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Early biopsychological changes during masculinizing gender-affirming hormone therapy in AFAB transgender individuals: a 4-month prospective study

AI Summary
  • Masculinizing GAHT produced expected endocrine changes within four months: decreased estradiol and increased testosterone in AFAB transgender participants.
  • Significant longitudinal reductions in anxiety and trauma symptoms and improvements in quality of life were observed over the 4-month follow up (p < 0.05).
  • Psychological gains were not solely proportional to hormonal magnitude; associations strengthened by month four, implying psychosocial and treatment factors and need for larger longitudinal studies.
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Front Psychiatry. 2026 Jun 17;17:1847778. doi: 10.3389/fpsyt.2026.1847778. eCollection 2026.

ABSTRACT

OBJECTIVE: Transgender individuals frequently experience elevated levels of psychological distress, including anxiety and trauma-related symptoms. Gender-affirming hormone therapy (GAHT) has been associated with improvements in mental health and quality of life; however, early biopsychological changes occurring during the initial phase of masculinizing hormone therapy remain insufficiently understood. The present exploratory longitudinal study investigated early endocrine and psychological changes in transgender individuals assigned female at birth undergoing masculinizing GAHT.

METHODS: We conducted a 4-month prospective observational study involving 30 transgender individuals assigned female at birth initiating masculinizing GAHT. Participants were assessed at baseline (prior to treatment initiation), after 2 months, and after 4 months of therapy. Hormonal parameters (estradiol, testosterone, prolactin) and psychological measures including anxiety (HAM-A), trauma-related symptoms (TSC-40), and quality of life (MANSA) were evaluated. Due to the exploratory character of the study and the relatively small sample size, analyses were performed primarily using non-parametric statistical methods, including repeated-measures analyses.

RESULTS: During follow-up, expected endocrine changes were observed, including decreased estradiol levels and increased testosterone concentrations. These changes were accompanied by reductions in anxiety and trauma-related symptoms and by improvements in quality of life measures over time. Repeated-measures analyses demonstrated significant longitudinal improvements in psychological outcomes across follow-up assessments (p < 0.05). Exploratory associations between hormonal and psychological variables appeared more pronounced after 4 months of treatment, particularly for estradiol in relation to anxiety and quality of life. Earlier assessments demonstrated weaker and less consistent associations. Psychological improvements were not directly proportional to the magnitude of hormonal changes alone, suggesting that psychosocial and treatment-related factors may also contribute to early adaptation during GAHT.

CONCLUSION: Early masculinizing GAHT in transgender individuals assigned female at birth was associated with favorable endocrine and psychological changes during the first 4 months of treatment. The findings support a complex and potentially time-dependent relationship between hormonal alterations and psychological adaptation during early transition. Given the exploratory nature and limited sample size of the present study, further longitudinal research with larger cohorts and comparison groups is needed to clarify the underlying biopsychological mechanisms of GAHT.

PMID:42389397 | PMC:PMC13319074 | DOI:10.3389/fpsyt.2026.1847778

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