Encyclopedia of

Androstenedione 11
serum testosterone (ng/dl)
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Fig. 5 Serum testosterone levels during 12 hr of frequent
blood sampling in postmenopausal women. Circles represent
control subjects receiving no supplement, triangles those
receiving 50 mg of androstenedione, and squares those
receiving 100 mg. (Adapted from Ref. [18] .)
(estradiol was not measured). [19] Importantly, in both
of these studies, the peak testosterone levels achieved
by the older and younger women taking androstenedione
were often significantly above the normal range.
Together, these results predict that the physiological
effects of the supplement may be different in men
and women, as might their potential toxicities. To
date, however, there have been no published reports
investigating the long-term physiological effects
in women.
ADVERSE EFFECTS AND TOXICITY
Ever since the publicity surrounding androstenedione
exploded in 1999, many reports in the lay press have
focused on the potential dangerous side effects. Nonetheless,
with the exception of a single case description
of a man who developed 2 episodes of priapism in
the setting of androstenedione ingestion, [20] there have
been no published reports of androstenedioneassociated
serious adverse events. This fact should
be only partially reassuring, however, because androstenedione’s
classification as a dietary supplement (as
opposed to a drug) allows manufacturers to avoid
responsibility for rigorously monitoring any potential
toxicity of their product.
It is well known that oral administration of certain
testosterone derivatives can cause severe liver diseases,
and anabolic steroid use in general is associated with
anecdotal reports of myocardial infarction, sudden
cardiac death, and psychiatric disturbances (‘‘roid
rage’’). Nonetheless, despite androstenedione’s close
chemical similarity to these substances, it is important
to note that it is not a potent anabolic steroid; nor
does it have a chemical structure similar to those specific
compounds that cause liver problems. Thus, the
potential of androstenedione to cause these particular
serious side effects appears to be limited. Of more
pressing concern to clinicians are the possible longterm
effects in specific populations. In clinical trials,
the supplement was generally well tolerated, though
several studies did report that it reduces high-density
lipoprotein (HDL, or ‘‘good cholesterol’’) levels in
men. Importantly, however, even the longest of these
studies lasted only several months. It thus remains
quite possible that androstenedione use, especially at
high doses, could cause subtle physiologic changes
over prolonged periods that could directly lead to
adverse health consequences. In men, for example,
the dramatic increase in estradiol levels observed with
androstenedione administration could, over time, lead
to gynecomastia (male breast enlargement), infertility,
and other signs of feminization. In women, because
the supplement increases testosterone levels above the
normal range, it could cause hirsutism (excess body
hair growth), menstrual irregularities, or male-like
changes in the external genitalia. In children, increases
in both testosterone and estrogen levels could cause
precocious puberty or premature closure of growth
plates in bone, thereby compromising final adult height.
PURITY OF COMMERCIALLY AVAILABLE
ANDROSTENEDIONE
Androstenedione is available from multiple manufacturers
and can be purchased as a tablet, capsule,
sublingual tablet, or even nasal spray. Often, it is
combined with other products that claim to limit its
potential side effects (such as chrysin, for example,
which is purported to decrease androstenedione’s
conversion to estrogens). Because the manufacture of
dietary supplements is not subject to the same
regulations as are pharmaceuticals, the purity and
labeling of androstenedione-containing products may
not be accurate. Catlin and colleagues, for example,
reported the surprise finding that urine samples
from men treated with androstenedione contained
19-norandrosterone, a substance not associated with
androstenedione metabolism, but rather with the use
of a specific banned anabolic steroid. [21] Further investigation
revealed that the androstenedione product
used contained a tiny amount of the unlabeled steroid
‘‘19-norandrostenedione.’’ Though the amount of
19-norandrostenedione was not physiologically significant,
it was enough to cause a ‘‘positive’’ urine test for
illegal anabolic steroid use when tested in the standard
fashion. In fact, it is precisely this type of contamination
that may explain the recent increase in competitive
athletes testing positive for 19-norandrosterone and
other banned substances in well-known standard
testing methods.
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