Let's talk DHEA...
Here is an interesting study on transdermal DHEA. From what I can tell, the dose used is something like 142 mg/day!
Physiological changes in dehydroepiandrosterone are not reflected by serum levels of active androgens and estrogens but of their metabolites: intracrinology.
Labrie F, Belanger A, Cusan L, Candas B.
Medical Research Council Group in Molecular Endocrinology, Centre Hospitalier de l'Universite Laval Research Center, Le Centre Hospitalier Universitaire de Quebec, Canada.
This study analyzes in detail the serum concentration of the active androgens and estrogens, as well as a series of free and conjugated forms of their precursors and metabolites, after daily application for 2 weeks of 10 mL 20% dehydroepiandrosterone (DHEA) solution on the skin to avoid first passage through the liver. In men, DHEA administration caused 175%, 90%, 200% and 120% increases in the circulating levels of DHEA and its sulfate (DHEA-S), DHEA-fatty acid esters, and androst-5-ene-3 beta,17 beta-diol, respectively, with a return to basal values 7 days after cessation of the 14-day treatment. Serum androstenedione increased by approximately 80%, whereas serum testosterone and dihydrotestosterone (DHT) remained unchanged. In parallel with the changes in serum DHEA, the concentrations of the conjugated metabolites of DHT, namely androsterone glucuronide, androstane-3 alpha,17 beta-diol-G, and androstane-3 beta,17 beta-diol-G increased by about 75%, 50%, and 75%, respectively, whereas androsterone-sulfate increased 115%. No consistent change was observed in serum estrone (E1) or estradiol (E2) in men receiving DHEA, whereas serum E1-sulfate and E2-sulfate were slightly and inconsistently increased by about 20%, and serum cortisol and aldosterone concentrations were unaffected by DHEA administration. Almost superimposable results were obtained in women for most steroids except testosterone, which was about 50% increased during DHEA treatment. This increase corresponded to about 0.8 nM testosterone, an effect undetectable in men because they already have much higher (approximately 15 nM) basal testosterone levels. In women, the serum levels of the conjugated metabolites of DHT, namely androsterone glucuronide, androstane-3 alpha,17 beta-diol-G, androstane-3 beta,17 beta-diol-G, and androsterone-sulfate were increased by 125%, 140%, 120% and 150%, respectively. The present study demonstrates that the serum concentrations of testosterone, DHT, E1, and E2 are poor indicators of total androgenic and estrogenic activity. However, the esterified metabolites of DHT appear as reliable markers of the total androgen pool, because they directly reflect the intracrine formation of androgens in the tissues possessing the steroidogenic enzymes required to transform the inactive precursors DHEA and DHEA-S into DHT. As well demonstrated in women, who synthesize almost all their androgens from DHEA and DHEA-S, supplementation with physiological amounts of exogeneous DHEA permits the biosynthesis of androgens limited to the appropriate target tissues without leakage of significant amounts of active androgens into the circulation. This local or intracrine biosynthesis and action of androgens eliminates the inappropriate exposure of other tissues to androgens and thus minimizes the risks of undesirable masculinizing or other androgen-related side effects of DHEA.
PMID: 9253308 [PubMed - indexed for MEDLINE]
J Clin Endocrinol Metab. 1999 Jun;84(6):2170-6. [PMID: 10372727]
Biotransformation of oral dehydroepiandrosterone in elderly men: significant increase in circulating estrogens.
Arlt W, Haas J, Callies F, Reincke M, Hubler D, Oettel M, Ernst M, Schulte HM, Allolio B.
The author makes a series of statements in which he cites the 1997 Labrie study (above), saying:
"Labrie et al. (19) administered a 20% DHEA cream in a daily dose of 10 mL for 14 days to a total of eight elderly men and women and found no significant increase in serum estrogen levels in either gender. These results differ from the findings of our study and those of Young et al. (18), but may be explained by the route of DHEA administration. As previously reported for transvaginal (20) and sublingual (13) administration of DHEA, Labrie et al. (18) also described an increased DHEA/DHEAS ratio after percutaneous DHEA administration compared to oral ingestion. Although many tissues contain sulfotransferases (21, 22) and may contribute to the peripheral conversion of DHEA to DHEAS, the hepatic sulfotransferase activity seems to be of predominant importance and is bypassed by nonoral DHEA administration due to avoidance of the hepatic first pass effect. An increased DHEA/DHEAS ratio may lead to a reduced conversion of DHEA to androgens and/or estrogens inside peripheral target cells, as DHEAS has a much longer half-life than DHEA, and it can be continuously converted back to DHEA by widespread tissue sulfatase activity (23, 24, 25, 26) followed by further bioconversion. Furthermore, avoidance of the first pass effect by nonoral administration of DHEA also leads to avoidance of hepatic aromatase and 5-reductase activities. This may explain a lack of conversion to estrogens in men as well as the reduced conversion to androgens in women after percutaneous DHEA administration (19). This view is supported by the data of Casson et al. (20), who found an increase in DHEA, but not in DHEAS and T, after transvaginal DHEA administration. Serum estrogen levels were not reported in this study (20).
In agreement with our results, Labrie et al. (19) and Morales et al. (12) found no significant changes in serum T and DHT in their elderly male volunteers, whereas Young et al. (18) in their patients with hypopituitarism (including six men with unreplaced secondary hypogonadism) reported a slight, but significant, increase in serum androgens still below the normal range for men even after the administration of 200 mg DHEA. However, although total T and DHT remained unaffected in our male volunteers, a small, but significant, increase in serum free T was observed. This may be explained by transient interference of DHEA and DHEAS with binding proteins (e.g. competitive binding of DHEA and free T to SHBG or albumin) rather than by changes in binding protein concentrations. Both DHEA and T bind to SHBG and albumin (27, 28), and the rapid increase in DHEA as well as in DHEAS after oral ingestion of DHEA may be sufficient to displace a significant percentage of the protein-bound fraction of T. However, the increase in free T was short-lived and is most likely of minor importance.
Additionally, in our male volunteers a significant increase in serum ADG, a major metabolite of DHT and also of androstenedione, was observed. This may indicate an enhanced conversion of DHEA to androgens inside peripheral target cells that is not reflected by circulating androgen concentrations. A DHEA-induced increase in androgenic capacity in men may be supported by the findings of Yen et al. (13), who described increased muscular strength and decreased body fat mass in men after 6 months of treatment with a daily dose of 100 mg DHEA, but this may also be a consequence of the reported increase in insulin-like growth factor I (13).
In accordance with previous results both in men (12, 19) and women (12, 13, 17, 19, 29), DHEA administration to our male volunteers also led to a significant increase in serum androstenedione. Thus, DHEA induces a significant increase in serum androstenedione in both sexes, but the direction of further bioconversion may differ depending on the surrounding hormonal background, which may affect peripheral 17�-hydroxysteroid dehydrogenase, 5-reductase, and aromatase activities."
One thing all of these studies have in common (and I can post more) is that DHEA increases ADG and DHT. ADG increases the potential for prostate growth and DHT can cause some to loose their hair. However, controlling estrogen, and E2 in paticular, should alieviate both issues.
