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Androstenedione

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[Advertised Claims] [Description] [ Commercial Availability and General Use] [Ergogenic Effects] [Risks and Disadvantages] [Recommendations]

Advertised Claims
  • Increases muscle size and strength
  • Testosterone precursor
  • Enhances libido

Description

Androstenedione (chemically known as 4- or 5-androstene-3beta,17beta-dione ) is a steroid hormone that is the precursor to testosterone, the steroid hormone associated with masculinity (1,2). Androstenedione has a very short half-life in the blood and is produced by the adrenal glands and the gonads from either 17alpha-hydroxyprogesterone or dehydroepiandrosterone (DHEA). DHEA is also sold as a dietary supplement. Androstenedione may be converted into either testosterone or an estrogen (estrone) within the blood (4,5).

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The conversion of androstenedione to testosterone is catalyzed by 17beta-hydroxysteroid dehydrogenase, a process activated by luteinizing hormone and thus controlled by the hypothalamus and the pituitary gland (1,2).

(See Androstenedione Conversion Table)

However, androstenedione may also be converted to the estrogen, estrone, by aromatase (estrogen synthase). Furthermore, testosterone itself may be converted to the estrogen, estradiol, by aromatase or dihydrotestosterone by 5alpha -reductase (6,7).

Commercial Availability and General Use

Androstenedione supplements are sold in health food stores. However, the use of androstenedione supplements is banned by the International Olympic Committee, the National Football League, and the National Collegiate Athletic Association. It is classified as a dietary supplement.

Androstenedione is available in various forms including 4-androstenedione and 5-androstenedione. Analogs of androstenedione also available include 4- or 5-androstenediol and 4- or 5-norandrostene- dione or diol. Androstenedione is typically sold in the form of tablets and capsules but is also available in other forms including percutaneous gels, transdermal patches, and chewing gums.

The typical, suggested method of intake is to consume 50-200 mg of androstenedione per day. Many manufacturers of androstenedione suggest that the supplement be consumed about an hour prior to exercise. Also, many manufacturers suggest cycling the use of the supplement (e.g. "four weeks on/one week off). Cost of the supplement is approximately $15-$40 for a 30-day supply.

Ergogenic Effects

Androstenedione itself is a relatively weak androgen (8,9). However, the anabolic effects of testosterone are well documented. One study reported that supraphysiologic doses of testosterone significantly increased muscle size and strength in normotestosterogenic men after 10 weeks (10). Supplementation with androstenedione, the immediate precursor to testosterone, is believed to elevate blood testosterone levels in both males and females and thus increase lean body mass (muscle mass) and physical strength.

Research Trials

Mahesh and Greenblatt

A study conducted in 1962 by Mahesh and Greenblatt (8) reported that two female subjects who ingested 100 mg of androstenedione had dramatically elevated blood testosterone levels within 90 minutes of ingestion. At 60 minutes, serum testosterone concentration increased by approximately 400% in one of the subjects and nearly 700% in the other subject. Serum testosterone concentration remained elevated in both subjects for about 90 minutes before returning to the normal level (8).

However, this study did not examine whether the acute increase in testosterone had any implication regarding muscle strength or size. It should be noted that the elevated levels of testosterone within the subjects were sharply reduced within 1 hour to 90 minutes after ingestion of androstenedione and returned to normal levels after 90 minutes. Furthermore, it should also be noted that the study only involved four female subjects. (Two subjects were treated with DHEA and the other two subjects were treated with androstenedione) (8). Thus, this particular study does not provide sufficient data to suggest that androstenedione supplementation can raise blood testosterone levels in normotestosterogenic men.

German patent

The German patent for androstenedione claims that androstenedione increased testosterone concentration by over 200% in humans and maintained elevated testosterone levels for about a week (11). However, this patent did not provide much of the data necessary to support the validity of its claims.

King et al.

A recent study conducted by Douglas King et al. (5) reported no increased levels of testosterone in normotestosterogenic, male subjects who were supplemented with androstenedione. Ten male subjects aged 19-29 years old orally consumed 300 mg of androstenedione while another 10 subjects consumed a placebo. The subjects underwent a resistance-training program during the study. The study was conducted for 8 weeks and was a double blind, randomized trial. No change in serum free or total testosterone levels were observed in any of the subjects compared to baseline during the 8-week period (5).

Ten additional male subjects participated in an acute trial (testing for an acute hormone response). This trial was a randomized, double-blinded, crossover study with a one-week washout period. The subjects either consumed 100 mg of androstenedione or a placebo after an overnight fast. Blood samples were drawn every 30 minutes for 6 hours. No change in serum free or total testosterone levels were observed during the 6-hour period (5).

However, androstenedione concentration did increase by as much as 100% during the 8-week study in the subjects treated with androstenedione. During the acute trial, serum androstenedione was elevated by about 175% at 60 minutes and 325% to 350% at 90-270 minutes. After 270 minutes, the androstenedione concentration decreased but remained elevated above baseline (5).

