Rationale:In healthy eugonadal men, it is known that blocking estrogen formation stimulates thehypothalamic-pituitary-testicular (HPT) axis to increase in vivo androgen production. Recently, a new class of dietary supplements has appeared that claim to inhibit the aromatase enzyme (i.e., decrease the transformation of aromatizable androgens [androstenedione, DHEA, testosterone] into estrogens [estriol, estrone, estradiol]), leading to an increase in androgen and testosterone formation. Purpose: As the first step in a series of experiments on a popular, over-the-counter aromatase inhibitor, the purpose of this pilot study was to examine the effects of Novedex XT™(NOV-XT) administration on selected hormonal responses (total testosterone [TT], bioavailable testosterone [BT] and estradiol [E2]), as well as serum and plasma markers of renal, hepatic, andhematological function. Methods: Using an open-label, proof-of-concept design, five eugonadal men (mean ± SD age, height, weight, body fat: 31.0 ± 5.3 yr, 177.0 ± 3.8 cm, 86.6 ± 8.7 kg, 15.2 ± 5.4 %) ingested 4 capsules of NOV-XT prior to bed for 28 consecutive days. According to themanufacturer, each capsule of NOV-XT contains 60 mg of a proprietary blend of three naturally-occurring aromatase inhibitors: 6, 17-keto-etiocholene-3-ol tetrahydropyranol ether, 3, 17-keto-etiochol-triene, and 3’,5,7-trihydroxy-4’-methoxyflavone (supplements were provided by an FDA-registered, pharmaceutically licensed manufacturer; confirmation by an external laboratory is pending). Blood samples obtained at baseline (prior to supplementation), and at weekly intervals thereafter for 28 days, were analyzed for TT, BT, and E2 by radioimmunometric and chemilluminetric assays. Subjects were required to maintain their normal dietary and training patterns during the study. All blood samples were obtained at the same time of day (0700-0900) to minimize diurnal variation. Hormone concentrations were statistically analyzed by ANOVA and Tukey’s HSD post-hoc test. Dependent t-tests were used to compare changes in blood chemistries. Statistical significance was accepted at p<0.05. Results: Compared to baseline, NOV-XTadministration rapidly and significantly increased TT and BT. Mean changes from baseline for TT (Figure 1) after one, two, three, and four weeks of NOV-XT administration were: +145% (p<0.006), +183% (p<0.0005), +232% (p<0.0002), and +240% (p<0.0002), respectively. Meanchanges from baseline for BT (Figure 2) after one, two, three, and four weeks of NOV-XTadministration were: +300% (p<0.01), +402% (p<0.0009), +511% (p<0.0002), and +528% (p<0.0002), respectively. Despite these large increases in TT and BT, no significant aromatization to estradiol was observed (i.e., E2 concentrations remained 3-6 pg/mL below baseline at all timepoints). No statistically significant changes in clinical blood chemistries (fasting glucose, BUN, creatinine, bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, sodium, potassium, chloride, calcium, albumin, globulin, CO2, total protein, total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol) or systemic hemodynamics (heart rate, systolic blood pressure, diastolic blood pressure) were observed, nor were any adverse events reported during the study.
Conclusions: Within the framework of the current experimental design, these preliminary data indicate that four weeks of NOV-XT administration significantly elevates serum TT and BT, likelyvia the inhibition of estradiol formation and the shifting of the HPT axis towards androgen/testosterone production. In healthy, eugonadal men, supplementation with NOV-XT does not appear to result in any deleterious effects on blood chemistry or systemic hemodynamics. Ongoing research is being conducted to confirm and refine these results in a larger sample size, aswell as examine the impact of NOV-XT on androgenic and estrogenic metabolites, bodycomposition, and muscular performance. Supported in part by a research grant from Gaspari Nutrition (Neptune, NJ).
