A European Network for the Investigation of Gender Incongruence in adolescents.

BACKGROUND: Knowledge regarding the effects and side effects of gender-affirming hormone therapy (GAHT) in adults is rapidly growing, partly through international research networks such as the European Network for the Investigation of Gender Incongruence (ENIGI). However, data on the effects of puberty suppression (PS) and GAHT in transgender and gender diverse (TGD) youth are limited, although these data are of crucial importance, given the controversies surrounding this treatment. AIM: We sought to present a detailed overview of the design of the ENIGI Adolescents study protocol, including the first baseline data. METHODS: The ENIGI Adolescents study is an ongoing multicenter prospective cohort study. This study protocol was developed by 3 European centers that provide endocrine care for TGD adolescents and were already part of the ENIGI collaboration: Amsterdam, Ghent, and Florence. OUTCOMES: Study outcomes include physical effects and side effects, laboratory parameters, bone mineral density, anthropometric characteristics, attitudes toward fertility and fertility preservation, and psychological well-being, which are measured in the study participants during PS and GAHT, up to 3 years after the start of GAHT. RESULTS: Between November 2021 and May 2023, 172 TGD adolescents were included in the ENIGI Adolescents protocol, of whom 51 were assigned male at birth (AMAB) and 121 were assigned female at birth (AFAB); 3 AFAB participants reported a nonbinary gender identification. A total of 76 participants were included at the start of PS, at a median (IQR) age of 13.7 (12.9-16.5) years in AMAB and 13.5 (12.4-16.1) years in AFAB individuals. The remaining 96 participants were included at start of GAHT, at a median (IQR) age of 15.9 (15.1-17.4) years in AFAB and 16.0 (15.1-16.8) years in AMAB individuals. At the time of this report the study was open for inclusion and follow-up measurements were ongoing. CLINICAL IMPLICATIONS: In response to the rising demand for gender-affirming treatment among TGD youth, this ongoing study is fulfilling the need for prospective data on the effects and safety of PS and GAHT, thus providing a foundation for evidence-based healthcare decisions. STRENGTHS AND LIMITATIONS: This study has a strong multicenter, prospective design that allows for systematic data collection. The use of clinical and self-reported data offers a broad range of outcomes to evaluate. Nevertheless, the burden of additional measurements and questionnaires may lead to withdrawal or lower response rates. Few participants with a non-binary gender identity have been included. CONCLUSION: With the ENIGI Adolescents study we aim to create a comprehensive dataset that we can use for a wide range of studies to address current controversies and uncertainties and to improve healthcare for TGD adolescents.

Addition of progesterone to feminizing gender-affirming hormone therapy in transgender individuals for breast development: a randomized controlled trial.

BACKGROUND: Feminizing gender-affirming hormone therapy (GAHT) for transgender individuals traditionally includes estradiol and androgen deprivation. Research has demonstrated that breast size as a result of GAHT in transgender women is often limited. Therefore, transgender women often choose to undergo breast augmentation surgery. Progesterone is important for breast development in cisgender women during puberty. A potential role for progesterone in breast development in transgender women has not been investigated in a randomized controlled experimental set-up. The primary objective of this study is to explore the effects on breast volume of addition of oral progesterone to GAHT with estradiol in transgender women after vaginoplasty or orchiectomy. Secondary objectives include assessment of safety, satisfaction, mood, sleep and sexual pleasure. METHODS: This is a non-blinded, non-placebo, randomized controlled trial using a factorial design in adult transgender individuals assigned male sex at birth who have undergone GAHT for at least one year and underwent vaginoplasty or orchiectomy. The study design allows for rapid assessment of potential synergistic effects of various dose combinations of estradiol and progesterone on breast volume change: Ninety participants will be randomized into six groups of 15 subjects each, receiving either the baseline dose of estradiol, the baseline dose of estradiol and progesterone 200 mg daily, the baseline dose of estradiol and progesterone 400 mg daily, twice the baseline dose of estradiol, twice the baseline dose of estradiol and progesterone 200 mg daily or twice the baseline dose of estradiol and progesterone 400 mg daily, all for a duration of 12 months. The main study parameters include changes in breast volume as determined by 3D measurements. Participants will be followed-up with laboratory testing including serum progesterone concentrations as well as surveys for satisfaction, mood, sleep quality and sexual pleasure. DISCUSSION: This study will indicate whether progesterone is safe and of additional value with regard to breast volume change in transgender individuals receiving feminizing GAHT. The results of this study will be useful for innovation of feminizing GAHT. TRIAL REGISTRATION: WHO International Clinical Trials Registry Platform: EUCTR2020-001952-16-NL; date of registration: 12 December 2020 https://trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2020-001952-16-NL .

Mobile Phone Applications Voice Tools and Voice Pitch Analyzer Validated With LingWAVES to Measure Voice Frequency.

OBJECTIVES: Voice frequency can be measured to assess the voice change in transgender men and women during treatment. There are many applications that can analyze voice frequency. This validation study aimed to compare the ability to measure voice frequency of the mobile phone applications "Voice Tools" and "Voice Pitch Analyzer" with the registration program LingWAVES as the gold standard. STUDY DESIGN: Prospective validation study. METHODS: A total of 45 participants of whom 20 transgender individuals were included. They were asked to read "The North Wind and the Sun" twice. The first measurement compared voice frequency measured by Voice Tools with LingWAVES while the second measurement compared Voice Pitch Analyzer with LingWAVES. The two applications that were being compared simultaneously measured the voice frequency. Pearson's regression correlations were performed to test for correlation between the mobile phone applications and LingWAVES. RESULTS: Significant correlations were demonstrated between the measurements of Voice Tools and LingWAVES (P < 0.001) and between Voice Pitch Analyzer and LingWAVES (P < 0.001). Voice Tools overestimated voice frequency with a median deviation of 2Hz (range -4 to 20). The overestimation was more pronounced in the high ranges. Voice Pitch Analyzer showed underestimation of voice frequency in high ranges. Median deviation was -2Hz (range -16 to 14). CONCLUSIONS: This validation study shows that voice frequency can be reliably measured with the mobile phone applications "Voice Tools" and "Voice Pitch Analyzer". Combined with the ease of use, these applications can be used to measure voice frequency in clinical practice and for research purposes.