Androstenedione
Natural Breakthrough In Testosterone
Replacement Therapy
by Jim English and Ward Dean, M.D.
Recently, a new dietary supplement has taken
the sports nutrition market by storm. Androstenedione, (pronounced
“an-dro-stene-die-own,” chemical name: andro-4-ene-3,17-dione) is a metabolite
of DHEA and a natural precursor of testosterone. To understand why androstenedione has
become so popular with athletes and bodybuilders, as well as how it may benefit health in
general, we first need to look at testosterone.
Testosterone is responsible for the normal
growth and development of the male sex organs, muscles, beard and body hair, and plays a
key role in maintaining human health, strength and energy. In short, testosterone is
responsible for making the male body “masculine.” In fact, every anabolic
steroid is a synthetic analog of testosterone (growth hormone, although anabolic, is not a
steroid—i.e., it is not derived from cholesterol). Having normal testosterone levels
is essential for health and well-being. Lest we give the impression that testosterone is
only a “male” hormone, testosterone also promotes muscle growth, maintains mood,
and boosts sex drive in women.
Testosterone and Aging
Like many other physiological and biochemical changes that occur with aging, testosterone
levels (especially free testosterone—that portion of testosterone in the blood that
is not bound to sex hormone binding globulin [SHBG]) drop significantly with advancing age. Often, symptoms like decreased sex drive and ability to perform (libido),
fatigue, depression, and signs like increased body fat, reduced muscle mass, and loss of
bone density are preceded by decreased testosterone production.
These signs of lowered testosterone production
can occur at wildly different times for different men, and some older men may maintain
testosterone levels within the normal range even at advanced ages. However, most of us
will experience a more dramatic decline—and even those fortunate seniors who manage
to maintain testosterone in the normal range probably had even higher levels in their
youth.
Conditions other than advanced age that can
lead to lower-than-normal testosterone levels include: alcoholism, AIDS, chronic anemia,
chronic corticosteroid use, chronic kidney failure, diabetes, liver disease, obesity,
osteoporosis, rheumatoid arthritis and hypogonadism.
Testosterone Replacement Therapy
(TRT)
The usual method to restore low testosterone levels to normal is to use testosterone
replacement therapy (TRT). This is normally done with injections, pills, or transdermal
patches—preferably in a manner designed to mimic the normal daily rise and fall of
testosterone. One problem with many testosterone replacement therapies is that they use
synthetic testosterone (like the hepato-toxic/liver-damaging
methyltestosterone) which may
cause a number of adverse effects.
Another challenge is to mimic the bodys
normal rhythmic production of testosterone. Testosterone is naturally produced in a
pulsatile fashion, with the greatest amount being produced throughout the evening, with
much smaller amounts produced during the day. Although somewhat safer than oral
pills, testosterone injections and transdermal patches can cause testosterone levels to
remain elevated for days or weeks (depending on the protocol used). The testosterone will
then either drop to subnormal values until the next treatment is given or applied, or the
next treatment may result in an overload or be converted into estrogens or toxic
metabolites.
The abnormally low levels of testosterone
which may occur following conventional TRT is caused by feedback inhibition of the
hypothalamus, pituitary, and testicles. This can adversely influence natural endogenous
testosterone production, and even lead to testicular atrophy. None of these problems are
known to occur with physiological (in terms of both dose and timing) supplementation of
androstenedione.
Androstenedione
Androstenedione is produced in the body from either 17-a-hydroxyprogesterone or
dehydroepiandrosterone (DHEA). It is also found in meat and in the pollen of the Scotch
Pine Tree. Since this natural testosterone precursor occurs naturally in plants and in the
human body, it falls within the classification of a “dietary supplement” under
the Dietary Supplement Health and Education Act (DSHEA).
Androstenedione was first synthesized in
1935.6 In 1936, Dr. Charles Kochakian, a world expert on steroid hormones, discovered that
it had both androgenic (masculinizing) and anabolic (tissue building) properties. The
anabolic effects of androstenedione were ignored by the scientific community until 1962.
At that time, two researchers conducted an experiment in which normal women were given
either 100 mg of DHEA or 100 mg of androstenedione. The study found that both hormones led
to elevated testosterone levels—but androstenedione increased testosterone levels
twice as much as DHEA (Mahesh and Greenblatt).8
In the women given
DHEA, testosterone levels
(normally less than 199 ng/dl), rose to 280 ng/dl within 60 minutes. The second group,
taking androstenedione, had testosterone levels elevated as high as 660
ng/dl an hour
later—a three-fold increase above normal levels!
