Search Results (27)

Gonadotropin-releasing hormone agonists are used to treat central precocious puberty and are increasingly prescribed in gender-affirming care. Despite well-established reproductive effects, their broader physiological effects during puberty remain poorly understood. Male and female Wistar rats received a depot triptorelin injection at pubertal onset. Body mass, food intake, and locomotor activity were monitored. After 28 days, reproductive function was assessed, and pituitary and hypothalamic gene expression was analyzed. Changes in gonadal weight, estrous cycle, folliculogenesis, seminiferous tubules’ morphology, and sperm count confirmed the suppression of pubertal maturation. Triptorelin downregulated Gnrhr and Lhb, demonstrating suppression of gonadotrope function. Despite comparable reproductive suppression, metabolic responses to triptorelin were strongly sex-dependent. Females exhibited increased body weight gain accompanied by delayed hyperphagia, whereas males showed reduced body weight gain, unchanged food intake, and increased mean locomotor speed. Female-specific transcriptional remodeling was observed in the hypothalamus, characterized by downregulation of Npy and Lepr and upregulation of Sst and Kiss1 expression. Collectively, these findings demonstrate that pubertal triptorelin treatment induces profound reproductive suppression in both sexes while eliciting sex-specific hypothalamic adaptations in pathways regulating energy homeostasis. This suggests that puberty blockers exert broader neuroendocrine effects beyond the suppression of reproductive maturation. Full article

Introduction: Medical care for transgender minors is understudied, largely because these forms of care are relatively recent. The primary objective of this work was to describe the cohort of transgender adolescents who initiated follow-up at the Strasbourg University Hospital before the age of 18, whether or not they began hormone therapy prior to reaching adulthood. Method: This was an observational, retrospective, single-center, descriptive study conducted among adolescents who had attended at least one consultation in our center before the age of 18 between January 2017 and March 2024. Results: Our population consisted of 115 patients predominantly made up of transmasculine (AFAB) adolescents (68%). Compared with the general population, we observed significantly higher rates of psychiatric co-occurrences, autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). Only 46.1% initiated gender-affirming hormone therapy (GAHT) in our cohort, and just 34.8% before age 18. A total of 6% of adolescents received puberty blockers as monotherapy. The mean age at GAHT initiation was 16.99 years. Transition pathways appear to differ according to the adolescent’s type of schooling. The rate of retransition/treatment interruption in our sample ranged from 0% to 6.1%, depending on the criteria applied. We did not identify any adolescent who retransitioned to their sex assigned at birth after starting GAHT by the end of the data collection. Discussion: The high prevalence of psychiatric co-occurrences raises important questions regarding how to improve care for these adolescents. The predominance of AFAB adolescents similarly prompts reflection on the barriers that transfeminine adolescents may face when seeking to transition before adulthood. In addition, the substantial number of adolescents presenting with ASD or ADHD underscores the need for particular vigilance regarding their specific needs and overall well-being. Finally, the variability in retransition rates depending on the criteria applied highlights the absence of a consensual definition, which limits the comparability and validity of existing studies. Conclusions: Long-term prospective studies are needed to objectively demonstrate the effectiveness of current transition pathways. Academic research in this field should be strengthened, along with the development of larger prospective datasets, to improve the overall health of this population. Full article

Venous thromboembolism (VTE) remains a major cause of morbidity and mortality globally. The incidence of VTE continues to increase over time, contributed to by demographic shifts and emerging risk factors, such as novel cancer treatments and exposure to gender-affirming hormonal therapies. While the introduction of direct oral anticoagulants (DOACs) revolutionized VTE management, increasing complexity in select patient cohorts has driven the need for alternative treatment strategies, including pharmacological and interventional approaches. Concurrently, contemporary patient populations have exposed limitations in existing risk assessment models, highlighting the need for revision and consideration of novel biomarkers. In this review, we provide an overview of the changing VTE landscape, highlighting emerging risk factors, advances in treatment, and the utility of current risk stratification tools and novel biomarkers in guiding care. Full article

