Login to Access Video or Poster Abstract: MP89-06
Sources of Funding: Support from Trimel/Acerus Pharmaceuticals for Phase 3 clinical trial.

Introduction

One of the recognized effects of standard forms of testosterone (T) therapy is suppression of the pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) via negative feedback from sustained increases in serum T concentrations. We report here the results of treatment with a 4.5% testosterone gel administered intranasally (nasal testosterone gel - NTG) on serum total testosterone (TT), LH, and FSH in hypogonadal men.

Methods

Hypogonadal men were randomized into a 90-day, open-label, dose-ranging study. A 4.5% NTG (125 uL/nostril, 11.0mg testosterone/dose) was self-administered using a multiple-dose dispenser either twice daily (BID, n=122) or 3 times a day (TID, n=151) for a total dose of 22.0mg or 33.0mg, respectively. Titration was performed based on blood levels so as to achieve the eugonadal range (300 -1050 ng/dL). Serum samples were obtained at baseline and after 90 days of treatment to determine relevant hormone levels.

Results

Total serum testosterone increased from a mean Cavg 200.8 ng/dL at baseline to a mean Cmax 818.49 ng/dL at ~40 minutes. After 90 days, 90% (95% CI = 83-97%) of men in the TID group, and 71% (95% CI = 62-79%) of men in the BID group reached normal T levels, and a mean total testosterone Cavg 421 ng/dL and 375 ng/dL, respectively. Baseline FSH (BID) was 8.49 IU/L, mean at Day 90 was 5.99 IU/L. Baseline FSH (TID) was 6.42 IU/L, mean at Day 90 was 3.12 IU/L. Baseline LH (BID) was 5.42 IU/L, mean at Day 90 was 3.56 IU/L. Baseline LH (TID) was 5.25 IU/L, mean at Day 90 was 2.20 IU/L.

Conclusions

Treatment with 4.5% NTG restored serum TT to normal levels while FSH and LH levels were reduced but remained well within the normal range mitigating the decline in LH and FSH. This maintenance of normal gonadotropins differs from the usual suppression seen with other exogenous T preparations, particularly injections. The mechanism for this reduced gonadotropin suppression is uncertain, but may be due to return of serum T to baseline between doses. Further studies are needed to determine to what extent this reduced gonadotropin suppression may result in preservation of testicular volume and fertility.

Funding

Support from Trimel/Acerus Pharmaceuticals for Phase 3 clinical trial.