Effectiveness of low dose cyproterone acetate compared to standard dose in feminizing hormone treatment: a single institutional retrospective pilot study.

Background: Data regarding the effectiveness of low-dose cyproterone acetate (CPA) in testosterone suppression as feminizing hormone therapy (FHT) in individuals assigned male at birth (AMAB) are sparse. Aim: To assess the effectiveness in testosterone suppression using low-dose CPA (<25 mg/day) compared to standard-dose CPA (25-50 mg/day) in FHT. Methods: A retrospective cohort study of 59 individuals AMAB using CPA was done at a tertiary care center in Bangkok, Thailand between January 2014 and July 2022. Outcomes: The main outcomes included a median time when the testosterone was suppressed (<50 ng/dL), the proportion of individuals AMAB who achieved the targeted testosterone level at 3 months, and the testosterone level at each follow-up. Changes in clinical data were assessed. Results: Among 59 individuals AMAB, 37 initiated CPA with available testosterone levels at the 3-month follow-up. Twenty-two individuals AMAB started with low-dose CPA (12.5 mg/day), and 15 individuals AMAB started with standard-dose CPA. The median time to reach targeted testosterone was 3 months in both groups (adjusted hazard ratio 0.60, P = .489). At 3 months, 72.7% of those on low-dose CPA and 86.7% of those on standard-dose CPA achieved targeted testosterone (adjusted relative risk 0.85, P = .606). Testosterone levels at all follow-up visits were not significantly different. The standard dose group had higher high-density lipoprotein cholesterol (HDL-C) but lower low-density lipoprotein cholesterol (LDL-C) and alanine aminotransferase (ALT). Clinical Translation: This study supports a paradigm shift toward using lower-dose CPA in FHT. Strengths and Limitations: This is one of a few studies showing the effectiveness of low-dose CPA in testosterone suppression within 3 months. Limitations include a small sample size and missing data. Conclusions: Testosterone suppression is comparable between CPA 12.5 mg/day and the standard dose in FHT.

Assessment of parenteral estradiol and dihydroxyprogesterone use among other feminizing regimens for transgender women: insights on satisfaction with breast development from community-based healthcare services.

The practice of hormone therapy is crucial in aligning secondary sex characteristics with the gender identity of transgender adults. This study examines the effects of a commonly used injectable hormone combination, specifically estradiol enanthate with dihydroxyprogesterone acetophenide (EEn/DHPA), on serum hormonal levels and self-reported satisfaction with breast development in transwomen. Our research focused on a retrospective longitudinal study involving a large cohort of transwomen evaluated between 2020 and 2022, comprising 101 participants. We assessed serum levels of estradiol (E2), testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH), comparing the EEn/DHPA hormonal regimen with other combined estrogen-progestogen (CEP) therapies. Additionally, a subset of 43 transwomen completed a 5-question survey to evaluate self-reported satisfaction with breast development using Tanner scales. Our findings indicated that participants using the EEn/DHPA regimen exhibited significantly higher serum E2 levels (mean: 186 pg/mL ± 32 pg/mL) than those using other therapies (62 ± 7 pg/mL), along with lower FSH levels, but no significant differences in T and LH levels. Concerning satisfaction with breast development, 76% reported increased fulfillment with breast augmentation while using EEn/DHPA. These results suggest that an injectable, low-cost EEn/DHPA administered every three weeks could serve as an alternative feminizing regimen, particularly considering the extensive long-term experience of the local transgender community. Further longitudinal studies on the efficacy of feminizing-body effects and endovascular risks of various parenteral CEP types are warranted to improve primary healthcare provision for transgender persons.

Evaluating the Risk of Venous Thromboembolism in Transfeminine and Gender Diverse People: A Retrospective Analysis.

OBJECTIVE: The risk of venous thromboembolism (VTE) with feminizing gender-affirming hormone therapy is an area of concern. This analysis aimed to assess whether gender-affirming hormone therapy and other potential risk factors are associated with VTE in transfeminine and gender diverse individuals. METHODS: We conducted a chart review of 2126 transfeminine and gender diverse adults receiving care within a large urban health system. The primary outcomes were the prevalence of VTE and odds ratios for the association of VTE with insurer, use of estrogen, and select comorbidities. RESULTS: A history of VTE was documented in 0.8% of the cohort. Those with a history of VTE were older (P < .001), more often self-identified as Hispanic or Black compared to White or Asian (P < .05) and were more likely to have Medicaid or Medicare (P < .01) when compared to those without a history of VTE. The prevalence of hyperlipidemia (P < .001), diabetes mellitus (P < .05), and hypercoagulable conditions (P < .001) were all greater in the positive VTE group. Hyperlipidemia (P < .001), diabetes mellitus (P < .05), and insurer (P < .05) were associated with increased odds of VTE in univariate analyses. None of the exposure variables analyzed were associated with VTE when controlling for age, race, and the number of comorbidities. CONCLUSIONS: The prevalence of VTE in our cohort was lower than previously observed. VTE was not associated with any one risk factor, including estrogen use, when controlling for age, race, and the number of comorbidities. Those of advanced age and those with multiple cardiometabolic comorbidities may benefit from increased surveillance and mitigation of modifiable risk factors.

