44456 Federal Register / Vol. 77, No. 146 / Monday, July 30, 2012 / Rules and Regulations 

PART 50—CLEARING REQUIREMENT 

Authority: 7 U.S.C. 2 as amended by Pub. 

L. 111–203, 124 Stat. 1376. 

§ 50.25 Clearing requirement compliance 

schedule. 

(a) Definitions. For the purposes of 

this paragraph: 

Active Fund means any private fund 

as defined in section 202(a) of the 

Investment Advisers Act of 1940, that is 

not a third-party subaccount and that 

executes 200 or more swaps per month 

based on a monthly average over the 12 

months preceding the Commission 

issuing a clearing requirement 

determination under section 2(h)(2) of 

the Act. 

Category 1 Entity means a swap 

dealer, a security-based swap dealer; a 

major swap participant; a major 

security-based swap participant; or an 

active fund. 

Category 2 Entity means a 

commodity pool; a private fund as 

defined in section 202(a) of the 

Investment Advisers Act of 1940 other 

than an active fund; or a person 

predominantly engaged in activities that 

are in the business of banking, or in 

activities that are financial in nature as 

defined in section 4(k) of the Bank 

Holding Company Act of 1956, provided 

that, in each case, the entity is not a 

third-party subaccount. 

Third-party Subaccount means an 

account that is managed by an 

investment manager that is independent 

of and unaffiliated with the account’s 

beneficial owner or sponsor, and is 

responsible for the documentation 

necessary for the account’s beneficial 

owner to clear swaps. 

(b) Upon issuing a clearing 

requirement determination under 

section 2(h)(2) of the Act, the 

Commission may determine, based on 

the group, category, type, or class of 

swaps subject to such determination, 

that the following schedule for 

compliance with the requirements of 

section 2(h)(1)(A) of the Act shall apply: 

(1) A swap between a Category 1 

Entity and another Category 1 Entity, or 

any other entity that desires to clear the 

transaction, must comply with the 

requirements of section 2(h)(1)(A) of the 

Act no later than ninety (90) days from 

the date of publication of such clearing 

requirement determination in the 

Federal Register. 

(2) A swap between a Category 2 

Entity and a Category 1 Entity, another 

Category 2 Entity, or any other entity 

that desires to clear the transaction, 

must comply with the requirements of 

section 2(h)(1)(A) of the Act no later 

than one hundred and eighty (180) days 

from the date of publication of such 

clearing requirement determination in 

the Federal Register. 

(3) All other swaps for which neither 

of the parties to the swap is eligible to 

claim the exception from the clearing 

requirement set forth in section 2(h)(7) 

of the Act and § 39.6, must comply with 

the requirements of section 2(h)(1)(A) of 

the Act no later than two hundred and 

seventy (270) days from the date of 

publication of such clearing 

requirement determination in the 

Federal Register. 

(c) Nothing in this rule shall be 

construed to prohibit any person from 

voluntarily complying with the 

requirements of section 2(h)(1)(A) of the 

Act sooner than the implementation 

schedule provided under paragraph (b). 

Issued in Washington, DC, on July 24, 

2012, by the Commission. 

Sauntia Warfield, 

Assistant Secretary of the Commission. 

Appendices to Swap Transaction 

Compliance and Implementation 

Schedule: Clearing Requirement under 

Section 2(h) of the CEA—Commission 

Voting Summary and Statements of 

Commissioners 

Note: The following appendices will not 

appear in the Code of Federal Regulations. 

Appendix 1—Commission Voting 

Summary 

On this matter, Chairman Gensler and 

Commissioners Sommers, Chilton, O’Malia 

and Wetjen voted in the affirmative; no 

Commissioner voted in the negative. 

Appendix 1—Statement of Chairman 

Gary Gensler 

I support the final rule to establish a 

schedule to phase in compliance with the 

clearing requirement provisions in the DoddFrank Wall Street Reform and Consumer 

Protection Act. 

The rule gives market participants an 

adequate amount of time to comply and 

helps facilitate an orderly transition to the 

new clearing requirements for the swaps 

market. The rule provides greater clarity to 

market participants regarding the timeframe 

for bringing their swaps into compliance 

with the clearing requirement. 

