Fractionated (twice-daily) testosterone gel administration was associated with a higher proportion of patients achieving biochemical targets and a reduced peak-to-pre-dose difference within the observed sampling window, without short-term biochemical safety signals.
Fractionated twice-daily testosterone gel dosing produced lower peak serum total testosterone levels compared to once-daily dosing at the same total daily dose.
Fractionated twice-daily testosterone gel dosing produced higher nadir (pre-dose) serum total testosterone levels compared to once-daily dosing.
Fractionated dosing resulted in a reduced peak-to-pre-dose difference within the observed sampling window compared to once-daily dosing.
The proportion of patients achieving target total testosterone levels at peak increased substantially with fractionated dosing.
Calculated free testosterone showed a similar pattern to total testosterone with fractionated dosing.
No clinically relevant differences were observed in biochemical safety parameters between the two dosing regimens.
The study population was small and retrospective, limiting the generalizability of findings.
This research suggests that splitting a daily testosterone gel dose into two smaller applications (one in the morning and one later in the day) rather than applying it all at once may lead to more stable hormone levels throughout the day. In a small group of 12 men with low testosterone (hypogonadism) who switched from once-daily to twice-daily application of the same total dose of 2% testosterone gel, the twice-daily approach produced lower hormone spikes shortly after application and higher hormone levels just before the next dose was due. This means the gap between the highest and lowest testosterone readings during the day was smaller, suggesting a more even hormonal profile. A particularly notable finding was that far more patients reached their target testosterone levels when using the split dosing: 83% achieved the target compared to only 33% with once-daily dosing. Importantly, safety markers including prostate-specific antigen, red blood cell levels, and other hormone measures did not show any concerning changes with the fractionated approach, at least in the short term. This research suggests that splitting the testosterone gel dose could be a practical option for men whose hormone levels fluctuate too widely with standard once-daily treatment, potentially improving both effectiveness and tolerability. However, the authors themselves emphasize that the findings are preliminary and hypothesis-generating due to the very small sample size (12 patients) and retrospective study design. Larger, prospective studies would be needed to confirm these findings before any changes to clinical practice could be recommended.
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Upload Your LabsMaltese V, Delbarba A, Gatta E, Vetrugno S, Sansone A, Cappelli C. (2026). Fractionated testosterone gel replacement therapy in clinical practice: A real-world exploratory clinical experience.. Endocrine. https://doi.org/10.1007/s12020-026-04659-8