Older Men & Testosterone

They found that testosterone did not significantly decline with aging SHBG increased significantly with age and BT and FTC showed the most significant decline with age. FTD, FTA, and FAI also declined significantly with age. BT and FTC showed the best correlation with FTD. T , FAI , and FT also correlated with FTD. Sensitivity and specificity of BT to predict hypogonadism by FTD was 85.7% and 66.9% respectively. Similarly, the sensitivity and specificity of FTD to predict hypogonadism by BT was 50% and 92.3%. Based on the data reported here, we conclude that FTD, BT, and FTC are equivalent assays to predict hypogonadism. Other assays appear less accurate. T is a poor assay for detecting the age-related decline in testosterone because of the increase in SHBG which binds up most of the T. (1)

There was a highly significant correlation between plasma and salivary testosterone when these have been compared by researchers. In men, free testosterone constituted 78% of salivary testosterone but only 4% of plasma testosterone; mean +/- SE salivary testosterone was 193.7 +/- 6.7 pg/ml compared to plasma testosterone of 5,140 +/- 298.0 pg/ml.

Salivary testosterone decreased significantly from a morning (0800 hours) level of 208 +/- 7.5 to an evening (1800 hours) level of 174 +/- 8.4 pg/ml (p = less than 0.001) (n = 23). Similarly, plasma testosterone was significantly higher in the morning (6,584 +/- 472 pg/ml) than in the evening (5,571 +/- 357 pg/ml) (p = less than 0.005) (n =3D 25).

Free testosterone in saliva and plasma (FTD) also showed significantly higher morning than evening levels. The coefficients of variability for hourly changes (0900 to 1800 hours) in salivary testosterone and free testosterone were 13.6% and 16.7% compared to 12.7% and 20.9% for plasma testosterone and free testosterone, respectively.

In women, salivary testosterone during the proliferative phase of the menstrual cycle was 108.3 +/- 5.8 pg/ml, and it increased significantly to 130.5 +/- 6.0 pg/ml in the secretory phase (p =3D less than 0.02). This study indicated that measurements of salivary testosterone reflect plasma testosterone and may be a useful noninvasive method of assessing levels of free testosterone. (2)

Testosterone administration to older men has significant beneficial effects on muscle metabolism. Determining the mechanisms mediating these effects will result in the development of treatment paradigms that maximize the anabolic benefit while minimizing side-effects. (3)

This increase in IGF-1 was highly significant as growth hormone has been claimed to promote IGF-1 as a mechanism of its action. We know that T on its own can raise the levels of this growth promoting factor. The age-related decline in serum testosterone concentration may contribute to the concomitant decrease in GH secretion and IGF-1 levels.

To gain insight in the role of testosterone in the decreased growth hormone (GH) secretion evident in older men. Angella Gentili et al., from Medical College of Virgina/Virginia Commonweath Unversity and Hunter Holmes McGuire VA Medical Center, Richmond; Salem VA Medical Center, Salem; University of Virginia, conducted a randomized, double-blind, cross-over study of two doses of testosterone versus placebo on GH secretion in young and older men.

Testosterone (100mg and 200mg) IM weekly for three weeks versus placebo. To estimate GH secretion, they used an ultrasensitive chemiluminescence-based GH assay and multi-parameter deconvolution analysis. Low or high dose testosterone had no significant effect on GH secretion in young subjects, nor did low dose testosterone have a significant effect in older subjects. However, older men who received high dose testosterone had on average:

1) a 2.12 fold increase in mean GH [95% CI =1.12 - 4.00, (p=0.0265)], 2) a 2.28 fold increase in GH secretory burst mass [95% CI = 1.32 - 3.91, (p=0.0086)], and 3 ) a 1.27 fold increase in GH secretory burst amplitude [95% CI = 1.16 - 3.59 p=0.0202] relative to their baseline response. (4)

Although most men know on some "gut level" when their testosterone level is down, various technieques have been developed to confirm their suspicions of "impending sexual dysfunction". However the free T (FT) or bioactive T seems to be the best indicator of hypogonadism. (5)

While DHT is not aromatizable at sufficient concentration, it decreases T and E2 levels. In other words it regulates its own pathway of production. This phenomenon will be discussed later. DHT conversion does not take place in the liver. Most DHT is produced from FT in serum , gonads and saliva and skin. (6) However, the concentrations of DHT and T in the plasma are interdependent. The ratio of T/DHT provides some indication of the activity of 5AR in both serum and saliva. Normally T/DHT ratio is about 10/1.

Abstracts were presented at Endo 2000, Toronto, Canada.

1.John E Morley, Ping Patrick, HM P Perry, III . Comparison of Various Assays to Measure testosterone in Males across the Lifespan.Geriatric Medicine, Saint Louis University; GRECC, St. Louis VA Medical Center, St. Louis, MO.

2. Khan-Dawood FS, Choe JK, Dawood MY. Salivary and plasma bound and "free" testosterone in men and women. Am J Obstet Gynecol 1984 Feb 15;148(4):441-5.

3. Randall J Urban, Charles Gilkison, Jie Jiang, Taylor Marcell, Kevin Tipton, Melinda Sheffield-Moore, Cathy W, Yeckel, Steven Lieberman, Arny A Ferrando . Testosterone Administration to Older Men for Six Months Increases Skeletal Muscle Strength, Net Muscle Protein Balance, and the Expression of Intramuscular IGF-I Transcripts. Departments of Internal Medicine and Surgery, The University of Texas Medical Branch, Galveston, TX

4. Angela Gentili, Thomas Mulligan, Michael Godschalk, John Clore, Jim Patrie, Ali Iranmanesh, Johannes Veldhuis. Testosterone Supplementation Increases Growth Hormone Secretion in Older Men. Medical College of Virgina/Virginia Commonweath Unversity and Hunter Holmes McGuire VA Medical Center, Richmond; Salem VA Medical Center, Salem; University of Virginia, Charlottesville, Va

5. Tianshu Gao, Michael J McPhaul . Characterization of a Rat Model in Which to Study the Differential Control of Gene Regulation by testosterone (T) and 5a-Dihydrotestosterone (DHT). Internal Medicine, UT Southwestern Medical Center, Dallas, TX

6. Bartsch W. Interrelationships between sex hormone-binding globulin and testosterone, 5 alpha-dihydrotestosterone and oestradiol-17 beta in blood of normal men. Maturitas 1980 Jul;2(2):109-18

7.Nawata H, Kato K, Ibayashi H . Age-dependent change of serum 5alpha-dihydrotestosterone and its relation to testosterone in man. Endocrinol Jpn 1977 Feb;24(1):41-5.

8. Bartsch G, Rittmaster RS, Klocker H. Dihydrotestosterone and the concept of 5alpha-reductase (5 AR) inhibition in human benign prostatic hyperplasia. Eur Urol 2000 Apr;37(4):367-80