madman
Super Moderator
Introduction
Treatment of male hypogonadism with testosterone (T), most profoundly with long-acting injections and pellets, has been shown to inhibit the hypogonadal-pituitary-gonadal (HPG) axis[4]. T injections result in a reduction in both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations to undetectable levels as quickly as 2 weeks following initiation of therapy[5]. The decrease in LH and FSH impairs critical components of spermatogenesis. In a phase 3 study of an oral testosterone undecanoate (TU) capsule (JATENZO®), complete suppression of LH and FSH concentrations was not observed in all men[6], although the impact on gonadotropin suppression by age was not studied.
Objectives
To determine the impact of oral TU administration on LH and FSH concentrations, stratified by age, in hypogonadal men after four months of treatment.
Methods
In the inTUne trial, 166 hypogonadal men (diagnosis by the Endocrine Society guideline criteria of two-morning serum T < 300 ng/dL and signs/symptoms of hypogonadism), age 18 – 65 y/o, were recruited into a 105 day, randomized, open-label, multicenter, dose-titration trial. Full methods have been previously published3. We conducted a post hoc analysis of the LH and FSH levels, stratified by age. The age groups were 18-40, 41-50, and > 50 y/o.
Results
At study completion, the mean serum equivalent T Cavg for the oral TU group was 489 ± 154.9 ng/dL. When stratified by age, there were 26, 36, and 104 men in the 18 – 40, 40 – 50, and > 50 y/o groups, respectively. Overall, the LH concentrations significantly suppressed ~75%; and the FSH concentrations significantly suppressed ~65% (See Table). While LH and FSH concentrations significantly suppressed for all age groups, the concentrations of FSH remained in the normal range, in all age groups. In contrast, the concentration of LH remained in the normal range only for the 18 – 40 y/o group (See table).
Conclusion
Oral TU caused reductions in gonadotropins in this cohort of hypogonadal men, but gonadotropin concentrations remained within normal limits in younger men. Although the impact of these findings on spermatogenesis and fertility needs additional evaluation, these results suggest that oral TU does not have as significant of a suppressive impact on the HPG axis as some other forms of T replacement, which could potentially result in a reduced suppression of spermatogenesis in men 18-40 yrs.
Table: Changes in gonadotropin concentrations, stratified by age
* Denotes p < 0.001 when compared to the baseline (BL) levels.
Normal ranges for LH = 1.3 – 8.1 mIU/mL and FSH = 1.4 – 9.5 mIU/mL
Treatment of male hypogonadism with testosterone (T), most profoundly with long-acting injections and pellets, has been shown to inhibit the hypogonadal-pituitary-gonadal (HPG) axis[4]. T injections result in a reduction in both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations to undetectable levels as quickly as 2 weeks following initiation of therapy[5]. The decrease in LH and FSH impairs critical components of spermatogenesis. In a phase 3 study of an oral testosterone undecanoate (TU) capsule (JATENZO®), complete suppression of LH and FSH concentrations was not observed in all men[6], although the impact on gonadotropin suppression by age was not studied.
Objectives
To determine the impact of oral TU administration on LH and FSH concentrations, stratified by age, in hypogonadal men after four months of treatment.
Methods
In the inTUne trial, 166 hypogonadal men (diagnosis by the Endocrine Society guideline criteria of two-morning serum T < 300 ng/dL and signs/symptoms of hypogonadism), age 18 – 65 y/o, were recruited into a 105 day, randomized, open-label, multicenter, dose-titration trial. Full methods have been previously published3. We conducted a post hoc analysis of the LH and FSH levels, stratified by age. The age groups were 18-40, 41-50, and > 50 y/o.
Results
At study completion, the mean serum equivalent T Cavg for the oral TU group was 489 ± 154.9 ng/dL. When stratified by age, there were 26, 36, and 104 men in the 18 – 40, 40 – 50, and > 50 y/o groups, respectively. Overall, the LH concentrations significantly suppressed ~75%; and the FSH concentrations significantly suppressed ~65% (See Table). While LH and FSH concentrations significantly suppressed for all age groups, the concentrations of FSH remained in the normal range, in all age groups. In contrast, the concentration of LH remained in the normal range only for the 18 – 40 y/o group (See table).
Conclusion
Oral TU caused reductions in gonadotropins in this cohort of hypogonadal men, but gonadotropin concentrations remained within normal limits in younger men. Although the impact of these findings on spermatogenesis and fertility needs additional evaluation, these results suggest that oral TU does not have as significant of a suppressive impact on the HPG axis as some other forms of T replacement, which could potentially result in a reduced suppression of spermatogenesis in men 18-40 yrs.
Table: Changes in gonadotropin concentrations, stratified by age
18 – 40 y/o (n = 26) | 40 – 50 y/o (n = 36) | >50 y/o (n = 103) | Overall (N = 165) | ||||||
BL | 4 Mo | BL | 4 Mo | BL | 4 Mo | BL | 4 Mo | ||
Total T (ng/dL ± SD) | 240.5 ± 118.1 | 444.7 ± 138.0* | 242.7 ± 82.3 | 474.9 ± 149.0* | 255.3 ± 97.4 | 492.7 ± 154.9* | 251.3 ± 80.7 | 489.0 ± 154.9* | |
LH (mIU/mL ± SD) | 4.58 ± 6.4 | 1.76 ± 3.7* | 3.45 ± 2.5 | 1.03 ± 2.2* | 4.21 ± 3.6 | 0.87 ± 2.1* | 4.10 ± 4.0 | 1.05 ± 2.4* | |
FSH (mIU/mL ± SD) | 5.66 ± 9.6 | 2.63 ± 6.2* | 4.09 ± 4.5 | 1.68 ± 4.9* | 5.72 ± 7.1 | 1.70 ± 5.7* | 5.35 ± 7.1 | 1.84 ± 5.6* | |
* Denotes p < 0.001 when compared to the baseline (BL) levels.
Normal ranges for LH = 1.3 – 8.1 mIU/mL and FSH = 1.4 – 9.5 mIU/mL
