Evaluation of Serum Irisin Levels in Individuals with Gender Incongruence and Its Metabolic Correlations

Abstract

Introduction:

Irisin, a myokine implicated in energy homeostasis, has been proposed as a biomarker for metabolic dysfunction. This study aimed to assess serum irisin levels and their associations with metabolic parameters in gender-incongruent individuals compared to healthy cisgender controls and to assess the predictive value of irisin and related metabolic indices for metabolic syndrome (MetS) using both affirmed and birth-assigned gender criteria.

Methods:

A cross-sectional “observational, non-randomised” study was conducted from June 2024 to February 2025 among 123 participants (transgender women, transgender men, cisgender women and cisgender men), matched for age and body mass index. Individuals with confounding metabolic conditions were excluded. Serum irisin was measured using a sandwich enzyme-linked immunosorbent assay, and metabolic parameters were evaluated. Statistical analyses assessed the diagnostic utility of irisin and various metabolic indices for MetS.

Results:

In transgender women, serum irisin showed inverse correlation with diastolic blood pressure (r = –0.307, P = 0.036). In transgender men, it was inversely correlated with high-density lipoprotein (HDL) cholesterol (r = –0.339, P = 0.046) and prolactin (r = –0.357, P = 0.035). Receiver operating characteristic analysis revealed a limited predictive value of irisin for MetS (area under the curve (AUC) <0.5). The triglyceride (Ty)/HDL index performed better in transgender women (AUC = 0.748) and the triglyceride-glucose index (Ty/G index) in transgender men (AUC = 0.67).

Conclusion:

Serum irisin is associated with select metabolic parameters but has limited utility in predicting MetS in gender incongruent individuals. Affirmed gender-based assessment enhances risk stratification, with Ty/HDL and Ty/G indices offering better predictive value in transgender populations.

INTRODUCTION

Irisin, a myokine cleaved from Fibronectin Type III Domain-Containing Protein 5 and primarily expressed in skeletal muscle, regulates various metabolic processes, including glucose homeostasis, lipid metabolism and thermogenesis.[1] It enhances glucose uptake, improves insulin sensitivity, promotes fat oxidation, reduces circulating lipids and increases energy expenditure by inducing browning of white adipose tissue,[2,3] which is important for metabolic and cardiovascular disease pathogenesis.[4] Irisin also protects endothelial cells by mitigating oxidative stress and promoting vascular health.[5]

Given these effects, irisin’s therapeutic potential in type 2 diabetes mellitus (T2DM), obesity and cardiovascular disorders has been thoroughly investigated. Higher circulating levels correlate with lower body mass index (BMI), reduced visceral fat and improved insulin sensitivity, suggesting its potential as a metabolic health biomarker and therapeutic target. Strategies enhancing irisin secretion, such as exercise, may complement existing weight management and T2DM treatments, especially for patients resistant to conventional therapies.

Despite research in cisgender populations, irisin’s role in gender-incongruent individuals remains underexplored. Gender-affirming hormone therapy (GAHT), which forms a significant part of gender-affirming care, significantly alters muscle mass, fat distribution and hormonal milieu, potentially influencing myokine secretion. However, its effect on irisin levels and subsequent metabolic effects on glucose tolerance, lipid profiles and metabolic syndrome (MetS) remains poorly explored.[6]

Investigating irisin in this context is important for understanding how gender-affirming therapies influence metabolic health and inform personalised clinical strategies.[6] Further research could elucidate the intersection of biological sex, gender identity and metabolic regulation, guiding more effective management of obesity, T2DM and cardiovascular diseases in gender-incongruent populations. This study aimed to (1) characterise serum irisin levels in gender-incongruent individuals, (2) evaluate the impact of GAHT on irisin levels and (3) explore the associations between irisin and key metabolic parameters, including BMI, lipid profiles and glucose levels.

MATERIALS AND METHODS

Study Design and Participants: A single-centre, cross-sectional “observational, non-randomised” study conducted over 9 months (June 2024 to February 2025) at a tertiary care hospital in Bangalore. Gender-incongruent individuals aged ≥18 years, diagnosed with Gender Dysphoria, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition,[7] who had undergone gender-affirming surgery (GAS) and were on GAHT, for at least 6 months, as well as age- and BMI-matched healthy controls (cisgender men and women), were included after taking informed consent. The transmen who were on a minimum dose of testosterone of 250 mg intramuscular route every 3–4 weeks, and transwomen were on 4–8 mg of oral oestradiol valerate at the time of inclusion into the study. The transwomen who had not undergone GAS were on leuprolide either 3.75 mg every month or on 11.25 mg every 12 weeks or spironolactone ranging from 100 to 200 mg daily oral tablets. Exclusion criteria were chronic kidney disease, diabetes mellitus, human immunodeficiency virus, chronic liver disease, thyroid disorders (non-euthyroid), hypertension or autoimmune disorders.

