SUN-220 The Effect of Testosterone Nasal Gel on Reproductive Hormones and Semen Parameters

PURPOSE: To evaluate the effects of testosterone nasal gel on reproductive hormones and semen parameters after 3 and 6 months of therapy. HYPOTHESIS: Exogenous testosterone use leads to negative feedback on the hypothalamic-pituitary-gonadal (HPG) axis and inhibits male fertility. Because testosterone nasal gel is short-acting and more closely mimics normal physiology, we hypothesized that it will have less inhibitory effect on the HPG axis and allow for maintained spermatogenesis. MATERIALS AND METHODS: We prospectively enrolled men aged 18-55 with at least two T levels < 350 ng/dL (drawn before 10 AM) and two semen analyses (SA) with total motile sperm count (TMSC) > 5 million. Eligible men were treated with testosterone nasal gel three times daily for a period of 6 months. T, LH, FSH, semen analysis (X 2), International Index of Erectile Function (IIEF), and Short Form Health Survey (SF-36) were collected at baseline and after 3 and 6 months of therapy. A single testosterone level was collected after 1 month. Hormone levels were drawn with 2 hours after administering nasal testosterone. Data are presented as median (interquartile range); medians were compared using the Mann-Whitney test, significance was set at p<0.05. RESULTS: We have enrolled 36 men. Mean age is 36.8 years. A total of 25 men have completed 1 month of therapy, 12 have completed 3 months, and 7 have completed 6 months. T increased significantly from baseline 238.5 (197.5-282.0) ng/dl to 554 (359.5-778.0) ng/dl at 1 month, 509.8 (318.3-919.1) ng/dl at 3 months and 629.0 (447.4-784.2) ng/dl at 6 months (p<0.05 at 1,3 and 6 months). LH declined from a baseline of 4.3 (2.2-4.5) IU/ml to 2.0 (1.1-3.6) IU/ml at 3 months and 1.9 (0.6-3.1) IU/ml at 6 months (p<0.5 at 3 and 6 months). FSH declined from a baseline of 3.2 (2.3-5.8) IU/ml to 2.7 (1.1-3.6) IU/ml at 3 months and 2.1 (1.3-7.4) IU/ml at 6 months. This decline was not statistically significant at 6 months (p=0.16). Median FSH levels remained within normal lab range (1.5-12.4 IU/ml). Median TMSC remained statistically unchanged, 29.0 (14.5-41.0) million at baseline, 31.5 (13.8-62) million at 3 months and 26.0 (3.75-51.8) million at 6 months. No men became azoospermic while on nasal testosterone. IIEF and SF-36 remained statistically unchanged. CONCLUSION: This is an interim analysis of a phase IV clinical trial. Nasal gel testosterone increased serum T levels while maintaining FSH levels within normal range and, importantly, maintained semen parameters. Nasal gel testosterone has the potential to be paradigm-shifting in our approach to develop a safe and effective treatment for men with low T who wish to restore normal serum T levels while preserving fertility.