Estrogen and Muscle — The Scientific Guide
I remember the first time I held a vial of estradiol.
In my hand was not just medicine, but the key to a future I had only dared to imagine. It was a terrifying, exhilarating, and monumental moment.
Two weeks ago, I wrote a larger piece on Estrogen and Muscle, and it contained an oversimplification for a complex and important topic. To do it justice, I've decided to split this into a Multi-part series where I can dive deeper into the science and then share my personal connection in the following posts. This is Part 1 in totality.
The Feminization Effect: Science, Mechanisms, and New Insights
Feminizing hormone therapy fundamentally rewrites the body's hormonal programming, transitioning it from a testosterone-driven system to one guided by estrogen.
This deep-seated change affects everything from metabolic functions at the cellular level to the structural composition of muscle and bone. While the most visible results, like fat redistribution and softer skin, are widely discussed, the profound and nuanced effects on muscle and athletic performance are a critical part of this journey. This article dives into the science behind these changes, drawing on recent research to provide a comprehensive understanding of how estrogen interacts with muscle for transgender women. Disclaimer- this is not Medical Advice.
Not All Estrogen Delivery Is the Same
The extent of body and muscle composition change is strongly moderated by several key factors related to HRT administration. The route of delivery significantly impacts how your body receives and processes estrogen, influencing everything from hormone stability to potential health risks.
Injectable estradiol (valerate or cypionate): This route produces high serum estradiol peaks, often ranging from 600–1,200 pmol/L, which then gradually decline over several days (Rothman et al., 2024). These fluctuations can lead to more robust feminization signals, but they may also contribute to mood and energy swings.
Oral estradiol: This method undergoes significant first-pass metabolism in the liver, which can affect bioavailability and increases the risk of venous thromboembolism (VTE) or blood clots (Hembree et al., 2017). Serum estradiol levels with this route are often lower and less stable, typically around 200–400 pmol/L.
Transdermal estradiol (patches or gel): This route offers a stable and consistent delivery of estradiol into the bloodstream, producing serum concentrations of 200–600 pmol/L with a lower risk of hepatic side effects. This makes it a favorable option for those with cardiovascular risk factors (Deutsch et al., 2015).
Key Takeaway: Estrogen dosage and delivery method matter. Higher, more stable levels within the therapeutic range (200-800 pmol/L) are linked to more significant feminizing effects.
How Muscle Composition Rebalances Under HRT
The hormonal transition from a testosterone-driven system to one guided by estrogen is a dual-action process.
The suppression of androgens is arguably the most significant factor in a body's physical changes, as testosterone is the primary driver of muscle hypertrophy—the growth and enlargement of muscle tissue. Without this anabolic signal, the body's rate of protein synthesis declines, making it easier to lose muscle mass.
However, estrogen is not merely a passive replacement. It introduces its own set of signals that actively remodel how the body functions. Rather than promoting raw strength and bulk, estrogen shifts the body's priorities toward a state of equilibrium, favoring recovery, endurance, and metabolic efficiency. This nuanced interplay of hormonal signals explains why the changes in muscle mass and strength are both predictable and highly individual.
Estrogen as a Coach, Not an Eraser
Think of testosterone as a coach that emphasizes raw size and strength, and estrogen as a coach that prioritizes resilience and efficient function. At the most basic level, the feminization effect begins with the binding of estradiol to estrogen receptors (ERα and ERβ) that are present in skeletal muscle tissue (Velders & Diel, 2013). Once bound, estrogen initiates pathways involved in muscle regeneration, oxidative stress, and mitochondrial biogenesis (Collins et al., 2022).
A key function is the enhanced activation of satellite cells, a type of muscle stem cell essential for repairing micro-damage. This estrogen-mediated repair is crucial for maintaining muscle health, even if it doesn't lead to significant hypertrophy. This is particularly important for upper-body muscles, which have a high density of androgen receptors and thus lose mass more readily when androgenic drive is suppressed (Wiik et al., 2020).
Recent research has highlighted estrogen's crucial role in metabolic function. Estrogen improves mitochondrial morphology and efficiency, enhancing the production of ATP (cellular energy) and reducing the damage from reactive oxygen species (ROS) (Collins et al., 2022). This supports why endurance and aerobic capacity are often preserved, and sometimes even improved, for transgender women on HRT, as their muscles become more metabolically efficient.
