Does Hormone Replacement Therapy Increase Muscle Mass?

Hormone replacement therapy can increase muscle mass, but the size of the effect depends enormously on which hormone is being replaced, who is taking it, and how it is delivered. Testosterone replacement in men with low levels produces reliable, well-documented gains in lean mass and strength. Estrogen-based therapy in postmenopausal women tells a murkier story, with large trials showing only modest or temporary effects on lean tissue when estrogen is used alone. The picture sharpens once you look at specific combinations, delivery routes, and training habits.

Estrogen Replacement in Postmenopausal Women

The largest dataset on this question comes from the Women’s Health Initiative (WHI), which tracked thousands of women on either estrogen alone or estrogen-plus-progestin therapy over six years. At the three-year mark, women on active hormone therapy had lost less lean body mass than those on placebo. But between years three and six, the relationship flipped: the hormone groups started losing lean mass faster. By the end of the full six years, the net difference in lean body mass between hormone users and placebo was essentially zero.¹

A 2019 meta-analysis pooling data from multiple randomized trials reached a similar conclusion. On average, women using hormone therapy lost a trivial amount less lean mass than controls, but the difference was not statistically meaningful. Stratifying by treatment type, dosage, duration, or time since menopause did not change the result.²

That sounds discouraging, but the averages hide some interesting variation. A smaller crossover trial reported that lean body mass actually increased during hormone therapy phases and fell during placebo phases, with a meaningful difference between the two.³ And a review of both human and animal research concluded there is “compelling evidence” that estrogen-based therapy can help maintain muscle mass and protect against muscle damage, even if that does not always show up in large population-level averages.⁴

When it comes to muscle strength specifically, a separate systematic review of randomized trials found that hormone therapy was not associated with significant strength gains in postmenopausal women overall. That result held regardless of treatment type, which muscle group was tested, or how long the therapy lasted.⁵

So the honest summary for postmenopausal women is that estrogen replacement, on its own, probably slows down muscle loss in the first few years but does not reliably build new muscle or produce lasting strength gains. That changes when you add exercise to the equation, which we will get to shortly.

Testosterone Replacement in Men

The evidence here is far more straightforward. In men with clinically low testosterone, replacement therapy consistently increases lean mass and muscle size. One study of hypogonadal men found that testosterone replacement produced an average increase in fat-free mass of about five kilograms, with measurable growth in arm and leg muscle cross-sectional area on MRI.⁶ Another found that muscle mass increased by roughly 20% in every participant, driven by a substantial rise in the rate of muscle protein production.⁷

Even in men with normal testosterone levels, supraphysiologic doses increase muscle size and strength, and the combination of testosterone and exercise produces larger gains than either alone. A landmark trial showed that men given high-dose testosterone without exercising still gained more arm and leg muscle than men who exercised on placebo.⁸ That study used doses well above replacement levels, so it speaks more to the pharmacology of testosterone than to typical clinical therapy. But the direction is unambiguous: testosterone is potently anabolic for skeletal muscle.

A meta-analysis looking specifically at how the route of testosterone delivery affects muscle found that intramuscular injections produced three to five times greater changes in lean mass and strength compared with transdermal patches or gels. Injections were linked to roughly a 6% increase in fat-free mass and 10–13% increases in strength measures, while transdermal forms produced only about a 2% gain in fat-free mass and smaller or absent strength improvements, particularly in the lower body.⁹

Why the Delivery Route Matters for Estrogen Too

The question of how you take a hormone turns out to matter for estrogen as well, though for a different reason. When estrogen is taken orally, it passes through the liver before reaching the rest of the body. This “first-pass” effect suppresses the liver’s production of insulin-like growth factor 1 (IGF-1), a protein that plays a key role in stimulating muscle growth. One study found that oral estrogen reduced IGF-1 levels by more than 40%, while transdermal estrogen (absorbed through the skin, bypassing the liver) actually raised IGF-1 to levels comparable to those in premenopausal women.¹⁰

This distinction has real consequences for muscle. A study in growth-hormone-deficient women found that oral estrogen lowered protein synthesis both before and during growth hormone therapy, essentially blunting the muscle-building effect.¹¹ A separate trial confirmed that oral estrogen significantly reduced IGF-1, while transdermal estrogen did not.¹²

