Abstract
Purpose:
In this retrospective study our purpose was to assess whether hormone interventions for gender dysphoria pose additional somatic risks for adolescents. We examined changes in metabolic laboratory parameters, body mass index (BMI), and blood pressure (BP) and analyzed adverse effects during gender-affirming hormonal treatment (GAHT).
Methods:
We analyzed follow-up data on 119 transgender adolescents using GAHT at the adolescent gynecology clinic in Helsinki University Hospital, Finland from January 2010 to January 2022.
Results:
During the study period, 99 (83%) transgender males and 20 (17%) transgender females started GAHT. The median GAHT follow-up duration was 34.0 (interquartile range 17.2) months. Mean hemoglobin (HB) and hematocrit (HCT) levels increased by 16% (p < 0.001) during testosterone treatment, decreased by 10% (p < 0.01) during estrogen treatment, and plateaued after one year. During the initial follow-up, no clinically relevant changes were seen in glucose and lipid metabolism, BMI, or BP. Adverse effects leading to testosterone dose reduction were reported in 19% of transgender males and were less common when gonadotropin-releasing hormone analog was used in testosterone treatment initiation (11.1% vs. 27.8%, p = 0.04). Somatic adverse effects requiring hospitalization or permanent discontinuation of GAHT were not reported.
Conclusion:
The somatic changes observed in this study were typical for GAHT. No serious somatic adverse effects occurred. Regular measuring of HB and HCT in transgender males undergoing GAHT is warranted, but excessive monitoring of glucose and lipid metabolism, BMI, and BP during the initial follow-up period may not be necessary for somatically healthy adolescents.
Keywords: adolescents, gender dysphoria, gender-affirming hormonal treatment, hematocrit, metabolism
Introduction
Gender dysphoria (GD) refers to the distress and unease experienced if one’s affirmed gender and assigned sex are incongruent.1,2 Untreated GD in adolescence is associated with an increased risk for depression, anxiety, and self-harm,3 and may significantly and negatively impact quality of life.4 In addition to psychological support, symptoms of GD may be alleviated by gender-affirming hormonal treatment (GAHT), which may include testosterone, estrogen, antiandrogens or antiestrogens, gonadotropin-releasing hormone (GnRH) analogs, and hormonal interventions to suppress menstruation.1,5–7
GnRH analogs have an official indication in treating precocious puberty in children. Testosterone and estrogen have long been utilized in treating hypogonadism, and the experience in adult patients with GD using GAHT is extensive.8 However, little research exists on the effects of GnRH analog treatment and GAHT on the somatic health of adolescents. Furthermore, as all use of GnRH analogs and GAHT to alleviate GD among adolescents and adults is off label, there is no official reporting of adverse effects, highlighting the importance of clinical studies investigating the safety of GAHT.
Testosterone induces erythrocytosis and thus may present an elevated risk for thrombosis.9–14 Other possible adverse effects of testosterone include liver dysfunction, disadvantageous changes in lipid metabolism, and elevated blood pressure (BP). Elevated burden of cardiovascular disease (CVD) among transgender males due to long-term use of GAHT has been a question of interest,15–17 although not all studies have confirmed a higher risk of CVD.18
Estrogen treatment, especially when using ethinyl estradiol or high-dose oral estradiol, is a known risk factor for deep vein thrombosis.19 Cyproterone acetate has commonly been used as an antiandrogen in feminizing hormonal treatment, but it currently has usage restrictions imposed by health officials20 due to an associated elevated relative risk for meningioma.21 The long-term effects of estrogen and testosterone on cardiovascular health, gonads and fertility are not well known.21–24
While most of the effects of GnRH analog treatment are fully reversible, risks involved in long-term GnRH analog treatment without hormonal replacement include its possible disadvantageous effects on bone mineral density25 and influence on height gain.26–28
We have previously described the somatic health, psycho-social background, and female predominance in sex designated at birth-ratio of a nationwide cohort of 124 Finnish adolescents with GD who had been referred to the adolescent gynecology clinic in Helsinki University Hospital, Finland between 2010 and 2018.29 For the present study, we studied the same cohort and analyzed follow-up data among those adolescents who underwent GAHT. Our study period extended until January 2022.
