2010 New Prohormone Ban – 1-04-2010

Classification of Three Steroids as Schedule III Anabolic Steroids Under the Controlled Substances Act

[Federal Register: December 4, 2009 (Volume 74, Number 232)]
[Rules and Regulations]
[Page 63603-63610]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr04de09-21]

——————————————————————

DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1300

[Docket No. DEA-285F]
RIN 1117-AB17

Classification of Three Steroids as Schedule III Anabolic
Steroids Under the Controlled Substances Act

AGENCY: Drug Enforcement Administration (DEA), Department of Justice.

ACTION: Final rule.

———————————————————————–

SUMMARY: With the issuance of this final rule, the Deputy Administrator
of the Drug Enforcement Administration (DEA) classifies the following
three steroids as “anabolic steroids” under the Controlled Substances
Act (CSA): Boldione, desoxymethyltestosterone, and 19-nor-4,9(10)-
androstadienedione. These steroids and their salts, esters, and ethers
are schedule III controlled substances subject to the regulatory
control provisions of the CSA.

DATES: Effective Date: January 4, 2010.

FOR FURTHER INFORMATION CONTACT: Christine A. Sannerud, Ph.D., Chief,
Drug and Chemical Evaluation Section, Drug Enforcement Administration,
8701 Morrissette Drive, Springfield, VA 22152, (202) 307-7183.

1-Andro Rx is NOT banned!

1-ANDRO Rx™ PRO-HORMONE
(1-Androstene-3b-ol, 17-one)
1-Andro Rx
BUY NOW!

SUPPLEMENTARY INFORMATION:

I. Background Information

In a Notice of Proposed Rulemaking (NPRM) (73 FR 22294) published
April 25, 2008, the DEA proposed the classification of three steroids
as schedule III anabolic steroids under the CSA. These three steroids
included boldione, desoxymethyltestosterone, and 19-nor-4,9(10)-
androstadienedione. With the publication of this Final Rule, DEA
classifies these three steroids as schedule III anabolic steroids.
Background information in support of this Final Rule is provided below.
On November 29, 1990, the President signed into law the Anabolic
Steroids Control Act of 1990 (Title XIX of Pub. L. 101-647), which
became effective February 27, 1991. This law established and regulated
anabolic steroids as a class of drugs under schedule III of the CSA. As
a result, a new anabolic steroid is not scheduled according to the
procedures set out in 21 U.S.C. 811, but can be administratively
classified as an anabolic steroid through the rulemaking process by
adding the steroid to the regulatory definition of an anabolic steroid
in 21 CFR 1300.01(b)(4).
On October 22, 2004, the President signed into law the Anabolic
Steroid Control Act of 2004 (Pub. L. 108-358), which became effective
on January 20, 2005. Section 2(a) of the Anabolic Steroid Control Act
of 2004 amended 21 U.S.C. 802(41)(A) by replacing the existing
definition of “anabolic steroid.” The Anabolic Steroid Control Act of
2004 classifies a drug or hormonal substance as an anabolic steroid if
the following four criteria are met: (A) The substance is chemically
related to testosterone; (B) the substance is pharmacologically related
to testosterone; (C) the substance is not an estrogen, progestin, or a
corticosteroid; and (D) the substance is not dehydroepiandrosterone
(DHEA). Any substance that meets the criteria is considered an anabolic
steroid and must be listed as a schedule III controlled substance. DEA
finds that boldione, desoxymethyltestosterone, and 19-nor-4,9(10)-
androstadienedione meet this definition of anabolic steroid and is
adding them to the list of anabolic steroids in 21 CFR 1300.01(b)(4).
Anabolic steroids are a class of drugs with a basic steroid ring
structure that produces anabolic and androgenic effects. The
prototypical anabolic steroid is testosterone. Anabolic effects include
promoting the growth of muscle. The androgenic effects consist of
promoting the development of male secondary sexual characteristics such
as facial hair, deepening of the voice, and thickening of the skin.
In the United States, only a small number of anabolic steroids are
approved for either human or veterinary use. Approved medical uses for
anabolic steroids include treatment of androgen deficiency in
hypogonadal males, adjunctive therapy to offset protein catabolism
associated with prolonged administration of corticosteroids, treatment
of delayed puberty in boys, treatment of metastatic breast cancer in
women, and treatment of anemia associated with specific diseases (e.g.,

[[Page 63604]]

anemia of chronic renal failure, Fanconi’s anemia, and acquired
aplastic anemia). However, with the exception of the treatment of male
hypogonadism, anabolic steroids are not the first-line treatment due to
the availability of other preferred treatment options. DEA is not aware
of any legitimate medical use or New Drug Applications (NDA) for the
three substances that DEA is classifying as anabolic steroids under the
definition set forth under 21 U.S.C. 802(41)(A). Moreover, DEA has not
identified any chemical manufacturers currently using these substances
as intermediates in their manufacturing process(es).
Adverse effects are associated with the use or abuse of anabolic
steroids. These effects depend on several factors (e.g., age, sex,
anabolic steroid used, the amount used, and the duration of use). In
early adolescence, the use of testosterone and other anabolic steroids
that have estrogenic effects can cause premature closure of the growth
plates in long bones resulting in a permanently stunted growth. In
adolescent boys, anabolic steroid use can cause precocious sexual
development. In both girls and women, anabolic steroid use induces
permanent physical changes such as deepening of the voice, increased
facial and body hair growth, and the lengthening of the clitoris. In
men, anabolic steroid use can cause shrinkage of the testicles,
decreased sperm count, and sterility. Gynecomastia (i.e., enlargement
of the male breast tissue) can develop with the use of those anabolic
steroids with estrogenic actions. In both men and women, anabolic
steroid use can damage the liver and can cause high cholesterol levels,
which may increase the risk of strokes and heart attacks. Furthermore,
anabolic steroid use is purported to induce psychological effects such
as aggression, increased feelings of hostility, and psychological
dependence and addiction. Upon abrupt termination of long-term anabolic
steroid use, a withdrawal syndrome may appear including severe
depression.

II. Evaluation of Statutory Factors for Classification as an Anabolic
Steroid

With the issuance of this Final Rule, DEA is classifying boldione,
desoxymethyltestosterone, and 19-nor-4,9(10)-androstadienedione as
anabolic steroids under the definition set forth under 21 U.S.C.
802(41)(A). As noted previously, a drug or hormonal substance is
classified as an anabolic steroid by meeting the following four
definitional requirements: (A) The substance is chemically related to
testosterone; (B) the substance is pharmacologically related to
testosterone; (C) the substance is not an estrogen, progestin, or a
corticosteroid; and (D) the substance is not DHEA.