Furthermore, estrogen enhances insulin sensitivity and glucose uptake in muscle tissue, which aids in post-exercise recovery and reduces fat infiltration into the muscle itself (Ramos-Jiménez et al., 2024). This metabolic shift helps explain the observed changes in body composition, as the body becomes more adept at utilizing glucose for fuel rather than storing it as fat within muscle tissue.
The New Baseline: Redefining Strength and Training
When I first noticed my overhead press numbers slipping, I panicked. For years, strength had been my measure of progress, my way of proving that I could command my body against the odds. Watching those numbers decline felt like failure. But while my pressing strength faded, my legs and glutes told another story. They thrived under estrogen, responding beautifully to training, as though my body was asking me to shift my definition of power.
That realization marked the beginning of what I now call the new baseline: the point where my strength, physiology, and training philosophy recalibrated under hormone replacement therapy. To truly embrace training as a Transfemme, I had to stop seeing myself as losing strength and start recognizing the new potential estrogen created.
Training Smarter Under Estrogen
Understanding this new baseline requires more than accepting change—it demands training smarter. A structured approach that accounts for your body’s new hormonal state is key.
Absolute vs. Relative Strength
Yes, absolute strength—the maximum amount of weight lifted—often declines. But research shows that relative strength, or strength adjusted to body size and composition, remains relatively stable (Wiik, 2020). That means functional strength—carrying groceries, climbing stairs, holding your ground in sport—doesn’t collapse. In practice, I noticed this when I compared myself to training partners. My bench numbers dropped, but my ability to perform bodyweight exercises like squats or pushups stayed consistent. My body wasn’t broken; it was simply recalibrating.
Joint and Ligament Health
Estrogen alters collagen synthesis, increasing ligament laxity and raising THE risk of injuries like ACL tears (Casey, 2016). Instead of abandoning lifts, I redesigned my approach to focus on stability: prioritizing hamstring curls, hip thrusts, and posterior chain work for knee stability; incorporating balance drills and unilateral movements like Bulgarian split squats; and adding core stability training. Strength under estrogen is less about raw power and more about resilience—building connective tissue stability to support muscle performance.
Key Takeaway: Train for resilience. Estrogen can increase ligament laxity, so prioritize joint stability with posterior chain, core, and unilateral work to protect against injury.
Lean Mass and Strength Over Time
Clinical studies provide concrete data on how these cellular changes translate to physical outcomes. Within the first year of HRT, transgender women typically experience a loss of 4–6% of their thigh muscle volume and cross-sectional area (Wiik et al., 2020). However, strength declines are often less pronounced than the loss of muscle size might suggest, especially when adjusted for lean body mass. This phenomenon points to an increase in muscle quality and neuromuscular efficiency—the ability of the nervous system to activate muscle fibers effectively—which compensates for the SIZE REDUCTION.
Over longer durations, the reduction in lean mass continues but tends to plateau, and relative strength stabilizes closer to the baselines of cisgender women (Roberts et al., 2021; Toorians et al., 2022). This long-term stabilization suggests that while an initial reduction is inevitable, the body finds a new, stable muscular baseline in its feminized state.
Key Takeaway: The initial loss of muscle mass tends to plateau around the one-year mark. Your body finds a new, stable baseline where relative strength and endurance are preserved, even if absolute strength declines.
Nutrition for the Estrogen-Dominant Athlete
Training on estrogen requires you to pay close attention to your fuel. Your workouts are only as effective as what you eat.
Protein: With slower hypertrophy, higher protein intake (1.6–2.2 g/kg body weight) is essential to preserve lean mass.
Carbohydrates: Estrogen improves glucose uptake, meaning carbs are used efficiently during exercise. I lean on complex carbs around workouts for sustained energy.
Micronutrients: Vitamin D and calcium protect bone density. Iron is also crucial, since estrogen can influence red blood cell production.
Hydration & Electrolytes: Estrogen shifts water balance, so staying hydrated with added electrolytes helps prevent cramping.
The Mental Reframe: Redefining Strength
The hardest part wasn’t the science. It was psychological. Strength had always been my armor. Losing numbers on the barbell felt like losing my identity. But as I trained, I began to see that strength wasn’t disappearing—it was evolving.