Our specific aims were to (1) describe the use, administration routes, and doses of GAHT, (2) assess the changes in metabolic and anthropometric measurements during hormonal treatment, and (3) determine the potential adverse effects reported during the study period.
Materials and Methods
Gender-affirming hormonal interventions
In this retrospective study our purpose was to assess whether hormone interventions for GD pose additional somatic risks for adolescents.
We have previously described the process of diagnostics of GD in Finland and the collection of baseline data used in this study.29 In accordance with international guidelines,1,5–7 the GAHT protocol in Helsinki University Hospital (HUH) states that adolescents should preferably start GnRH analog treatment to suppress endogenic hormonal production 3–6 months before testosterone or estradiol treatment and continue it parallel to GAHT for the next 3–6 months. Adolescents 18 or older may start GAHT without prior GnRH analog treatment, although it may be used to enhance masculinization in transgender males.1,7
In transgender females, estrogen treatment alone is insufficient in suppressing endogenic testosterone production; thus, using GnRH analog or an antiandrogenic medication in the form of spironolactone or cyproterone acetate is recommended until possible gonadectomy.21
Table 1 presents GAHT regimens and commonly used hormonal medications and doses used in HUH. Transgender males typically start GAHT by using daily transdermal testosterone gel. After 6–12 months, the regimen can be switched to an intermediate-acting testosterone injection and later to a long-acting injection. In transgender females, estradiol can be administered orally or as a transdermal patch or gel.
Table 1.
Gender-Affirming Hormonal Treatment Regimens in Helsinki University Hospital During the Study Period
| Regimen | Protocol | Composition | Form | Route | Starting Dose |
|---|---|---|---|---|---|
| GnRH analog | If under 18, start at 3–6 months before testosterone or estrogen treatment and continue for 3–6 months in parallel | Leuprorelin acetate | Injection | SC | 3.75 mg every 4 weeks |
| Testosterone | Apply 6–12 months transdermal gel daily, then switch to intermediate depot injection for 6–12 months, then switch to long-acting injectable testosterone | Testosterone | Gel | TD | 20–25 mg, up to 50–60 mg daily |
| Testosterone propionate, phenylpropionate, isocaproate, and decanoate | Intermediate intramuscular depot injection | IM | 250 mg every 3 weeks | ||
| Testosterone undecanoate | Long-acting intramuscular depot injection | IM | 1000 mg every 3 months | ||
| Estrogen | Preferably start with a transdermal patch and increase the dosage; if necessary, switch to a gel or tablet | Estradiol hemihydrate | Patch | TD | 25 μg, up to 100 μ per 24 h |
| Estradiol hemihydrate | Gel | TD | 1.5 mg, up to 3 mg daily | ||
| Estradiol valerate or estradiol hemihydrate | Tablet | PO | 2 mg, up to 4 mg daily | ||
| Antiandrogen | Start at estradiol initiation unless GnRH analog is used. If GnRH analog is used, start antiandrogen when GnRH analog use ends. Continue until gonadectomy | Cyproterone acetate | Tablet | PO | 25 mg, up to 50 mg daily |
| Spironolactone | Tablet | PO | 50 mg, up to 200 mg daily | ||
| Finasteridea | Tablet | PO | 1 mg daily |
In addition to cyproterone acetate and spironolactone, finasteride may in some cases be used in combination with other antiandrogen medications to alleviate male-type baldness.
GnRH, gonadotropin-releasing hormone; SC, subcutaneous; TD, transdermal; IM, intramuscular; PO, peroral.
