madman
Super Moderator
Oral testosterone therapy: past, present, and future (2023)
Jake A. Miller, MD, Tuan T. Nguyen, MD, Charles Loeb, MD, Mohit Khera, MD, Faysal A. Yafi, MD
Abstract
Introduction: Testosterone replacement therapy (TRT) remains a commonly utilized treatment for men with testosterone deficiency (TD). Despite the recent FDA approval of new oral TRT medications, concerns remain regarding their efficacy and safety, and prescription rates for these medications have decreased compared to those for TD medications with other routes of administration.
Objective: In this study, we sought to investigate the efficacy and safety of oral testosterone undecanoate (oTU), a new oral TRT medication. Methods: A comprehensive review of the literature was performed using the Medline, EMBASE, and Cochrane Library databases; 1269 articles were identified, with 44 articles included in the final review and 12 used to perform meta-analyses to investigate the change in serum total testosterone (TT) and risk of adverse effects following oral testosterone undecanoate (oTU) use. Articles were also reviewed to investigate the reported effects of oTU on body composition, liver function, hematologic assays, lipid profiles, hormone assays, prostate growth, hypertension, and symptoms of TD.
Results: Across placebo-controlled randomized trials, there was no significant increase in TT for those receiving oTU vs placebo (mean difference, −0.26 [95% CI, −1.26 to 0.73]). On subanalysis, when eugonadal participants received oTU, a significant decrease in TT was demonstrated (mean difference −0.86 [95% CI, −1.28 to 0.43]). When participants who were hypogonadal at baseline received oTU, a significant increase in TT compared to placebo was seen (mean difference 1.25 [95% CI, 0.22-2.29]). There was no significant risk of adverse effects (RR, −0.03 [95% CI, −0.08 to 0.03]) or serious adverse effects (RR, 0.15 [95% CI, −0.66 to 0.96]) in the oTU groups compared to placebo.
Conclusion: oTU was found to be well tolerated in hypogonadal patients, resulting in improved testosterone levels, height velocity, and sexual symptoms, without significant hepatotoxicity, prostatic enlargement, or worsening hypertension. There was no consensus regarding the effect of oTU on lean and fat mass percentages, hematologic assays, lipid profiles, mood, and general well-being.
Introduction
Testosterone replacement therapy (TRT) remains a commonly used treatment option for men with testosterone deficiency (TD), with additional trials investigating the use of TRT in boys with congenital delay of growth and puberty (CDGP). Treatment with TRT has been associated with improvements in libido, erectile function, body composition, and mood, with possible improvements described for insulin sensitivity, cognition, and overall quality of life.1-7 The popularity of TRT has grown, with rapidly increasing prescription rates noted within recent decades8,9 and ongoing clinical trials featuring varying formulations of TRT. Recent literature suggests that injectable and topical formulations have become more commonplace within the United States, United Kingdom, and Canada, while prescription rates for oral formulations have steadily declined.8-10 However, given recent trends in the fields of oncology, endocrinology, and rheumatology demonstrating that patients prefer oral therapies over other regimens,11-13 the decreasing prescription rate of oral TRT raises questions. To further investigate the safety and efficacy of oral TRT, a literature review was performed to examine the history of oral TRT, its current place within urology and endocrinology guidelines, and recent trials featuring oral TRT.
*History of oral testosterone
*Oral testosterone within current guidelines
Conclusion
To the authors’ knowledge, this is the first systematic review and meta-analysis to include a sufficiently large number of trials comparing oral TRT to placebo to allow for a meta-analysis to be performed and for a discussion of the efficacy and safety of oral TRT to be conducted. The above results suggest that oTU is a well-tolerated option for TD that results in improved TT levels, height velocity, and sexual symptoms in hypogonadal patients, without leading to significant hepatotoxicity, prostatic changes, or worsening hypertension. Despite these findings, the impact of oTU on lean and fat body mass, hematologic assays, and lipid profiles remains unclear. As well, the use of oTU to improve general well-being and mood is yet to be described consistently.
Given the results reported here, the current depiction of oral TRT within guidelines on the management of TD may not accurately represent the current literature. As newer oral agents are formulated and tested, additional trials on the use of oral TRT should be performed and a further discussion on the place of oral TRT in treating varying conditions may be merited.
