Nasal Testosterone Gel Shown to Normalize Androgen Levels, Improve Erectile Function & Mood in Hypogonadal Men

Two research reports from the 2017 American Urological Association’s annual meeting, May 12-16 in Boston, demonstrated that treatment with the novel 4.5% nasal testosterone gel, (marketed as NatestoR), restored total serum testosterone to normal levels while preserving normal concentrations of pituitary gonadotropins in men with hypogonadism1, and led to clinical improvements in both erectile function and mood. 2 

In an open-label, dose-ranging study, reported by William Conners, MD, from Harvard Medical School and Men’s Health Boston, hypogonadal subjects were randomized to self-administer NatestoR either twice daily (BID) (n=122) or 3 times daily (TID) (n=151), for a total daily dose of 22.0 mg or 33.0 mg, respectively, over 90 days. Titration was based on men’s blood levels, aiming to achieve the eugonadal range of 300-1050 ng/dL. Serum samples were obtained from subjects at baseline and after 90 days. 1

The treatment resulted in an increase in total serum testosterone from a mean Cavg 200.8 ng/dL at baseline to a mean Cmax 818.49 ng/dL at about 40 minutes. 

After 90 days, 90% of men in the TID group, and 71% of men in the BID group reached normal testosterone levels, and a mean total testosterone Cavg 421 ng/dL and 375 ng/dL, respectively.1

Baseline follicle-stimulating hormone (FSH) in the BID group was 8.49 IU/L: the mean at day 90 FSH was 5.99 IU/L. Baseline FSH in the TID daily group was 6.42 IU/L. The mean at day 90 was 3.12 IU/L. Baseline luteinizing hormone (LH) in the BID group was 5.42 IU/L. The mean at day 90 was 3.56 IL/L. The baseline TID group was 5.25 IU/L. The mean at day 90 was 2.20 IU/L. 1

The authors concluded that treatment with the 4.5% nasal testosterone gel, NatestoR, restored serum total testosterone to normal levels. Although FSH and LH levels were reduced, they noted that mean levels remained well within the normal range, in a finding that contrasts with other therapies for hypogonadism, injections in particular. 1

In another evaluation of the efficacy and safety of the 4.5% nasal gel, NatestoR, authors led by Dr. Larry Lipshultz, from Baylor University College of Medicine, reported the extent of clinical improvements in erectile function and mood, in a 90-day, randomized, open-label, dose-ranging study in hypogonadal men, with sequential safety extensions to one year. 2 

The investigators evaluated erectile function and mood at baseline (day 0), and at 30-day intervals throughout the 90-day treatment period using the International Index of Erectile Function (IIEF) and the Positive and Negative Affect Schedule (PANAS). 

Results demonstrated that treatment with NatestoR resulted in statistically significant improvements in each of the 5 domains of erectile function (F(3,8,13) =83.96, p<.001). Most of the benefit was evident by day 30 (t= -9.8714, df=288, p- value <.001), with smaller increases until completion of the study (Figure 1) 

NatestoR also produced clinically and statistically significant improvements in mood, as assessed by PANAS, by day 30. Continued improvements in mood were seen through the study’s completion (Figure 2).

Gerwin Westfield, PhD, Medical Affairs Manager with Aytu BioScience, spoke with UroToday about these results, which are unique when compared with effects of other forms of testosterone therapy, especially by a notable lack of suppression of pituitary gonadotropins LH and FSH. 

“Men who were treated with NatestoR nasal testosterone gel had significant improvements in mood as early as 30 days, and continued improvement all the way out to Day 90—representing both significant improvements in the positive mood attributes and significant improvement in negative mood attributes.” This finding was quantified by the self-reporting instrument PANAS, (Positive and Negative Affect Schedule). 

Moreover, said Dr. Westfield, treatment with NatestoR showed statistically significant improvement in all five domains of erectile function as early as Day 30, and the improvement continued to Day 90.

1. Conners W, Morgentaler A, Guidry M, Westfield G, Bryson N, Goldstein I. Preservation of normal concentrations of pituitary gonadotropins despite achievement of normal serum testosterone levels in hypogonadal men treated with a 4.5% nasal testosterone gel. American Urological Association. May 12-16, 2017. Poster MP89-06.
2. Lipshultz LI, Westfield G, Guidry M, et al. Clinical improvements in erectile function and mood in hypogonadal men treated with 4.5% nasal testosterone gel. American Urological Association. May 12-16, 2017. Poster PD69-06.