A validated age-related normative model for male total testosterone shows increasing variance but no decline after age 40 years.

Thomas W Kelsey,Lucy Q Li,W Hamish B Wallace,Ashley Whelan,Richard A Anderson,Rod T Mitchell,Bin He

doi:10.1371/journal.pone.0109346

Abstract

The diagnosis of hypogonadism in human males includes identification of low serum testosterone levels, and hence there is an underlying assumption that normal ranges of testosterone for the healthy population are known for all ages. However, to our knowledge, no such reference model exists in the literature, and hence the availability of an applicable biochemical reference range would be helpful for the clinical assessment of hypogonadal men. In this study, using model selection and validation analysis of data identified and extracted from thirteen studies, we derive and validate a normative model of total testosterone across the lifespan in healthy men. We show that total testosterone peaks [mean (2.5–97.5 percentile)] at 15.4 (7.2–31.1) nmol/L at an average age of 19 years, and falls in the average case [mean (2.5–97.5 percentile)] to 13.0 (6.6–25.3) nmol/L by age 40 years, but we find no evidence for a further fall in mean total testosterone with increasing age through to old age. However we do show that there is an increased variation in total testosterone levels with advancing age after age 40 years. This model provides the age related reference ranges needed to support research and clinical decision making in males who have symptoms that may be due to hypogonadism.

Highlights

In the male, testosterone secretion from the Leydig cells in the testes has a central role in developing secondary sexual characteristics, supporting spermatogenesis and regulating libido [1]
As the diagnosis of hypogonadism includes identification of serum testosterone levels below the normal range for healthy males, there is an underlying assumption that normal ranges of testosterone for the healthy population are known for all ages
We show that TT peaks [mean (2.5–97.5 percentile)] at 15.4 (7.2–31.1) nmol/L at an average age of 19 years, and falls in the average case [mean (2.5–97.5 percentile)] to 13.0 (6.6–25.3) nmol/ L by age 40 years, but we find no evidence for a further fall in mean TT with increasing age through to old age

Summary

Introduction

Testosterone secretion from the Leydig cells in the testes has a central role in developing secondary sexual characteristics, supporting spermatogenesis and regulating libido [1]. A number of studies have reported decreasing testosterone levels in men with age. Longitudinal observation in the Massachusetts Male Aging Study showed a decrease in total testosterone (TT) with increasing age [6], when accompanied by increasing obesity. Testosterone replacement in young hypogonadal men results in significant improvement of libido and sexual function and is of clear benefit [16], but it remains to be established in older men that general health and other manifestations of the metabolic syndrome are improved [17,18,19]. As the diagnosis of hypogonadism includes identification of serum testosterone levels below the normal range for healthy males, there is an underlying assumption that normal ranges of testosterone for the healthy population are known for all ages. In this study we derive and validate a normative model of TT across the lifespan

Methods

Results

Discussion

A Validated Age-Related Normative Model for Male Total Testosterone