Background and Objectives: There is a worldwide increase in the demand for gender-affirming surgical treatments among transgender and gender-diverse (TGD) adults and adolescents. In Poland, transgender people generally lack trust in healthcare providers, which makes it more difficult for them to begin their transition process. This patient population is not well understood by many of the specialists who may potentially be involved in their care, in some way, reinforcing their concerns. The aim of this study is to present the sociodemographic characteristics of a group of female-to-male transgender patients who were admitted to a privately based plastic surgery center to undergo chest wall reconstruction. Materials and Methods: This study comprises a statistical analysis of data retrospectively obtained from the medical records of 100 patients from across the country undergoing female-to-male transition, who were operated on between 2021 and 2025 at a specialized private clinic in Poland. All individuals had already started gender-affirming medical treatment with testosterone at the time of first consultation. Results: The results show a trend toward a decreasing age at the time of the decision to undergo gender-affirming surgery. In the study group, 100% of patients were already undergoing hormone therapy. In our group of transgender individuals, we did not observe a correlation between cultural or social background, religion, and gender dysphoria. It is encouraging that more than half of the patients reported no longer needing psychiatric support, and that those who were still under specialist supervision stated that they experienced a significant improvement in their overall well-being. Conclusions: The rising demand for transgender healthcare highlights the need for studying and analyzing this group of patients in order to provide the best patient-centered care throughout the gender transition process by all specialists involved. Gender-affirming mastectomy, when combined with testosterone therapy, has a positive mental health impact on transgender individuals. Full article

Objectives: This study aimed to evaluate the implementation of a formalized fertility preservation (FP) program for transgender and nonbinary patients assigned male at birth (TGNB-AMAB) at our institution. Methods: We reviewed TGNB-AMAB patients who were referred to the FP program at our academic institution between 2016 and September 2023. We compared the number of referrals and the percentage of patients who underwent FP per year. Clinical and demographic information including age at referral, time from referral to banking, semen parameters, and serum hormone values were evaluated. Results: In total, 154 TGNB-AMAB patients were referred to the FP program since 2016; 131 (85.1%) met with a reproductive urologist or advanced practice provider for FP consultation; and 124 (94.7%) completed sperm cryopreservation. The number of annual referrals significantly increased over time (p = 0.001). The average age (±standard deviation) at referral was 20.5 ± 5.7 years. The median time from referral to sperm cryopreservation was 14 days. The average semen parameters among all the patients were volume 2.7 ± 1.7 mL, sperm concentration 36.0 ± 31.6 M/mL, sperm motility 56.8 ± 19.0%, and sperm morphology 4.7 ± 2.9%. There was no significant difference in semen parameters between TGNB-AMAB patients previously on gender-affirming hormonal therapy prior to banking and those not on prior hormonal treatment (p > 0.05). Conclusions: Our fertility preservation program significantly increased the number of TGNB-AMAB patients who received consultation and underwent sperm cryopreservation. The institution of a formalized FP program can be used to increase access for TGNB-AMAB patients who desire future fertility. Full article

The goal of gender-affirming hormone therapy (GAHT) is to align an individual’s physical characteristics with their gender identity by suppressing endogenous sex hormones and replacing them with those consistent with their gender. Transgender women undergoing GAHT are at higher risk of cardiovascular complications, and since clinical evidence suggests that hypertension is associated with increased bone loss, we investigated the effects of estrogen treatment on bone health in a hypertensive transgender animal model. Male spontaneously hypertensive rats were orchiectomized (Orch), and half of them received estrogen treatment (Orch + Es), while a third group remained intact as controls. Bone marrow progenitor cells (BMPCs) were isolated to assess osteogenic potential, and femurs were collected for histological and mechanical analysis. BMPCs from Orch + Es rats exhibited enhanced osteogenic potential compared to those from Orch rats. Histological analysis revealed a higher number of osteocytes and fewer adipocytes in the Orch + Es group. Mechanical testing showed reduced bone strength in Orch rats, which was partially preserved in Orch + Es animals. In conclusion, estrogen administration mitigated the deleterious effects of testosterone depletion on BMPCs and provided protective effects on bone structure and strength in this preclinical model of GAHT in hypertensive rats. Full article

Background/Objectives: Gender-affirming hormone therapy (GAHT) is known to influence the lipid profiles of trans men and transmasculine individuals. Recent data show that moderate prolactin (PRL) elevations might exert beneficial metabolic effects (“HomeoFIT-PRL model”). The aim of this study is to investigate changes in PRL levels and possible associations between PRL and lipid profiles in this population after a year of GAHT. Methods: In a retrospective cohort study, 97 participants, who received GAHT with testosterone, were included. Blood lipids, PRL, and sex steroid hormone levels were evaluated prior to and at 10–14 months after treatment started. Results: The difference in PRL levels between baseline and follow-up was significant (p = 0.007) with a median difference of +2.3 ng/mL. Concerning blood lipids, the decline in high-density lipoprotein cholesterol (HDL-C) reached statistical significance (median 56 mg/dL versus 50 mg/dL; p < 0.001), and low-density lipoprotein cholesterol (LDL-C) and triglyceride levels increased (p = 0.023 and p = 0.045, respectively). Individuals with a PRL > 25 ng/mL at follow-up (n = 20, 20.6%) revealed increases in total cholesterol and LDL-C significantly less often. Overall, participants frequently displayed unfavorable changes in their lipid profile after 10–14 months of GAHT, as well as a slight but significant increase in PRL. About 20% of patients showed mild-to-moderate hyperprolactinemia (PRL > 25 ng/mL). However, such changes were associated with potentially beneficial dynamics in the lipid profile, at least for triglycerides. Conclusions: These findings seem in line with the HomeoFIT-PRL model suggesting that moderate elevations in PRL levels might exert beneficial metabolic effects. Increases in PRL after testosterone were common. Full article

