Oral testosterone therapy: past, present, and future.

Across all placebo-controlled randomized trials, there was no significant increase in serum total testosterone for those receiving oral testosterone undecanoate versus placebo.

• Meta-analysis included 12 articles from a pool of 1269 identified and 44 included in the final review
• Mean difference in total testosterone was -0.26 (95% CI, -1.26 to 0.73)
• Databases searched included Medline, EMBASE, and Cochrane Library
• The result was not statistically significant as the confidence interval crossed zero

When eugonadal participants received oral testosterone undecanoate, a significant decrease in total testosterone was demonstrated compared to placebo.

• This was found on subanalysis of placebo-controlled randomized trials
• Mean difference was -0.86 (95% CI, -1.28 to 0.43)
• The confidence interval did not cross zero, indicating statistical significance
• This suggests a suppressive effect on endogenous testosterone production in eugonadal men

When participants who were hypogonadal at baseline received oral testosterone undecanoate, a significant increase in total testosterone compared to placebo was observed.

• Mean difference was 1.25 (95% CI, 0.22-2.29)
• The confidence interval did not include zero, indicating statistical significance
• This subanalysis contrasted with the overall non-significant finding across all participants
• This finding supports the use of oTU specifically in hypogonadal patients

Oral testosterone undecanoate was not associated with a significant risk of adverse effects or serious adverse effects compared to placebo.

• Risk ratio for adverse effects: -0.03 (95% CI, -0.08 to 0.03)
• Risk ratio for serious adverse effects: 0.15 (95% CI, -0.66 to 0.96)
• Both confidence intervals crossed zero, indicating no statistically significant difference from placebo
• oTU was described as 'well tolerated in hypogonadal patients'

Oral testosterone undecanoate did not produce significant hepatotoxicity, prostatic enlargement, or worsening hypertension in hypogonadal patients.

• These findings were based on review of articles reporting effects on liver function, prostate growth, and hypertension
• The absence of hepatotoxicity is notable given historical concerns with oral androgen formulations
• Articles reviewed also investigated body composition, hematologic assays, lipid profiles, hormone assays, and symptoms of testosterone deficiency

There was no consensus in the literature regarding the effect of oral testosterone undecanoate on lean and fat mass percentages, hematologic assays, lipid profiles, mood, and general well-being.

• These outcomes were reviewed across included articles but yielded inconsistent findings
• Body composition outcomes including lean and fat mass percentages were among the contested findings
• Mood and general well-being also lacked consensus across studies
• Hematologic assays and lipid profiles showed variable results across the reviewed literature

Prescription rates for oral testosterone replacement therapy medications have decreased compared to those for testosterone deficiency medications with other routes of administration, despite recent FDA approval.

• This trend was noted in the context of concerns about efficacy and safety of oral TRT
• The paper notes that new oral TRT medications have received recent FDA approval
• The decrease in prescriptions is presented as a motivation for the review
• Other routes of administration appear to be preferred over oral formulations in clinical practice

Oral testosterone undecanoate improved height velocity and sexual symptoms in hypogonadal patients.

• Improvement in height velocity suggests utility in adolescent or growth-related hypogonadal populations
• Sexual symptoms were among the outcomes reviewed across included articles
• These benefits were noted alongside the favorable safety profile in hypogonadal patients
• The review included 44 articles in the final review across multiple outcome categories