Since people have been talkin DHEA alot i have been looking up studies. Specifically to see what metabolic pathways it follows in the body
In men, something rather odd is seen. DHEA and its sulfate increase alot and so does the downstream DHT metabolite 5alpha-androstane-3alpha-17beta-diol (5alpha-Adiol). Thats about it though
Now if you know your steroid pathways (almost no one here really does offhand i am sure) you might have noticed something odd about the above factoid. Thats cuz for DHEA to go to 5alpha-Adiol it has to go through stuff like androstenedione, testosterone, DHT etc. Yet these hormones are not elevated in the blood. Just the end metabolite is
This tells us that DHEA must be metabolized extensively in certain target tissues. In other words these tissues will take in DHEA and then spit out 5alpha-Adiol. In between they do with the intermediate horomones whatever it is that tissue does with the hormones (activate receptors, signal relevant physiological processess etc).
But what tissues are these? Well it has to be a tissue that at least is rich in 5alpha-reductase because the end product is 5alpha-reduced. That eliminates muscle because it has virtually no 5-AR. It would leave just about every other androgen dependent tissue however because they all pretty much have good amounts of 5-AR. Which tissues DHEA undergoes its paracrine conversion in I am not sure but i have heard skin mentioned as one of them.
ok i am kind of rambling and thinking as i go along but if skin is one of them then that may bode well for transdermal dhea products (unless you are a chick and/or apply to your scalp). That is because by this route you may end up with substantial conversion to 5alpha-Adiol by the time the hormone gets into the dermal blood supply. this may result in enough 5alpha-Adiol to make it physiologically significant as a DHT source, and of course that would mean modest anabolic and ergogenic effects (with the coinciding down sides of course)
comments?
Fertil Steril. 2004 Mar;81(3):595-604. Links
Pharmacokinetics of dehydroepiandrosterone and its metabolites after long-term daily oral administration to healthy young men.Acacio BD, Stanczyk FZ, Mullin P, Saadat P, Jafarian N, Sokol RZ.
Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
OBJECTIVE: To determine the effects of dehydroepiandrosterone (DHEA) supplementation on the pharmacokinetics of DHEA and its metabolites and the reproductive axis of healthy young men. DESIGN: A prospective, randomized, double-blind, placebo-controlled pharmacokinetic study. SETTING: General Clinical Research Center and laboratories at the Keck School of Medicine of the University of Southern California, Los Angeles, California. PATIENT(S): Fourteen healthy men, ages 18-42 years. INTERVENTION(S): Daily oral administration of placebo (n = 5), 50 mg DHEA (n = 4), or 200 mg DHEA (n = 5) for 6 months. Blood samples were collected at frequent intervals on day 1 and at months 3 and 6 of treatment. MAIN OUTCOME MEASURE(S): Quantification of DHEA, DHEA sulfate (DHEAS), androstenedione, T, E(2), dihydrotestosterone (DHT), and 5alpha-androstane-3alpha-17beta-diol glucuronide (ADG). Physical examination, semen analysis, serum LH, FSH, prostate-specific antigen, and general chemistries were carried out. RESULT(S): Baseline DHEA, DHEAS, and ADG levels increased significantly from day 1 to months 3 and 6 in the DHEA treatment groups but not in the placebo group. No significant changes were observed in pharmacokinetic values. Clinical parameters were not affected. CONCLUSION(S): DHEA, DHEAS, and ADG increased significantly during 6 months of daily DHEA supplementation. Although the pharmacokinetics of DHEA and its metabolites are not altered, sustained baseline elevation of ADG, a distal DHT metabolite, raises concerns about the potential negative impact of DHEA supplementation on the prostate gland.
PMID: 15037408 [PubMed - indexed for MEDLINE]
In men, something rather odd is seen. DHEA and its sulfate increase alot and so does the downstream DHT metabolite 5alpha-androstane-3alpha-17beta-diol (5alpha-Adiol). Thats about it though
Now if you know your steroid pathways (almost no one here really does offhand i am sure) you might have noticed something odd about the above factoid. Thats cuz for DHEA to go to 5alpha-Adiol it has to go through stuff like androstenedione, testosterone, DHT etc. Yet these hormones are not elevated in the blood. Just the end metabolite is
This tells us that DHEA must be metabolized extensively in certain target tissues. In other words these tissues will take in DHEA and then spit out 5alpha-Adiol. In between they do with the intermediate horomones whatever it is that tissue does with the hormones (activate receptors, signal relevant physiological processess etc).
But what tissues are these? Well it has to be a tissue that at least is rich in 5alpha-reductase because the end product is 5alpha-reduced. That eliminates muscle because it has virtually no 5-AR. It would leave just about every other androgen dependent tissue however because they all pretty much have good amounts of 5-AR. Which tissues DHEA undergoes its paracrine conversion in I am not sure but i have heard skin mentioned as one of them.
ok i am kind of rambling and thinking as i go along but if skin is one of them then that may bode well for transdermal dhea products (unless you are a chick and/or apply to your scalp). That is because by this route you may end up with substantial conversion to 5alpha-Adiol by the time the hormone gets into the dermal blood supply. this may result in enough 5alpha-Adiol to make it physiologically significant as a DHT source, and of course that would mean modest anabolic and ergogenic effects (with the coinciding down sides of course)
comments?
Fertil Steril. 2004 Mar;81(3):595-604. Links
Pharmacokinetics of dehydroepiandrosterone and its metabolites after long-term daily oral administration to healthy young men.Acacio BD, Stanczyk FZ, Mullin P, Saadat P, Jafarian N, Sokol RZ.
Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
OBJECTIVE: To determine the effects of dehydroepiandrosterone (DHEA) supplementation on the pharmacokinetics of DHEA and its metabolites and the reproductive axis of healthy young men. DESIGN: A prospective, randomized, double-blind, placebo-controlled pharmacokinetic study. SETTING: General Clinical Research Center and laboratories at the Keck School of Medicine of the University of Southern California, Los Angeles, California. PATIENT(S): Fourteen healthy men, ages 18-42 years. INTERVENTION(S): Daily oral administration of placebo (n = 5), 50 mg DHEA (n = 4), or 200 mg DHEA (n = 5) for 6 months. Blood samples were collected at frequent intervals on day 1 and at months 3 and 6 of treatment. MAIN OUTCOME MEASURE(S): Quantification of DHEA, DHEA sulfate (DHEAS), androstenedione, T, E(2), dihydrotestosterone (DHT), and 5alpha-androstane-3alpha-17beta-diol glucuronide (ADG). Physical examination, semen analysis, serum LH, FSH, prostate-specific antigen, and general chemistries were carried out. RESULT(S): Baseline DHEA, DHEAS, and ADG levels increased significantly from day 1 to months 3 and 6 in the DHEA treatment groups but not in the placebo group. No significant changes were observed in pharmacokinetic values. Clinical parameters were not affected. CONCLUSION(S): DHEA, DHEAS, and ADG increased significantly during 6 months of daily DHEA supplementation. Although the pharmacokinetics of DHEA and its metabolites are not altered, sustained baseline elevation of ADG, a distal DHT metabolite, raises concerns about the potential negative impact of DHEA supplementation on the prostate gland.
PMID: 15037408 [PubMed - indexed for MEDLINE]