Significantly, this testosterone increase was
transient, and lasted only a couple of hours—and remained at peak-levels for only a
few minutes—just as occurs naturally in our bodies.8 Confirmation of the
effectiveness of androstenedione is contained in a German patent which claims that 50 mg
of oral androstenedione can raise plasma testosterone levels in men from 140% to 183% of
normal. Thus, we may now have arrived at a truly physiologic (natural) way to restore
flagging testosterone levels in aging men and women to those of young, healthy adults.
Germanys Secret Weapon
Use of androstenedione as a performance-enhancing substance was later introduced by East
German researchers. Documents released after the unification of East and West Germany
reveal that in the ‘70s a team of biologists, physiologists, and physicians was
assembled to develop new scientific programs to enhance the performance of elite German
Democratic Republic (GDR) athletes. In the 1970s and 1980s the researchers recruited
over 200 male and female athletes for a test program to develop a delivery system for
androstenedione as an adjunct to testosterone-based anabolic steroids.
The idea of developing androstenedione as a
nasal spray was later introduced by Michael Oettel, a research director with the drug
company Jenapharm. Studies subsequently found that plasma testosterone levels were
dramatically elevated shortly following nasal administration of
androstenedione. The
researchers were convinced that this sudden elevation of testosterone serum levels could
enhance muscle strength and performance.
According to the research, “By nasal
intake of androstenedione, the testosterone/epitestosterone ratio increases and returns to
normal within one day. [This is an important ratio used to detect cheaters in drug
testing.] However, even though the ratio returns to normal, the total serum testosterone
level remains elevated.”
In other words, use of androstenedione
resulted in a “natural” elevation of plasma testosterone levels, thereby
defeating the Olympic drug testing program, an important goal of the GDR program.
Using Androstenedione
For those whose testosterone levels may need a boost, we recommend that 25-50 mg. of
androstenedione be taken at bedtime, and perhaps again first thing in the morning. This
will result in mimicking the bodys normal diurnal rhythms. The same dose may also be
taken 30-60 minutes before exercise (for enhanced performance) or after completion of
exercise (to enhance muscle recovery and growth).
Serum levels of testosterone start rising
about 15 minutes after oral administration and stay elevated for around 3 hours. Blood
testosterone levels usually peak in around 1 to 1.5 hours after ingestion. Because the
elevated testosterone levels swiftly return to normal baseline levels, there is little
risk of negative feedback suppression of the hypothalamus, pituitary or testicles.
Women may also benefit from occasional
low-dose androstenedione use. It will probably be found to be of use in the maintenance of
bone density and actual reversal of osteoporosis. Also, occasional use of androstenedione
as a libido-enhancer has been reported, with onset of effects occurring within 30-60
minutes. Women using androstenedione for any use should be careful to adjust the dose
downward—or discontinue use—should signs of secondary male characteristics be
noted (i.e., voice deepening, hair or whiskers on upper lip, etc).
References:
Colgan M. Hormonal Health. Vancouver: Apple
Publishing, 1996.
Kochakian CD. Metabolites of testosterone. Significance in the vital economy. Steroids,
1990; 55: 92-97.
Colgan M. Optimum Sports Nutrition. New York: Advanced Research Press, 1993.
Stryer L. Biochemistry, 2nd Ed. New York: WH Freeman, 1981.
Yesalis CE (ed). Anabolic Steroids in Sport and Exercise. Human Kinetics, Champaign IL:
1993.
Ruzicka L, Wettstein A. The crystalline production of the testicle hormone testosterone
(Androsten-3-ol-17-ol). Helvetica Chimica Acta, 1935;18:1264-1275.
Kochakian CD, Murlin JR. The relationship of synthetic male hormone androstenedione to
the protein and energy metabolism of castrated dogs and the protein metabolism of a normal
dog. Amer J Physiol, 1936;117:642-657.
Mahesh VB, Greenblatt
RB. The in-vivo conversion of dehydroepiandrosterone and
androstenedione to testosterone in the human. Acta Endocrinol, 1962;41:400-406. Athletes
and Testosterone Levels.
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