ORF09-01 - Trajectories of Health-Related Outcomes after Testosterone Discontinuation in Men with HIV and without HIV

Background: The long-term safety and efficacy of testosterone replacement therapy (TRT) in older men remain uncertain and some men choose to discontinue treatment. However, TRT cessation may lead to recurrent hypogonadal symptoms and adverse physical and mental health outcomes. This clinical dilemma is particularly relevant for older men with HIV, a population with a high prevalence of TRT use and lower rates of discontinuation. We examined trajectories of health-related outcomes after TRT discontinuation among men with HIV and at risk for HIV.

Methods: We identified men from the Multicenter AIDS Cohort Study who reported discontinuing TRT at any semi-annual visit between 2013 and 2022. We used linear mixed-effects models to evaluate longitudinal changes in hematocrit (HCT), grip strength, walking speed, weight, waist circumference, insulin resistance (HOMA-IR), and quality of life (QOL) before and after TRT discontinuation. Outcomes were analyzed within ±3 years of the TRT discontinuation visit with time modeled continuously and adjusted for age, race, BMI (except for the weight and waist circumference models), and HIV serostatus.

Results: Among the 126 men who discontinued TRT, the median age was 60 years (range: 40–81); 91 participants (72%) were White, and 93 (74%) were living with HIV at the TRT discontinuation visit. The median body mass index was 26.8 kg/m² (range: 18.2–50.9). In adjusted models, mean HCT at the last pre-discontinuation visit was 41.8% and declined significantly by the discontinuation visit (estimate −0.80%, p = 0.01). While there was no change in weight or waist circumference, HOMA-IR tended to increase faster after discontinuation, compared to before discontinuation (p=0.09). There were no observed changes in grip strength, walk speed, mental QOL, physical QOL or fatigue after TRT discontinuation.

Conclusion: Among older men with and without HIV, TRT discontinuation was associated with a modest decline in hematocrit and a trend towards increasing insulin resistance. Physical function, body composition, and quality of life remained stable after TRT discontinuation. These findings suggest that TRT discontinuation in older men may not precipitate a clinically significant decline in health outcomes. Longer follow-up is needed to determine whether metabolic changes, including insulin resistance, emerge over time and to better inform clinical decision-making regarding TRT discontinuation.