The study program consists of a yearly assessment as part of the long-term routine follow-up. Participants' data collection includes a mix of digital and in-person methods. Demographical information, clinical and laboratory parameters such as hormone levels which are part of standard clinical care

If GAS is administered, additional assessments are performed preoperatively, and postoperatively in analogy with routine clinical visits, e.g. one week after surgery and then three, six and twelve months later (then once yearly) (e.g. type of surgery, outcome, patient' satisfaction). If participants undergo gender-affirming genital surgery, a genital swab and urine analysis (from the urine sample taken for routine testing) will additionally be performed for microbiome analyses as part of the study assessment.

The Decision Regret Scale is a validated tool that is used in this study to measure the regret after detransition. The scale ranges from 0 to 100, with higher scores indicating greater regret and lower scores reflecting less or no regret. It is widely applicable across different healthcare contexts to assess the emotional impact of decision-making.

The Body Image States Scale is a validated measure that is used in this study to assess an individual's momentary body image satisfaction after detransition. The scale ranges from 0 to X, with higher scores indicating greater body image satisfaction and lower scores reflecting greater dissatisfaction.

The quality of life is meassured using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire.The EQ-5D-5L is a standardized measure, assessing mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The scale provides a utility score ranging from 0 (equivalent to death) to 1 (perfect health), with higher scores indicating better health-related quality of life.

To evaluate treatment satisfaction an adapted Treatment Satisfaction Questionnaire for Medication 1.4 (TSQM-1.4) is used. TSQM-1.4 is a validated tool, assessing patients' satisfaction with their treatments across four domains: effectiveness, side effects, convenience, and overall satisfaction. The scale provides scores ranging from 0 to 100 for each domain, with higher scores indicating greater satisfaction.

The Beck Depression Inventory-II (BDI-II), a validated self-report measure, is used to assess depressive symptoms. The scale ranges from 0 to 63, with higher scores indicating greater severity of depressive symptoms and lower scores reflecting minimal or no depression.

Detransition is assessed as the percentage of individuals who interrupt or stop therapy over time.

The reasons for stopping/reversing transition is assessed using a questionnaire adapted from MacKinnon et al., 2024 (21 possible reasons for stopping/reversing transition).

The Gender Minority Stress and Resilience Measure (GMSR) is a validated, assessing experiences of minority stress and resilience factors specific to transgender and gender-diverse individuals. The scale includes multiple subscales with scores reflecting the levels of stress (e.g., discrimination, internalized transphobia) and resilience (e.g., community connectedness, pride). Higher stress subscale scores indicate greater experiences of minority stress, while higher resilience subscale scores reflect stronger protective factors.

Sex hormone are profiled on GAHT and in relation to the different outcome measures

Blood pressure is taken (by unattended automated office blood pressure measurement =UAOBPM)

Body weight is measured and body mass index (BMI) calculated.

Dietary quality is assessed via Dietary Approaches to Stop Hypertension (DASH) scoring on a scale from 1-100, with higher score indicating healthier dietary habits.

Dietary quality is assessed via Mediterranean Eating Pattern (MEPA) scoring on a scale from 1-100, with higher score indicating healthier dietary habits.

Glucose homesostasis is assessed by measuring blood glucose, HOMA-Index, HbA1C.

hsCRP concentration measured in venous blood as part of routine laboratory assessment and reported as a continuous variable

Inflammatory markers are assessed including IL-6

National Health and Nutrition Examination Survey (NHANES) questionnaires assesses smoking, alcohol, physical activity.

Pittsburgh Sleep Quality Index (PSQI) which ranges from 0 to 21. Higher scores indicate poorer sleep quality, with a score greater than 5 suggesting significant sleep difficulties.

Insomnia Severity Index (ISI) is a self-assessment questionnaire ranging from 0-28, while higher score worse sleep quality

Cortisol concentration measured in a proximal 3-cm scalp hair segment collected from the posterior vertex region

Steroid profile measured in a 24-hour urine sample to capture integrated steroid excretion over 24 hours.

IL-6, TNF-α, IL-1β, IL-10 concentration measured in stored blood samples and reported as a continuous variable.

Assessment of antibody levels

The reported value will be the number and percentage of participants selecting each response category for prespecified fertility-related items, including fertility intentions, prior fertility preservation, interest in future fertility preservation, and fertility-related counseling needs, as assessed using a SPECTRA-specific self-assessment questionnaire. This study-specific questionnaire is not summarized as a total score.

The reported value will be the number and percentage of participants who report current tucking practices on the SPECTRA questionnaire.

Sexual Desire Inventory (SDI). The scores for the two dimensions of sexual desire are summed up separately. Dyadic sexual desire: Scores will range from 0 to 62; while there is no universally established cutoff score that applies across all populations, higher scores at around 50 and upward indicate hypersexuality in the dyadic dimension. Solitary sexual desire: Scores will range from 0 to 39; while there is no universally established cutoff score that applies across all populations, higher scores at around 31 and upward indicate hypersexuality in the solitary dimension.

The reported value will be the number and percentage of eligible participants in each predefined semen quality category at each assessment time point. Semen quality status will be derived from standard semen analysis parameters according to prespecified laboratory criteria and categorized as normal semen quality, impaired semen quality, severe impairment, azoospermia, or not classifiable due to insufficient sample quality or missing parameters.

Dermatology life quality index (DLQI) is calculated by adding the score of each question, resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired. A score higher than 10 indicates that the patient's life is being severely affected by their skin disease.

disease activity is assessed by Visual analogue scale (VAS)

Percentage of hairs with reduced caliber assessed using TrichoScan software in a circular 1-cm² scalp area.

For the detection of skin wrinkles Visia device will be used as standardized photography

Skin swabs from defined sites to perform 16S rRNA amplicon based sequencing of the cutaneous bacterial microbiome

In transmen, prosthesis outcome is assessed including complication rates, revision rates, survival rates, patient- and partner-related satisfaction rate e.g. with validated Questionnaire Quality of Life and Sexuality with Penile Prosthesis (QoLSPP)

The reported value will be the number and percentage of eligible participants in each predefined urethral complication category at each assessment time point, as assessed by clinical examination and medical record review. Categories will include no urethral complication, urethral stricture, urethral fistula, both urethral stricture and fistula, and other urethral complication. For participants with urethral stricture or fistula, the type of management will be recorded descriptively according to predefined categories, including conservative management, catheter-based management, endoscopic treatment, surgical repair, or other management.

Lower Urinary Tract Symptom Questionnaire is a self-assessment tool to grade lower urinary tract symptoms. It ranges from 0-35, while typically a score of 0-7 indicates mild symptoms, 8-19 moderate symptoms and 20-35 severe symptoms. Higher scores indicate more severe symptoms.

Alpha diversity, beta diversity, microbial richness and relative abundance diversity of the gut microbiome measured in stool samples and reported using a predefined diversity index.