Anthropometric and clinical parameters

Standardised protocols were followed for measuring weight (kg), height (cm), BMI (kg/m²),[8] and waist circumference (cm). Systolic (SBP) and diastolic blood pressures (DBP) were recorded while the participants were seated.[9] Physical activity was assessed by a self-reported questionnaire.

Biochemical parameters

Serum irisin levels were measured using a sandwich enzyme-linked immunosorbent assay kit (REF: KBH3253). The assay had a quantification limit of 1.8 ng/ml, with intra- and inter-assay coefficients of variation of <15% and <18%, respectively.

Statistical analysis

Data were analysed using Statistical Package for the Social Sciences 25.0. Median and interquartile ranges (IQR) were used for non-normally distributed data. Group differences were analysed using Mann–Whitney U tests. Analysis of variance was performed with oestrogen and testosterone levels as covariates, and Spearman’s correlation was used to assess relationships between variables. Parameters with P < 0.05 were entered into a linear regression model. Receiver operating characteristic (ROC) curve analysis determined serum irisin cut-offs for predicting MetS in transgender individuals.

Ethics aspects

The study was approved by the Institutional Ethics Committee of Ramaiah Medical College (MSRMC/EC/AP-01/05-2024 dated 20.05.2024). The principles of ethical and professional conduct have been followed, written informed consents were obtained from all the persons involved in this study prior to their inclusion, and it was ensured that their identity will be kept confidential and the data obtained will be used for publication. The research was completed in accordance with the Declaration of Helsinki, which was revised in 2013.

RESULTS

Patient Characteristics: A total of 123 participants were included, consisting of 47 transgender women (38.2%) and 35 transgender men (28.5%), 23 cisgender women (18.7%) and 18 cisgender men (14.6%). Baseline characteristics are summarised in Table 1. The median duration of GAHT in transgender women was 18 months (range 8–36 months), and in transgender men was 24 months (range 18–51 months). The testosterone dose was 200–250 mg every 3–4 weeks ng/dl and the oral oestradiol valerate dose was 4–6 mg per day. The Ferriman Gallwey score in transgender men was 26.51 ± 5.33.

Table 1.

Baseline characteristics, including clinical markers, lab parameters, hormonal tests and levels of biomarkers

Variable	Transgender Women (n=47)	Cisgender Women (n=23)	P	Transgender Men (n=35)	Cisgender Men (n=18)	P
Patient Characteristics
Age (years)	28.81±4.3	32.35±4.108	0.002*	27.89±6.4	30.56±3.148	0.010
BMI (kg/m2)	25.07±2.27	28.89±4.03	<0.001*	25.57±3.94	26.61±3.48	0.348
Waist circumference (cm)	88.4±9.24	86.3±6.23	0.329	89.4±6.31	86.6±6.42	0.132
Hip circumference (cm)	106±13.11	101.3±9.123	0.128	110.57±11.55	105.3±10.8	0.117
W/H ratio	0.82±0.06	0.84±0.038	0.153	0.80±0.059	0.82±0.04	0.397
SBP (mmHg)	119.7±10.78	120.6±8.95	0.729	115.20±12.6	115.8±7.04	0.832
DBP (mmHg)	76.7±6.69	78.7±6.32	0.238	73.9±5.2	77±6.43	0.070
Lab Parameters
Lab Parameters	Transgender Women	Cisgender Women	P	Transgender Men	Cisgender Men	P
FBS (mg/dl)	98.3±17.3	85.5±11.9	0.002*	93±20.7	84.27±7.52	0.088
HbA1c (%)	5.55±0.62	5.28±0.63	0.094	55±0.65	5.63±0.49	0.463
Total cholesterol (mg/dl)	186.6±33.42	173.34±22.7	0.090	180.2±31.6	179.5±21.99	0.937
Triglycerides (mg/dl)	167 [132-215]	112 [102-156]	0.004*	130 [98-176]	112 [100-125.7]	0.221
LDL (mg/dl)	119 [92-136]	112 [100-114]	0.296	112 [96-138]	102 [98-120 ]	0.408
HDL (mg/dl)	45 [41-55]	34 [32-43]	<0.001*	41[34-48]	34 [32-45]	0.077
VLDL (mg/dl)	26.4 [20–39.2 ]	23 [21–26]	0.021*	24 [20-34]	21 [18–23.25]	0.018
hs–CRP (mg/l)	1.55 [0.66-5.92]	NA	–	1.99 [0.92-4.52]	NA	–
Ty/HDL	3.78±1.91	3.52±1.17	P=0.546	1.73±0.59	3.29±0.75	P=0.367
Ty/G	1.73±0.	1.52±0.44	P=0.478	1.55±0.513	1.41±0.26	P=0.282