Transgender people experience distress due to gender incongruence (i.e., a discrepancy between their gender identity and sex assigned at birth). Gender-affirming hormone treatment (GAHT) is a part of gender reassignment treatment. The therapeutic goals of the treatment are to develop the physical characteristics of the affirmed gender as far as possible. Guidelines have been developed for GAHT, which recommend dosage as well as different formulations of oestrogen and testosterone for treatment. Questions arise about the metabolic side effects of hormone treatment. Establishing reference ranges for common analytes in transgender individuals remains a task for laboratory medicine. It has been suggested once GAHT is commenced, the reference ranges for affirmed gender are reported for red blood cells, haemoglobin and haematocrit. For transgender assigned-female-at-birth (AFAB) people, testosterone concentrations are recommended to be within the reference interval established for cisgender men and for transgender assigned-male-at-birth (AMAB) people, estradiol concentrations are within the reference range for cisgender women. Sex-specific reference ranges are available for certain laboratory tests, and these may be organ (e.g., heart)-specific. Transgender-specific reference ranges may be a requirement for such tests. Laboratories may need to make decisions on how to report other tests in the transgender population, e.g., eGFR. Interpretation of further tests (e.g., reproductive hormones) can be individualized depending on clinical information. Electronic medical record systems require fields for gender identity/biological sex at birth so that laboratory results can be flagged appropriately. In this review, we aim to summarise the current position of the role of the laboratory in the clinical care of the transgender individual. Prior to the review, we will summarise the genetics of sex determination, the aetiology of gender incongruence, and the recommendations for GAHT and monitoring for the transgender population. Full article

Cardiovascular kidney metabolic (CKM) syndrome represents a complex interplay of cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic comorbidities, posing a significant public health challenge. Gender exerts a critical influence on CKM syndrome, affecting the disease severity and onset through intricate interactions involving sex hormones and key physiological pathways such as the renin–angiotensin system, oxidative stress, inflammation, vascular disease and insulin resistance. It is widely known that beyond the contribution of traditional risk factors, men and women exhibit significant differences in CKM syndrome and its components, with distinct patterns observed in premenopausal women and postmenopausal women compared to men. Despite women generally experiencing a lower incidence of CVD, their outcomes following cardiovascular events are often worse compared to men. The disparities also extend to the treatment approaches for kidney failure, with a higher prevalence of dialysis among men despite women exhibiting higher rates of CKD. The impact of endogenous sex hormones, the correlations between CKM and its components, as well as the long-term effects of treatment modalities using sex hormones, including hormone replacement therapies and gender-affirming therapies, have drawn attention to this topic. Current research on CKM syndrome is hindered by the scarcity of large-scale studies and insufficient integration of gender-specific considerations into treatment strategies. The underlying mechanisms driving the gender disparities in the pathogenesis of CKM syndrome, including the roles of estrogen, progesterone and testosterone derivatives, remain poorly understood, thus limiting their application in personalized therapeutic interventions. This review synthesizes existing knowledge to clarify the intricate relationship between sex hormones, gender disparities, and the progression of CVD within CKM syndrome. By addressing these knowledge gaps, this study aims to guide future research efforts and promote tailored approaches for effectively managing CKD syndrome. Full article

Background: As transgender people initiate gender-affirming hormone therapy (GAHT), they are exposed to exogenous sex hormones that have effects that have not yet been fully studied. While exogenous estrogen is associated with a risk of venous thrombosis, the full impact of estrogen on the liver is unknown. Conversely, the erroneous attribution of risks from GAHT presents a barrier to treatment for some patients. We present a case of obliterative portal venopathy (OPV) and possible DILI occurring after the initiation of estrogen in a transgender woman. Case presentation: A 28-year-old transgender woman on GAHT was referred to hepatology for liver enzyme elevations. She did not have any notable comorbid conditions, family history, or psychosocial history. Lab and imaging workup were unremarkable, and the patient underwent liver biopsy. The patient’s biopsy results showed OPV. The patient continued GAHT at a lower dose and liver enzyme elevations resolved. Conclusions: OPV is a vascular disease that falls under the category of porto-sinusoidal vascular disorder. Patients with this condition can present with or without overt clinical signs of portal hypertension. Porto-sinusoidal vascular disorder is rare and given the timing and possible dose dependence, it might be reasonable to consider that the observed OPV was influenced by the exogenous estrogen administered in an association not previously reported. Alternatively, the patient’s continued estrogen treatment without ill effect could suggest that the events were not connected and that the fear of harm could have served as a barrier to the patient receiving indicated care. Full article