Treatment follow-up
GAHT follow-up visits are first organized at 3–6 months and then at 6–12 months. Blood hemoglobin (HB), hematocrit (HCT), plasma alanine aminotransferase (ALT), and serum testosterone (if testosterone is used) levels are monitored on all visits. In addition, serum estradiol and serum prolactin (if estradiol is used), fasting plasma glucose, plasma HbA1c, total plasma cholesterol, and plasma high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol are measured at 6–12-month intervals. The initial follow-up at the university hospital is continued until an adult dose of GAHT medication is reached. Somatic follow-up continues at a primary health care provider at 1–2-year intervals.
Data collection
Follow-up data on GnRH analog use, GAHT medications, metabolic laboratory results, BMI, BP, and adverse effects during GAHT were obtained from medical records. If the GAHT follow-up period was still in progress at the end of the study period, the data were collected until that point. These data were included in the study if the duration of their GAHT use had exceeded 6 months. The same applies to adolescents who discontinued GAHT.
Overweight and obesity were defined as a BMI between 25 and 30 kg/m2 and BMI > 30 kg/m2, respectively. Blood samples were analyzed routinely for clinical use by accredited methods (HUSLAB, Helsinki University Hospital laboratory).
Somatic adverse effects were defined as events leading to GAHT dose reduction. In addition, self-reported adverse effects such as skin dryness, acne, or spotting, were analyzed in chart data.
Ethical approval
The Research Committee of HUH approved the study plan. Approval from the Ethics Committee was not needed in our register-based study because, for this type of study, formal consent is unrequired. All data were pseudonymized before analysis.
Statistical analyses
Statistical analyses were conducted by using IBM SPSS 28 software. Data are expressed as median and interquartile range (IQR) for nonparametric or mean ± standard deviation (SD) for parametric distributions when not otherwise stated. To assess differences between groups, independent and paired samples t-tests were used for parametric, Mann–Whitney U and Wilcoxon signed-rank test for nonparametric, and Pearson chi-squared test for categorical variables. We used a linear mixed model with random intercepts for each adolescent and a fixed effect of time to analyze changes in repeated measures of BMI, BP, and laboratory parameters. This procedure prevented listwise deletion due to partly missing follow-up data.30 A p value of < 0.05 was considered significant.
Results
Use of GnRH analog treatment and GAHT
During the study period, 119 adolescents (96.0% of the initial cohort; 99 transgender males [83%] and 20 transgender females [17%]) started GAHT. Five (4%) transgender males within the initial cohort were not prescribed GAHT during the study period due to severe psychiatric comorbidities.
Table 2 presents the median duration of GnRH treatment and median GAHT follow-up. Forty-five (45%) transgender males and six (30%) transgender females used GnRH analog before and during initiating treatment with testosterone or estradiol. The median age for starting testosterone treatment was lower among transgender males who used GnRH analog than among those who did not (18.0 [1.41] years vs. 18.6 [0.74] years, p = 0.007, Mann–Whitney U test). No similar difference was observed in transgender females. In transgender females not using GnRH analog, 13 (93%) adolescents were prescribed cyproterone acetate and one (7%) spironolactone to suppress endogenic testosterone production.
Table 2.
Gender-Affirming Hormonal Treatment Use Among Transgender Adolescent Males and Females
| Total | Transgender males | Transgender females | p b | |
|---|---|---|---|---|
| Cohort, n (%)a | 124 | 104 (84%) | 20 (16%) | |
| Started GAHT, n (%) | 119 (96%) | 99 (95%) | 20 (100%) | |
| GnRH analog use, n (%) | 51 (43%) | 45 (45%) | 6 (30%)c | |
| Median duration of GnRH treatment before GAHT, months (IQR) | 2.7 (0.9) | 2.7 (0.85) | 2.8 (2.4) | 0.82 |
| Median total duration of GnRH, months (IQR) | 7.5 (5.1) | 7.2 (5.3) | 8.1 (4.2) | 0.99 |
| Median age at GnRH initiation, years (IQR) | 17.8 (1.28) | 17.8 (1.43) | 17.9 (2.25) | 0.56 |
| Median age at GAHT initiation, years (IQR) | 18.4 (1.23) | 18.5 (1.29) | 18.3 (1.41) | 0.35 |
| Prior GnRH use, years (IQR) | 18.0 (1.2)* | 18.0 (1.41)* | 18.2 (1.41) | 0.58 |
| No prior GnRH use, years (IQR) | 18.6 (0.86)* | 18.6 (0.74)* | 18.6 (1.23) | 0.41 |
| Median GAHT follow-up, months (IQR) | 34.0 (17.2) | 31.7 (15.9) | 39.7 (18.9) | 0.062 |
We have previously described a nationwide cohort of 124 Finnish adolescents with GD referred to the adolescent gynecology clinic in Helsinki University Hospital, Finland between 2010 and 2018.29
Comparison between transgender males and transgender females.