This increase in androstenedione occurred concomitantly with a significant increase in estrone and estradiol, indicating that increased concentration of androstenedione and a transient increase in testosterone led to increased aromatization of both androgens into the undesirable estrogens. (More on estrogen and aromatase activity below.) King's study observed no significant differences in strength, lean body mass, or muscle size between the placebo group and the treatment group during the 8-week period.

It should be noted, however, that the subjects were not highly trained (in resistance-training) before the study. Therefore, it is possible that gains attributable to androstenedione supplementation were undetectable in light of the gains in muscle size and strength that tend to occur relatively quickly during the initial phases of resistance-training. Furthermore, the dosage of androstenedione used in this study (300 mg/d) were less than the amount suggested by some of the commercial manufacturers of the supplement (as much as 1200 mg/d) (26).

Furthermore, King's study reported significantly lowered serum concentrations of high-density lipoprotein cholesterol (HDL-C) in the subjects who consumed androstenedione during the 8 week study (5). This finding is consistent with previous studies that reported similar results in subjects treated with other androgenic-anabolic steroids (though the changes in blood lipid levels were much greater in the subjects taking the illegal, androgenic-anabolic steroids) (5,22). Reduced HDL-C is associated with an increased risk of cardiovascular disease (23).

Androstendione and Estrogen

Some researchers suggest that androstenedione supplementation may increase serum estrogen levels in both males and females due to the conversion (aromatization) of the excess androstenedione and testosterone by aromatase (3,5). There is much evidence to suggest that aromatase activity occurs quite readily in the human body since both adipose tissue and muscle tissue reportedly have a large aromatizing capacity (12,13). High levels of estrogen have been linked to gynecomastia (breast development in men) (14), breast cancer (15), pancreatic cancer (16), and an increased risk of cardiovascular disease (17).

Some manufacturers of androstenedione supplements have included within their products certain compounds such as chrysin (flavone X) that are believed to temporarily inhibit the conversion of androstenedione and testosterone into estrogens. These compounds called "flavones" or "flavonoids" are derived from plants or may be synthetically produced. They appear to have a slightly higher affinity for aromatase (the enzyme, also known as estrogen synthase, that converts androstenedione and testosterone into estrogens) than the steroid substrates. The flavones are believed to either compete with androstenedione and testosterone for aromatase directly or alter the binding capacity of aromatase (18). However, studies that indicate that these flavones inhibit aromatase activity have only been conducted in vitro, and there is no evidence that this process can occur in humans.

Risks and Disadvantages
  • To date, no studies have indicated that androstenedione has any ergogenic or anabolic effects in normal, human subjects.
  • Androstenedione supplementation may result in elevated concentrations of plasma estrogen. High levels of estrogen have been linked to gynecomastia (breast development in men) (14), breast cancer (15), pancreatic cancer (16), and an increased risk of cardiovascular disease (17).
  • Elevated serum levels of androstenedione have been linked to prostrate cancer (19) and pancreatic cancer (20).
  • If androstenedione supplementation does increase testosterone levels, it may lead to the undesirable effects associated with the use androgenic-anabolic steroids. For males, such effects may include kidney and liver damage, acne, premature baldness, gynecomastia, an enlarged prostate, reduced sperm production, and heightened aggression. For females, effects could include a disrupted menstrual cycle, a deepened voice, hirsutism (increased facial hair growth), an enlarged clitoris, acne, masculinization, kidney damage, and liver damage (21).
  • An elevated testosterone level may cause the hypothalamus and the pituitary gland to suppress the body’s natural production of testosterone leading to testicular atrophy (2, 21).
  • Androstenedione supplementation may result in reduced HDL plasma concentration (5). (See King's study above)
  • It is not known if excess androstenedione or testosterone binds to other receptor sites, causing a disruption in liver metabolism and/or in the endocrine system (5, 24). Furthermore, alterations in hormone balance can be particularly detrimental to children and teenagers. An increase in serum androgens in adolescents may lead to the premature closure of bone plates (leading to stunted growth) and severe acne (2,21).
  • The excess testosterone may be converted into dihydrotestosterone (DHT) (7) which is linked to increased facial and body hair, an enlarged prostate, male-pattern baldness, and decreased serum HDL levels. DHT is not associated with increases in muscle size or strength (3).
  • It is not known if an increased production of testosterone can occur without an increased level of luteinizing hormone (24). King's study reported no increase in luteinizing hormone during the 8-week study of subjects consuming an androstenedione supplement (5). Certain androstenedione products may contain ingredients such as tribulus terrestris that are claimed to elevate luteinizing hormone levels. However, few scientific studies have indicated that such ingredients can enhance the effects of androstenedione supplementation.
  • Use of androstenedione supplements is banned by the International Olympic committee, the National Football League, and the National Collegiate Athletic Association. Use of androstenedione supplements may increase the testosterone/epitestosterone ratio and thus may be detectable in drug tests (24, 25).


Recommendations

Avoid this supplement (children and teenagers especially) until further investigation supports the safety as well as the efficacy of the supplement.

Article by Richard Chiang 08/02/99
Revised 12/22/99




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