Your heartbeat is perhaps the most intimate bodily process. It is the rhythmic contraction of cardiac muscle, the enmeshed network of ordered muscle fibers in the heart’s walls. Underneath these, your heart is a series of four open chambers (two atria and two ventricles).
Heartbeats are electric. Charged ions move through cardiac muscles to coordinate contractions. In response to these ions, proteins within cardiac muscles tug on and shrink their cell, unidirectionally pushing blood through your heart and into the unique tangle of vessels underneath your skin.
Biologists have long fixated on the differences between (cis) men and (cis) women. Numerous bimodal variations in physiology between the two groups have been described as “sexually dimorphic.”
Researchers’ explanations for these differences have consistently centered on chromosomal and/or gonadal sex, asserting that physiology is hard-wired into the body’s genetics and anatomy. Under this thinking, sex hormones (i.e. estrogens and androgens) have very little impact on the body’s basic functioning.
If this were true, then trans people on hormone replacement therapy (HRT) would not see any changes in their physiology during hormonal transition. This hypothesis is readily testable. Indeed, at least five studies since 2024 have shed direct light on cardiac physiology during transition, and all five have reached the opposite conclusion. Together, their data suggest that hormonal sex is a major influence on the heart’s day-to-day physiology.
For healthy people, an electrocardiogram (EKG or ECG) will produce a characteristic wave pattern, shown in the graphic below. Each inflection of the curve is a measure of the electrical activity that drives the heartbeat. The P wave denotes the contraction of the atria, and the QRS waves together mark the contraction of the ventricles. Last, the T wave signifies the relaxation of the ventricles as they return to rest, in preparation for the next beat.
From an EKG, you can extract additional information about the heart’s physiology. For example, observations about the wave pattern can help clinicians reach diagnoses. The relative timing of each wave also contains valuable information such as the QT interval, the time interval between the Q wave and the T wave. Given the significance between the Q and T waves. Thus, the QT interval is also the total duration of ventricle activity for a single heartbeat. QT interval is sexually dimorphic, ~20 milliseconds longer in cis women than in cis men.
In July 2025, a team of French researchers published in JAMA Network Open their results on QT interval in trans people on HRT. The team analyzed EKGs from 64 transmascs and 56 transfemmes. Most of these participants had already begun HRT at the time of their participation in the study, but 18 transmascs and 15 transfemmes had not. These participants received an EKG both before and after starting HRT.
In the total cohort, the QT interval corrected for heart rate (QTc interval) was longer in transfemmes receiving HRT and shorter in trasmascs receiving HRT. These values are comparable to published data on QTc intervals is cis adults. Further, researchers were able to capture this shift directly in participants who received an EKG both before and after starting HRT. The QTc interval in transmascs decreased by an average of 17 milliseconds after starting HRT, while the interval increased by 21 milliseconds (on average) in transfemmes on HRT.
These results confirm the conclusions of on Australian research team who, in 2024, published their study in JAMA Network Open on QTc interval in transfemmes. This Australian study analyzed EKGs of 55 transfemmes before starting HRT and 6 months after starting hormones. On average, participants in this study displayed an average increase in QTc interval of 19 milliseconds.
Together, these data strongly suggest that HRT shifts the heart’s electrical activity to mirror that of one’s hormonal sex. A large body of evidence on the role of sex hormones in QTc interval in cis people also supports this conclusion. Yet, the French researchers still missed the mark, given that they tie their results to anti-trans pseudoscience. Their claim that their data “warrants attention in the exponentially increasing transgender population” is a regurgitation of the debunked theory of dangerous “rapid onset gender dysphoria”.
On the other hand, the Australian researchers were more clear-eyed in their analysis, focusing on the implications for clinicians treating trans patients: “Our findings would support use of the female reference range for interpretation of the QTc interval in people taking feminizing hormone therapy”. Given the results of the French study, this conclusion should be extended to suggest using the male reference range for transmascs on masculinizing hormone therapy.
It is impossible to divorce the idea of the heart as a pump from the actual material that it pumps around the body. In fact, the content of blood can help indicate different states of health. Human blood is generally composed of red blood cells (to carry oxygen), white blood cells (to fight pathogens), platelets (to promote clotting when necessary), and plasma (the liquid component). Blood plasma contains a coterie of proteins, hormones and other biomolecules which indicate states of health.
For example, high levels of a protein named troponin (especially cardiac troponin I, or cTnI) are associated with heart damage such as a heart attack. Troponins act within cardiac muscle to promote contraction by linking cellular fibers within muscle cells to the motor protein that generates the contractile force. Most cTnI is located within cardiac cells, but small amounts circulate in the blood. Cis men and cis women display differences in healthy levels of cTnI, where healthy cis men have higher levels of circulating cTnI than healthy cis women.