If GnRH analog was not used, antiandrogen medication was routinely initiated to suppress testosterone.
p < 0.05 comparing GnRH user groups (Mann–Whitney U test).
GAHT, gender-affirming hormonal treatment; IQR, interquartile range.
Five (4%) adolescents (three transgender males and two transgender females) discontinued GAHT during the follow-up. Reasons reported included dropping out of follow-up, discovering their gender identity as being nonbinary rather than transgender, wishing to discontinue hormonal treatment to see whether symptoms of GD returned, and, in one case, committing suicide. According to the medical records, none of these adolescents contacted the clinic to report regretting using GAHT.
Metabolic changes during GAHT
Transgender males
The mean HB increased by 15.7% and HCT by 15.5% (p < 0.001, linear mixed models analysis) during 33 months of testosterone treatment follow-up. Both increased from baseline to 12 months and then plateaued. The mean ALT and testosterone levels increased, while HDL cholesterol levels decreased during testosterone treatment; however, all remained within male reference ranges after treatment initiation (Fig. 1).
FIG. 1.
Changes in metabolic parameters in transgender adolescent males during testosterone treatment. The arrow indicates the male laboratory reference range. The data are expressed as a mean; error bars indicate a 95% confidence interval. * significant difference to series mean (p < 0.001, linear mixed models analysis for repeated measures); ALT, alanine aminotransferase; HDL, high-density lipoprotein; LDL, low-density lipoprotein.
No significant changes were observed in the mean LDL cholesterol, total cholesterol, triglycerides, HbA1c, or fasting plasma glucose (see Supplementary Table S1). Increased HB, HCT, and other metabolic changes were similar in adolescents with and without GnRH analog use before testosterone treatment (data not shown).
Transgender females
Mean HB and HCT levels decreased by 10.0% (p = 0.003 and 0.002, respectively, linear mixed models analysis) during 33 months of estradiol treatment follow-up. Both plateaued after 12 months. (Fig. 2) Mean estradiol levels remained within the female reference range after treatment initiation. Serum prolactin levels exceeded the female reference range in some adolescents but decreased spontaneously during the follow-up. ALT remained unchanged during the follow-up. The number of available measurements was insufficient for statistical analysis in HDL and LDL cholesterol, total cholesterol, triglycerides, HbA1c, and fasting plasma glucose (see Supplementary Table S2).
FIG. 2.
Changes in metabolic parameters in transgender adolescent females during estradiol treatment. The arrow indicates the female laboratory reference range. The data are expressed as a mean; error bars indicate a 95% confidence interval.* significant difference to series mean (p < 0.001, linear mixed models analysis for repeated measures).
Observed metabolic changes were similar between adolescents with and without GnRH analog use (data not shown).
Anthropometric measures
Median BMI before GAHT initiation was higher among transgender males than transgender females. (Table 3) The proportions of transgender males and females who were overweight (22.2% vs. 10.0%, respectively) or obese (11.1% vs. 5.0%, respectively) before GAHT initiation did not differ significantly.
Table 3.