My body taught me a new definition:
Strength is lifting less overhead but running farther without fatigue.
Strength is squatting deeply with stability, even if the bar is lighter.
Strength is training consistently, even when the changes are subtle and slow.
In many ways, estrogen didn’t weaken me. It expanded my relationship to strength, showing me resilience, patience, and adaptability.
Final Thoughts: From Fear to Foundation
When I first began hormone replacement therapy, the greatest fear I carried was not the risk of blood clots or brittle bones—it was the fear of losing strength. Strength had been my shield for so long, the proof that I could endure whatever the world hurled at me. I clung to it the way a warrior clings to armor. To imagine it slipping away was to imagine being exposed. Vulnerable.
But what I did not yet understand was that HRT would not take my strength—it would transform it. It would strip away the armor I thought I needed and replace it with something sturdier: alignment between my inner identity and my outer form. That is a strength that endures when numbers on the barbell rise and fall, when muscle fades and reforms, when training plateaus and starts again.
The Early Fears
Starting estrogen in 2013 felt monumental. Back then, the Harry Benjamin Standards of Care (now WPATH SOC7/8) required me to secure two therapist letters just to begin treatment. I had already been living openly as trans without a medical transition, exposing myself to discrimination and misunderstanding, and yet still had to prove my legitimacy to strangers who could write or withhold my future on a prescription pad.
I walked into HRT believing it would change everything overnight. I dreamed of instant curves, of breasts budding like spring after a long winter, of a voice that would soften without effort. Instead, I found myself exhausted after injections, emotionally volatile, and, at times, disinterested in things that once gave me joy. Breast development was slow, hair growth unchanged, and my voice remained stubbornly the same. I began to question the very power of estrogen.
When my muscle mass began to fade and my body fat redistributed in ways I could not control, I grew resentful. Estrogen felt like an antagonist, something that eroded me rather than built me up. I skipped doses when the effort felt pointless. I fretted over every ache, every sign of fragility, every warning of clotting risk or bone loss.
It felt like I had traded certainty for doubt.
The Mistakes and Their Lessons
The truth is, I made mistakes along the way. Once I achieved results that I considered “enough,” I stopped being consistent. I skipped appointments, ignored bloodwork, drifted back into old habits. Each break in therapy wreaked havoc on my system, making resumption harder and my body more resistant to equilibrium.
Those lapses taught me one of the most painful lessons of transition: consistency matters more than expectation. HRT is not a miracle switch. It is a process of slow, subtle, cumulative changes. Like fitness, it demands patience. Like training, it punishes inconsistency.
When I stopped treating HRT as a passive medicine and began treating it like training, a practice requiring discipline, monitoring, and gradual adaptation, my relationship to it shifted. I stopped looking for dramatic overnight change and started appreciating the quiet persistence of progress.
The Parallel to Fitness
I realized, in retrospect, that HRT mirrors a fitness journey almost perfectly. At first, the changes are invisible. You doubt it’s working. You wonder if the pain and effort are worth it. Then, months later, you notice the first signs—a new curve, a softened jawline, a muscle that feels subtly different in texture. Progress compounds quietly, like strength built set after set, day after day.
Both HRT and fitness require faith in the unseen, accountability to routine, and respect for expert guidance. I needed endocrinologists to monitor my levels the way I needed trainers to refine my form. I needed bloodwork the way I needed progressive overload charts. And in both, I had to trust that what I was doing today would blossom into results tomorrow.
That realization reframed estrogen in my mind. It was not an adversary but a training partner, reshaping me at a pace my impatient heart resisted, but my wiser self came to honor.
Combat Sports and Accountability
In my first post, I wrote about how combat sports saved me during an existential crisis. Stepping onto the mat forced me to be accountable in ways I couldn’t avoid. Combat sports teach you the price of inattention—you lose the match, you get caught in a choke, you learn humility. That accountability transferred into my approach to health, including HRT.
When I framed transition as combat training, I approached it with the discipline of an athlete:
Checking my dosages like I would track macros.
Treating injections like training sessions I couldn’t skip.
Respecting my recovery days and sleep as seriously as my gym sessions.
What once felt like a passive medical treatment became an active practice of self-alignment.
