Back then, we were commenting on a study that had been designed to see if DHEA had any beneficial or detrimental effects on a population of elderly persons. Specifically, they wanted to see if there was an increase in muscle mass, stamina, or bone density; whether glucose regulation improved; or whether quality of life improved. They also looked for evidence of harm.
From: F. Labrie et al. /
Journal of Steroid Biochemistry & Molecular Biology
100 (2006) 52–58 53
What they found was, basically, nothing. There were slight improvements in a few areas, but nothing significant. No harm was detected, either.
With that as background, I read the Life Extension article. I must say, I found it to be both informative, and irritating...
The magazine is published by the Life Extension Foundation. Along with the article cited above, there was an another on the same subject: Congress Seeks to Ban DHEA, by William Faloon (not available on line).
The gist of the two articles is this: bills have been introduced in Congress (S. 762 and H.R. 1249) that would classify DHEA as an anabolic steroid under the Controlled Substances Act. The result would be that the substance could not be purchased without a prescription.
The Senate bill was introduced by Chuck Grassley, cosponsored by McCain and Durbin. The House bill was introduced by Peter Roskam, and has no cosponsors. As far as I could tell, Grassley is the only one who mentions it on his website:
GRASSLEY CONTINUES EFFORTS TO CRACK DOWN ON STEROID ABUSE
Bill Adds a Common Steroid to List of Banned Substances
WASHINGTON – Senator Chuck Grassley today introduced legislation that would add dehydroepiandrosterone, or DHEA, to the list of anabolic steroids that are classified as controlled substances under the Anabolic Steroid Control Act. The legislation was introduced with Senators John McCain of Ariz. and Dick Durbin of Ill...
...Like all steroids, DHEA has a number of potential long-term physical and psychological effects, including heart disease, cancer, stroke, liver damage, severe acne, baldness, dramatic mood swings and aggression.
Life Extension took exception to that last paragraph. They inquired about the basis for the claims. They were sent a copy of a paper by Fernand Labrie, et. al.
Dehydroepiandrosterone (DHEA) is an anabolic steroid like dihydrotestosterone (DHT), the most potent natural androgen, and tetrahydrogestrinone (THG)
The Journal of Steroid Biochemistry and Molecular Biology
Volume 100, Issues 1-3, July 2006, Pages 52-58
We have recently taken advantage of the unique power of DNA microarrays to compare the genomic expression profile of tetrahydrogestrinone (THG) with that of dihydrotestosterone (DHT), the most potent natural androgen, thus clearly demonstrating that THG is an anabolic steroid. In 2004, the U.S. Controlled Substances Act has been modified to include androstenedione (4-dione) as an anabolic steroid. However, despite the common knowledge that dehydroepiandrosterone (DHEA) is the precursor of testosterone, DHEA has been excluded from the list of anabolic steroids. We thus used the same DNA microarray technology to analyze the expression profile of practically all the 30 000 genes of the mouse genome modulated by DHEA and DHT in classical androgen-sensitive tissues. Daily subcutaneous injections of DHT (0.1 mg) or DHEA (3 mg) for 1 month in gonadectomized C57BL6/129 SV mice increased ventral prostate, dorsal prostate, seminal vesicle and preputial gland weight (p < 0.01 for all tissues). As early as 24 h after single injection of the two steroids, 878, 2681 and 14 probe sets were commonly stimulated or inhibited (p < 0.01, change ≥ 30%), in the prostate (ventral + dorsal), seminal vesicles and preputial glands, respectively, compared to tissues from gonadectomized control animals. After 7 days of daily treatment with DHEA and DHT, 629, 919 and 562 probe sets were commonly modulated in the same tissues while after 27 days of treatment, 1195, 5127 and 2883 probe sets were modulated, respectively. In analogy with the data obtained with THG, the present microarray data provide an extremely precise and unquestionable genomic signature and proof of the androgenic/anabolic activity of DHEA. Such data add to the literature showing that DHEA is transformed into androgens in the human peripheral tissues as well as in laboratory animal species, including the monkey, thus exerting potent androgenic/anabolic activity. The present microarray approach to identify anabolic compounds is applicable to all potential androgenic/anabolic compounds.
The abstract indicates that study provides "proof of the androgenic/anabolic activity of DHEA". Never mind that tehy used 3mg injected doses in mice, while the usual human oral doses are about 15 to 200mg per day. I didn't do the math, but the LEF did:
The numbers came in showing that the human-equivalent dose of DHEA used in this gene expression study was 15,800 mg in the four-week arm, and an astounding 43,910 mg in the one-week arm.