Anthropometric Measures Before and During Gender-Affirming Hormonal Treatment
| Baseline | 6 Months | 18 Months | 30 Months | |
|---|---|---|---|---|
| Transgender males | ||||
| Median BMI (IQR) | 23.1 (7.03)* | 24.8 (7.85)** | 23.9 (10.20) | 24.8 (7.51) |
| n (%) | 90 (91.0) | 73 (73.7) | 41 (41.4) | 32 (32.3) |
| Mean systolic BP, mmHg ± SD | 127.8 ± 11.3 | 131.9 ± 11.3*** | 131.8 ± 11.4 | 130.1 ± 11.9 |
| Mean diastolic BP, mmHg ± SD | 77.2 ± 8.6 | 79.2 ± 8.7**** | 78.4 ± 8.7 | 79.5 ± 14.3 |
| n (%) | 68 (68.7) | 83 (83.8) | 45 (45.5) | 30 (30.3) |
| Transgender females | ||||
| Median BMI (IQR) | 19.5 (2.63)* | 20.0 (7.71) | 22.7 (9.19) | 23.7 (5.64) |
| n (%) | 20 (100) | 15 (75.0) | 9 (45.0) | 6 (30) |
| Mean systolic BP, mmHg ± SD | 137.2 ± 12.8 | 133.8 ± 14.3 | 137.6 ± 15.0 | 138.3 ± 16.6 |
| Mean diastolic BP, mmHg ± SD | 76.8 ± 8.1 | 76.2 ± 7.7 | 81.0 ± 12.0 | 82.1 ± 16.0 |
| n (%) | 15 (75.0) | 15 (75.0) | 9 (45.0) | 7 (35.0) |
The baseline is defined as 0–12 months before GAHT initiation.
p < 0.001 comparing transgender males and transgender females at baseline (Mann–Whitney U test).
p < 0.001 compared to baseline (Wilcoxon signed-rank test).
p = 0.007 compared to baseline (paired samples t-test).
p = 0.013 compared to baseline (paired samples t-test).
BMI, body mass index; BP, blood pressure; SD, standard deviation.
Transgender males
BMI increased by 7.4% (p < 0.001) between testosterone initiation and 6 months of treatment but did not change after that (Table 3). A similar pattern was observed when adolescents who were overweight or obese at testosterone initiation were analyzed separately (data not shown). The mean systolic and diastolic BP increased between testosterone initiation and 6 months of testosterone use but remained unchanged after that (Table 3).
Transgender females
BMI did not change during estradiol treatment follow-up. Mean systolic BP was higher among transgender females than males at baseline (p = 0.005, independent samples t-test). In transgender females, BP did not change during GAHT follow-up.
Adverse effects
Transgender males
Adverse effects leading to testosterone dose reduction were observed among 19 (19.1%) transgender males. Reported reasons for dose reductions included follow-up values of HB and HCT (14 cases [74%]), testosterone (2 cases [11%]), or ALT (1 case [5%]) increasing beyond the male reference range (HB >167 g/L, HCT >50%, testosterone >38 nmol/L, ALT > 50 U/L). Altogether, 66% of the dose reductions occurred during intermediate-acting testosterone injection use. In the cases observed in the study, dose reductions were a sufficient intervention for normalizing laboratory values.
Transgender males with GnRH analog before and during testosterone treatment initiation had fewer dose reductions than those without GnRH analog treatment (11.1% vs. 27.8%, p = 0.04, Pearson chi-square test). Psychiatric or somatic comorbidities, overweight, or obesity at baseline were unassociated with dose reductions.
Other reported adverse effects included skin dryness and acne (11 cases [11%]), occasional spotting or menstrual bleeding (3 cases [3%]), and galactorrhea (1 case [1%]). These were usually addressed by changing the testosterone administration route or combining a progestin regimen with the treatment.
Transgender females
Adverse effects reported included fatigue, galactorrhea, and icterus. Three adolescents (15%) reported previous use of self-prescribed hormonal treatment. During GAHT, three adolescents (15%) increased their estradiol dose without consultation.