(A) Chemically Related to Testosterone

To classify a substance as an anabolic steroid, a substance must be
chemically related to testosterone. DEA discussed its evaluation of the
chemical relationship of boldione, desoxymethyltestosterone, and 19-
nor-4,9(10)-androstadienedione in the NPRM published April 25, 2008 (73
FR 22294). A Structure Activity Relationship (SAR) evaluation for each
of the substances compared the chemical structure of the steroid to
that of testosterone, as substances with a structure similar to that of
testosterone are predicted to possess comparable pharmacological and
biological activity.
Boldione is also known by the following chemical name: Androsta-
1,4-diene-3,17-dione. DEA has determined that the chemical structure of
boldione is chemically related to that of testosterone. The chemical
structure of boldione differs from testosterone by only the following
structural features: A ketone group at carbon 17 and a double bond
between the carbon 1 and carbon 2. The human body would be expected to
metabolize the ketone group at carbon 17 into a hydroxyl group that is
present on testosterone (Payne and Hales, 2004; Peltoketo et al., 1999;
Moghrabi and Andersson, 1998). Furthermore, the scientific literature
reports that the additional double bond at carbon 1 in boldione does
not significantly decrease the anabolic activity of the substance
(Vida, 1969). Boldione is an anabolic steroid precursor, being
metabolized by the body into boldenone (Galletti and Gardi, 1971; Kim
et al., 2006), which is a schedule III anabolic steroid (21 U.S.C.
802(41)(A)(vi)).
Desoxymethyltestosterone (DMT) is also known by the following
names: 17[alpha]-Methyl-5[alpha]-androst-2-en-17[beta]-ol; and madol.
DEA has determined that the chemical structure of
desoxymethyltestosterone is chemically related to testosterone. The
chemical structure of desoxymethyltestosterone differs from
testosterone by the following four structural features: The lack of a
ketone group at the third carbon, a double bond between the second and
third carbon, the lack of a double bond between the fourth and fifth
carbon, and a methyl group at carbon 17. Each of these four chemical
features is known through the scientific literature not to eliminate
the anabolic and androgenic activity of the substance (Brueggemeir et
al., 2002; Vida, 1969).
19-Nor-4,9(10)-androstadienedione is also known by the following
chemical names: 19-Norandrosta-4,9(10)-diene-3,17-dione; and estra-
4,9(10)-diene-3,17-dione. DEA has determined that the chemical
structure of 19-nor-4,9(10)-androstadienedione is chemically related to
testosterone. The chemical structure of 19-nor-4,9(10)-
androstadienedione differs from testosterone by the following three
structural features: A ketone group at carbon 17, the absence of a
methyl group at carbon 19, and a double-bond between carbon 9 and
carbon 10. The human body would be expected to metabolize the ketone
group at carbon 17 into a hydroxyl group like that present in
testosterone (Payne and Hales, 2004; Peltoketo et al., 1999; Moghrabi
and Andersson, 1998). Furthermore, the scientific literature reports
that both the absence of the methyl group at carbon 19 and the
additional double bond in 19-nor-4,9(10)-androstadienedione increase
the anabolic activity of the substance (Vida, 1969).

(B) Pharmacologically Related to Testosterone

A substance must also be pharmacologically related to testosterone
(i.e., produce similar biological effects) to be classified as a
schedule III anabolic steroid. The pharmacology of a steroid, as
related to testosterone, can be established by performing one or more
of the following androgenic and anabolic activity assays: Ventral
prostate assay, seminal vesicle assay, levator ani assay, testicular
atrophy assay, gonadotropin suppression assay, and androgen receptor
binding and efficacy assays. These assays are described below.
Ventral Prostate Assay, Seminal Vesicle Assay, and Levator Ani
Assay: The classic scientific procedure for examining the effects of a
steroid as compared to testosterone is to perform the testosterone
sensitive assays, ventral prostate assay, seminal vesicle assay, and
levator ani assay in rats. Certain male accessory organs (i.e., the
ventral prostate, seminal vesicles, and levator ani muscle)
specifically need testosterone to grow and remain healthy. Upon the
removal of the testes (i.e., castration), the primary endogenous source
of testosterone is eliminated causing the atrophy of the ventral
prostate, seminal vesicles, and levator ani muscle (Eisenberg et al.,
1949; Nelson et al., 1940; Scow, 1952; Wainman and Shipounoff, 1941).
Numerous scientific studies have demonstrated the ability of exogenous
testosterone administered to rats following castration to maintain the
normal weight and size of all three

[[Page 63605]]

