Ingesting androstenedione alone or with herbal extracts, or androstenediol with herbal extracts purportedly increases serum [testosterone] in men. The addition of herbal extracts is purported to prevent the conversion of testosterone precursors into estrogens or dihydrotestosterone. The effects of ingesting androstenedione, androstenedione + herbal extracts, and androstenediol + herbal extracts on serum [testosterone], [estradiol], [dihydrotestosterone], [prostate specific antigen] (PSA), and blood lipids was investigated in 30 to 59 year old men. Subjects were randomly assigned to consume ASD (300 mg/day androstenedione; n = 28), DION (300-mg androstenedione, 150-mg dehydroepiandrosterone, 540-mg saw palmetto, 300-mg indole-3-carbinol, 625-mg chrysin, and 750-mg Tribulus terrestris per day; n = 28), AND-HB (300-mg androstenediol, 480-mg saw palmetto, 450-mg indole-3-carbinol, 300-mg chrysin, 1,500 mg gamma-linolenic acid, and 1,350-mg Tribulus terrestris per day; n = 28), or placebo (n = 27) for 28 days. Serum [free testosterone], [total testosterone], [androstenedione], [dihydrotestosterone], [estradiol], [PSA], and [lipids] were measured before and throughout the 4-week supplementation period. Serum [total testosterone] and [PSA] were unchanged by supplementation. Serum [androstenedione] (174%, 342%, and 300%), [free testosterone] (37%, 38%, and 45%), [dihydrotestosterone] (57%, 71%, and 83%), and [estradiol] (86%, 103%, 68%) were elevated (P < 0.05) for AND-HB, DION, and ASD, respectively. Serum [HDL-C] was reduced (P < 0.05) similarly by 0.13 mmol·l-1 in ASD, DION and AND-HB. There is no difference in the serum [testosterone], [estradiol], [dihydrotestosterone], [PSA], and [lipid] response to ingesting androstenedione alone, androstenedione + herbal extracts, or androstenediol + herbal extracts.;Orally ingested androgens undergo a large degree of digestive and hepatic breakdown. Therefore, we evaluated the hormonal response to sublingual cyclodextrin androstenediol. Eight males (22.9 +/- 1.2 y) consumed either 20 mg androstenediol in a sublingual cyclodextrin tablet (SL-DIOL) or placebo. Blood samples were collected before supplementation and every 30-min for 3 h after supplementation. Serum [androstenedione] was increased 125% at 120 min, serum [free testosterone] was increased 118% at 60 min, serum [total testosterone] was increased 110% at 60 min, and serum [estradiol] was 71% elevated at 180 min in SL-DIOL. These data indicate that, in contrast to ingested androstenediol, sublingual cyclodextrin androstenediol intake increases serum [androstenedione], [free testosterone], [total testosterone], and [estradiol].