(073) The Effects of Intranasal Testosterone (Natesto™) for Treatment of Hypogonadism on Maintenance of Spermatogenesis: Demographic Data from a Single-Institution, Prospective, Non-blinded Study
Authors: Campbell K , Potts S , Hernandez A , Bacchus M , Lipshultz L 
Published: May 2023

Abstract

Introduction
Testosterone therapy (TTh) is becoming increasingly common among men of reproductive age in the United States. An estimated 3 million men are on TTh; however, exogenous testosterone use can disrupt the hypothalamic-pituitary-gonadal axis, leading to reduced spermatogenesis and infertility. The spontaneous recovery of spermatogenesis after cessation of TTh is possible, but may take months to years and can lead the patient to experience hypogonadal symptoms. Recent preliminary results have suggested that a 4.5% intranasal testosterone gel (Natesto™) may offer the potential to offset these symptoms and re-establish eugonadal levels of circulating testosterone. It has also been shown that men on Natesto™ maintain follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels and total motile sperm count within the normal range. This prospective, non-blinded study seeks to confirm the role of Natesto™ to alleviate hypogonadal symptoms in men on gonadotropin therapy for restoration of spermatogenesis.

Objective
To determine if Natesto™ can alleviate hypogonadal symptoms while preserving the recovery of spermatogenesis. The primary objective of this study is to examine changes in total motile sperm count at baseline, 14 weeks, and 26 weeks. Secondary outcomes include changes in LH, FSH, testosterone, estrogen, and quality of life measurements at these time intervals.

Methods
IRB approval was obtained for this study. Male patients between 18 and 64 years of age with a diagnosis of testosterone-induced hypo-spermatogenesis were recruited from a tertiary referral male infertility clinic between December 2021 and June 2022. Patients ceased intramuscular testosterone therapy and initiated gonadotropin therapy with FSH 75IU and hCG 3000IU every other day as well as 4.5% testosterone gel (Natesto™) three times daily. Patients were evaluated at baseline, 14 weeks, and 26 weeks. Clinic visits consisted of a hormone profile with total testosterone, estradiol, FSH, LH, questionnaires (IIEF, SF36, and ADAM) as well as a semen analysis.

Results
A total of 9 patients who met inclusion criteria were identified and elected to take part in the study. Four of the patients obtained baseline intake questionnaires, bloodwork, and a semen analysis with at least 1 additional follow-up visit. Five patients are pending initial follow-up. Patient intake demographic data included a median age of 35, LH of 3.15, FSH of 3.2, testosterone 260ng/dl, IIEF 20, SF-36 energy/fatigue score of 42.5%, and ADAM of 5.5. Four patients had complete gonadotropin suppression, and 6 were azoospermic. Interval semen analyses revealed total motile sperm count increases from 17.9 to 25 million and 9.7 to 10.9 million, with 2 patients demonstrating persistent azoospermia. Mean testosterone increased by 297.5ng/dl. No patients reported adverse events.

Conclusions
Preliminary results are limited and suggest that men undergoing cessation of testosterone therapy for restoration of spermatogenesis have decreased sexual and overall function scores. Continuation of this study, with recruitment of a larger sample size, will provide important, novel data regarding the effect of Natesto™ therapy on the hypogonadal symptoms seen in men during TTh cessation for spermatogenesis restoration.

Disclosure
Any of the authors act as a consultant, employee or shareholder of an industry for: Endo Pharmaceuticals