testosterone sensitive tissues (Biskind and Meyer, 1941; Dorfman and
Dorfman, 1963; Kincl and Dorfman, 1964; Nelson et al., 1940; Scow,
1952; Wainman and Shipounoff, 1941). Thus, a steroid with testosterone-
like activity will also prevent the atrophy of these three
testosterone-dependent tissues in castrated rats.
Testicular Atrophy Assay: Administering testosterone to non-
castrated rats causes a decrease in serum levels of gonadotropins
(i.e., luteinizing hormone [LH] and follicle stimulating hormone [FSH])
from normal levels. Gonadotropins are pituitary hormones that affect
the size and function of the testes. The suppression of these
gonadotropins by excess testosterone results in a significant decrease
in the size and weight of the testes (Boris et al., 1970; McEuen et
al., 1937; Moore and Price, 1938). Accordingly, a steroid with
testosterone-like activity will also significantly diminish the size
and weight of the testes.
Gonadotropin Suppression Assay: The castration of rats causes a
substantial increase in the serum levels of gonadotropins (i.e., LH and
FSH) above normal levels due to the removal of the principal source of
endogenous testosterone (Gay and Bogdanove, 1969; Swerdloff et al.,
1972, 1973; Swerdloff and Walsh, 1973). The administration of
testosterone to castrated animals suppresses the increase in the serum
levels of gonadotropins (Gay and Bogdanove, 1969; Swerdloff et al.,
1972; Swerdloff and Walsh, 1973; Verjans et al., 1974). The
administration of anabolic steroids with testosterone-like activity
will also prevent this increase in serum levels of LH and FSH.
Androgen Receptor Binding and Efficacy Assay: Androgen receptor
binding and efficacy assays are also used to demonstrate that the
activity of a steroid is similar to that of testosterone. Testosterone
produces its anabolic effects subsequent to binding to and activating
the androgen receptor. Different cell-based assays can compare
candidate steroids to testosterone for their ability to bind to and
activate androgen receptors.
There are several different types of assays used to establish
androgen receptor binding and efficacy. In one assay, C3H10T1/2 stem
cells express androgen receptors and are used to assess steroids for
their ability to bind and activate the androgen receptor (Jasuja et
al., 2005a,b; Singh et al., 2003). In these stem cells, the
translocation of the androgen receptor to the nucleus of the cell in
the presence of the ligand (e.g., testosterone or its active metabolite
dihydroxytestosterone) confirms that the ligand bound to the androgen
receptor and activated the downstream signaling cascade. When
activated, the C3H10T1/2 stem cells differentiate into skeletal muscle
cells as demonstrated by the increase in the expression of muscle
specific proteins (i.e., myogenic determination transcription factor
[MyoD] and myosin heavy chain [MHC]). Another assay uses human breast
cancer cells genetically altered to contain a specific reporter gene
(e.g., luciferase gene) regulated by androgen receptor activation
(Hartig et al., 2002; Wilson et al., 2002). The expression of a
bioluminescent protein (e.g., luciferase) signals both androgen
receptor binding and activation.
Results of the Androgenic and Anabolic Activity Assays: As
discussed in the NPRM, in January 2006, DEA reviewed the published
scientific literature for pharmacological data on the anabolic and
androgenic activity of boldione, desoxymethyltestosterone, and 19-nor-
4,9(10)-androstadienedione using the assays described above. As
discussed further below, there was sufficient information on the
pharmacology of desoxymethyltestosterone in the reviewed scientific
literature to determine that desoxymethyltestosterone is
pharmacologically related to testosterone (i.e., produces biological
effects similar to those of testosterone). However, the published
literature contained insufficient pharmacological data to determine
whether boldione and 19-nor-4,9(10)-androstadienedione were
pharmacologically related to testosterone. Consequently, as discussed
further below and in the NPRM, DEA sponsored pharmacological studies
involving several different androgenic and anabolic activity assays to
generate the data necessary to make this determination.
Androgenic and anabolic activity assay results indicate that
boldione, desoxymethyltestosterone, and 19-nor-4,9(10)-
androstadienedione have similar pharmacological activity as
testosterone.
Boldione
DEA sponsored a study \1\ by the Veteran’s Administration Puget
Sound Health Care System to determine the anabolic and androgenic
effects of boldione in intact and castrated rats (Matsumoto and Marck,
2006). The results of these studies were compared to the results of a
study by the same laboratory using a similar protocol to characterize
the androgenic and anabolic effects of testosterone (Marck et al.,
2003). Boldione administered to castrated male rats by silastic
capsules implanted under the skin prevented atrophy of the ventral
prostate, seminal vesicles, levator ani muscle, and the rise in serum
gonadotropin (LH and FSH) associated with castration. Boldione
administration also produced testicular atrophy in intact rats. Another
DEA sponsored study \2\ at a laboratory at Boston University examined
the ability of boldione to bind to the androgen receptor and to cause
the differentiation of C3H10T1/2 stem cells into muscle cells (Bhasin,
2005). All of these effects caused by boldione in C3H10T1/2 stem cells
were comparable to those of testosterone as established in experiments
using the same or similar methodology (Singh et al., 2003).
Collectively, the evidence indicates that the pharmacology of boldione
is similar to testosterone.
—————————————————————————

\1\ The study by the Veteran’s Administration Puget Sound Health
Care System may be found at Regulations.gov in the
electronic docket associated with this rulemaking.
\2\ The study by Boston University may be found at http://
www.regulations.gov in the electronic docket associated with this
rulemaking.
—————————————————————————

Desoxymethyltestosterone
Desoxymethyltestosterone was administered subcutaneously, orally,
or intramuscularly to castrated rats (Dorfman and Kincl, 1963; Kincl
and Dorfman, 1964; Nutting et al., 1966). By all three routes of
administration, desoxymethyltestosterone prevented the atrophy of
ventral prostate, seminal vesicles, and levator ani muscle.
Desoxymethyltestosterone also induced the expression of the
bioluminescent protein luciferase in CAMA-1 breast cancer cells
signaling androgen receptor binding and activation (Ayotte et al.,
2006). Collectively, the evidence indicates that the pharmacology of
desoxymethyltestosterone is similar to testosterone.
19-Nor-4,9(10)-Androstadienedione
As discussed in the NPRM, DEA sponsored a study \3\ by the
Veteran’s Administration Puget Sound Health Care System to determine
the anabolic and androgenic effects of 19-nor-4,9(10)-
androstadienedione in intact and castrated rats (Matsumoto and Marck,
2006). The results of these studies were compared to the results of a
study by the same laboratory using a similar protocol to characterize
the androgenic and anabolic effects of testosterone (Marck et al.,
2003). 19-Nor-4,9(10)-

[[Page 63606]]

androstadienedione administered to castrated male rats by silastic
capsules implanted under the skin prevented the atrophy of the ventral
prostate, seminal vesicles, levator ani muscle, and the rise in serum
gonadotropins (LH and FSH) associated with castration. Another DEA
sponsored study at a laboratory at Boston University \4\ examined the
ability of 19-nor-4,9(10)-androstadienedione to bind to the androgen
receptor and to cause the differentiation of C3H10T1/2 stem cells into
muscle cells (Bhasin, 2005). 19-Nor-4,9(10)-androstadienedione induced
the translocation of the androgen receptor to the nucleus of the
C3H10T1/2 stem cells, demonstrating binding affinity and efficacy for
the androgen receptor. All of these effects caused by 19-nor-4,9(10)-
androstadienedione in C3H10T1/2 stem cells were comparable to those of
testosterone as established in experiments using the same or similar
methodology (Singh et al., 2003). Collectively, the evidence indicates
that the pharmacology of 19-nor-4,9(10)-androstadienedione is similar
to testosterone.
—————————————————————————

\3\ The study by the Veteran’s Administration Puget Sound Health
Care System may be found at Regulations.gov in the
electronic docket associated with this rulemaking.
\4\ The study by Boston University may be found at http://
www.regulations.gov in the electronic docket associated with this
rulemaking.
—————————————————————————

(C) Not Estrogens, Progestins, and Corticosteroids

As discussed in the NPRM, DEA has determined that boldione,
desoxymethyltestosterone, and 19-nor-4,9(10)-androstadienedione are
unrelated to estrogens, progestins, and corticosteroids. DEA evaluated
the SAR for each of the substances. The chemical structure of each
substance was compared to that of estrogens, progestins, and
corticosteroids because the chemical structure can be related to its
pharmacological and biological activity. DEA found that the three
substances lacked the necessary chemical structures to impart
significant estrogenic activity (e.g., aromatic A ring) (Duax et al.,
1988; Jordan et al., 1985; Williams and Stancel, 1996), progestational
activity (e.g., 17[beta]-alkyl group) (Williams and Stancel, 1996), or
corticosteroidal activity (e.g., 17-ketone group or 11[beta]-hydroxyl
group) (Miller et al., 2002).