To put this in context, LEF sells DHEA in 100mg capsules, #60 for $30. You would have to take 158 of them at a cost of $79 per day to get a dose comparable to what the mice got in the lower-dose arm of the study. That is not completely out of the question; drug abusers, after all, have been known to do some pretty strange things to get whatever effect they are looking for. But the abstract refers to "potent androgenic/anabolic activity". Potency, of course, refers to the magnitude of the effect per milligram of dose. Their own data do not show that DHEA is "potent," rather the opposite.
The paper simply does not support the contention that DHEA should be a controlled substance. The paper that Orac, Tara, and I commented upon earlier also does not show that. If anything, it shows that Congress can safely ignore the whole issue.
So what is going on here?
LEF points out one possibility. The lead author of the JSBMB paper, Fernand Labrie, happens to hold a US patent on the medical use ofa combination of DHEA and selective estrogen receptor modulators (SERMs). (US Patent 7,005,428) The medical rationale for such treatment is outlined in another of his papers:
Future perspectives of selective estrogen receptor modulators used alone and in combination with DHEA
Endocrine-Related Cancer 13 (2) 335-355
...However, it is expected that a SERM alone will not meet all the requirements of women’s health at the postmenopause when ovarian estrogen secretion has ceased and peripheral formation of androgens and estrogens from DHEA by intracrine mechanisms is decreased by 60% or more. One possibility is to combine a SERM with DHEA, a precursor of sex steroids that permits, somewhat like SERMs, tissue-specific formation of androgens and/or estrogens according to the level of expression of the steroidogenic and steroid-inactivating enzymes. DHEA could thus compensate for the important loss of androgens that accompanies aging and could also permit sex steroid formation and action in the brain while breast cancer prevention would be achieved by the SERM.
Tamoxifen is a SERM, and it happens to be a generic drug. DHEA is now available over the counter. So if his approach is proven to be efficacious, the patent could enable him (and his company, Endorecherche, Inc.) to market a combination drug at a high price, but only if DHEA is not otherwise available. If anyone can get it, then anyone with a prescription for generic tamoxifen could get the same result at a much lower cost.
There are two sides to this issue, and there are people on both sides who have a financial stake in the outcome. Endorecherche may be angling for patent protection for a product, while LEF wants to be able to sell DHEA for 50 cents a capsule. While that does not prove that they are not credible sources, it does give up good reason to cast a critical eye toward their arguments.
It is hard to know what motivates people, but large sums of money generally suffice. I can't determine if the LEF's allegations are true, that Congress is being manipulated into passing a law that could be financially favorable to Endorecherche. It would not be a huge surprise, though. Clearly, Senator Grassley, based upon his press release, has been hoodwinked.
On the other hand, Fernand Labrie is not the only one with scientific credentials who advocates for making DHEA an FDA-regulated substance. In an NEMJ editorial (not open-access), Dr. Paul Stewart argues the same thing:
In light of an evidence base for the efficacy of DHEA in patients with adrenal insufficiency, DHEA should no longer be accepted as a food supplement and should instead be treated as a regulated drug.
Gary Wadler, M.D, argues the same:
In conclusion, my own view is -- and I feel very strongly about it for the reasons I discussed earlier -- the steroid hormones, including DHEA and Androstenedione, should be reclassified as drugs requiring a consultation with a physician, and the obtaining of a written presciption for these substances, in accordance with the principles of medical practice.
So even though Grassley and the others are citing a paper that does not support their contentions, there are credible experts out there who would support the legislation. I don't happen to agree with them, but they are out there.
You see, Dr. Stewart argues that DHEA can be used to treat adrenal insufficiency, so it should be considered a drug. But water deficiency can be treated by, no big surprise, water. Water can be dangerous in overdose. But nobody is arguing that water should be a controlled substance. Arguing that DHEA is or is not an anabolic steroid is pointless; it is irrelevant from a legal standpoint.
The legal issue is this: does Government have a compelling interest that would justify regulation of the substance? I haven't seen anything that demonstrates that it does, to my satisfaction.
Comments
Government has a compelling interest ..a compelling interest in lining their own pockets and the drug companies and doctors assocations that they are in bed with. If DHEA becomes regulated, that means more money for doctors who people will have to go to to get a prescription for DHEA. That's what happened in Canada.
Posted by: Jesse | July 5, 2007 3:48 AM
Written in a different context, but admirably clear:
"Biologically rational decisions may not be politically possible once investment has occurred."
--- Science v315 (5 Jan. 2007) at 45.
10.1126/science.1135767
Posted by: Hank Roberts | July 6, 2007 11:31 PM