Subjects using androstenedione also showed a slight drop in levels of protective high density lipoprotein (HDL), which protects against cardiovascular disease onset. Reading the study, one can only conclude that androstenedione does not impart an anabolic effect comparable to using anabolic steroids, though it does mimic some of the negative aspects of steroid usage, such as the lowering of HDL and the increase in estrogen levels that occurs with some anabolic steroid drugs.
The University of Iowa followed up this study with a few others, all coming to the same conclusion: androstenedione has little to offer in terms of muscle-building effects in young men. Not long after the publication of these critical studies on androstenedione, a few opposing articles appeared, most of them questioning the results of the University of Iowa studies. Among the stated faults of the androstenedione study, said the critics, was that the study subjects tended to have a higher bodyfat level. This is important, because androstenedione, besides being an immediate precursor for testosterone, can also be converted into other substances. Fatty tissue contains high levels of the enzyme aromatase, which converts both testosterone and androstenedione into estrogen. Thus, men with higher bodyfat levels would be at greater risk for this type of conversion when using androstenedione.
In a recent reply to these critiques, the original authors of the androstenedione study from the University of Iowa responded in the February 9, 2000 issue of JAMA. They point out that the bodyfat level of the study subjects was below the threshold where androstenedione is converted into estrogen. They still maintain, however, that androstenedione isn’t capable of increasing testosterone levels.
This notion, however, is countered by a study published in the same issue of the journal.# This particular study was sponsored by major league baseball as a result of the controversy surrounding the use of androstenedione by home run slugger, Mark McGwire. McGwire admitted using andro during his quest to break the home run record, which he did. Since andro wasn’t a banned drug, and so little was known about it’s effects, baseball executives commissioned a group of researchers from Harvard University to examine the anabolic effects, if any, of androstenedione. The results were published in the new study.
The study involved 42 healthy men, age range of 20 to 40, who took either 100 milligrams of andro daily, 300 milligrams of andro, or no andro for 7 days. None of the study subjects had previously used andro, anabolic steroids, or any other medications known to affect steroid levels in the body. None of the men were competitive bodybuilders.
The study results showed that in the men who ingested 100 milligrams a day of andro, none showed blood testosterone levels that exceeded the upper limit of normal. However, in 4 of the men taking the 300 milligram dose, testosterone levels increased an average of 34%, though it returned to normal by the following day.
Concerning estrogen levels, 12 of 15 subjects taking 100 milligrams a day of andro, and 10 of 14 subjects taking the 300 milligram dose showed elevated estrogen levels. Those taking the 300 milligram dose of andro showed an average 128% increase in serum estrogen levels. The study authors point out that since the enzymes that convert andro to testosterone and estrogen exist in many body tissues, the levels of these hormones may have been higher in such tissues, since this study only measured blood levels of the hormones.
The study authors also say that,”Oral androstenedione administration increases serum testosterone levels suggests that it could have androgenic or anabolic effects.” But they also note that whether the testosterone increase promoted by andro actually does lead to increases in muscle size still remains unknown.
An important point noted in this study was the wide range in individual response to those taking andro. In short, some men showed higher conversion into testosterone than others. This likely relates to the activity of the converting enzymes that catalyze the conversion of andro into testosterone. In some men, such enzymes may be more active, or perhaps encounter less inhibitory effects from other substances.
Another study, reported in an endocrinology journal#, focused on whether androstenedione increases plasma testosterone levels, and if it has anabolic effects on skeletal muscle. This study featured 5 male subjects, who ingested 100 milligrams a day of andro for 5 days. While this dose may seem paltry, particularly in light of the previously discussed studies that found testosterone increases with 300 milligram doses of andro, 100 milligrams is the suggested level of many companies that sell andro.
One problem with this study was that the subjects were not lifting weights. This has both good and bad effects. It’s good because the rise in testosterone promoted by weight-training would not obscure any increases in testosterone induced by andro usage. The bad aspect is that you wouldn’t expect much of an anabolic response from andro without any type of accompanying resistance exercise.
The study results showed that andro didn’t promote any increases in blood testosterone levels, nor did it stimulate muscle protein anabolic effects. Instead, most of the ingested andro in this study was converted into estrogen, then conjugated or changed into a water-soluble form for excretion in the liver. A more problematic finding of this study was that andro appeared to increase muscle protein breakdown, which the study authors believe is linked to the elevated estrogen levels fostered by andro. They note that rat studies show that long-term exposure to elevated estrogen levels decreases muscle fiber size.
Before androstenedione came on the market, the only available prohormone was dehydroepiandrosterone (DHEA).DHEA is a steroid made in the adrenal glands, and in the form of DHEA-S (DHEA complexed with sulfur in the liver), circulates in the blood in levels far higher than any other steroid. The actual functions of DHEA aren’t completely understood, but many scientists consider it a “mother” hormone, since it can readily be converted into other steroids, such as testosterone and estrogen. The fact that it may convert into testosterone explained its initial attraction to bodybuilders.
Besides conversion into testosterone, DHEA is also often touted as a “fountain of youth” hormone. This is based on studies showing that it decreases dramatically after age 40, and studies show that when given to older people shown to be deficient in DHEA, it promotes increased well-being and a “younger feeling.” That latter effect is often attributed to the increase in insulinlike growth factor-1 (IGF-1) that usually occurs with DHEA usage in older people. IGF-1 is thought to be the active constituent of human growth hormone.
Some people suggest that DHEA also may help rid excess fat in the body, based on a study in which subjects ingested 1,600 milligrams of DHEA daily. This is in contrast to the 4 milligrams a day and 25 milligrams a day of DHEA and DHEA-S normally synthesized in younger people. Other studies, however, found no fat loss effects with DHEA. In fact, DHEA seems to work better in this regard in rats. A form of DHEA without any hormonal activity, called 7-keto DHEA, may offer some fat-loss effects due to a thermogenic effect and possible upgraded thyroid activity.