[FR Doc. 2012–18383 Filed 7–27–12; 8:45 am] 

BILLING CODE 6351–01–P 

DEPARTMENT OF JUSTICE 

Drug Enforcement Administration 

21 CFR Part 1300 

[Docket No. DEA–341F] 

RIN 1117–AB31 

Classification of Two Steroids, 

Prostanozol and Methasterone, 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 Administrator of the 

DEA classifies the following two 

steroids as ‘‘anabolic steroids’’ under 

the Controlled Substances Act (CSA): 

prostanozol (17b-hydroxy-5aandrostano[3,2-c]pyrazole) and 

methasterone (2a,17a-dimethyl-5aandrostan-17b-ol-3-one). 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: August 29, 2012. 

FOR FURTHER INFORMATION CONTACT: 

Alan G. Santos, Associate Deputy 

Assistant Administrator, Office of 

Diversion Control, Drug Enforcement 

Administration; Mailing Address: 8701 

Morrissette Drive, Springfield, Virginia 

22152; Telephone: (202) 307–7165. 

SUPPLEMENTARY INFORMATION: 

Legal Authority 

The DEA implements and enforces 

Titles II and III of the Comprehensive 

Drug Abuse Prevention and Control Act 

of 1970, often referred to as the 

Controlled Substances Act and the 

Controlled Substances Import and 

Export Act (21 U.S.C. 801–971), as 

amended (hereinafter, ‘‘CSA’’). The 

implementing regulations for these 

statutes are found in Title 21 of the 

Code of Federal Regulations (CFR), parts 

1300 to 1321. Under the CSA, controlled 

substances are classified in one of five 

schedules based upon their potential for 

abuse, their currently accepted medical 

use, and the degree of dependence the 

substance may cause. 21 U.S.C. 812. The 

initial schedules of controlled 

substances by statute are found at 21 

U.S.C. 812(c) and the current list of 

scheduled substances is published at 21 

CFR Part 1308. 

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 


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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 

is administratively classified as an 

anabolic steroid through the rulemaking 

process if it meets the regulatory 

definition of an anabolic steroid in 21 

CFR 1300.01. 

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 these criteria is 

considered an anabolic steroid and must 

be listed as a Schedule III controlled 

substance. 

Background 

In a Notice of Proposed Rulemaking 

(NPRM) published on November 23, 

2011 (76 FR 72355), DEA proposed 

classification of two steroids as 

Schedule III anabolic steroids under the 

CSA: Prostanozol and methasterone. 

DEA believes that prostanozol (17bhydroxy-5a-androstano[3,2-c]pyrazole) 

and methasterone (2a,17a-dimethyl-5aandrostan-17b-ol-3-one) meet this 

definition of anabolic steroid. 

Anabolic steroids are a class of drugs 

structurally related to the endogenous 

hormone testosterone that exert 

androgenic (masculinizing) as well as 

anabolic (body building) effects. These 

effects are mediated primarily through 

binding of the anabolic steroid to the 

androgen receptor in target tissues 

(Evans, 2004). Anabolic effects include 

promotion of protein synthesis in 

skeletal muscle and bone, while the 

androgenic effects are characterized by 

the development of male secondary 

sexual characteristics such as hair 

growth, deepening of the voice, 

glandular activity, thickening of the 

skin, and central nervous system effects 

(Kicman, 2008). Anabolic efficacy is 

characterized by positive nitrogen 

balance and protein metabolism, 

resulting in increases in protein 

synthesis and lean body mass (Evans, 

2004). These effects often come at a cost 

to the healthy individual who 

experiences clear physical and 

psychological complications (Trenton 

and Currier, 2005; Brower, 2002; Hall et 

al., 2005). 

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., 

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 

two substances that DEA is proposing to 

classify by this NPRM as anabolic 

steroids under the definition set forth 

under 21 U.S.C. 802(41)(A). Moreover, 

DEA has been unable to identify any 

chemical manufacturers currently using 

these substances as intermediates in 

their manufacturing processes. 

