>How to Limit the Loss</b> As I’ve navigated feminizing HRT while continuing to train and race, the number one question on my mind has been, “How much will this hurt my running?” This question is followed immediately by, “And what can I do about it?” The answer to the first question is as much a mystery to me as it’s ever been. I don’t know. Some literature suggests that feminizing HRT could cause a drop in hematocrit of about four percentage points (Defreyne et al., 2018). But how much that will change your pace on race day isn’t easy to predict. As I’ve eased into HRT, I’ve also become more consistent with my training. Better mental health has meant better and happier running, and now I’m faster than I’ve been in years. Maybe that drop in performance is still ahead. Or maybe I’ve gained more fitness since starting HRT than I’ve lost through an HRT-mediated reduction in red blood cells. The answer to the question “what can I do about it?” is a fair bit more concrete. I’d personally suggest a couple of specific training interventions. Altitude and heat exposure, long term easy running, and strength work have each played a role in my training to prevent some of the negative side effects of HRT from really impacting my running. <i>1. Altitude Exposure</i> The kidneys sense hypoxia to begin initiating EPO production. The most effective legal way to safely induce hypoxia is altitude exposure. There are hundreds of ways to include altitude into an endurance athlete’s training, but I’d recommend keeping things as straightforward as possible. Go up high as much as you can. Run at altitude, and run hard sometimes. STAY HYDRATED. Don’t do all your training at altitude because you can’t run as fast in Leadville as you can in Los Angeles, but don’t be afraid to move to Colorado if you can afford it ;) <i>2. Heat Exposure</i> Heat exposure may stimulate EPO, but its biggest effects come from increasing blood plasma volume and cardiac output (Kissling et al., 2019). Blood plasma makes up more than half of your blood, and it’s mostly water. Having more blood plasma aids in thermoregulation and buffering heat primarily through better heat transportation from muscle to skin and increased sweat rate (Kissling et al., 2019). Having more plasma increases the heart’s output allowing it to move blood around the body more quickly (Lorenzo et al., 2010). While blood plasma likely doesn’t directly stimulate the creation of red blood cells, it does allow them to be shuttled to and through the muscles more quickly and more effectively. Heat training protocols abound in scientific literature and in various training circles. I use a dry sauna 2-3 times a week for about 20 minutes each time. It’s not a time intensive intervention, and it pays massive dividends. If you can find a modality that’s convenient and sustainable, I’d strongly encourage you to give it a go and see if it helps. (<a href='https://homebrewhappiness.net/posts/i-acted-like-a-heat-amateur-and-dnf-d-my-long-run-a-science-story'>Read more about heat in my article here</a>) <i>3. Long-term training</i> The other side of the VO2max equation is the perfusion of oxygen from the blood and into the muscle. This side has less impact on VO2max than cardiac output and red blood cell count, but it's a variable that you can train over longer time horizons. Altitude and heat exposure can show fitness benefits in a couple of weeks. Improving oxygen perfusion at the muscle can take consistent training over months or years. Within the muscle body, blood travels through capillaries that run alongside individual fibers. When the blood contacts the fiber, the muscle fiber will take oxygen from the red blood cell and give it to the mitochondria where the oxygen molecule binds to two hydrogen ions during the final step of aerobic energy production to form water—a transformation that would wow even the most expert of alchemists. A recent meta-analysis showed that lots of moderate intensity work—easy running is considered a moderate intensity activity in this study—paired with some higher intensity training leads to more capillaries and more mitochondria per muscle fiber (Mølmen et al., 2024; Liu et al., 2022). So, run a lot for as many years as you can. Be patient, and your body will literally grow new tubes and powerhouses to make you better at running. <i>4. Resistance Training and Plyometrics</i> I want to save the topic of resistance training and plyometrics for another article, so I’ll keep things brief. Aerobic capacity and red blood cell count are all well and good, but running economy is how well you actually use that oxygen to run. A world class cyclist and world class runner can’t switch sports and still be world class. They likely have a similar VO2max, but their economy is sport specific. They’re more effective at using oxygen in the context of their respective sports. How does someone who’s already run a lot in their life improve their running economy? Weights and plyos. Stiffer and stronger muscles and tendons can produce rapid improvements in running economy over short time frames (Barnes & Kilding, 2015). Adding weights and/or plyometrics a couple of times a week could pay huge dividends if your body is ready to handle a little extra load. <b>In Summary</b> Feminizing HRT is a miracle of modern science—a blessing I have unending gratitude for—and it’s good at what it does. Losing