*P<0.05 – signifies statistical significance between the two groups

While most parameters showed no significant differences between groups; BMI, fasting blood glucose (FBS), triglycerides (TG), high density lipoprotein (HDL), and very low density lipoprotein (VLDL) levels were higher in transgender women compared to cisgender women (P < 0.05) and FBS, VLDL levels were higher in transgender men compared to cisgender men (P < 0.05). Median serum irisin levels were 11.6 [3.8–14.9] ng/ml in transgender women, 19.7 [2.3–32.2] ng/ml in cisgender women and the difference was statistically significant (P = 0.04); 7.2 [1.9–20.2] ng/ml in transgender men and 13.4 [2.7–33.2] ng/ml in cisgender men and the difference was statistically not significant (P = 0.185).

Serum Irisin levels and associations in gender-incongruent individuals

Table 2 shows serum irisin levels and their associations with various clinical, metabolic and hormonal parameters in gender-incongruent individuals. In transgender women, serum irisin levels significantly negatively correlated with DBP (rs = −0.307, P = 0.036), with DBP emerging as the strongest predictor (β = −0.345, P = 0.017). In transgender men, negative correlations were observed with HDL cholesterol (r = −0.339, P = 0.046) and prolactin (r = −0.357, P = 0.035), with prolactin identified as the strongest predictor (β = −0.361, P = 0.036).

Table 2.

Simple Spearman’s correlation and linear regression analysis of serum irisin levels in gender incongruent individuals

	Transgender Women		Transgender Men
Serum Irisin Levels
	R	P	R	P
Patient Characteristics
Age (years)	0.136	0.36	−0.062	0.723
BMI (kg/m2)	0.053	0.72	0.059	0.738
Waist circumference (cm)	0.116	0.437	−0.217	0.211
Hip circumference (cm)	0.01	0.946	−0.206	0.236
W/H ratio	0.208	0.161	0.088	0.616
Systolic BP (mmHg)	−0.286	0.052	−0.133	0.443
Diastolic BP (mmHg)	−0.307	0.036	0.037	0.833
Duration of GAHT (months)	−0.121	0.417	0.042	0.811
Physical activity	0.175	0.239	0.037	0.832
Lab Parameters
FBS (mg/dl)	0.203	0.173	0.037	0.832
HbA1c	0.16	0.282	0.081	0.644
Total cholesterol (mg/dl)	−0.038	0.8	−0.114	0.513
Triglycerides (mg/dl)	−0.035	0.817	0.176	0.312
LDL (mg/dl)	−0.084	0.573	0.024	0.046
HDL (mg/dl)	0.042	0.77	−0.339	0.046
VLDL (mg/dl)	−0.072	0.628	0.156	0.372
hs-CRP	0.0275	0.062	−0.006	0.972

No significant associations were found between serum irisin levels and other metabolic markers, including glycated hemoglobin (HbA1c), lipid profiles, BMI, waist-to-hip ratio, physical activity or the duration of GAHT in both transgender men and women.

The median (IQR) value of serum oestradiol and testosterone was 125 (117–156) pg/ml and 555.9 (411–865) ng/dl, respectively, in transwomen and transmen. Follicle stimulating hormone (6.48 mIU/ml (0.454–79.38) and 6.66 mIU/ml (5.28–9.12), P = 0.001), and luteinizing hormone (11.94 mIU/ml (1.85–44.6) and 7.71 mIU/ml (6.16–13.59), P = 0.005) in transwomen and transmen, respectively. No significant differences were observed in serum prolactin (26.30 ng/ml (18.21–32.0) and 28.90 ng/mL (19.13–38.68), P = 0.462), serum progesterone (0.116 ng/ml (0.075–0.22) and 0.162 ng/ml (0.08–0.319), P = 0.311), and dehydroepiandrosterone sulfate (269 ng/ml (140.2–425.4) and 240.3 ng/ml (118.7–317.3), P = 0.051) in trans women and trans men.