Gender-affirming hormone therapy (GAHT) plays a significant role in the medical care of transgender individuals, helping to align their physical characteristics with their gender identity. While numerous studies have investigated the impact of GAHT on adults, research focusing on its effects on the quality of life (QoL) of transgender youth is limited. In this opinion paper, we aim to address selected challenges associated with gender-affirming medical care, such as (1) the necessity for evidence-based youth gender-affirming medical care, (2) the urge to explore different approaches to gender-affirming medical care diversely in transgender youth research, and (3) understanding the challenges of the detransition process (which refers to stopping or reversing gender-affirming medical or surgical treatments), as well as suggest possible solutions for meaningful progress. Notably, the available evidence underlines a positive impact of GAHT on various aspects of QoL of transgender youth, such as mental health and social functioning, by alleviating gender dysphoria, improving body satisfaction, and facilitating appearance congruence (the degree to which an individual’s physical appearance represents their gender identity). However, challenges related to methodological limitations, as well as ethical considerations, and several sociocultural factors highlight the need for further research to better understand the long-term effects of GAHT on the QoL of transgender youth. Ethical considerations, such as ensuring informed consent and weighing potential benefits against risks, are pivotal in guiding healthcare decisions. Additionally, navigating these ethical responsibilities amid sociocultural contexts is crucial for providing inclusive and respectful care to transgender youth. Addressing these research gaps is, therefore, crucial to developing successful healthcare programmes, raising awareness, and promoting the holistic well-being of transgender youth through comprehensive and affirming care. Full article

In the biomedical field, the differentiation between sex and gender is crucial for enhancing the understanding of human health and personalizing medical treatments, particularly within the domain of orthopedics. This distinction, often overlooked or misunderstood, is vital for dissecting and treating musculoskeletal conditions effectively. This review delves into the sex- and gender-specific physiology of bones, cartilage, ligaments, and tendons, highlighting how hormonal differences impact the musculoskeletal system’s structure and function, and exploring the physiopathology of orthopedic conditions from an epidemiological, molecular, and clinical perspective, shedding light on the discrepancies in disease manifestation across sexes. Examples such as the higher rates of deformities (adolescent idiopathic and adult degenerative scoliosis and hallux valgus) in females and osteoporosis in postmenopausal women illustrate the critical role of sex and gender in orthopedic health. Additionally, the review addresses the morbidity–mortality paradox, where women, despite appearing less healthy on frailty indexes, show lower mortality rates, highlighting the complex interplay between biological and social determinants of health. Injuries and chronic orthopedic conditions such osteoarthritis exhibit gender- and sex-specific prevalence and progression patterns, necessitating a nuanced approach to treatment that considers these differences to optimize outcomes. Moreover, the review underscores the importance of recognizing the unique needs of sexual minority and gender-diverse individuals in orthopedic care, emphasizing the impact of gender-affirming hormone therapy on aspects like bone health and perioperative risks. To foster advancements in sex- and gender-specific orthopedics, we advocate for the strategic disaggregation of data by sex and gender and the inclusion of “Sexual Orientation and Gender Identity” (SOGI) data in research and clinical practice. Such measures can enrich clinical insights, ensure tailored patient care, and promote inclusivity within orthopedic treatments, ultimately enhancing the precision and effectiveness of care for diverse patient populations. Integrating sex and gender considerations into orthopedic research and practice is paramount for addressing the complex and varied needs of patients. By embracing this comprehensive approach, orthopedic medicine can move towards more personalized, effective, and inclusive treatment strategies, thereby improving patient outcomes and advancing the field. Full article