(D) Not Dehydroepiandrosterone

Dehydroepiandrosterone, also known as DHEA, is exempt from control
as an anabolic steroid by definition (21 U.S.C. 802(41)(A)). Boldione,
desoxymethyltestosterone, and 19-nor-4,9(10)-androstadienedione are not
dehydroepiandrosterone and are therefore not exempted from control on
this basis.

III. Comments Received

On April 25, 2008, DEA published a NPRM (73 FR 22294) proposing to
classify boldione, desoxymethyltestosterone, and 19-nor-4,9(10)-
androstadienedione as schedule III anabolic steroids. The proposed rule
provided an opportunity for all interested persons to submit their
comments on or before June 24, 2008. In response to the NPRM, DEA
received one comment from a consulting firm that described itself as
“[assisting] dietary supplement companies in understanding
governmental regulations while facilitating their growth.” These
comments are summarized and responded to below.
Desoxymethyltestosterone: The commenter indicated that the
scientific literature cited in the NPRM pertaining to
desoxymethyltestosterone was sufficient to meet the four criteria that
must be satisfied for DEA to designate the steroid as a schedule III
anabolic steroid. DEA agrees with this conclusion. Therefore, DEA is
placing desoxymethyltestosterone into schedule III as an anabolic
steroid as proposed.
Chemical relationship of boldione and 19-nor-4,9(10)-
androstadienedione to testosterone: The commenter claimed that DEA
failed to show that boldione and 19-nor-4,9(10)-androstadienedione are
chemically related to testosterone. The commenter claimed that both
steroids were distinctly different from testosterone in that each lacks
the 17[beta]-hydroxyl, which is present in testosterone. The commenter
noted that DEA did not provide any authority for the claim made that
“the human body would be expected to metabolize the ketone group at
carbon 17 into a hydroxyl group that is present on testosterone.”
DEA Response: DEA disagrees with this comment. The presence of the
ketone group at carbon 17 in boldione and 19-nor-4,9(10)-
androstadienedione is consistent with both steroids being chemically
related to testosterone, which has a hydroxyl group instead of a ketone
group at carbon 17. The enzyme 17[beta]-hydroxysteroid dehydrogenase is
known to be responsible for catalyzing the conversion of the 17-ketone
group to a 17[beta]-hydroxyl group in steroids such as androgens and
estrogens. This enzyme, in various isoenzymatic forms, has been
documented in many body tissues in humans and various animal species
(Payne and Hales, 2004; Peltoketo et al., 1999; Moghrabi and Andersson,
1998; Melewich et al., 1981). Considering the wide distribution of this
enzyme in tissues of humans and animals, it is expected that this
enzyme would convert the 17-ketone group found in boldione and 19-nor-
4,9(10)-androstadienedione to the 17[beta]-hydroxyl group, thereby
producing boldenone and 19-nor-4,9(10)-androstadiene-3-one-17[beta]-ol.
Direct evidence that this conversion takes place comes from two studies
showing that boldione is converted to boldenone, a schedule III
anabolic steroid, in the human body (Galletti and Gardi, 1971; Kim et
al., 2006). Therefore, the presence of the ketone group at carbon 17 in
boldione and 19-nor-4,9(10)-androstadienedione is consistent with both
steroids being chemically related to testosterone.
DEA-sponsored studies regarding pharmacological relationship: The
commenter claimed that the two studies sponsored by DEA were
insufficient to justify determining whether boldione and 19-nor-
4,9(10)-androstadienedione are pharmacologically related to
testosterone.
DEA Response: DEA disagrees with this statement. The study using
C3H10T1/2 cells demonstrates the ability of both steroids to act like
testosterone in binding and activation of the androgen receptor
resulting in protein synthesis and myotube formation. The second study
reveals the ability of the steroids to act like testosterone in
reversing the effects of castration of the rat on the size of selected
androgen-selective organs (ventral prostate, seminal vesicles, levator
ani muscle). This particular assay has been used in hundreds of studies
within the scientific and industrial community to evaluate steroids for
anabolic and androgenic activity similar to that found for testosterone
(Vida, 1969). In addition, the effects of these two steroids on LH and
FSH levels and testicular size in intact rats is also consistent with
producing pharmacological effects similar to those of testosterone.
Collectively, both studies demonstrate that boldione and 19-nor-
4,9(10)-androstadienedione are pharmacologically similar to
testosterone.
DEA-sponsored study at Boston University: The commenter claimed
that the pharmacological analysis of boldione and 19-nor-4,9(10)-
androstadienedione for androgenic activity using C3H10T1/2 stem cells
did not show a pharmacological relationship. According to the
commenter, this failure was due to: (1) Failure to obtain a random
sample of C3H10T1/2 cells; (2) erroneously assuming that mere binding
to an

[[Page 63607]]

