EP1410 - ECE_1202 - Individualized endocrine care in non-binary individuals: efficacy, safety, and long-term outcomes of microdosing and selective hormone modulators

Abstract Background Current gender-affirming hormone therapy (GAHT) guidelines are optimized for binary outcomes (full masculinization or feminization), leaving a critical evidence gap for the growing population of non-binary and gender-diverse (NBGD) individuals who seek partial physical changes. These non-traditional therapeutic goals often necessitate the off-label use of low-dose, intermittent GAHT (“microdosing”), or Selective Estrogen Receptor Modulators (SERMs). This study aimed to evaluate the efficacy, safety, and impact on long-term health markers in a cohort of NBGD individuals receiving individualized hormone protocols.

Methods: This retrospective cohort study analysed data from 180 NBGD adults over a median follow-up period of 3.5 years .The cohort was stratified into three groups:Group A(Microdosing MHT;N = 95;Natal Sex—Female;Low dose testosterone;25 mg/week);Group B(Microdosing FHT;N = 65;Natal Sex—Male;Low dose Estradiol;1 mg/day [oral]);Group C(SERM Protocol;N = 20;Natal Sex—Male;SERM ± GnRH Agonist; Raloxifene 60 mg/day).Primary Outcome: Change in patient-reported psychosocial outcomes (Gender Congruence Scale (GCS) and Quality of Life (QoL) scores).Secondary

Outcomes: Physical changes, Bone Mineral Density (BMD), lipid panels, and HbA1c.

Results: The mean age of the cohort was 31.2 ± 6.8 years.Baseline BMD T-scores were: Group A (LS T-score: −0.4 ± 0.9); Group B (LS T-score: −0.2 ± 1.0); Group C (LS T-score −0.5 ± 0.8). HbA1c and lipid profiles were comparable across groups and within the normal range.Both GCS and QoL scores demonstrated a statistically significant improvement across all groups from baseline to final follow-up (P < .001). Microdosing MHT(Group A) achieved initial voice deepening (75%) and facial hair growth (45%) in 88% of patients.Microdosing FHT (Group B) resulted in mild breast development (A-cup or small B-cup) in 70% of patients.The SERM Protocol (Group C) successfully achieved fat redistribution and skin softening with minimal/no palpable breast tissue in 95% of cases.Group A and C maintained stable BMD.Group B demonstrated a statistically significant, albeit small, decrease in Lumbar Spine BMD (−0.015 g/cm2, P = .045) in patients who maintained Estradiol levels below 100 pmol/L while achieving adequate Testosterone suppression.No major cardiovascular or thromboembolic events were recorded.

Conclusions: Microdosing and selective hormone modulator regimens represent a safe and effective strategy for achieving individualized, non-binary gender affirmation goals, resulting in significant improvements in GCS and QoL. While metabolic and cardiovascular profiles remained largely stable, the data highlights a risk of bone demineralization in a subset of Microdosing FHT patients, particularly those whose Estradiol levels are insufficient to provide skeletal protection.