An October 2025 study published in JAMA Network Open investigated whether HRT alters the level of circulating cTnI. This work was performed by the Australian research team that conducted the study on QTc intervals in transfemmes. The authors hypothesized that there would no changes in cTnI in trans folx because heart mass is thought to be the best predictor of healthy cTnI levels. By this thinking, the differences in cTnI between cis men and cis women would be explained by innate developmental differences.
To test this, researchers measured the levels of circulating cTnI in 31 trans men, 28 trans women, 47 cis men, and 46 cis women. Measurements were taken twice: once at baseline (before starting HRT for trans participants) and once 12 months later (after one year of HRT for trans folx).
Contrary to the researchers’ predictions, their results demonstrate that circulating cTnI levels are likely driven by sex hormones. Trans men had increased cTnI levels, levels indistinguishable from cis men, within one year of HRT. (Transmasc folx should not assume this means you are at elevated risk of heart attacks as this range is considered healthy for cis and trans men.) Similarly, trans women displayed decreased cTnI levels after one year of HRT, and these measures were comparable to cis women.
Overall, these results strongly suggest that circulating cTnI (and consequently cardiac physiology) is strongly influenced by sex hormones rather than sex assigned at birth. Critically, this is not the first study to report on shifting cTnI levels in trans people. A 2022 study reported similar shifts (without cisgender control comparisons). Together, these studies provide strong evidence that cTnI levels and cardiac physiology shift during hormonal transition to align one’s physiology with hormonal sex.
Some contents of blood plasma contents are associated with different life states (age, inflammation, mood, etc.). Two major components of blood plasma are proteins (like cTnI and other proteins produced by organ systems) and metabolites (like cholesterols and other biomolecules that actively promote basic cellular physiology). Very little attention has been paid to the role of sex hormones in regulating the contents of blood plasma.
To test this, a collaborative research team, led by some of the Australian researchers who performed the QTc and cTnI studies mentioned above, measured blood plasma changes in transfemmes on HRT in two recent studies. Their first study was published in November 2024 in The Journal of Endocrinology and Metabolism and traced plasma metabolites in 53 transfemmes before HRT as well as at 3 and 6 months after starting HRT.
All participants demonstrated shifts in their plasma metabolites toward known plasma metabolite profiles in cis women such as decreased concentrations of low-density lipoproteins and very low-density lipoproteins. Both are forms of cholesterol. This lipoprotein profile is thought to lower the risk of atherosclertoic heart disease in cis women.
The group’s second study on plasma contents in transfemmes was published in October 2025 in Nature Medicine. This second study analyzed the plasma protein content of 40 participants before starting HRT and six months after. Proteins associated with sperm production decreased after starting HRT. Further, the researchers compared the plasma protein composition with available data in the UK Biobank. This analysis revealed that participants’ plasma proteome most closely resembled the plasma proteome of cis women during menopause, including women receiving menopausal hormone therapy (which generally centers on prescription estradiol).
While these studies centered on transfemmes, the role of sex hormones in driving these changes suggest that transmasc people on HRT likely experience inverse effects on blood plasma contents. Future research should be able to directly test this hypothesis.
Together, these five studies suggest that sex hormones are major influences on cardiovascular physiology and that for trans people on HRT, heart function closely aligns with hormonal sex. To quote the authors of the Nature Medicine study on the plasma proteome, “sex hormones exert broadly comparable physiological effects across” chromosomal backgrounds.
Other studies suggest that cardiovascular health is not the only physiologic system that alters its functioning during HRT. The immune system adapts to hormonal sex by altering cytokine signaling. Microbiome composition, a component of digestive health, also aligns with hormonal sex. Overall cardiorespiratory fitness improves in transmasc adolescents on testosterone. Sex hormones do indeed exert broad effects on the body. Of course, anyone on HRT could tell you that too. No need for blood draws or EKGs.
Researchers have long assumed that sexually dimorphic physiologies are the result of chromosomal or gonadal sex, while ignoring the (obvious) role of hormones in executing homeostatic programs at the cellular level. This falsified assumption also props up the false notion of binary and immutable “biological sex.”
Sex is a multifaceted characterization of a human body. Chromosomes, reproductive anatomy, hormones, and more are distinct traits that each create a spectrum of possible healthy bodies. When combined into a single sex designation, these spectra cannot collapse into a man/woman binary. Assertions to the contrary are only made by those who reject the evidence of their eyes, ears, and heart.
Instead, sex is something much more elegant, an array of unique individuals occupying space in a multi-dimensional matrix of genetics, tissues, and hormones. What’s more, bodies and their sexed traits change over time.
Don’t believe me? Your body is living proof.
from the archive