androgen receptor and translocation to the nucleus is sufficient to
show androgenic activity; and (3) the lower potency of boldione and 19-
nor-4,9(10)-androstadienedione compared to dihydrotestosterone in the
assay.
DEA Response: DEA disagrees with these comments. First, to conduct
the study it was necessary, as provided in the protocol, to identify
batches of C3H10T1/2 cells that had the potential to differentiate into
myogenic cells when exposed to anabolic steroids. This was done and
verified using the schedule III anabolic steroid dihydrotestosterone as
a positive control. Second, this study did not simply examine androgen
receptor binding and subsequent translocation of the bound receptor to
the nucleus. Instead, with respect to boldione, 19-nor-4,9(10)-
androstadienedione, and dihydrotestosterone, the study also
demonstrated that this binding and translocation to the nucleus lead to
the commitment of these cells to form muscle cells as evidenced by
selected protein expression and the creation of myotubes. These various
effects have previously been induced by exposure of C3H10T1/2 cells to
the schedule III anabolic steroids testosterone, androstenedione, and
tetrahydrogestrinone (Singh et al., 2003; Jasuja et al., 2005a,b). The
fact that boldione and 19-nor-4,9(10)-androstadienedione were less
potent than dihydrotestosterone at producing these effects does not
preclude using this information to support the pharmacological
similarity of these steroids to testosterone. It simply means that a
higher dose of the two steroids is required to produce the effects.
DEA-sponsored study by the Veteran’s Administration Puget Sound
Health Care System: The commenter also asserted that DEA failed to show
in the rat study that boldione and 19-nor-4,9(10)-androstadienedione
produced androgenic and anabolic effects, thereby failing to show a
pharmacological relationship to testosterone. The commenter indicated
that this conclusion was based on the limited weight gain or lack of
weight gain found in animals given these steroids compared to control
animals not exposed to the steroids. Additionally, the commenter noted
as evidence for a failure to demonstrate androgenic activity the
statement in the study report that read “[t]he direct androgenic and
anabolic activity of 1,4-androstadien-3,17-dione in sham operated rats
is less clear.”
DEA Response: DEA disagrees with this comment. DEA believes that
using this assay, both steroids were found to produce pharmacological
effects like that of testosterone. Although body weight was recorded in
the study, it was not used as an endpoint for determining anabolic or
androgenic effects. This was due to the fact that the regulation of
body weight is complex, involving, among other factors, food intake,
changes in fat mass, and changes in lean body mass. Instead, the
androgenic and anabolic effects of both steroids were demonstrated by
their ability to reverse the effects of castration of male rats on the
size of the ventral prostate, seminal vesicles, and levator ani muscle,
all three being androgen sensitive tissues. As discussed in the NPRM,
numerous scientific studies have shown that exogenous testosterone
administered to castrated rats can reverse the effects of castration on
the ventral prostate, seminal vesicles, and levator ani muscle (Biskind
and Meyer, 1941; Dorfman and Dorfman, 1963; Kincl and Dorfman, 1964;
Nelson et al., 1940; Scow, 1952; and Wainman and Shipounoff, 1941).
This particular assay has been used extensively over the years by the
scientific community, including the pharmaceutical industry, to
evaluate steroids for anabolic and androgenic activity (Vida, 1969).
The authors of the DEA sponsored study specifically conclude that “In
summary, we found that, 1,4-androstadien-3,17-dione (A0100) and 4,9-
estradien-3,17-dione (E0160) demonstrated both androgenic activity, as
evidenced by stimulation of the androgenic tissues (prostate and
seminal vesicles) and anabolic activity, as evidenced by stimulation of
the levator ani muscle growth in castrated male rats.”
In regard to androgenic activity comment, the commenter did not
provide the full statement from the report which reads: “The direct
androgenic and anabolic activity of 1,4-androstadien-3,17-dione in sham
operated rats is less clear because of the measured increases in serum
T levels that could mediate the androgenic and anabolic activities of
1,4-androstadien-3,17-dione.” This statement in the report mentioned
the possibility that the pharmacological effects (reduction in LH and
FSH levels and testes size) of 1,4-androstadien-3,17-dione could result
indirectly by metabolism to an active steroid such as testosterone. As
noted in the report, it was not possible to determine whether or not
1,4-androstadien-3,17-dione actually metabolized to testosterone or
some other substance that cross reacted in the testosterone assay.
Regardless of whether 1,4-androstadien-3,17-dione acts directly or
serves as a prodrug, it still produced pharmacological effects similar
to that of testosterone when administered to rats.
DEA has evaluated the comment received and finds that it does not
provide any justification to dispute the determination that boldione,
desoxymethyltestosterone and 19-nor-4,9(10)-androstadienedione are
anabolic steroids.

IV. Conclusion and Impact of Final Rule

Conclusion

Therefore, based on the above, DEA concludes that boldione,
desoxymethyltestosterone, and 19-nor-4,9(10)-androstadienedione meet
the CSA definition of “anabolic steroid” because each substance is:
(A) Chemically related to testosterone; (B) pharmacologically related
to testosterone; (C) not an estrogen, progestin, or a corticosteroid;
and (D) not DHEA (21 U.S.C. 802(41)(A)). All anabolic steroids are
classified as schedule III controlled substances (21 U.S.C. 812(e)
schedule III). Once a substance is determined to be an anabolic
steroid, DEA has no discretion regarding the scheduling of these
substances. As discussed further below, upon the effective date of this
Final Rule all requirements pertaining to controlled substances in
schedule III pertain to these three substances.

Impact of Classifying These Substances as Anabolic Steroids

The classification of boldione, desoxymethyltestosterone, and 19-
nor-4,9(10)-androstadienedione as schedule III anabolic steroids makes
these three substances subject to CSA requirements. Any person who
manufactures, distributes, dispenses, imports, or exports boldione,
desoxymethyltestosterone, or 19-nor-4,9(10)-androstadienedione, or who
engages in research or conducts instructional activities with respect
to these three substances, must obtain a schedule III registration in
accordance with the CSA and its implementing regulations.
As of January 4, 2010, manufacture, import, export, distribution,
or sale of boldione, desoxymethyltestosterone, and 19-nor-4,9(10)-
androstadienedione, except by DEA registrants, is a violation of the
CSA that may result in imprisonment and fines (21 U.S.C. 841 and 960).
Possession of these three steroids, unless legally obtained, is also
subject to criminal penalties (21 U.S.C. 844).
In addition, under the CSA, these three substances may be imported
only

[[Page 63608]]

for medical, scientific, or other legitimate uses (21 U.S.C. 952(b))
under an import declaration filed with DEA (21 CFR 1312.18).
Importation of these substances will be illegal unless the person
importing these substances is registered with DEA as an importer or
researcher and files the required declaration for each shipment. An
individual who purchases any of these substances directly from foreign
companies and has them shipped to the U.S. is considered to be
importing even if the steroids are intended for personal use. Illegal
importation of these substances is a violation of the CSA that may
result in imprisonment and fines (21 U.S.C. 960).