Prevalence of metabolic syndrome according to National Cholesterol Education Program Adult Treatment Panel III criteria

The prevalence of MetS was significantly higher in transgender women (63.8%) and men (31.4%) compared to cisgender women (26.1%) and men (0%) when assessed using affirmed gender criteria. However, applying birth-assigned gender criteria led to reductions in MetS prevalence among transgender women (63.8–31.4%) and men (60–23.4%).

ROC curve analysis for serum irisin levels as a marker for MetS

This study evaluated serum irisin levels as a potential marker for MetS in gender-incongruent individuals. The ROC curve analysis identified optimal cut-off points of 10.1 ng/ml for transgender women (sensitivity 72%, specificity 64%) and 7.7 ng/ml for transgender men (sensitivity 100%, specificity 62%). However, serum irisin was not as reliable a biomarker for MetS.

Further ROC analysis based on birth-assigned and affirmed gender showed, for transgender women, an area under the curve (AUC) of 0.426 (affirmed) and 0.460 (birth-assigned), with sensitivities of 56.7–72% and specificities of 41.2–41.7%. For transgender men, AUC was 0.440 (affirmed) and 0.480 (birth-assigned), with sensitivities of 47.6–54.5% and specificities of 35.7–45.8%, as shown in Table 3.

Table 3.

Shows the ROC curve values of sensitivity, specificity and AUC of serum irisin levels for both birth-assigned and affirmed gender in gender incongruent individuals according to NTEP ATP III criteria

Group	Sensitivity	Specificity	AUC
Transgender women (affirmed)	56.7%	41.2%	0.43
Transgender women (birth-assigned)	72%	41.7%	0.46
Transgender men (affirmed)	47.6%	35.7%	0.44
Transgender men (birth-assigned)	54.5%	45.8%	0.48

*P<0.05 – signifies statistical significance between the two groups. ROC=Receiver Operative Characteristic, AUC=Area Under the Curve, NTEP ATP III=National Cholesterol Education Program Adult Treatment Panel III

Assessment of alternative metabolic indices in gender-incongruent individuals with MetS

The predictive utility of the triglyceride-to–high-density lipoprotein cholesterol (Ty/HDL) ratio and the triglyceride–glucose (Ty/G) index indices for MetS was evaluated in gender-incongruent individuals. Serum irisin levels showed no correlation with MetS, prompting further analysis. In transgender women, the Ty/HDL index had moderate predictive utility (AUC: 0.748, sensitivity: 45.6%, specificity: 70%), while the Ty/G index showed similar potential (AUC: 0.71, sensitivity: 59%, specificity: 64%). For transgender men, the Ty/HDL index demonstrated an AUC of 0.779 but low specificity (33%), whereas the Ty/G index had better predictive power (AUC: 0.67, sensitivity: 54.5%, specificity: 70%). These findings highlight the potential of Ty/HDL and Ty/G indices as MetS predictors, with the Ty/HDL index – a better indicator in transgender women and the Ty/G index – a better indicator in transgender men.

In transgender women, Ty/HDL index significantly correlated with low density lipoprotein (LDL) (rs = −0.346, P = 0.017), VLDL (rs = 0.396, P = 0.006) and on linear regression analysis both were statistically significant (β = −0.019, P = 0.049; β = −0.035, P = 0.016 respectively); Ty/G index significantly correlated with VLDL (rs = 0.392, P = 0.06) and serum progesterone (rs = −0.325, P = 0.026) on linear regression analysis both were statistically significant (β = 0.011, P = 0.012; β = −0.186, P = 0.047, respectively).

In transgender men, Ty/HDL correlations were observed with VLDL cholesterol (rs = 0.112, P = 0.000) and on linear regression was found to be statistically significant (β = 0.112, P = 0.00) and Ty/G index correlated with total cholesterol (TC) (rs = 0.521, P = 0.001), LDL (rs = 0.489, P = 0.001), VLDL (rs = 0.657, P = 0.000), prolactin (rs = −0.372, P = 0.014), and only VLDL identified as the strongest predictor (β = −0.027, P = 0.001).