This may explain part of the confusion in the clinical literature. Many of the large trials that found negligible effects of estrogen on muscle used oral formulations. When researchers specifically tested transdermal estrogen paired with resistance training, results were different: early postmenopausal women using estrogen patches saw roughly twice the increase in muscle cross-sectional area (about 8% versus 4%) and nearly double the increase in fat-free mass compared with women on placebo who did the same exercises.¹³

How Estrogen and Exercise Work Together

Your muscles contain satellite cells, which function as a repair-and-growth reserve. When you exercise hard enough to cause microscopic damage to muscle fibers, satellite cells activate, multiply, and fuse into the fibers to make them larger and stronger. Estrogen appears to be involved in keeping those satellite cells alive and functional, at least in women.

Animal studies have shown that estrogen receptor signaling in satellite cells is necessary to prevent those cells from dying off prematurely.¹⁴ When the estrogen receptor beta pathway was disrupted in female mice, muscle growth and regeneration after injury were impaired, while male mice were unaffected, suggesting this is a sex-specific mechanism.¹⁵ Additional lab work has confirmed that estrogen receptor beta activation promotes satellite cell proliferation and upregulates markers of muscle regeneration.¹⁶

This helps explain a striking finding in humans. When early postmenopausal women underwent 12 weeks of resistance training, those using transdermal estrogen saw a 26% increase in satellite cells associated with type I muscle fibers. Women in the placebo group doing the same training saw a 47% decrease. Type II fiber satellite cells dropped sharply in the placebo group as well.¹⁷ In other words, without estrogen, resistance training in these women was actually depleting their satellite cell pool rather than building it up.

Estrogen also appears to benefit muscle mitochondria. Studies in mice show that removing estrogen reduces mitochondrial function, increases oxidative stress, and worsens insulin sensitivity in skeletal muscle, while estrogen replacement restores all of these.¹⁸ Healthy mitochondria matter for exercise capacity and recovery, which feeds back into your ability to build and maintain muscle over time.¹⁹

Progesterone and Muscle Protein Synthesis

Most conversations about HRT and muscle focus on estrogen or testosterone, but progesterone deserves attention. In a randomized trial of postmenopausal women, progesterone treatment increased the muscle protein synthesis rate by about 50%, comparable to the effect of testosterone. Estradiol, by contrast, did not increase muscle protein synthesis at all in that same study.²⁰

This is a somewhat counterintuitive finding and worth keeping in perspective. The acute boost in protein synthesis from progesterone was measured over hours, and it does not automatically translate into meaningful long-term muscle gains. An earlier rat study found that progesterone actually reduced muscle protein synthesis rates, suggesting the effects may differ between species or depend on dose and duration.²¹ A review of the topic noted that while estrogen may not have a marked effect on resting muscle protein synthesis, progesterone’s acute stimulation has not yet been proven to translate into long-term changes in muscle mass.²²

Still, the finding is interesting because many combined HRT regimens include both estrogen and a progestogen. If progesterone contributes a separate, direct anabolic signal to muscle, that could partly explain why some combined-therapy users report feeling stronger, and why trials using different progestogen formulations sometimes get different results.

Muscle Quality, Not Just Quantity

Muscle mass measured in kilograms is one thing, but what that tissue actually looks like inside matters for function. As people age, fat tends to infiltrate muscle fibers, reducing the tissue’s density and its ability to produce force. This “marbling” effect is one reason older adults can lose strength faster than they lose visible muscle size.

A year-long study of early postmenopausal women found that hormone replacement therapy significantly improved muscle attenuation, a CT scan measure of muscle density that reflects how much fat has crept into the tissue. The improvement was seen with HRT alone, exercise alone, and the combination.²³ A study of identical twins where one sister used HRT and the other did not found that the HRT users had a greater proportion of muscle relative to fat in their thighs, along with better muscle power and mobility.²⁴ The twin design is especially informative because it controls for genetics and much of the shared environment, isolating the hormone effect more cleanly than a typical trial.

This suggests that even when HRT does not dramatically change the number on the scale, it may improve the functional quality of the muscle you have. For older adults concerned about maintaining independence and avoiding falls, muscle quality can matter as much as raw mass.