Requirements for Handling Substances Defined as Anabolic Steroids

Effective January 4, 2010, boldione, desoxymethyltestosterone, and
19-nor-4,9(10)-androstadienedione are subject to CSA regulatory
controls and administrative, civil, and criminal sanctions applicable
to the manufacture, distribution, dispensing, importation, and
exportation of a schedule III controlled substance, including the
following:
Registration. Any person who manufactures, distributes, dispenses,
imports, exports, or engages in research or conducts instructional
activities with a substance defined as an anabolic steroid, or who
desires to engage in such activities, must be registered to conduct
such activities with schedule III controlled substances in accordance
with 21 CFR part 1301.
Security. Substances defined as anabolic steroids are subject to
schedule III-V security requirements and must be manufactured,
distributed, and stored in accordance with 21 CFR 1301.71, 1301.72(b),
(c), and (d), 1301.73, 1301.74, 1301.75(b) and (c), 1301.76 and
1301.77.
Labeling and Packaging. All labels and labeling for commercial
containers of substances defined as anabolic steroids which are
distributed on or after January 4, 2010, shall comply with requirements
of 21 CFR 1302.03-1302.07.
Inventory. Every registrant required to keep records and who
possesses any quantity of any substance defined as an anabolic steroid
is required to keep an inventory of all stocks of the substances on
hand pursuant to 21 CFR 1304.03, 1304.04 and 1304.11. Every registrant
who desires registration in schedule III for any substance defined as
an anabolic steroid shall conduct an inventory of all stocks of the
substances on hand at the time of registration.
Records. All registrants are required to keep records pursuant to
21 CFR 1304.03, 1304.04, 1304.05, 1304.21, 1304.22, 1304.23.
Prescriptions. All prescriptions for these schedule III substances
or for products containing these schedule III substances are required
to be issued pursuant to 21 CFR 1306.03-1306.06 and 1306.21-1306.27.
All prescriptions for these schedule III compounds or for products
containing these schedule III substances, if authorized for refilling,
are limited to five refills within six months of the date of issuance
of the prescription.
Importation and Exportation. All importation and exportation of any
substance defined as an anabolic steroid must be in compliance with 21
CFR part 1312.
Criminal Liability. Any activity with any substance defined as an
anabolic steroid not authorized by, or in violation of, the Controlled
Substances Act or the Controlled Substances Import and Export Act
occurring on or after January 4, 2010 is unlawful.

Disposal of Anabolic Steroids

Persons who possess substances classified as anabolic steroids and
who wish to dispose of them rather than becoming registered to handle
them should contact their local DEA Diversion field office for
assistance in disposing of these substances legally. DEA Diversion
field offices will provide the person with instructions regarding the
disposal. A list of local DEA Diversion field offices may be found at
DEA Diversion Control Program.

Regulatory Certifications

Regulatory Flexibility Act
The Deputy Administrator hereby certifies that this rulemaking has
been drafted in accordance with the Regulatory Flexibility Act (5
U.S.C. 601-612). This regulation will not have a significant economic
impact on a substantial number of small entities. As of August 2008,
DEA identified 61 dietary supplements promoted for building muscle and
increasing strength that are purported to contain boldione,
desoxymethyltestosterone, or 19-nor-4,9(10)-androstadienedione. Seven
dietary supplements purport to contain boldione; twenty-three dietary
supplements purport to contain desoxymethyltestosterone; and thirty-one
dietary supplements purport to contain 19-nor-4,9(10)-
androstadienedione. All 61 dietary supplements are marketed and sold on
the Internet.
The manufacturers and distributors of the 61 identified dietary
supplements purported to contain boldione, desoxymethyltestosterone, or
19-nor-4,9(10)-androstadienedione also sell a variety of other dietary
supplements. DEA has identified a substantial number of Internet
distributors that sell these dietary supplements. However, these
distributors also sell a variety of other nutritional products. DEA did
not receive any information regarding the percentage of revenues
derived from these dietary supplements. DEA did not receive any
comments regarding legitimate uses of these three substances. DEA has
not identified any chemical manufacturers that are currently using
these substances as intermediates in their manufacturing process(es).
As of August 2008, DEA identified 32 chemical manufacturers and
distributors that sell at least one of the three substances. Most of
the companies are located in China and sell a variety of steroids. DEA
notes that, as the vast majority of entities handling these substances
are Internet based, it is virtually impossible to accurately quantify
the number of persons handling these substances at any given time.
Further, DEA has no information regarding the percentage of revenue
these substances constitute for each handler.
DEA has identified five companies based in the U.S. that are DEA
registrants that manufacture and/or distribute at least one of these
substances as reference products for testing laboratories. DEA notes,
upon placement into schedule III, these substances may be used for
analytical purposes. These companies are registered with DEA and are
already in compliance with the CSA and DEA implementing regulations
regarding the handling of schedule III substances.
Executive Order 12866
The Deputy Administrator hereby certifies that this rulemaking has
been drafted in accordance with Executive Order 12866 section 1(b). It
has been determined that this rule is a significant regulatory action.
Therefore, this action has been reviewed by the Office of Management
and Budget.
As discussed above, the effect of this rule removes products
containing these substances from the over-the-counter marketplace. DEA
has no basis for estimating the size of the market for these products.
DEA notes, however, that virtually all of the substances are imported.
According to U.S. International Trade Commission data, the import value
of all anabolic steroids for the first eleven months of 2008 was $2.1
million. These three substances are

[[Page 63609]]

a subset of those imports. The value of anabolic steroid imports for
the first eleven months of 2008 declined by 28.1 percent over the
comparable period in 2007; the quantity imported during the first
eleven months decreased by 60.1 percent over the comparable period in
2007. The total market for these products containing these substances,
therefore, is probably quite small. Moreover, DEA believes that the
importation of these three substances is for illegitimate purposes.
The benefit of controlling these substances is to remove from the
marketplace substances that have dangerous side effects and no
legitimate medical use in treatment in the United States. As discussed
in detail above, these substances can produce serious health effects in
adolescents and adults. If medical uses for these substances are
developed and approved, the drugs will be available as schedule III
controlled substances in response to a prescription issued by a medical
professional for a legitimate medical purpose. Until that time,
however, this action bars the importation, exportation, and sale of
these three substances except for legitimate research or industrial
uses.
Executive Order 12988
This regulation meets the applicable standards set forth in
Sections 3(a) and 3(b)(2) of Executive Order 12988 Civil Justice
Reform.
Executive Order 13132
This rulemaking does not preempt or modify any provision of state
law; nor does it impose enforcement responsibilities on any state; nor
does it diminish the power of any state to enforce its own laws.
Accordingly, this rulemaking does not have federalism implications
warranting the application of Executive Order 13132.
Paperwork Reduction Act
This rule regulates three anabolic steroids, which are neither
approved for medical use in humans nor approved for administration to
cattle or other non-humans. Only chemical manufacturers who may use
these substances as chemical intermediates for the synthesis of other
steroids are required to register with DEA under the CSA. However, DEA
has not identified any chemical manufacturers that are currently using
these substances as intermediates in their manufacturing process(es).
Thus, DEA does not expect this rule to impose any additional paperwork
burden on the regulated industry.
Unfunded Mandates Reform Act of 1995
This rule will not result in the expenditure by state, local, and
tribal governments, in the aggregate or by the private sector, of
$120,000,000 or more (adjusted for inflation) in any one year and will
not significantly or uniquely affect small governments. Therefore, no
actions were deemed necessary under the provisions of the Unfunded
Mandates Reform Act of 1995.
Congressional Review Act
This rule is not a major rule as defined by Section 804 of the
Small Business Regulatory Enforcement Fairness Act of 1996
(Congressional Review Act). This rule will not result in an annual
effect on the economy of $100,000,000 or more; a major increase in cost
or prices; or significant adverse effects on competition, employment,
investment, productivity, innovation, or on the ability of United
States-based companies to compete with foreign-based companies in
domestic and export markets.