Gender-affirming hormone therapy (GAHT) is an important component in the process of transitioning for many transgender and gender-diverse (TGD) individuals. Multiple medical organizations recommend fertility preservation counseling prior to initiation of GAHT; however, there remains little high-quality data regarding the impact of GAHT on fertility and reproductive function. A PubMed literature review was performed using Boolean search operators linking keywords or phrases such as “mouse”, “rat”, “primate”, “animal model”, “transgender”, “gender”, “estrogen”, “testosterone”, “fertility”, and “fertility preservation”. Recent research has produced a number of animal models of GAHT that utilize similar hormonal regimens and produce similar phenotypic results to those used and observed in human patients. Specific to testosterone(T)-containing GAHT, animals demonstrate loss of menstrual cyclicity with therapy, resumption of menses on cessation of therapy, suppression of gonadotropin levels, and physical changes such as clitoromegaly. Models mimicking GAHT for transmasculine individuals in the peripubertal period demonstrate that pretreatment with GnRHa therapy does not modify the effects of subsequent T administration, which were similar to those described in adult models. Both models suggest promising potential for future fertility with cessation of T. With estradiol (E)-containing GAHT, animals exhibit decreased size of testicles, epididymis, and seminal vesicles, as well as ongoing production of spermatocytes, and seminiferous tubule vacuolization. Given the ethical challenges of conducting human studies in this area, high-fidelity animal models represent a promising opportunity for investigation and could eventually transform clinical counseling about the necessity of fertility preservation. Future studies should better delineate the interactions (if any exist) between treatment attributes such as dosing and duration with the extent of reversibility of reproductive perturbations. The development of models of peripubertal feminizing GAHT is an additional area for future work. Full article

Transgender individuals often face elevated mental health challenges due to gender dysphoria, but gender-affirming treatments such as surgery and hormone therapy have been linked to significant improvements in mental well-being. The potential influence of time and circadian rhythms on these treatments is prevalent. The intricate interplay between hormones, clock genes, and fertility is profound, acknowledging the complexity of reproductive health in transgender individuals. Furthermore, risks associated with gender-affirming hormonal therapy and potential complications of puberty suppression emphasize the importance of ongoing surveillance for these patients and the need of fertility preservation and family-building options for transgender individuals. This narrative review delves into the intricate landscape of hormone therapy for transgender individuals, shedding light on its impact on bone, cardiovascular, and overall health. It explores how hormone therapy affects bone maintenance and cardiovascular risk factors, outlining the complex interplay of testosterone and estrogen. It also underscores the necessity for further research, especially regarding the long-term effects of transgender hormones. This project emphasizes the critical role of healthcare providers, particularly obstetricians and gynecologists, in providing affirming care, calling for comprehensive understanding and integration of transgender treatments. This review will contribute to a better understanding of the impact of hormone therapy on reproductive health and overall well-being in transgender individuals. It will provide valuable insights for healthcare providers, policymakers, and transgender individuals themselves, informing decision-making regarding hormone therapy and fertility preservation options. Additionally, by identifying research gaps, this review will guide future studies to address the evolving healthcare needs of transgender individuals. This project represents a critical step toward addressing the complex healthcare needs of this population. By synthesizing existing knowledge and highlighting areas for further investigation, this review aims to improve the quality of care and support provided to transgender individuals, ultimately enhancing their reproductive health and overall well-being. Full article

Introduction: In the last decade, healthcare for the transgender population has increased considerably in many countries thanks to depathologization movements and the easier accessibility of medical assistance. The age at which they request to start gender-affirming hormones (GAHs) is increasingly younger. The cardiovascular risk associated with hormonal treatment is a novel research field, and the published studies are heterogeneous and inconclusive. Our objective is to determine the metabolic impact of GAHs in the transgender people treated in our Gender Identity Treatment Unit. Methods: We designed a pre–post study to analyze changes in anthropometric parameters (weight and body mass index), analytical determinations (fasting blood glucose, glycated hemoglobin, and lipoproteins), and blood pressure control in the transgender population treated with GAHs in Puerta del Mar University Hospital. These variables were collected before and one year after hormonal therapy. Results: A total of 227 transgender people were recruited between 2017 and 2020, 97 (40.09%) transwomen and 136 (59.91%) transmen. The average age at which GAHs began was 18 years. Weight, body mass index, and blood pressure increased significantly in both genders. Transmen showed a more atherogenic lipid profile, with a decrease in cholesterol LDL (p < 0.001) and an increase in triglycerides (p < 0.001). The risk of developing prediabetes or diabetes did not increase one year after treatment, although non-specific alterations in carbohydrate metabolism were detected, such as an increase in glycated hemoglobin in transmen (p = 0.040) and fasting blood glucose in transwomen (p = 0.008). No thromboembolic processes or cardiovascular events were reported during the first year of treatment. Conclusion: In our setting, transgender people developed changes in their metabolic profiles in the first year after hormonal treatment. Both transmen and transwomen showed early alterations in lipid and carbohydrate metabolism, slight elevations in blood pressure, and a tendency to gain weight. This makes lifestyle interventions necessary from the beginning of GAHs. Full article