Hepatic Adenomatosis in a Transgender Man on Gender-Affirming Testosterone Therapy.

The management of hepatic adenoma in transgender individuals undergoing gender-affirming hormone therapy remains unclear, especially whether treatment should be based on sex assigned at birth or therapy patient received. We presented a transgender man, female at birth, with hepatic adenomatosis with molecular profile differed from typical adenomas in cisgender males on testosterone. Discontinuing testosterone led to autoinfarction of the adenoma, allowing the avoidance of invasive treatments and resumption of gender-affirming hormone therapy. This case underscores the necessity for personalized care in the growing transgender population and challenges current consensus of treatment based on sex assigned at birth, emphasizing a tailored approach.

Transgender patients and gender-affirming hormone therapy through the mid-life.

The menopause transition and post-menopause period marks a time of dynamic physiological and hormonal change. Cisgender women commonly experience vasomotor symptoms, genitourinary symptoms, and changes in bone health. The transgender population, including those assigned female at birth (AFAB) and those assigned male at birth (AMAB), has been understudied in terms of experiences through the menopause transition and midlife. Additionally, there is no formal recommendation or guidance on continuation of gender-affirming hormone therapy (GAHT) through midlife. While gender-affirming therapies for transgender patients are well defined and supported by organizational guidelines, including from the World Professional Association for TGD Health (WPATH) (Standards of Care 8, SOC8) and from the Endocrine Society (2017), evidence on continuation of therapy and dose adjustments into mid-life are lacking. Data from a few large cohort studies and small cross-sectional studies suggest increased risk of venous thromboembolism (VTE), stroke and myocardial infarction in those AMAB on GAHT. For those AFAB on testosterone therapy, risks of cardiovascular disease and stroke and to bone health are not well defined, given inconsistent findings from large cohort studies. Currently, the decision to continue GAHT for transgender patients is guided by patient preference along with clinician guidance. Further research is warranted regarding risks of continuing GAHT into mid-life for both AMAB and AFAB patients. Given the significant benefit of GAHT in this population, however, this data would be most helpful for counseling on risks along with appropriate monitoring and prevention for related morbidities during mid-life in the setting of GAHT use.

Incidence of High Risk and Malignant Pathological Findings in Transgender and Gender Diverse Individuals Undergoing Gender-Affirming Mastectomy.

BACKGROUND: Concrete, data-driven guidelines for breast cancer screening among the transgender and gender diverse (TGD) population is lacking. The present study evaluates possible associations of gender-affirming hormone therapy (GAHT) on incidental breast pathology findings in trans-masculine patients to inform decision making about breast cancer screening. PATIENTS AND METHODS: This was a retrospective cohort study of patients who had gender-affirming mastectomy or breast reduction at a single center from July 2019 to February 2024. A total of 865 patients met the inclusion criteria. Gender-affirming testosterone therapy and length of exposure were evaluated to seek differences in post-operative pathology findings. RESULTS: The median age at the time of surgery was 27 years [interquartile range (IQR) 21-30]. Most participants identified as female to male (658, 75.6%). A significant portion of the participants (688, 79.2%) were undergoing testosterone therapy at the time of surgery, with the median duration of testosterone use prior to surgery being 14 months (IQR 4-29). High risk or malignant findings were noted in pathology results for 12 of 1730 breasts (0.7%). Ordered logistic regression found that duration of testosterone therapy was not associated with increasing severity of incidental breast pathology. Additionally, patients under 25 years of age were 70% less likely to have any incidental finding on pathological evaluation than older patients [odds ratio (OR) 0.3, p < 0.01, confidence interval (CI) 0.18-0.50]. CONCLUSIONS: The present study found that patients undergoing GAHT should not be screened for breast cancer with increased frequency compared with cis-gender women. Additionally, it may be appropriate for trans women under the age of 25 with normal breast cancer risk to forego pathological breast tissue examination.

Empowering Health and Identity: The Vital Role of Gender-affirming Care for Individuals With HIV.

