Testosterone Replacement Therapy in Women Is Associated with Improved Symptom Burden and Favorable Biomarker Changes: A Retrospective Observational Study

Background: Testosterone is the most abundant biologically active sex steroid in women, yet the therapeutic implications of its age-related decline remain undercharacterized. Published trials have focused predominantly on sexual function, leaving gaps in understanding how testosterone replacement therapy (TRT) affects broader symptom domains and metabolic biomarkers in women. Objective: To investigate whether individualized, biomarker-guided TRT in women is associated with improvements across multiple symptom domains and favorable hormonal, hematologic, and cardiometabolic biomarker changes, and to examine whether symptomatic benefit varies with treatment duration. Methods: In this retrospective observational study, women (n = 332; ages 27 to 78; mean 45.7 ± 7.1 years) receiving TRT as part of routine clinical care through a telehealth-based platform completed a structured survey at a single post-treatment time point assessing eight symptom domains: energy/fatigue, memory, concentration, irritability, depression, anhedonia, sexual interest, and relationship satisfaction. Respondents were stratified by TRT duration (1 month to >12 months) and a subset (n = 120) underwent paired biomarker assessment at baseline and 12 weeks for total testosterone, free testosterone, SHBG, hemoglobin, and triglycerides. Results: Improvement was reported across all eight domains, with energy/fatigue showing the strongest response (84.3% improved). Depression, irritability, anhedonia, and sexual interest each exceeded 65% improvement. Cognitive domains showed a delayed trajectory, with meaningful gains emerging at 4 to 6 months. Quality of life improvement was reported by 89.7%, with significant improvement rising from 5.4% at 1 month to 51.5% at greater than 12 months. Energy/fatigue (64.2%) and mood (49.7%) ranked above sexual desire (41.3%) as self-identified areas of greatest benefit. All five biomarkers changed favorably: total testosterone +151.8% (d = 3.60), free testosterone +216.7% (d = 3.01), hemoglobin +5.5% (d = 2.03), SHBG −13.3% (d = 1.57), and triglycerides −12.6% (d = 1.28). Conclusions: Individualized TRT in women was associated with broad symptomatic improvement spanning energy/fatigue, depression, irritability, anhedonia, cognitive function, and sexual interest, with duration-dependent gains and favorable biomarker changes across all five markers assessed. These findings suggest that the value of testosterone in women extends beyond sexual function and supports the need for larger controlled trials with extended follow-up.