Adverse health effects are associated 

with abuse of anabolic steroids and 

depend on several factors (e.g., age, sex, 

anabolic steroid used, the amount used, 

and the duration of use) (Hall and Hall, 

2005; Quaglio et al., 2009). These 

include cardiovascular, dermatological, 

behavioral, hepatic, and gender specific 

endocrine side effects. Anabolic steroids 

have direct and indirect impact on the 

developing adolescent brain and 

behavior (Sato et al., 2008). 

Furthermore, adolescent abuse of 

anabolic steroids may result in stunted 

growth due to premature closure of the 

growth plates in long bones. 

In adolescent boys, anabolic steroid 

abuse can cause precocious sexual 

development. In both girls and women, 

anabolic steroid abuse induces 

permanent physical changes such as 

deepening of the voice, increased facial 

and body hair growth, menstrual 

irregularities, and clitoral hypertrophy. 

In men, anabolic steroid abuse can 

cause testicular atrophy, decreased 

sperm count, and sterility. 

Gynecomastia (i.e., enlargement of the 

male breast tissue) can develop with the 

abuse of those anabolic steroids with 

estrogenic actions. In both men and 

women, anabolic steroid abuse can 

damage the liver and may result in high 

cholesterol levels, which may increase 

the risk of strokes and cardiovascular 

heart attacks. Furthermore, anabolic 

steroid abuse is purported to induce 

psychological effects such as aggression, 

increased feelings of hostility, and 

psychological dependence and 

addiction (Brower, 2002; Kanayama et 

al., 2008). 

Upon abrupt termination of long-term 

anabolic steroid abuse, a withdrawal 

syndrome may appear including severe 

depression. Additionally, polysubstance 

abuse is routinely associated with 

anabolic steroid abuse, where ancillary 

drugs, including recreational and 

prescription drugs, are abused in 

response to unwanted side effects (Hall 

et al., 2005; Parkinson et al., 2005; 

Skarberg et al., 2009). 

A review of the scientific literature 

finds adverse health effects including 

liver toxicity with renal failure reported 

in conjunction with methasterone abuse 

(Shah et al., 2008; Jasiurkowski et al., 

2006; Singh et al., 2009; Nasr and 

Ahmad, 2008; and Krishnan et al., 

2009). In March 2006, the U.S. Food and 

Drug Administration (FDA) issued a 

Warning Letter in response to adverse 

health effects associated with the 

product Superdrol (methasterone). In 

July 2009, FDA issued a warning 

regarding bodybuilding products 

containing steroid or steroid-like 

substances. In this warning, a product 

containing the THP ether derivative of 

prostanozol was named in conjunction 

with other products presenting safety 

concerns. 

Evaluation of Statutory Factors for 

Classification as an Anabolic Steroid 

With the issuance of this Final Rule, 

DEA classifies prostanozol (17bhydroxy-5a-androstano[3,2-c]pyrazole) 

and methasterone (2a,17a-dimethyl-5aandrostan-17b-ol-3-one) 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 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. A structure 

activity relationship (SAR) evaluation 

for each substance compared the 

chemical structure of the steroid to that 

of testosterone. Substances with a 


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44458 Federal Register / Vol. 77, No. 146 / Monday, July 30, 2012 / Rules and Regulations 

structure similar to that of testosterone 

are predicted to possess comparable 

pharmacological and biological activity. 

Prostanozol is also known by the 

following name: 17b-hydroxy-5aandrostano[3,2-c]pyrazole. DEA 

determined that the chemical structure 

of prostanozol is similar to testosterone, 

differing by only the attachment of a 

pyrazole ring at carbon 2 (C2) and 

carbon 3 (C3) positions of the 

androstane skeleton, replacing the C3- 

keto group and the lack of a double 

bond between carbon 4 (C4) and carbon 

5 (C5) positions. Similar modifications 

to testosterone’s chemical structure have 

been documented and, in general, they 

have been found to be well tolerated, 

displaying both anabolic and 

androgenic activity (Fragkaki et al., 

2009; Vida, 1969). Clinton and 

coworkers, in their synthesis of 

prostanozol, described the modification 

as a fusion of a pyrazole ring to the 

androstane steroidal nucleus at C2 and 

C3 (Clinton et al., 1961). Further 

analysis finds the chemical structure of 

prostanozol to be very similar to the 

anabolic steroid stanozolol. The two 

structures differ only about a 17amethyl group (alpha methyl group 

attached to carbon 17). 

