Four weeks of androstenedione supplementation diminishes the treatment response in middle aged men. (Original Article).

Objectives: To examine baseline hormonal concentrations and the pharmacokinetic response on day 0 and day 28 of 28 days of androstenedione supplementation.

Methods: Eight men (mean (SD) age 44.1 (3.0) years (range 40-48), weight 76.3 (9.4) kg, and percentage body fat 20.6 (6.7)) participated in a randomised, double blind, cross over, 2 x 28 day placebo controlled study. Subjects were tested on day 0 and 28 days after receiving 200 mg/day oral androstenedione and a placebo treatment with a 28 day washout period between treatments. Serum hormone concentrations were examined at baseline (time 0) and then at 30 minute intervals for 180 minutes to measure day 0 and day 28 pharmacokinetic responses. Analytes included androstenedione, total testosterone, dehydroepiandrosterone sulfate (DHEAS), aestradiol, and sex hormone binding globulin (SHBG). Lipid concentrations, weight, body composition, resting heart rate, and blood pressure were also measured.

Results: Analysis of integrated area under the curve (AUC) and time 0 hormonal concentrations by repeated measures multivariate analysis of variance (p<0.05) and Fisher's post hoc analysis showed a significant increase in AUG far serum androstenedione at day 0 (108.3 (27.6) nmol/l) in the supplemented condition as compared with day 28 (43.4 (13.1) nmol/l) and placebo (2.1 (0.8) nmol/l) conditions. No other significant AUG changes were noted. After 28 days of supplementation, DHEAS levels were significantly elevated (p = 0.00002) at time 0 (12.9 (1.3) [micro]mol/l) compared with placebo (7.0 (0.8) [micro]mol/l) with a trend (p = 0.08) toward elevation of time 0 androstenedione concentrations (16.4 (7.0) [micro]mol/l) compared with placebo (5.6 (0.4) nmol/l). No changes were found for lipids, resting heart rate, or blood pressure, weight, or percentage body fat.

Conclusion: Although supplementation with 200 mg/day androstenedione increases AUC for serum androstenedione in the day 0 condition, continued supplementation is characterised by a diminished treatment response, coupled with time 0 increases in testosterone precursors but not testosterone.

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Androstenedione is marketed to middle aged ([greater than or equal to]40 years ) men to ameliorate the effect of aging on the hypothalamic pituitary gonadal axis. Some studies of male androgenic function report no decline in serum total testosterone concentration with age, (1) whereas others report decreasing concentration at age 45-50 years that may be within the normal range for young men. (2-4) As androstenedione is a testosterone precursor, (5) and supplementation has been shown to raise serum androstenedione concentration, (6-12) it is plausible that elevated androstenedione concentrations could result in increased conversion of androstenedione into testosterone, especially in an aging population. Several studies have reported that supplementation with 200-300 mg/day androstenedione can produce acute (9,11) and chronic (8) increases in total and free testosterone concentrations, whereas others have reported no changes (6-8,10) in younger (<40 years) and middle aged ([greater than or equal to]40 years) me n. These studies used different dosages, dosing patterns, lengths of supplementation, as well as, a variety of age groups, which may contribute to these inconsistent findings.

Of perhaps greater concern is the potential for alterations in hormonal balance with prolonged supplementation. Strong regulatory mechanisms exist that alter the production and conversion of hormones after prolonged administration of androgens. (5) The purpose of this study was to determine if baseline (time 0 ) and pharmacokinetic hormonal responses to androstenedione supplementation are altered after four weeks of supplementation with 200 mg/day androstenedione in middle aged men.

METHODS

Subjects

Eight healthy men volunteered to participate in this study which was approved by the Institution's human research review committee. Before the study, each subject completed and signed a medical history and consent form that described the study protocol and potential risks and discomforts. Baseline characteristics were mean (SD) age 44.1 (3.0) years (range 40-48), body mass 76.3 (9.4) kg, and height 175 (5.3) cm. Only two subjects participated in a resistance training programme; both had participated for five years or more. For the duration of the trial, all subjects agreed not to change the frequency, intensity, or volume of their exercise programme, or their dietary habits.

Study design

A randomised, double blind, cross over, placebo controlled design was used to assess subject responses to supplemented and placebo treatment conditions. A cross over design was chosen to control for initial differences in hormonal concentrations and the effects this may have on individual responses to supplementation. Each subject was tested at the beginning (day 0) and end of a 28 day supplementation period with 200 mg/day androstenedione and a placebo. Figure 1 shows a schematic of the testing protocol. A 28 day washout period was used between the two supplementation periods. During both treatments, subjects were examined to determine hormonal concentrations at time 0, as well as a 180 minute pharmacokinetic response to each treatment.

Treatment

The treatments consisted of 200 mg/day androstenedione (two 100 mg tablets) or two tablets of a rice powder placebo. administered each morning. Each treatment was distributed in bottles that …