Comprehensive healthcare for all includes gender-affirming hormone therapy for transgender and nonbinary individuals. It is the unique privilege of HIV providers, who take care of a disproportionate number of transgender people, to provide gender-affirming hormone therapy along with antiretroviral therapy. It could increase viral suppression rates, increase overall health outcomes, and decrease gender health disparities.

Endocrine, gender dysphoria, and sexual function benefits of gender-affirming bilateral orchiectomy: patient outcomes and surgical technique.

Background: Gender-affirming bilateral orchiectomy (GABO) may be completed as either a standalone procedure (sGABO) or at the same time as gender-affirming vaginoplasty (vGABO). GABO is postulated to decrease gender-affirming hormone therapy (GAHT) dosages and reduce gender dysphoria, but these phenomena are not empirically described in the medical literature. Aim: The primary aim of this study was to describe changes in GAHT dosages after sGABO and vGABO. A secondary aim was to assess sGABO patients' preoperative decision-making priorities and postoperative satisfaction. Methods: A retrospective chart review identified 204 patients who completed GABO as either a standalone procedure (64% of patients) or at the same time as vaginoplasty (36%). Patient demographic data, surgical outcomes, and pre- and postoperative GAHT dosage data were recorded. Patients completed an opinion questionnaire to assessed decision-making priorities, as well as postoperative satisfaction and changes in quality-of-life measures. Outcomes: Primary outcomes included pre- and postoperative dosages of estradiol, progesterone, and spironolactone. Secondary outcomes included sGABO patient priorities, satisfaction with sGABO, changes in quality-of-life measures between sGABO and vGABO patients, and sGABO recommendations to future patients. Results: The sGABO and vGABO patients experienced a statistically significant dosage reduction in all three GAHT assessed: estradiol, progesterone, and spironolactone (P < .05). All patients discontinued spironolactone postoperatively. Zero complications related to GABO were recorded for patients in either group. The patient questionnaire revealed that sGABO patients prioritize decreasing endogenous testosterone and reducing their GAHT as most important in their decision to undergo sGABO prior to vaginoplasty. A majority of sGABO patients reported improvement in all nine quality-of-life indices. None of the sGABO patients would recommend against sGABO to a friend who is waiting for vaginoplasty. Clinical Implications: For patients who are interested in vaginoplasty, sGABO may serve as a more immediate, low-risk, intermediary step that comes with the benefits of GABO, including significant GAHT medication reduction and gender dysphoria relief. Strengths and Limitations: This study offers a comprehensive evaluation of the impact of GABO on patients, combining empirical data with subjective patient feedback. Limitations include the retrospective design and the use of unvalidated survey questions. Conclusion: Prevaginoplasty GABO is a viable option to more immediately alleviate gender dysphoria and reduce GAHT medications for patients who are interested in gender-affirming vaginoplasty.

Transgender and Nonbinary Individuals' Perceptions Regarding Gender-Affirming Hormone Therapy and Cardiovascular Health: A Qualitative Study.

BACKGROUND: Transgender and nonbinary individuals face substantial cardiovascular health uncertainties. The use of gender-affirming hormone therapy can be used to achieve one's gender-affirming goals. As self-rated health is an important predictor of health outcomes, an understanding of how this association is perceived by transgender and nonbinary individuals using gender-affirming hormone therapy is required. The objective of this research was to explore transgender and nonbinary individuals' perceptions of cardiovascular health in the context of using gender-affirming hormone therapy. METHODS: In this qualitative study, English-speaking transgender and nonbinary adults using gender-affirming hormone therapy for 3 months or more were recruited from across Canada using purposive and snowball sampling methods. Semistructured interviews were conducted through videoconference to explore transgender and nonbinary individuals' perceptions of the association between gender-affirming hormone therapy and cardiovascular health between May and August 2023. Data were transcribed verbatim, and transcripts were analyzed independently by 3 reviewers using thematic analysis. RESULTS: Twenty-one participants were interviewed (8 transgender women, 9 transgender men, and 3 nonbinary individuals; median [range] age, 27 [20-69] years; 80% White participants). Three main themes were identified: cardiovascular health was not a primary concern in the decision-making process with regard to gender-affirming hormone therapy, the improved well-being associated with gender-affirming hormone therapy was felt to contribute to improved cardiovascular health, and health care provider knowledge and attitude facilitate the transition process. CONCLUSIONS: Gender-affirming hormone therapy in transgender and nonbinary individuals is perceived to improve cardiovascular health. Given the positive associations between care aligned with patient priorities, self-rated health, and health outcomes, these findings should be considered as part of shared decision-making and person-centered care.

Gender-affirming hormone therapy for transgender and gender-diverse adults in Australia.