Transgender Hormone Therapy

Gender-affirming hormone therapy produces some of the most dramatic body composition changes because it is deliberately shifting the dominant hormone environment. For trans men (assigned female at birth, taking testosterone), the effects parallel what is seen in cisgender hypogonadal men. One prospective study documented a 10.4% increase in lean body mass and a 9.7% decrease in total body fat during the first year of testosterone treatment, along with an 18% increase in grip strength.²⁵ Another study found a 15% increase in thigh muscle volume and a 15% increase in quadriceps cross-sectional area after 12 months.²⁶

Interestingly, even lower testosterone doses appear to produce meaningful changes. A long-term study found that both low-dose and standard-dose testosterone regimens led to decreased body fat and increased lean mass during the first year, though the standard-dose group gained more lean mass initially.²⁷

For trans women (assigned male at birth, taking estrogen and anti-androgens), the effect runs in reverse. Muscle volume typically decreases by about 5% and cross-sectional area by about 4% in the first year.²⁶ A systematic review found that while lean mass and strength decrease meaningfully after 12 months of feminizing therapy, these values generally remain above those of cisgender women even after three years.²⁸ This has been at the center of ongoing debates about athletic eligibility policies, but the clinical takeaway is that feminizing HRT does reduce muscle mass, just not all the way to the average female range within the first few years.

The Androgen Receptor Pathway

The reason testosterone is so reliably anabolic comes down to how it signals inside muscle cells. Testosterone binds to androgen receptors, which then trigger a cascade of growth-promoting signals, including the well-known IGF-1/PI3K/Akt/mTOR pathway that drives muscle protein synthesis and fiber enlargement.²⁹ When researchers blocked the androgen receptor with a drug, training-induced muscle growth was substantially diminished, confirming that the receptor is doing essential work.

This is why testosterone replacement increases both muscle mass and strength, while selective androgen receptor modulators (SARMs) are being developed as potential alternatives. These experimental compounds aim to activate the androgen receptor selectively in muscle and bone while limiting effects on the prostate, liver, and cardiovascular system. Meta-analyses confirm that testosterone supplementation increases fat-free mass and strength across multiple populations, including older men with low testosterone and men with chronic illness, but the side-effect profile has pushed researchers to look for more targeted molecules.³⁰ SARMs remain largely in early clinical development and are not approved for general use, though they are widely sold in unregulated supplement markets.

What Happens When Hormone Therapy Stops

A practical concern for anyone considering HRT for body composition is what happens to the gains when the therapy ends. There is not a large body of work on this specific question, but the available evidence is not encouraging for retention. The WHI data showed that the lean-mass preservation seen at three years reversed by year six, and the active groups were losing lean mass faster than placebo groups in the latter half of the trial.¹ A study of growth-hormone-deficient young adults found that after stopping growth hormone treatment, quadriceps strength and size fell to about 94% of baseline within 12 months, while body fat percentage climbed.³¹ While that study dealt with growth hormone rather than sex steroids, the pattern is instructive: hormone-dependent body composition changes tend to fade when the hormonal stimulus is removed.

For people using testosterone replacement, the expectation should be similar. If testosterone levels drop back to their pre-treatment state, the extra muscle mass is unlikely to persist without the continued hormonal support that built it. Maintaining an exercise habit becomes even more important if you want to hold on to as much lean tissue as possible after discontinuation.

Putting the Pieces Together for Practical Decisions

If you are a postmenopausal woman thinking about HRT partly for muscle health, the evidence suggests that estrogen alone is unlikely to produce noticeable muscle gain, but it may slow the rate of muscle loss and improve the quality of the muscle you retain. Transdermal estrogen appears preferable to oral for this purpose, because it avoids suppressing IGF-1. And the biggest gains come when estrogen therapy is combined with resistance training, which allows estrogen to do its job of supporting satellite cells while the exercise provides the mechanical stimulus those cells need.

If you are a man with clinically low testosterone, replacement therapy will very likely increase your lean mass and strength, with intramuscular injections producing the largest effects.⁹ Exercise will amplify those gains substantially.

For transgender individuals, hormone therapy reshapes body composition powerfully and predictably in the direction of the target sex’s typical pattern, though the timeline and degree of change vary by individual and dose. Neither the muscle gain from testosterone nor the muscle loss from estrogen-based therapy reaches its full plateau within the first year, and long-term data beyond three years remains thin for many outcomes.²⁸

Across all of these populations, one theme keeps emerging: hormones set the conditions for muscle growth, but they do not do the building alone. The people who see the most meaningful, lasting changes in muscle mass are the ones who combine hormonal therapy with progressive resistance training. Hormones open the door; the weights push you through it.