No cases required hospitalization or permanent discontinuation of testosterone or estradiol treatment due to somatic adverse effects.
Discussion
The metabolic and anthropometric changes observed in this study were typical for GAHT. HB and HCT levels increased in transgender males and decreased in transgender females during the first year of GAHT, but other metabolic and anthropometric parameters monitored during the follow-up remained within the reference ranges of the target sex or did not change significantly. Adverse effects leading to testosterone dose reduction were mainly related to erythrocytosis, and no adverse effects requiring hospitalization were observed. Our findings question whether excessive monitoring of glucose and lipid metabolism, BMI, and BP during the initial follow-up of GAHT is necessary for somatically healthy adolescents.
The median follow-up duration in our study was longer and the number of participants was greater than in most other studies with similar settings focusing on transgender adolescents.10,31–34 The changes observed in HB and HCT during GAHT align with earlier studies for both transgender males and transgender females.10,32–36 Furthermore, changes in ALT, cholesterol metabolism, and glucose metabolism were within the same range as reported in earlier studies for transgender adolescent males using GAHT.10,31–37 In transgender adolescent females, similar findings in prolactin and ALT during GAHT have been reported.36 However, due to the low number of transgender adolescent females in this study, a reliable comparison for changes in lipid and glucose metabolism likely cannot be made.
In our study, changes reported in ALT, lipids, and fasting glucose during testosterone treatment were clinically irrelevant, and no statistically significant changes were observed during estradiol treatment. On the contrary, a recent study with a large cohort of transgender and gender-diverse youth in the United States showed that estradiol treatment slightly increased mean HDL cholesterol levels in adolescents designated as male at birth, but obesity partly blunted this effect.38 In some transgender females, serum prolactin levels exceeded the female reference range but decreased during follow-up. Elevated prolactin levels have been reported during cyproterone acetate use,21 but in this retrospective study, the effect of cyproterone acetate on prolactin levels cannot be evaluated.
Clinically relevant changes in glucose metabolism have not been reported among transgender adolescents. Notably, however, even if clinically significant changes in these parameters did not emerge during the initial follow-up, unfavorable changes in lipid or glucose metabolism or weight take time to develop. Thus, awareness of the potential long-term risks is vital.
Among other metabolic changes, overweight or obesity may affect the future metabolic risk profile and long-term health of transgender adolescents. Our earlier study showed that the proportion of overweight and obesity in Finnish transgender adolescent males seeking GAHT was higher than in the general female adolescent population.29 In this study, we observed a clinically irrelevant increase in BMI and BP in transgender males during the first 6 months of GAHT use; otherwise, BMI and BP did not change during the initial testosterone or estradiol treatment follow-up.
Previous studies have reported no change,32 or a statistically significant but clinically minor increase in BMI during testosterone treatment for GD.31,33,34,39 The same applies to changes in BP. Nevertheless, regular follow-up visits should include measuring metabolic and cardiovascular health factors after the initial follow-up period.
Population-level data regarding GAHT adverse effects is lacking, possibly because the treatment is off label. To the best of our knowledge, this is the first study reporting the prevalence of adverse effects leading to dose reductions among transgender adolescents. Although dose reductions were relatively common, we observed no serious adverse effects during the median follow-up of 34 months. A recent French study showed that officially reported adverse drug reactions related to GAHT were rare and included mostly cardiovascular or thromboembolic complications in young adult transgender males, or meningiomas and cardiovascular events in transgender females.40
Most of the adverse effects leading to testosterone dose reduction were due to elevated HB or HCT and were observed when using intermediate-acting testosterone injections, which have been associated with a potentially higher risk for supraphysiological testosterone levels and psychological adverse effects.13,14 Currently, interest has shifted towards long-acting testosterone injections, which are also recommended in treating hypogonadism in cisgender men.14
Transgender males who used GnRH analog before and during GAHT initiation showed fewer adverse effects leading to dose reduction than adolescents using only testosterone. Our protocol suggests increasing testosterone doses more slowly when treating younger adolescents, to whom using GnRH analog treatment is also suggested. We hypothesize that increasing the testosterone dose more slowly would stimulate the bone marrow less, which in turn would decrease the chance of excess erythrocytosis. However, both GnRH users and non-users showed similar mean testosterone levels. Further research is needed to clarify this finding.