DISCUSSION

The primary goal of this study was to assess serum irisin levels in gender incongruent individuals post GAS and associated metabolic correlations. These findings provide new perspectives into associations between irisin and metabolic markers in this population, contributing to the understanding of gender-related differences in metabolic health. The results reveal key findings, which are discussed below.

Differences among transgender and cisgender populations

Our study revealed notable differences in metabolic markers and serum irisin levels between transgender and cisgender individuals. Transgender women showed higher levels of BMI, FBS, TG, HDL and VLDL compared to cisgender women, suggesting a potential impact of GAHT on metabolic health. This aligns with previous research by Fernandez et al.,[10] indicating that oestrogen therapy in transgender women may lead to increased fat mass and altered lipid metabolism. In a study by Nokoff et al.,[11] higher BMI observed in transgender women could also be linked to both hormonal changes and reduced physical activity levels. Similarly, transgender men exhibited elevated FBS and VLDL levels compared to cisgender men, consistent with findings from van Zijverden et al.,[12] that testosterone therapy in transgender men may increase insulin resistance and alter lipid profiles. A study by Spanos et al.,[6] showed that testosterone’s effects on muscle mass and fat distribution may contribute to these metabolic differences.

A key finding was the significant difference in serum irisin levels, with transgender women showing lower levels (11.6 ng/ml vs. 19.7 ng/ml in ciswomen), which aligns with the study by Barbagallo et al.,[13] which showed that irisin may be negatively regulated by oestrogen. However, the difference in irisin levels between transgender men and cisgender men was not statistically significant (P = 0.185), suggesting testosterone therapy might not similarly impact irisin secretion.

Gender differences in serum irisin levels and metabolic correlations

In this study, in transgender women, we observed a significant inverse correlation between serum irisin levels and DBP, with a correlation coefficient of r = −0.307 (P = 0.036). This association remained significant in stepwise linear regression analysis (β = −0.345, P = 0.017), suggesting that higher irisin levels may be associated with improved cardiovascular health in this population. These findings are consistent with previous research indicating a relationship between irisin and blood pressure. For instance, a study by Almeida Gonzalez et al.,[14] demonstrated that heart rate inversely correlated with irisin, while DBP directly correlated with irisin levels in both sexes. Additionally, a study by Fu et al.,[15] reported that serum irisin levels were positively correlated with insulin resistance, DBP, estimated glomerular filtration rate and LDL cholesterol, highlighting irisin’s potential role in cardiovascular health.

In the context of transgender individuals, studies have examined the effects of GAHT on cardiovascular risk factors. In a study by Patel et al.,[16] it was found that oestrogen treatment in transgender women led to a significant decrease in SBP, while progestin administered with oestrogen may have adverse effects on arterial stiffness. Collectively, these studies suggest that irisin may play a remarkable role in cardiovascular health and blood pressure regulation. Serum irisin levels and DBP had an inverse correlation in transgender women, indicating that higher irisin levels may be associated with improved cardiovascular function. Nevertheless, the exact mechanisms underlying this association warrant further investigation.

In transgender men, serum irisin levels negatively correlated with HDL cholesterol (r = −0.339, P = 0.046) and prolactin (r = −0.357, P = 0.035), with prolactin being the strongest predictor (β = −0.361, P = 0.036). These findings suggest that prolactin may impact irisin levels in transgender men, potentially reflecting the impact of testosterone therapy and metabolic alterations while receiving GAHT.

Prolactin influences metabolic health in various aspects, including lipid metabolism and insulin sensitivity. Increased prolactin levels are associated with altered lipid profiles and insulin resistance, contributing to MetS.[17] Additionally, prolactin is associated with changes in fat distribution and adipocyte function.[18] These associations may explain the observed correlation between prolactin and irisin in this study, suggesting a potential role for prolactin in regulating metabolic processes in transgender men undergoing GAHT.