Androstenedione replaced DHEA as the prohormone of choice because the conversion of Andro into testosterone is more direct than that of DHEA. Studies consistently show that women tend to convert DHEA into testosterone (especially older women), while men convert DHEA into androstenedione. In a worst-case scenario, DHEA may take a direct route to conversion into estrogen in men, or possibly dihydrotestosterone (DHT), a testosterone metabolite linked to among other things, prostate enlargement, male pattern baldness, and acne.
A new study# compared the effects of DHEA to androstenedione in 40, healthy men, average age 40, with over one year of weight-training experience.The men were randomly divided into 3 groups: 1) Placebo; 2) DHEA; 3) Androstenedione. Those taking the DHEA or andro took 50 milligram capsules, twice daily
for 12 weeks. One good aspect of this study was the age of the study subjects. DHEA would have little or no effect in those under age 40, and some people have also suggested that andro may work better in middle-aged men or older.
Despite this, however, the study found that neither supplement significantly increased lean body mass or strength levels compared to those taking the fake pills or placebo. However, 4 of the men taking DHEA and 3 of those taking andro had subjective increased feelings of well-being. These included increased feelings of relaxation, sleep quality, energy increases, and better stress management.Two other subjects in both groups also experienced increased sex drive, as did one man in the placebo group. No adverse effects were reported.
The study authors, while noting the ease at which andro is converted into estrogen in men, also note that this increased estrogen may trigger formation of additional androgen receptors in muscle. Since testosterone must lock on to these receptors in order to exert an anabolic effect, one wonders if this may constitute an anabolic effect of andro. The men taking DHEA also showed a slight increase in IGF-1, though this rise was considered insignificant relative to those in the placebo group.
Concerning andro, the study authors noted that a doubling of serum andro levels isn’t harmful, and that the bioavailability of oral steroid use is only 5% due to such factors as digestion, liver metabolism, and specific enzyme activity. They also note that”percent uptake decreases with higher doses, thereby demonstrating other intrinsic safety mechanisms.” This notion of decreased uptake is in direct contrast to opinions expressed by others that taking higher doses of prohormones would lead to increased uptake.
The same researchers from the University of Iowa who “exposed” the failure of andro to increase blood testosterone levels also examined the effects of DHEA in resistance-trained young men.# This study involved 10 men, average age, 23, who ingested 50 milligrams a day of DHEA, which resulted in a 150% increase in blood androstenedione levels within one hour, without affecting either testosterone or estrogen levels. Another 19 men, also with an average age of 23, ingested either 150 milligrams a day of DHEA or a placebo during the course of an 8-week weight-training program. Both the placebo group and those taking the DHEA supplement made similar lean mass gains, with no hormonal changes in those taking the DHEA.
While androstenedione significantly rose in those taking both doses of DHEA in this study, neither testosterone nor estrogen levels increased. However, andro levels dropped after the 8th week in those taking the higher dose of DHEA. This effect is surmised to occur because of decreased activity of the enzyme that transforms DHEA into andro. The lack of estrogen increase, even with higher doses of DHEA is also interesting, since this was always considered one of the perils of taking DHEA in men under age 40. Curiously, early promotional material about andro frequently stated that one of its advantages over DHEA was less chance of conversion into estrogen; an effect that this study shows to be the opposite.
Another study showed that men taking 50 milligrams a day of DHEA for 18 months didn’t show any increases in testosterone levels, but the good news is that it also didn’t promote any adverse change in the prostate gland. Previous to this, DHEA was thought to be a risk factor in promoting prostate gland enlargement.
While DHEA apparently doesn’t increase estrogen levels in young men, another study found that it does increase estrogen in older men.# This study, which featured 14 men, average age 58, taking either 50 or 100 milligrams of DHEA, found that while DHEA didn’t increase testosterone levels in the men, it did increase estrogen levels in a dose-dependent manner. The study authors suspect that this rise in estrogen in older men may offer some cardiovascular disease protection.
Another study of DHEA in older people# examined the subjective increased feelings of youth reported in previous studies of DHEA in older people, and came up empty. This study found no increased feelings of well-being nor any improvement in sexual function in senior men and women ingesting 100 milligrams a day of DHEA for 3 months compared to those taking a placebo. Interestingly, however, this study did find a statistically significant increase in free testosterone in those taking the DHEA, though no gains in lean body mass or fat losses.
Adding to the confusion over the currently believed effects of prohormones is another study#, comparing the effects of androstenedione and androstenediol in 8 men, average age, 23. The men took 200 milligrams of either androstenedione, 200 milligrams of androstendiol (popularly referred to as 4-AD) or a placebo. Prohormone experts have frequently touted 4-AD as being far superior to andro because prior studies show that it has a conversion rate into free testosterone 3-times greater than that of andro. A common trade name for 4-AD is Androdiol.
According to this study, while both prohormones readily convert into testosterone in young men, with the 4-AD producing a 103% increase in both andro and testosterone, the 4-AD is more likely to convert into andro rather than testosterone. In short, this study found that andro is more readily converted into testosterone than is 4-AD, despite the latter having the reputation of being far superior in this regard!
Thus, it’s clear from these studies that all the data concerning the true effects of various prohormones isn’t in yet, and conversions that were thought to occur aren’t necessarily what actually happens in the body. This highlights the dangers of extrapolating in vitro or test tube studies to what occurs in the whole body.
©,2013 Jerry Brainum. Any reprinting in any type of media, including electronic and foreign is expressly prohibited.