Transgender females had a relatively high percentage of reported self-prescribed hormone use and self-adjusting of estradiol dosages during GAHT, which has been noted in earlier studies in adults.41,42 Self-prescribed testosterone was not reported but could not be excluded in a retrospective study, although studies indicate that it is rare among transgender men.43
Limitations
The study has limitations due to its retrospective nature. Individual factors, such as adherence to follow-up, dose adjustments due to adverse effects, or changes in mental well-being may have caused variances in the follow-up schemes and could not fully be controlled for in this retrospective study. Further, different administration routes of estrogen may potentially have affected metabolism differently in transgender females. However, a recent study36 reported similar findings in both oral and transdermal estrogen users, which would suggest that especially in generally healthy adolescents, administration routes may have little significance to the metabolic changes observed during early GAHT follow-up.
However, the data includes an extensive amount of GAHT follow-up data, with the cohort covering approximately two-thirds of all transgender adolescents who received GAHT in our country during the study period.
The number of transgender adolescent females in the study was low, and the data likely cannot be generalized to the whole transgender adolescent female population. However, the distribution of transgender adolescent males and females in our study aligned with the current global dominance of transgender adolescent males seeking gender-affirming care.44 All adolescents in our cohort had completed puberty before starting GAHT; therefore, the results cannot be generalized to younger adolescents with incomplete spontaneous pubertal development. The percentage of adolescents discontinuing GAHT (4%) was higher than in previous reports (0%–2%),10,31–33,35 although not all studies reported their exclusion criteria.
Conclusions
Monitoring erythrocytosis during testosterone treatment is warranted, while excessive monitoring of lipid and glucose metabolism, BMI, or BP during the initial follow-up period of GAHT may not be necessary for somatically healthy adolescents. Severe adverse effects are rare among healthy adolescents. Retrospective and prospective studies on changes in symptoms of GD, secondary sex characteristics, and quality of life during GAHT are required to estimate an optimal GAHT protocol for adolescents.
Acknowledgment
The authors kindly thank Sarah Richards for proofreading the article.
Abbreviations Used
- ALT
Alanine aminotransferase
- BMI
Body mass index
- BP
Blood pressure
- CVD
Cardiovascular disease
- GAHT
Gender-affirming hormonal treatment
- GD
Gender dysphoria
- GnRH
Gonadotropin releasing hormone
- HB
Hemoglobin
- HbA1c
Hemoglobin A1C
- HCT
Hematocrit
- HDL
High-density lipoprotein
- HUH
Helsinki University Hospital
- IQR
Interquartile range
- LDL
Low-density lipoprotein
- SD
Standard deviation
- TG
Transgender
Authors’ Contributions
N.V.: Conceptualization, investigation, visualization, and preparing the original draft. E.H. and H.S.-P.: Conceptualization, reviewing and editing, supervision.
Author Disclosure Statement
N.V. declares no conflict of interest. E.H. has been a consultant for Merck. H.S.-P. has been a speaker for Mylan and Exeltis and a consultant for Astellas, Ferring, Merck, and Orion.
Funding Information
The Finnish Medical Foundation, The Finnish Society of Pediatric and Adolescent Gynecology (N.V.), The Finnish State Research Funding, and The Finnish Academy of Sciences (H.S.-P.) supported this study.
Cite this article as: Vehmas N, Holopainen E, Savolainen-Peltonen H (2025) Metabolic and anthropometric changes and adverse effects in Finnish adolescents using gender-affirming hormonal treatment, Transgender Health 10:4, 306–315, DOI: 10.1089/trgh.2024.0012.
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