Several studies have examined the relationship between irisin levels and metabolic markers, yielding mixed results. For instance, a study on obese individuals found that higher serum irisin levels were associated with lower waist circumference and waist-to-hip ratio but not with BMI, SBP, DBP, body fat percentage, lipid profiles, fasting plasma glucose, insulin or HbA1c levels.[19] Similarly, research involving 24-hour blood pressure monitoring and body fat measurements reported no significant associations between irisin levels and BMI, waist circumference or waist-to-hip ratio.[20] Conversely, a study on children found that irisin levels were positively correlated with BMI percentile and waist circumference, suggesting a link between irisin and adiposity in this population.[21]

In our study, serum irisin levels did not show a significant correlation with physical activity in both transgender women and men. Most had no physical activity, and some engaged in light activity. These findings align with the study by Bonfante et al.,[22] which demonstrated that a 16-week combined training program enhanced thermogenic fat activity in individuals with overweight and T2DM, particularly via increased brown adipose tissue activity and improved thermogenic gene expression. While the study highlighted the benefits of physical training, serum irisin, a hormone linked to adipocyte metabolism, was not identified as a key mediator of these effects. In various studies,[23,24,25] all exercise types appeared to increase circulating irisin in people with T2DM; high-intensity interval training (HIIT) was superior for improving cardiopulmonary fitness and reducing body fat percentage in obese adults compared with traditional exercise.[25] This suggests that exercise in transgender populations should be of moderate to high intensity, primarily including HIIT, to improve metabolic parameters and prevent chronic illness.

Serum irisin as a metabolic marker for MetS in gender-incongruent individuals

Our study also sought to explore the potential of serum irisin levels as a biomarker for MetS in gender-incongruent individuals. The cut-off values for serum irisin in predicting MetS were found to be 7.7 ng/ml for transmen and 10.1 ng/ml for transwomen, with moderate sensitivity and specificity, suggesting that serum irisin levels may not be a strong predictor of MetS in this population. Specifically, the sensitivity and specificity of serum irisin as a diagnostic tool for MetS were suboptimal, with an AUC below 0.5 for both groups, indicating that irisin is not a reliable marker for MetS screening in gender-incongruent individuals. These results are consistent with the study done by Cosio et al.,[26] which suggested that irisin’s role as a metabolic marker is still unclear, and its utility as a diagnostic tool requires further validation.

Comparison of MetS criteria for birth-assigned and affirmed gender

A key finding of this study is that the application of the NCEP ATP III criteria for MetS using affirmed gender resulted in higher MetS prevalence in both transgender women (63.8%) and men (60%) compared to when the criteria were applied based on birth-assigned gender (31.4% in transgender women and 23.4% in transgender men). These findings highlight the complex relationship between GAHT, gender identity and metabolic health.

Ty/HDL and Ty/G indices as better predictors in gender incongruent individuals

Interestingly, our study found that the Ty/HDL ratio and Ty/G index offered better diagnostic potential for MetS as alternative metabolic indices. Specifically, the Ty/HDL index demonstrated better sensitivity and specificity for MetS in transgender women, while the Ty/G index was noticeably better in transgender men. This study is the first to consider the significance of these metabolic indices in gender-incongruent individuals; however, further research on a larger scale to assess their efficacy is needed.

Limitations and future directions

Despite its contributions, this study has limitations. First, the small sample size, while reasonably large, may not fully represent the diversity of the transgender population across different geographical and cultural contexts. Second, the cross-sectional design limits conclusions about causality or long-term effects of GAHT on metabolic health (the duration of GAHT might not be sufficient to observe long-term metabolic changes). Longitudinal studies are needed to establish the role of irisin and other biomarkers in the metabolic health of gender-incongruent individuals, particularly during gender-affirming treatments. Further research should also explore molecular mechanisms underlying the relationship between prolactin, irisin, and metabolic markers in transgender individuals.

CONCLUSION

This study provides a few insights into serum irisin levels and their potential role in MetS, focusing on the metabolic health of gender-incongruent individuals. Our findings demonstrate significant correlations between serum irisin and blood pressure in transgender women and prolactin in transgender men, suggesting metabolic influences. However, serum irisin did not emerge as a reliable biomarker for MetS, with suboptimal sensitivity and specificity across groups. The importance of considering gender identity in metabolic assessments was highlighted, as the use of affirmed gender criteria increased MetS prevalence in both groups. Moreover, Ty/HDL and Ty/G indices emerged as more reliable predictors of MetS in transgender women and men, respectively. These findings underscore the complexity of metabolic health in gender-incongruent individuals and the need for further research to refine diagnostic tools and strategies tailored to this unique population.

Authors’ contribution

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Dr. Pooja U.K., Dr. Umamaheswara R Golamari, Dr. Pramila Kalra and Dr. Anjana S Nair. The first draft of the manuscript was written by Dr. Pooja U.K. and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Conflicts of interest

There are no conflicts of interest.

Use of artificial intelligence

AI was not used for the preparation of the manuscript.

Data availability statement

Data will be made available on reasonable request.

Funding Statement

Nil.