Gender-affirming hormone therapy (GAHT) is used by many transgender and gender-diverse adults to align physical characteristics with their gender identity, reduce gender incongruence and improve psychological functioning. This narrative review provides an overview of the initiation and monitoring of GAHT in an Australian context. Trans individuals treated with testosterone typically receive standard testosterone doses and formulations recommended for cisgender men, whereas those receiving estradiol GAHT are typically treated with estradiol in combination with an anti-androgen in those without orchidectomy. Proactive monitoring and mitigation of cardiovascular risk factors is pertinent in all transgender and gender-diverse adults and bone health is an important consideration in those using estradiol GAHT.

Evaluation of Sexual Function of Transgender Individuals.

PURPOSE: The current study sought to evaluate the sexual function of transgender men and women and to identify associated factors. METHODS: Trans individuals who were outpatients at our gender incongruence (GI) center for follow-up of gender-affirming hormone therapy with age ranging 27 to 50 years were invited to participate in this cross-sectional study. Clinical data were collected from the medical records. Two scales, the Female Sexual Function Index (FSFI) and the Male Sexual Function Index (MSFI), were administered to all females (n = 50) and all males (n = 58). Each participant also responded to a semi-structured questionnaire that assessed feelings regarding being transgender and satisfaction with sexual life. RESULTS: Relative to trans women, trans men had a higher total FSFI score, and higher scores in the FSFI domains of arousal, lubrication, orgasm, and satisfaction (all p < 0.01), and in the total MSFI score, and higher scores in the MFSI domains of arousal, erection, orgasm, and satisfaction (all p < 0.01). A separate semi-structured evaluation indicated that more than half of the trans men and almost half of the trans women were satisfied or very satisfied with their sexual life. CONCLUSIONS: The total scores from the FSFI and MSFI indicated a high risk of sexual dysfunction in trans men and especially, in trans women. However, the semi-structured evaluation showed that more than half of the trans men and almost half of the trans women were satisfied with their sexual life.

Corrigendum: Clinicians in the Veterans Health Administration initiate gender-affirming hormone therapy in concordance with clinical guideline recommendations.

[This corrects the article DOI: 10.3389/fendo.2024.1086158.].

Effectiveness and Safety of Different Estradiol Regimens in Transgender Females: A Randomized Controlled Trial.

Background: A goal of gender-affirming hormone therapy (GAHT) for transgender women is to use estradiol to suppress endogenous production of testosterone. However, the effects of different estradiol regimens and route of administration on testosterone suppression is unknown. This is the first open-label randomized trial comparing different GAHT regimens for optimal estradiol route and dosing. Objective: To evaluate 1 month and 6 months testosterone suppression <50 ng/dL with pulsed (once- or twice-daily sublingual 17-beta estradiol) and continuous (transdermal 17-beta estradiol) GAHT. Methods: This study was conducted at an outpatient adult transgender clinic. Thirty-nine transgender women undergoing initiation of GAHT were randomly assigned to receive either once-daily sublingual, twice-daily sublingual, or transdermal 17-beta estradiol. All participants received spironolactone as an antiandrogen. Doses were titrated at monthly intervals to achieve total testosterone suppression <50 ng/dL. Results: Transdermal 17-beta estradiol resulted in more rapid suppression of total testosterone, lower estrone levels, with no differences in estradiol levels when compared to once-daily and twice-daily sublingual estradiol. Moreover, there was no difference in the mean estradiol dose between the once-daily and twice-daily sublingual 17-beta estradiol group. Conclusion: Continuous exposure with transdermal 17-beta estradiol suppressed testosterone production more effectively and with lower overall estradiol doses relative to once or twice daily sublingual estradiol. Most transgender women achieved cisgender women testosterone levels within 2 months on 1 or 2 0.1 mg/24 hours estradiol patches. Given no difference between once- or twice-daily sublingual estradiol, pulsed 17-beta estradiol likely provides no benefit for testosterone suppression.

Transgender Women With Suppressed Testosterone Display Lower Burden of Coronary Disease Than Matched Cisgender Men.