List of Subjects in 21 CFR Part 1300

Chemicals, Drug traffic control.

0
For the reasons set out above, 21 CFR Part 1300 is amended as follows:

PART 1300–DEFINITIONS

0
1. The authority citation for part 1300 continues to read as follows:

Authority: 21 U.S.C. 802, 821, 829, 871(b), 951, 958(f).

0
2. Section 1300.01 is amended in paragraph (b)(4) by:
0
A. Redesignating paragraphs (b)(4)(xiii) through (b)(4)(lx) as
(b)(4)(xiv) through (b)(4)(lxi),
0
B. Adding a new paragraph (b)(4)(xiii),
0
C. Further redesignating newly designated paragraphs (b)(4)(xvii)
through (b)(4)(lxi) as (b)(4)(xviii) through (b)(4)(lxii),
0
D. Adding new paragraph (b)(4)(xvii),
0
E. Further redesignating newly designated paragraphs (b)(4)(xlvii)
through (b)(4)(lxii) as (b)(4)(xlviii) through (b)(4)(lxiii), and
0
F. Adding new paragraph (b)(4)(xlvii) to read as follows:

Sec. 1300.01 Definitions relating to controlled substances.

* * * * *
(b) * * *
(4) * * *
(xiii) boldione (androsta-1,4-diene-3,17-dione)
* * * * *
(xvii) desoxymethyltestosterone (17[alpha]-methyl-5[alpha]-androst-
2-en-17[beta]-ol) (a.k.a., madol)
* * * * *
(xlvii) 19-nor-4,9(10)-androstadienedione (estra-4,9(10)-diene-
3,17-dione)
* * * * *

Dated: November 20, 2009.
Michele M. Leonhart,
Deputy Administrator.

List of References

Ayotte, C., Goudreault, D., Gauthier, J., Ayotte, P., Larochelle,
C., and Poirier, D. (2006). Characterization of chemical and
hormonal properties of new steroid related to doping of athletes.
Presented at the Cologne Workshop on Dope Analysis, June 2006.
Bhasin, S. (2005). [Pharmacological analysis of boldione and 19-nor-
4,9(10)-androstadienedione for androgenic activity using C3H10T1/2
stem cells]. Unpublished report.
Biskind, G.R. and Meyer, M.A. (1941). The comparative androgenic
potency of testosterone, methyltestosterone and testosterone
propionate administered in pellet form. Endocrinology, 28(2): 217-
221.
Boris, A., Stevenson, R.H., and Trmal,- T. (1970). Comparative
androgenic, myotrophic and antigonadotrophic properties of some
anabolic steroids. Steroids, 15(1): 61-71.
Brueggemeier, R.W., Miller, D.D., and Dalton, J.T. (2002). Estrogen,
Progestins and Androgens. In D.A. Williams and T.L. Lemke (Eds.)
Foye’s Principle of Medicinal Chemistry (5th ed.). Philadelphia,
Lippincott Williams and Wilkins.
Dorfman, R.I. and Dorfman, A.S. (1963). The assay of subcutaneously
injected androgens in the castrated rat. ACTA Endocrinologica, 42:
245-253.
Dorfman, R.I. and Kincl, F.A. (1963). Relative potency of various
steroids in an anabolic-androgenic assay using the castrated rat.
Endocrinology, 72: 259-266.
Duax, W.L., Griffin, J.F., Weeks, C.M., and Wawrzak, Z. (1988). The
mechanism of action of steroid antagonists: Insights from
crystallographic studies. Journal of Steroid Biochemistry and
Molecular Biology, 31: 481-492.
Eisenberg, E., Gordan, G.S. and Elliott, H.W. (1949). Testosterone
and tissue respiration of the castrate male rat with possible test
for myotrophic activity. Endocrinology, 45(2): 113-119.
Galletti, F. and Gardi, R. (1971). Metabolism of 1-
dehydroandrostanes in man: 1. Metabolism of 17beta-hydroxyandrosta-
1,4-dien-3-one, 17beta-cyclopent-1′-enloxyandrosta-1,4-dien-3-one
(quinbolone) and androst-1,4-diene-3,17-dione. Steroids, 18(1): 39-
50.
Gay, V.L. and Bogdanove, E.M. (1969). Plasma and pituitary LH and
FSH in the castrated rat following short-term steroid

[[Page 63610]]