1
PubMed Central. Effect of hormone therapy on lean body mass, falls, and fractures: Six-year results from the Women’s Health Initiative Hormone Trials
2
JAMA Network Open. Association Between Hormone Therapy and Muscle Mass in Postmenopausal Women
3
PubMed. Obesity and sarcopenia after menopause are reversed by sex hormone replacement therapy
4
PubMed Central. Benefits of estrogen replacement for skeletal muscle mass and function in post-menopausal females: evidence from human and animal studies
5
PubMed. Effect of hormone therapy on muscle strength in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials
6
The Journal of Clinical Endocrinology & Metabolism. Testosterone Replacement Increases Fat-Free Mass and Muscle Size in Hypogonadal Men
7
The Journal of Clinical Endocrinology & Metabolism. Effects of testosterone replacement on muscle mass and muscle protein synthesis in hypogonadal men–a clinical research center study
8
PubMed. The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men
9
PubMed Central. Muscular responses to testosterone replacement vary by administration route: a systematic review and meta-analysis
10
The Journal of Clinical Endocrinology & Metabolism. Contrasting Effects of Oral and Transdermal Routes of Estrogen Replacement Therapy on 24-Hour Growth Hormone (GH) Secretion, Insulin-Like Growth Factor I, and GH-Binding Protein in Postmenopausal Women
11
PubMed. Oral estrogen antagonizes the metabolic actions of growth hormone in growth hormone-deficient women
12
PubMed. Effects of oral and transdermal estrogen on IGF1, IGFBP3, IGFBP1, serum lipids, and glucose in patients with hypopituitarism during GH treatment: a randomized study
13
Frontiers in Physiology. Transdermal Estrogen Therapy Improves Gains in Skeletal Muscle Mass After 12 Weeks of Resistance Training in Early Postmenopausal Women
14
PubMed Central. Estrogen Regulates the Satellite Cell Compartment in Females
15
Stem Cell Reports. Estrogen Receptor β Controls Muscle Growth and Regeneration in Young Female Mice
16
PubMed. Selective estrogen receptor-β activation stimulates skeletal muscle growth and regeneration
17
PubMed. Effects of transdermal estrogen therapy on satellite cell number and molecular markers for muscle hypertrophy in response to resistance training in early postmenopausal women
18
PubMed Central. 17β-Estradiol Directly Lowers Mitochondrial Membrane Microviscosity and Improves Bioenergetic Function in Skeletal Muscle
19
PubMed Central. Estrogens, Estrogen Receptors Effects on Cardiac and Skeletal Muscle Mitochondria
20
PubMed Central. Testosterone and progesterone, but not estradiol, stimulate muscle protein synthesis in postmenopausal women
21
PubMed. Effects of estradiol and progesterone on body composition, protein synthesis, and lipoprotein lipase in rats
22
Proceedings of the Nutrition Society. Female hormones: do they influence muscle and tendon protein metabolism?
23
PubMed. The effect of hormone replacement therapy and/or exercise on skeletal muscle attenuation in postmenopausal women: a yearlong intervention
24
PubMed. Postmenopausal hormone replacement therapy modifies skeletal muscle composition and function: a study with monozygotic twin pairs
25
European Journal of Endocrinology. Body composition, bone turnover, and bone mass in trans men during testosterone treatment: 1-year follow-up data from a prospective case–controlled study (ENIGI)
26
The Journal of Clinical Endocrinology & Metabolism. Muscle Strength, Size, and Composition Following 12 Months of Gender-affirming Treatment in Transgender Individuals
27
PubMed. Trans men can achieve adequate muscular development through low-dose testosterone therapy: A long-term study on body composition changes
28
PubMed Central. How does hormone transition in transgender women change body composition, muscle strength and haemoglobin? Systematic review with a focus on the implications for sport participation
29
PubMed Central. Crucial role of androgen receptor in resistance and endurance trainings-induced muscle hypertrophy through IGF-1/IGF-1R- PI3K/Akt- mTOR pathway
30
PubMed Central. Drug insight: Testosterone and selective androgen receptor modulators as anabolic therapies for chronic illness and aging
31
PubMed. Changes in skeletal muscle and body composition after discontinuation of growth hormone treatment in growth hormone deficient young adults