Utility of a single serum testosterone measurement to determine response to topical testosterone replacement in hypogonadal men

Abstract

Objective:

To evaluate the utility of single serum testosterone measurement in patients receiving transdermal testosterone therapy.

Research design and methods:

Data were from an open-label, 120 day, multi-center titration trial in androgen-deficient men receiving an initial daily dose of 60 mg testosterone (testosterone topical solution 2%) applied to axillae (30 mg/axilla). Average concentration (C_avg) of serum testosterone (TT) was determined on days 15, 60, and 120; doses were adjusted to maintain normal C_avg (300–1050 ng/dL [10.4–36.4 nmol/L]). Accuracy of single serum TT measurements (2, 4, 8, 12, 16, and 20 hours post-dose) was assessed in patients with C_avg TT within and below (<300 ng/dL [<10.4 nmol/L]) the normal range.

Clinical trial registration:

Clinicaltrials.gov – NCT00702650.

Main outcome measure:

Serum testosterone levels.

Results:

In patients with normal C_avg (n = 85), 79% to 92% had serum testosterone levels within normal range 2, 4, 8, 12, 16, and 20 hours post-dose; significant effects of time post-dose for single testosterone measurement accuracy (P = 0.01) were observed: testing accuracy peaked 4–8 hours post-dose and tapered ∼16 hours post-dose. In 28/63 instances with low C_avg TT throughout the study a normal 2 hour serum TT level was observed. The average percentage (across all days) of discordant results between C_avg (<300 ng/dL [<10.4 nmol/L]) and single serum TT measurements (300–1050 ng/dL [10.4–36.4 nmol/L]) declined with increasing time from dose application (44% at 2 hours, 38% at 4 hours, 22% at 8 hours, 3% at 16 hours).

Conclusions:

Reliance on a single serum testosterone measurement to determine the need for dose adjustment of testosterone topical solution 2% may lead clinicians to change the dose unnecessarily, or alternatively, not increase the dose when necessary. The results reported here are limited to testosterone topical solution 2% and may not be applicable to other topical agents.

Keywords: :

• Absorption
• Accuracy
• Hypogonadism
• Testosterone
• Topical administration
• Transdermal administration

Transparency

Declaration of funding

This study was sponsored by Eli Lilly and Company and/or its subsidiaries.

Declaration of financial/other relationships

D.M. and X.N. have disclosed that they are full-time employees and shareholders of Eli Lilly and Company.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors thank Dr. Alexandra Heinloth and Ms. Angela Lorio, both full-time employees of inVentiv Health Clinical LLC, for writing and editorial services; and Ms. Qun Cai and Ms. Cynthia Huang, both full-time employees of inVentiv Health Clinical LLC, for statistical support. Eli Lilly and Company contracted inVentiv Health Clinical for statistical, writing, and editorial services.

Previous presentation: Endocrine Society 97th Annual Meeting & Expo, San Diego, CA, USA, 5–8 March 2015.

Notes

*Axiron is a registered trade name of Eli Lilly and Company, Indianapolis, IN, USA