treatment. Endocrinology, 84: 1132-1142.
Hartig, P.C., Bobseine, K.L., Britt, B.H., Cardon, M.C., Lambright,
C.R., Wilson, V.S., and Gray, L.E. (2002). Development of two
androgen receptor assays using adenoviral transduction of MMTV-Luc
reporter and/or hAR for endocrine screening. Toxicological Sciences,
66: 82-90.
Jasuja, R., Catlin, D.H., Miller, A., Chang, Y.-C., Herbst, K.L.,
Starcevic, B., Artaza, J.N., Singh, R., Datta, G., Sarkissian, A.,
Chandsawangbhuwana, C., Baker, M., and Bhasin, S. (2005a).
Tetrahydrogestrinone is an androgenic steroid that stimulates
androgen receptor-mediated, myogenic differentiation in C3H10T1/2
multipotent mesenchymal cells and promotes muscle accretion in
orchidectomized male rats. Endocrinology, 146(10): 4472-4478.
Jasuja, R., Ramaraj, P., Mac, R.P., Singh, A.B., Storer, T.W.,
Artaza, J., Miller, A., Singh, R., Taylor, W.E., Lee, M.L.,
Davidson, T., Sinha-Hikim, I., Gonzalez-Cadavid, N.F., and Bhasin,
S. (2005b). Delta-4-Androstene-3,17-dione binds androgen receptor,
promotes myogenesis in vitro, and increases serum testosterone
levels, fat-free mass, and muscle strength in hypogonadal men.
Journal of Clinical Endocrinology and Metabolism, 90(2): 855-863.
Jordan, V.C., Mittal, S., Gosden, B., Koch, R., and Lieberman, M.E.
(1985). Structure-activity relationships of estrogen. Environmental
Health Perspectives, 61: 97-110.
Kim, Y., Jun, M., and Lee, W. (2006). Characterization of boldione
and its metabolites in human urine by liquid chromatography/
electrospray ionization mass spectrometry and gas chromatography/
mass spectrometry. Rapid Communications in Mass Spectrometry, 20: 9-
20.
Kincl, F.A. and Dorfman, R.I. (1964). Anabolic-androgenic potency of
various steroids in a castrated rat assay. Steroids, 3: 109-122.
Marck, B.T., Wolden-Hanson, T., Tolliver, J.M., Matsumoto, A.M.
(2003). Use of DEXA to assess the anabolic actions of androgens on
relative lean body mass and bone mineral density in orchidectomized
prepubertal rats. Unpublished manuscript, Veteran’s Affairs Puget
Sound Health Care System, Seattle, WA.
Matsumoto, A.M. and Marck, B.T. (2006). DEA Agreement No. DEA-04-
P0007 Final Report [Analysis of the androgenic and anabolic
activities of 1,4-androstadien-3,17-dione and 19-nor-4,9(10)-
androstadienedione in male Sprague Dawley rats]. Unpublished report.
McEuen, C.S., Selye, H., and Collip, J.B. (1937). Effects of
testosterone on somatic growth. Proceedings of the Society for
Experimental Biology and Medicine, 36: 390-394.
Melewich, L., Bradfield, D.J., Coe, L.D., Masters, B.S.S. and
MacDonald, P.C. (1981). Metabolism of 1,4-androstadiene-3,17-dione
by human placental microsomes. Enzyme properties and kinetic
parameters in the formation of estrogens and 17beta-hydroxy-1,4-
androstadien-3-one. Journal of Steroid Biochemistry, 14: 1115-1125.
Miller, D.D., Brueggemeier, R.W., and Dalton, J.T. (2002).
Adrenocorticoids. In D.A. Williams and T.L. Lemke (Eds.) Foye’s
Principle of Medicinal Chemistry (5th ed.). Philadelphia, Lippincott
Williams and Wilkins.
Moghrabi, N. and Andersson, S. (1998). 17Beta-Hydroxysteroid
dehydrogenases: Physiological roles in health and disease. Trends in
Endocrinology and Metabolism, 9(7): 265-270.
Moore, C.R. and Price, D. (1938). Some effects of testosterone and
testosterone-propionate in the rat. The Anatominal Record, 71(1):
59-78.
Nelson, D., Greene, R.R. and Wells, J.A. (1940). Variations in the
effectiveness of percutaneously applied androgens in the rat.
Endocrinology, 26: 651-655.
Nutting, E.F., Klimstra, P.D., and Counsell, R.E. (1966). Anabolic-
androgenic activity of A-ring modified androstane derivatives. Part
I: A comparison of parenteral activity. ACTA Endocrinologica, 53:
627-634.
Payne A.H. and Hales D.B. (2004). Overview of steroidogenic enzymes
in the pathway from cholesterol to active steroid hormones.
Endocrine Reviews, 25(6): 947-970.
Peltoketo, H., Luu-The, V., Simard, J. and Adamski, J. (1999).
17Beta-Hydroxysteroid dehydrogenase (HSD)/17-ketosteroid reductase
(KSR) family; nomenclature and main characteristics of the 17HSD/KSR
enzymes. Journal of Molecular Endocrinology, 23: 1-11.
Scow, R.O. (1952). Effect of testosterone on muscle and other
tissues and on carcass composition in hypophysectomized,
thyroidectomized, and gonadectomized male rats. Endocrinology, 51:
42-51.
Singh, R., Artaza, J.N., Taylor, W.E., Gonzalez-Cadavid, N.F., and
Bhasin, S. (2003). Androgens stimulate myogenic differentiation and
inhibit adipogenesis in C3H10T1/2 pluripotent cells through an
androgen receptor-mediated pathway. Endocrinology, 144(11): 5081-
5088.
Swerdloff, R.S., Grover, P.K., Jacobs, H.S., and Bain, J. (1973).
Search for a substance which selectively inhibits FSH–Effects of
steroids and prostaglandins on serum FSH and LH levels. Steroids,
21(5): 703-722.
Swerdloff, R.S. and Walsh, P.C. (1973). Testosterone and oestradiol
suppression of LH and FSH in adult male rats: Duration of
castration, duration of treatment and combined treatment. ACTA
Endocrinologica, 73: 11-21.
Swerdloff, R.S., Walsh, P.C., and Odell, W.D. (1972). Control of LH
and FSH secretion in the male: Evidence that aromatization of
androgens to estradiol is not required for inhibition of
gonadotropin secretion. Steroids, 20(1): 13-22.
Verjans, H.L., Eik-Nes, K.B., Aafjes, J.H., Vels, F.J.M., and van
der Molen, H.J. (1974). Effects of testosterone propionate, 5alpha-
dihydrotestosterone propionate and oestradiol benzoate on serum
levels of LH and FSH in the castrated adult male rat. ACTA
Endocrinologica, 77: 643-654.
Vida, J.A. (1969). Androgens and Anabolic Agents: Chemistry and
Pharmacology. New York: Academic Press.
Wainman, P. and Shipounoff, G.C. (1941). The effects of castration
and testosterone propionate on the striated perineal musculature in
the rat. Endocrinology, 29(6): 975-978.
Williams, C.L. and Stancel, G.M. (1996). Estrogens and Progestins.
In J.G. Hardman, L.E. Limbird, P.B. Molinoff, R.W. Ruddon, A.
Goodman Gilman (Eds.) Goodman and Gilman’s The Pharmacological Basis
of Therapeutics (9th ed.). New York: McGraw-Hill, 1411-1440.
Wilson, V.S., Bobseine, K., Lambright, C.R., and Gray, L.E. (2002).
A novel cell line, MDA-kb2, that stably expresses an androgen- and
glucocorticoid-responsive reporter for the detection of hormone
receptor agonists and antagonists. Toxicological Sciences, 66: 69-
81.

Federal Document

1-Andro Rx is NOT banned!

1-ANDRO Rx™ PRO-HORMONE
(1-Androstene-3b-ol, 17-one)
1-Andro Rx
BUY NOW!

CLOSE
CLOSE