Neither oral nor gel testosterones show significant effect on liver function test results.
New data from phase 3 clinical trials provide further evidence supporting the safety and effectiveness of the first-to-market oral testosterone undecanoate treatment for hypogonadism (Jatenzo), reported Stanton Honig, MD.
Honig presented results for secondary end points from 2 randomized studies comparing the lipoprotein-coated testosterone undecanoate formulation with topical testosterone treatments showing that both the oral and gel products were associated with statistically significant improvements in psychosocial well-being and bone and body composition parameters. Safety analyses showed the oral testosterone undecanoate was associated with a modest increase in blood pressure, which was slightly higher in men with hypertension at study entry than in men with normal blood pressure and that neither the oral nor gel testosterones had any significant effect on liver function test results.
“This novel formulation of testosterone undecanoate is a first-in-class oral testosterone replacement that does not have liver issues,” said Honig, professor of clinical urology and director, Men’s Health, Yale University School of Medicine, New Haven, Connecticut.
“Taken twice daily, it provides hypogonadal men with total testosterone concentrations in the mid-eugonadal range. Its safety profile is generally consistent with injectable and topical testosterone preparations, although the product labeling for oral testosterone undecanoate includes a black box warning about the potential for increased blood pressure. The data collected in the oral testosterone undecanoate studies underscore the need to check blood pressure at some point in men who are started on this therapy, especially those who are hypertensive at baseline.”
The 2 trials comprised a 4-month study and a 12-month investigation. Eligibility criteria were similar in the 2 trials. Men ages 18 to 65 years (to 75 years in the 12-month study) were included if they had hypogonadism (serum testosterone <300 ng/dL on 2 morning samples approximately 7 days apart), had signs and symptoms consistent with hypogonadism, and were either naive to or underwent washout from testosterone therapy.
The 4-month study randomized 222 men 3:1 to oral testosterone undecanoate 237 mg twice daily or once-daily topical testosterone solution. A total of 325 men were randomized 1:1 to oral testosterone undecanoate 200 mg twice daily or topical testosterone gel in the 12-month trial. Dose adjustments were allowed based on serum testosterone levels.
The 4 treatment groups were similar with respect to demographics and clinical characteristics in terms of baseline age, body mass index, comorbidities (prediabetes, diabetes, and hypertension), and mean baseline testosterone levels. Time-weighted average testosterone concentration increased to reach mid-eugonadal levels in all 4 treatment groups, with values ranging from 425 ng/dL to 524 ng/dL across all 4 study groups.
Data on psychosocial well-being were collected in both trials using the Psychosexual Daily Questionnaire. Results showed statistically significant improvements from baseline to study completion in mood, sexual desire, weekly sexual activity, and sexual energy with and without a partner with both the oral and topical treatments, Honig reported.
General well-being was evaluated in the 12-month study using the 36-Item Short Form Health Survey questionnaire. In the individual domains, statistically significant improvements were achieved in both the oral testosterone undecanoate and testosterone gel group and occurred in physical functioning, physical and emotional role limitation, social functioning, and bodily pain.
Changes in body composition parameters were also investigated in the 12-month study. The results for the oral testosterone undecanoate group showed spine bone mineral density, hip bone mineral density, lean body mass, and fat mass all improved significantly from baseline at 6 months with further improvements achieved at month 12.
Both the oral testosterone undecanoate and topical testosterone treatments were associated with minimal increases in serum prostate-specific antigen. Overall, the oral and topical treatments were associated with an increase of hematocrit in approximately 5% to 6% of patients.
“Importantly, there were no clinical events associated with the hematocrit increases in the oral testosterone undecanoate or the testosterone gel group, nor did any patient discontinue treatment because of elevated hematocrit,” Honig said.
Changes in blood pressure were followed using ambulatory monitoring. Among men treated with oral testosterone undecanoate, mean changes in 24-hour systolic and diastolic blood pressure were approximately 5 mm Hg and 2.5 mm Hg, respectively. Comparisons between men with and without hypertension at baseline showed that the average change was slightly higher in the hypertensive group.
Honig said, “It is unclear whether the blood pressure rise is just for oral testosterone undecanoate or a general class effect, as it has been seen with subcutaneous testosterone preparations as well. Most importantly, both oral testosterone undecanoate and topical gel groups showed no significant changes in liver enzyme measurements over a 12-month period.”
Disclosure: Honig is a consultant to Clarus Therapeutics and Endo.