madman
Super Moderator
Abstract
Testosterone replacement therapies have been shown to increase blood pressure (BP) in hypogonadal men. We studied the effects of a new formulation of testosterone undecanoate (Kyzatrex™) on ambulatory blood pressure (ABP) and heart rate, in 155 men with hypogonadism (mean age, 50.5 years, 76.8% white, 36.1% on antihypertensive therapy). The ABP, heart rate, and clinical assessments were obtained at baseline and following 120 and 180 days of therapy. Mean changes from baseline in 24-h ambulatory systolic BP of 1.7 mmHg (95% CI, 0.3, 3.1) at day 120 and 1.8 mmHg (95% CI, 0.3, 3.2) at day 180 were observed post-treatment. For those men on antihypertensive drug therapy, increases in mean 24-h systolic BP were greater than those not taking antihypertensive drugs (3.4 vs 0.7 mmHg at day 120, and 3.1 vs 1.0 mmHg at day 180, respectively). Changes from baseline in 24-h diastolic BP and heart rate at day 120 were smaller (<1 mmHg and <1 beat/min, respectively). There were no relationships observed between testosterone concentration or hemoglobin levels with ABP. Multivariable analyses showed that baseline ambulatory BP and antihypertensive therapy were significantly correlated with BP changes. These data demonstrate small increases in ambulatory BP following 120 days on this oral testosterone undecanoate with no further changes at 180 days. Changes in ambulatory BP were minimal in patients not taking antihypertensive therapy.
1 | INTRODUCTION
Testosterone replacement therapy for male hypogonadism or androgen deficiency has been administered by intramuscular and subcutaneous injections, transdermal gels and lotions, dermal patches, intranasal gels, and oral delivery.1 Testosterone itself has limited oral bioavailability. Long-chain fatty acid esterification of testosterone to create testosterone undecanoate allows for absorption via the intestinal lymphatic system and bypasses the first-pass metabolism in the liver.2 Testosterone is then liberated from testosterone undecanoate by endogenous non-specific esterases. Oral formulations of testosterone undecanoate have been developed to provide average serum testosterone levels in the eugonadal range (typically 300–1000 ng/dl) and avoid peak concentrations above 1500 ng/dl. During recent studies with both injectable and oral testosterone formulations, increases in both clinic and ambulatory blood pressure (BP) have been observed3,4 but the mechanism of these increases has not been elucidated nor has there been clarity regarding clinical predictors associated with BP increases. In the present BP safety study, we evaluated a new oral testosterone undecanoate therapy using ambulatory BP monitoring performed at baseline and following 120 and 180 days of daily therapy along with standard clinical and laboratory safety parameters.
5 | CONCLUSIONS
In conclusion, this new oral formulation of testosterone undecanoate dosed between 100 mg once daily and 400 mg twice daily induced small increases in clinic and ambulatory BP. There were minimal increases in ambulatory heart rate that were not related to ambulatory BP changes. Study participants with a history of hypertension taking antihypertensive therapy and those with type 2 diabetes had larger increases in both ambulatory BP and heart rate following chronic oral testosterone undecanoate therapy than those without these 2 comorbidities. Hypogonadal men who were not receiving antihypertensive medication had negligible changes in ambulatory BP and heart rate.
Testosterone replacement therapies have been shown to increase blood pressure (BP) in hypogonadal men. We studied the effects of a new formulation of testosterone undecanoate (Kyzatrex™) on ambulatory blood pressure (ABP) and heart rate, in 155 men with hypogonadism (mean age, 50.5 years, 76.8% white, 36.1% on antihypertensive therapy). The ABP, heart rate, and clinical assessments were obtained at baseline and following 120 and 180 days of therapy. Mean changes from baseline in 24-h ambulatory systolic BP of 1.7 mmHg (95% CI, 0.3, 3.1) at day 120 and 1.8 mmHg (95% CI, 0.3, 3.2) at day 180 were observed post-treatment. For those men on antihypertensive drug therapy, increases in mean 24-h systolic BP were greater than those not taking antihypertensive drugs (3.4 vs 0.7 mmHg at day 120, and 3.1 vs 1.0 mmHg at day 180, respectively). Changes from baseline in 24-h diastolic BP and heart rate at day 120 were smaller (<1 mmHg and <1 beat/min, respectively). There were no relationships observed between testosterone concentration or hemoglobin levels with ABP. Multivariable analyses showed that baseline ambulatory BP and antihypertensive therapy were significantly correlated with BP changes. These data demonstrate small increases in ambulatory BP following 120 days on this oral testosterone undecanoate with no further changes at 180 days. Changes in ambulatory BP were minimal in patients not taking antihypertensive therapy.
1 | INTRODUCTION
Testosterone replacement therapy for male hypogonadism or androgen deficiency has been administered by intramuscular and subcutaneous injections, transdermal gels and lotions, dermal patches, intranasal gels, and oral delivery.1 Testosterone itself has limited oral bioavailability. Long-chain fatty acid esterification of testosterone to create testosterone undecanoate allows for absorption via the intestinal lymphatic system and bypasses the first-pass metabolism in the liver.2 Testosterone is then liberated from testosterone undecanoate by endogenous non-specific esterases. Oral formulations of testosterone undecanoate have been developed to provide average serum testosterone levels in the eugonadal range (typically 300–1000 ng/dl) and avoid peak concentrations above 1500 ng/dl. During recent studies with both injectable and oral testosterone formulations, increases in both clinic and ambulatory blood pressure (BP) have been observed3,4 but the mechanism of these increases has not been elucidated nor has there been clarity regarding clinical predictors associated with BP increases. In the present BP safety study, we evaluated a new oral testosterone undecanoate therapy using ambulatory BP monitoring performed at baseline and following 120 and 180 days of daily therapy along with standard clinical and laboratory safety parameters.
5 | CONCLUSIONS
In conclusion, this new oral formulation of testosterone undecanoate dosed between 100 mg once daily and 400 mg twice daily induced small increases in clinic and ambulatory BP. There were minimal increases in ambulatory heart rate that were not related to ambulatory BP changes. Study participants with a history of hypertension taking antihypertensive therapy and those with type 2 diabetes had larger increases in both ambulatory BP and heart rate following chronic oral testosterone undecanoate therapy than those without these 2 comorbidities. Hypogonadal men who were not receiving antihypertensive medication had negligible changes in ambulatory BP and heart rate.