The Redefinition of Strength
Strength no longer meant a number on the bar. It meant congruence. It meant having the patience to build a body that reflected who I truly was, even if the results unfolded at a glacial pace.
The strongest version of me is not the one who pressed the most weight overhead—it’s the one who learned to show up for herself again and again, even when progress felt invisible.
I discovered new definitions of strength:
strength to trust medicine that frightened me.
strength to face my reflection when it didn’t yet match my vision.
strength to persevere when I wanted to quit.
strength to embrace joy in training not as punishment but as celebration.
Health as the Anchor
As I grew more consistent, I also became more intentional. I began weightlifting not just for aesthetics but for bone density, knowing estrogen could leave me vulnerable. I embraced cardio not as a chore but as a lifeline for cardiovascular health, guarding against cholesterol and blood sugar risks.
Training became less about sculpting a fantasy and more about extending my lifespan, preserving my health, and ensuring that the woman I was becoming would thrive long into the future.
Estrogen did not weaken my health—it demanded I take responsibility for it.
From Armor to Alignment
Looking back, I had a fundamental misunderstanding of what strength really was. I thought it was armor—something I wore to protect myself from the world. But that armor was heavy, and the tension kept me from truly connecting with my own body.
When I started HRT, I learned to let go of the need for that protection and instead focused on finding alignment. My strength didn't come from resisting who I was, but from finally being congruent with myself.
This change completely shifted my mindset around training. It wasn't about forcing my body into submission anymore; it became an act of love and devotion.
The Foundation Ahead
The greatest strength I've built through this journey is the one that brings my physical form into harmony with my inner self. The journey for self-actualization is incredibly powerful, whether it is through gender transition, fitness, or education.
Launching this blog platform and the subsequent exploration of sports medicine and endocrinology has led to a more intentional approach to my health, WHICH has given me a new sense of agency and ownership in my future. I've learned to speak with confidence about my body's needs and to advocate for myself within the medical community. This isn't just about my personal journey; it's about claiming my space and building a foundation that is strong enough to hold me, even when I doubt it.
And this is the final truth HRT gave me: strength is not what I had. Strength is who I am becoming.
References
Velders, Martina, and Patrick Diel. "How Sex Hormones Promote Skeletal Muscle Regeneration." Sports Medicine, 2013.
Collins, Brianna C., et al. "Mechanisms of Estrogen Influence on Skeletal Muscle: Mass, Regeneration, and Mitochondrial Function." Sports Medicine, 2022.
Wiik, A., et al. "Muscle Strength, Size, and Composition Following 12 Months of Gender-Affirming Treatment." Journal of Clinical Endocrinology & Metabolism, 2020.
Roberts, T. A., et al. "Changes in Muscle Mass, Strength, and Aerobic Capacity Following Gender-Affirming Hormone Therapy in Transgender Women." British Journal of Sports Medicine, 2021.
Toorians, A. W. F. T., et al. "Influence of Androgen Deprivation and High-Dose Estrogen on Muscle Function in Transgender Women." European Journal of Endocrinology, 2022.
Casey, Mary, et al. "Sex Hormones." In Sex Differences in Sports Medicine, 2016.
Ramos-Jiménez, A., et al. "Hormonal Influences on Skeletal Muscle Function in Women across the Life Span: A Systematic Review." MDPI Cells, 2024.
Micol S. Rothman, ET AL. “The Use of Injectable Estradiol in Transgender and Gender Diverse Adults: A Scoping Review of Dose and Serum Estradiol Levels”, Endocrine Practice, Volume 30, Issue 9, 2024
Hembree, W. C., et al. "Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline." Journal of Clinical Endocrinology & Metabolism, 2017.
Deutsch, Madeline B., et al. "Transgender Hormone Therapy: Medical Considerations." Endocrinology and Metabolism Clinics of North America, 2015.
M. den Heijer et al. "Long-Term Hormonal Treatment for Transgender People." BMJ: British Medical Journal, 2017.
Ford, Ky, Elizabeth Huggins, and Patricia Sheean. "Characterising Body Composition and Bone Health in Transgender Individuals receiving Gender-Affirming Hormone Therapy." Journal of Human Nutrition & Dietetics, 2022.
S. Sipilä. "Body Composition and Muscle Performance During Menopause and HRT." Journal of Endocrinological Investigation, 2003.