access to male levels of testosterone limits the body’s ability to produce red blood cells and thus feminizing HRT will lower an individual’s aerobic capacity. Although this drop in aerobic capacity can be substantial, effective training interventions like altitude and heat exposure, high volume training, and resistance training can mitigate some of the loss. Over time, consistent training that includes some specialized stimuli can lead to exceptional performances from anyone regardless of their body’s hormonal context. <b>References:</b> Antun, A., Zhang, Q., Bhasin, S., Bradlyn, A., Flanders, W. D., Getahun, D., Lash, T. L., Nash, R., Roblin, D., Silverberg, M. J., Tangpricha, V., Vupputuri, S., & Goodman, M. (2020). Longitudinal Changes in Hematologic Parameters Among Transgender People Receiving Hormone Therapy. Journal of the Endocrine Society, 4(11), bvaa119. https://doi.org/10.1210/jendso/bvaa119 Bachman, E., Travison, T. G., Basaria, S., Davda, M. N., Guo, W., Li, M., Connor Westfall, J., Bae, H., Gordeuk, V., & Bhasin, S. (2014). Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point. The journals of gerontology. Series A, Biological sciences and medical sciences, 69(6), 725–735. https://doi.org/10.1093/gerona/glt154 Barnes, K. R., & Kilding, A. E. (2015). Strategies to improve running economy. Sports medicine (Auckland, N.Z.), 45(1), 37–56. https://doi.org/10.1007/s40279-014-0246-y Beggs, L. A., Yarrow, J. F., Conover, C. F., Meuleman, J. R., Beck, D. T., Morrow, M., Zou, B., Shuster, J. J., & Borst, S. E. (2014). Testosterone alters iron metabolism and stimulates red blood cell production independently of dihydrotestosterone. American journal of physiology. Endocrinology and metabolism, 307(5), E456–E461. https://doi.org/10.1152/ajpendo.00184.2014 Bhasin, S., Taylor, W. E., Singh, R., Artaza, J., Sinha-Hikim, I., Jasuja, R., Choi, H., & Gonzalez-Cadavid, N. F. (2003). The mechanisms of androgen effects on body composition: mesenchymal pluripotent cell as the target of androgen action. The journals of gerontology. Series A, Biological sciences and medical sciences, 58(12), M1103–M1110. https://doi.org/10.1093/gerona/58.12.m1103 Collado-Boira, E., Baliño, P., Boldo-Roda, A., Martínez-Navarro, I., Hernando, B., Recacha-Ponce, P., Hernando, C., & Muriach, M. (2021). Influence of Female Sex Hormones on Ultra-Running Performance and Post-Race Recovery: Role of Testosterone. International journal of environmental research and public health, 18(19), 10403. https://doi.org/10.3390/ijerph181910403 Defreyne, J., Vantomme, B., Van Caenegem, E., Wierckx, K., De Blok, C. J. M., Klaver, M., Nota, N. M., Van Dijk, D., Wiepjes, C. M., Den Heijer, M., & T'Sjoen, G. (2018). Prospective evaluation of hematocrit in gender-affirming hormone treatment: results from European Network for the Investigation of Gender Incongruence. Andrology, 6(3), 446–454. https://doi.org/10.1111/andr.12485 Gagliano-Jucá, T., Pencina, K. M., Ganz, T., Travison, T. G., Kantoff, P. W., Nguyen, P. L., Taplin, M. E., Kibel, A. S., Li, Z., Huang, G., Edwards, R. R., Nemeth, E., & Basaria, S. (2018). Mechanisms responsible for reduced erythropoiesis during androgen deprivation therapy in men with prostate cancer. American journal of physiology. Endocrinology and metabolism, 315(6), E1185–E1193. https://doi.org/10.1152/ajpendo.00272.2018 Kissling, L. S., Akerman, A. P., & Cotter, J. D. (2019). Heat-induced hypervolemia: Does the mode of acclimation matter and what are the implications for performance at Tokyo 2020?. Temperature (Austin, Tex.), 7(2), 129–148. https://doi.org/10.1080/23328940.2019.1653736 Liu, Y., Christensen, P. M., Hellsten, Y., & Gliemann, L. (2022). Effects of Exercise Training Intensity and Duration on Skeletal Muscle Capillarization in Healthy Subjects: A Meta-analysis. Medicine and science in sports and exercise, 54(10), 1714–1728. https://doi.org/10.1249/MSS.0000000000002955 Lorenzo, S., Halliwill, J. R., Sawka, M. N., & Minson, C. T. (2010). Heat acclimation improves exercise performance. Journal of applied physiology (Bethesda, Md. : 1985), 109(4), 1140–1147. https://doi.org/10.1152/japplphysiol.00495.2010 Mølmen, K. S., Almquist, N. W., & Skattebo, Ø. (2025). Effects of Exercise Training on Mitochondrial and Capillary Growth in Human Skeletal Muscle: A Systematic Review and Meta-Regression. Sports medicine (Auckland, N.Z.), 55(1), 115–144. https://doi.org/10.1007/s40279-024-02120-2 Semenza, G. L. (2023). Regulation of Erythropoiesis by the Hypoxia-Inducible Factor Pathway: Effects of Genetic and Pharmacological Perturbations. Annual Review of Medicine, 74(Volume 74, 2023), 307–319. https://doi.org/10.1146/annurev-med-042921-102602 Tracz, M. J., Sideras, K., Boloña, E. R., Haddad, R. M., Kennedy, C. C., Uraga, M. V., Caples, S. M., Erwin, P. J., & Montori, V. M. (2006). Testosterone use in men and its effects on bone health. A systematic review and meta-analysis of randomized placebo-controlled trials. The Journal of clinical endocrinology and metabolism, 91(6), 2011–2016. https://doi.org/10.1210/jc.2006-0036 *I won’t go into the different methods of accomplishing these goals because transfemscience.org already has that covered, but I’d recommend reading up on the specific mechanisms through which each form of feminizing HRT accomplishes those goals. There may be side effects that go beyond the scope of this article.