Context: Cardiovascular disease (CVD) in transgender women (TW) may be affected by gender-affirming hormone therapy (GAHT) and HIV, but few data compare TW on contemporary GAHT to well-matched controls. Objective: We compared CVD burden and biomarker profiles between TW and matched cisgender men (CM). Methods: Adult TW on GAHT (n = 29) were recruited for a cross-sectional study (2018-2020). CM (n = 48) from the former Multicenter AIDS Cohort Study were matched 2:1 to TW on HIV serostatus, age ±5 years, race/ethnicity, BMI category and antiretroviral therapy (ART) type. Cardiac parameters were measured by CT and coronary atherosclerosis by coronary CT angiography; sex hormone and biomarker concentrations were measured centrally from stored samples. Results: Overall, median age was 53 years and BMI 29 kg/m2; 69% were non-white. All participants with HIV (71%) had viral suppression on ART. Only 31% of TW had testosterone suppression (<50 ng/dL, TW-S). Traditional CVD risk factors were similar between groups, except that TW-S had higher BMI than TW with non-suppressed testosterone (TW-T). TW-S had no evidence of non-calcified coronary plaque or advanced coronary stenosis, whereas TW-T and CM had similar burden. TW had lower prevalence of any coronary plaque, calcified plaque and mixed plaque than CM, regardless of testosterone concentrations and HIV serostatus. Estradiol but not testosterone concentrations moderately and negatively correlated with the presence of coronary plaque and stenosis. Small sample size limited statistical power. Conclusion: Older TW with suppressed total testosterone on GAHT had no CT evidence of non-calcified coronary plaque or advanced coronary stenosis. Longitudinal studies to understand relationships between GAHT and CVD risk in TW are needed.

'Boy smell': transgender and nonbinary people's experiences of bodily smell.

Although smell is sometimes treated with little regard, it is invested with cultural meaning and conveys a great deal of information, including about gender, sexuality and identity. This article draws on interviews with 11 transgender and nonbinary people who have accessed gender affirming hormone therapy (GAHT), and focuses on how they understand and explain changes in how their own bodies smell. Although it is well documented that GAHT causes changes in skin oiliness, changes in smell are inconsistently documented, and within the medical literature are often commented on only in passing. Taking a discourse analytic approach, the article finds that participants noticed changes in their own smell during hormonal transition, that in many cases this change was understood as significant in some way, and that these changes could be experienced as affirming. Understandings of what changes in bodily smell meant were often derived relationally or socially, although participants' discussion of the experience frequently focused on their own embodiment. Smell seems to form part of a process of (re)identification with the physical self and gender affirmation that can be facilitated by GAHT.

Mental Health Diagnoses and Suicidality Among Transgender Youth in Hospital Settings.

Purpose: The purpose of this analysis is to: 1) describe the most common mental health diagnoses in the emergency department (ED) and inpatient hospital settings among transgender and gender diverse (TGD) youth vs. matched controls and 2) evaluate if a gender-affirming hormone therapy (GAHT) or gonadotropin-releasing hormone agonist (GnRHa) prescription decreased the risk of suicidality within these settings. Methods: Using the PEDSnet dataset (years 2009-2019), TGD youth aged 8-18 (n = 3414, with a median age at last visit of 16.2 [14.4, 17.7] years, were propensity-score matched to controls (n = 13,628, age 16.6 [14.2, 18.3] years). Relative risks of the most common mental health diagnoses within ED and inpatient settings were calculated for TGD youth compared with controls. Recurrent time-to-event analysis was used to examine whether GAHT or GnRHa attenuated the risk of suicidality among subsamples of TGD youth. Results: TGD youth had a higher relative risk (95% confidence interval [CI]) of mental health diagnoses and suicidality in the ED (5.46 [4.71-6.33]) and inpatient settings (6.61 [5.28-8.28]) than matched controls. TGD youth prescribed GAHT had a 43.6% lower risk of suicidality (hazard ratio [HR] = 0.564 [95% CI 0.36-0.89]) compared with those never prescribed GAHT during our study period or before GAHT initiation. TGD youth who were prescribed GnRHa therapy had a nonstatistically significant reduction in ED or inpatient suicidality diagnoses compared with those never prescribed GnRHa (HR = 0.79 [0.47-1.31]). Conclusion: Although risk of mental health diagnoses and suicidality in ED and inpatient settings was high among TGD youth, a GAHT prescription was associated with a significant reduction in suicidality risk.

The Effects of Gender-Affirming Hormone Therapy on Quality of Life: The Importance of Research on Youth.

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.

Reproductive Considerations in the Transgender and Gender Diverse Population: A Review.

Many transgender and gender diverse (TGD) individuals will be considering gender-affirming treatments during their reproductive lifespan. These medically necessary treatments have a negative impact on reproductive potential. All TGD individuals should be counseled regarding fertility. Options for fertility preservation for individuals who have undergone puberty include mature oocyte, embryo, and sperm cryopreservation. In prepubertal individuals, ovarian tissue cryopreservation may be considered, but testicular tissue cryopreservation remains experimental only. While there have been advances in the technology and standardization of reproductive health care for this population, many gaps remain in our knowledge which require further research.