Jake A. Miller, MD, Tuan T. Nguyen, MD, Charles Loeb, MD, Mohit Khera, MD, Faysal A. Yafi, MD
Abstract
Introduction: Testosterone replacement therapy (TRT) remains a commonly utilized treatment for men with testosterone deficiency (TD). Despite the recent FDA approval of new oral TRT medications, concerns remain regarding their efficacy and safety, and prescription rates for these medications have decreased compared to those for TD medications with other routes of administration.
Objective: In this study, we sought to investigate the efficacy and safety of oral testosterone undecanoate (oTU), a new oral TRT medication. Methods: A comprehensive review of the literature was performed using the Medline, EMBASE, and Cochrane Library databases; 1269 articles were identified, with 44 articles included in the final review and 12 used to perform meta-analyses to investigate the change in serum total testosterone (TT) and risk of adverse effects following oral testosterone undecanoate (oTU) use. Articles were also reviewed to investigate the reported effects of oTU on body composition, liver function, hematologic assays, lipid profiles, hormone assays, prostate growth, hypertension, and symptoms of TD.
Results: Across placebo-controlled randomized trials, there was no significant increase in TT for those receiving oTU vs placebo (mean difference, −0.26 [95% CI, −1.26 to 0.73]). On subanalysis, when eugonadal participants received oTU, a significant decrease in TT was demonstrated (mean difference −0.86 [95% CI, −1.28 to 0.43]). When participants who were hypogonadal at baseline received oTU, a significant increase in TT compared to placebo was seen (mean difference 1.25 [95% CI, 0.22-2.29]). There was no significant risk of adverse effects (RR, −0.03 [95% CI, −0.08 to 0.03]) or serious adverse effects (RR, 0.15 [95% CI, −0.66 to 0.96]) in the oTU groups compared to placebo.
Conclusion: oTU was found to be well tolerated in hypogonadal patients, resulting in improved testosterone levels, height velocity, and sexual symptoms, without significant hepatotoxicity, prostatic enlargement, or worsening hypertension. There was no consensus regarding the effect of oTU on lean and fat mass percentages, hematologic assays, lipid profiles, mood, and general well-being.
Introduction
Testosterone replacement therapy (TRT) remains a commonly used treatment option for men with testosterone deficiency (TD), with additional trials investigating the use of TRT in boys with congenital delay of growth and puberty (CDGP). Treatment with TRT has been associated with improvements in libido, erectile function, body composition, and mood, with possible improvements described for insulin sensitivity, cognition, and overall quality of life.1-7 The popularity of TRT has grown, with rapidly increasing prescription rates noted within recent decades8,9 and ongoing clinical trials featuring varying formulations of TRT. Recent literature suggests that injectable and topical formulations have become more commonplace within the United States, United Kingdom, and Canada, while prescription rates for oral formulations have steadily declined.8-10 However, given recent trends in the fields of oncology, endocrinology, and rheumatology demonstrating that patients prefer oral therapies over other regimens,11-13 the decreasing prescription rate of oral TRT raises questions. To further investigate the safety and efficacy of oral TRT, a literature review was performed to examine the history of oral TRT, its current place within urology and endocrinology guidelines, and recent trials featuring oral TRT.
*History of oral testosterone
*Oral testosterone within current guidelines
Conclusion
To the authors’ knowledge, this is the first systematic review and meta-analysis to include a sufficiently large number of trials comparing oral TRT to placebo to allow for a meta-analysis to be performed and for a discussion of the efficacy and safety of oral TRT to be conducted. The above results suggest that oTU is a well-tolerated option for TD that results in improved TT levels, height velocity, and sexual symptoms in hypogonadal patients, without leading to significant hepatotoxicity, prostatic changes, or worsening hypertension. Despite these findings, the impact of oTU on lean and fat body mass, hematologic assays, and lipid profiles remains unclear. As well, the use of oTU to improve general well-being and mood is yet to be described consistently.
Given the results reported here, the current depiction of oral TRT within guidelines on the management of TD may not accurately represent the current literature. As newer oral agents are formulated and tested, additional trials on the use of oral TRT should be performed and a further discussion on the place of oral TRT in treating varying conditions may be merited.
