Muscle Memory Mechanisms (Myonuclei Permanence, Epigenetic Marks) in Transgender Athletes

What the evidence says

Muscle memory mechanisms specific to transgender individuals undergoing gender-affirming hormone therapy (GAHT) have not been directly studied. One narrative review states plainly that "this area has not been explored in those undergoing GAHT," leaving the topic without primary human data in this population.

The broader literature on myonuclei-based muscle memory that this topic borrows from is itself unsettled. A comprehensive review and a separate systematic review and meta-analysis, cited in one source, found no clear evidence for muscle memory via myonuclei retention in either animal or human studies, and the same source describes the phenomenon as "not observed in many studies or not retained long term." A second source, however, describes primary studies pointing the other way: in mice, myonuclear numbers were retained for at least 3 months after testosterone withdrawal even though muscle cross-sectional area returned to baseline within 3 weeks; in an observational study of sedentary men, powerlifters, and current and former androgenic-steroid users, myonuclei numbers per fibre stayed stable across groups despite longitudinal declines in muscle cross-sectional area; and a small cross-sectional study of recreational strength trainees found higher myonuclei density 4 years after steroid cessation than at baseline.

Epigenetic evidence is thinner and points in different directions depending on population. In androgenic-steroid users generally, DNA methylation and histone acetylation "can persist" after steroid cessation, though no source gives a magnitude or duration for that persistence. For transgender individuals specifically, the only claim available is speculative: one review raises, without empirical support, the possibility that epigenetic marks from prior training "would be easily modified or overridden" by the hormonal changes of GAHT.

Where the evidence is direct and measured, it concerns physical performance rather than the underlying cellular mechanism. U.S. Air Force data show transgender women's physical performance declining by as much as 31% as testosterone levels fell over 2 years of feminizing hormone therapy. A separate longitudinal analysis found handgrip strength declining 7-13% and countermovement jump declining 23-29% after 1 year of testosterone suppression. Neither of these performance studies measures myonuclei counts or epigenetic marks directly; they measure functional outcomes only.

The link between the two bodies of evidence — cellular retention mechanisms and athletic performance after transition — remains hypothetical. One source frames it explicitly as conditional: "If verified, transgender women who experienced male puberty and later reduced testosterone levels retain physical advantages, particularly in strength-based sports." No claim here supplies direct empirical evidence on transgender athlete performance relative to cisgender athletes post-transition.

Where the evidence splits

Sources disagree on whether myonuclei-based muscle memory is supported by evidence at all. One source's cited comprehensive review and systematic review/meta-analysis conclude there is no clear evidence for myonuclei retention as a muscle-memory mechanism in animal or human studies. Another source describes specific primary studies — a mouse washout experiment, an observational study of steroid users, and a small cross-sectional study — that report myonuclei numbers staying stable or increasing after androgen withdrawal or cessation. The claims do not state why the synthesis-level reviews and the individual primary studies reach opposite conclusions; the difference in evidence tier (secondary synthesis vs. small primary studies, one of them explicitly noted as a small sample) is visible in the claims themselves, but no source reconciles it.

The two epigenetic claims also point opposite directions on persistence versus override, though for different populations. One claim, describing androgenic-steroid users generally, states epigenetic marks "can persist" after steroid cessation. Another claim, addressing GAHT-treated transgender individuals specifically, raises the possibility that such marks "would be easily modified or overridden" by hormonal change. The source presenting the override possibility explicitly labels it debatable and unsupported by empirical data in trans individuals, so this is not a direct empirical conflict — but the two claims describe opposite expected outcomes of hormonal change on the same molecular mechanism, and the sources do not explain why steroid users would show persistence while GAHT recipients might show override beyond the difference in population.

Thresholds and dose-response

No threshold established in the current sources.

Open empirical questions

• No source has measured myonuclei counts or epigenetic marks directly in GAHT-treated transgender individuals.
• Whether the measured performance declines in transgender women (7-31% depending on measure) are mediated by, or independent of, any myonuclei or epigenetic retention has not been tested.
• Whether transgender women who suppress testosterone for longer than the 1-2 years covered here show continued performance decline, plateau, or partial recovery is not measured.
• Whether transgender athletes retain measurable performance differences relative to cisgender comparators after transition has no direct empirical study in these sources.