Methasterone is known by the 

following chemical names: 2a,17adimethyl-5a-androstan-17b-ol-3-one; 

2a,17a-dimethyl-17b-hydroxy-5aandrostan-3-one; 17a-methyldrostanolone; methasteron; 

methyldrostanolone; 2a,17adimethyldihydrotestosterone; and 

2a,17a-dimethyl-etiocholan-17b-ol-3- 

one. DEA has determined that the 

chemical structure of methasterone is 

chemically related to testosterone. The 

chemical structure of methasterone 

differs from testosterone by the 

following three chemical groups: An 

alpha methyl group at carbon 17 (C17), 

an alpha methyl group at C2, and the 

lack of a double bond between spanning 

C4 and C5. Removal of the C4–C5 

double bond (A-ring) and methylation at 

the C2 and C17 positions has been 

shown to increase anabolic activity 

(Zaffroni, 1960; Fragkaki et al., 2009). 

Furthermore, methyl group substitution 

at the C2 and C17 has been reported to 

impair aromatization, thus, prolonging 

the anabolic effect (Fragkaki et al., 

2009). 

(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, 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 

evaluating androgenic (masculinizing) 

and anabolic (muscularizing) effects of a 

steroid is the ventral prostate assay, 

seminal vesicle assay, and levator ani 

assay. This testing paradigm allows for 

the direct comparison to testosterone. 

Select male accessory tissues (i.e., the 

ventral prostate, seminal vesicles, and 

levator ani muscle) are testosterone 

sensitive, specifically requiring 

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 or a pharmacologically 

similar steroid administered to rats 

following castration to maintain the 

normal weight and size of all three 

testosterone sensitive organs (Biskind 

and Meyer, 1941; Dorfman and 

Dorfman, 1963; Dorfman and Kincl, 

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 organs in 

castrated rats. 

Castrated male rats are administered 

the steroid for a number of days, then 

the rats are euthanized and the 

previously described tissues are excised 

and weighed. Tissue weights from the 

three animal test groups are compared, 

castrated animals alone, castrated 

animals receiving the steroid, and 

healthy intact animals (control), to 

assess anabolic and androgenic activity. 

A reduction in tissue weights relative to 

the control group suggests a lack of 

androgenic and/or anabolic activity. An 

increase in tissue weights relative to the 

castrated rats receiving no steroid 

suggests an androgenic and/or anabolic 

effect. 

Androgen Receptor Binding and 

Efficacy Assay: Anabolic steroids bind 

with the androgen receptor to exert their 

biological effect. Affinity for the 

receptor is evaluated in the receptor 

binding assay, while the transactivation 

(functional) assay provides additional 

information as to both affinity and 

ability to activate the receptor. Receptor 

binding and transactivation studies are 

valuable tools in evaluating 

pharmacological activity and drawing 

comparisons to other substances. A 

steroid displaying affinity for the 

androgen receptor and properties of 

being an agonist in transactivation 

studies is determined to be 

pharmacologically similar to 

testosterone. 

Studies used to evaluate anabolic 

steroids are the androgen receptor 

binding assay and the androgen receptor 

transactivation assay. Both are wellestablished and provide significant 

utility in evaluating steroids for affinity 

to their biological target and the 

modulation of activity. The androgen 

receptor binding assay provides specific 

detail as to the affinity of a steroid for 

the androgen receptor (biological target 

of anabolic steroids). To assess further 

whether the steroid is capable of 

activating the androgen receptor, the 

androgen receptor transactivation assay 

evaluates the binding of a steroid to the 

androgen receptor and subsequent 

interaction with DNA. In this study, 

transcription of a reporter gene provides 

information as to a steroid’s ability to 

modulate a biological event. This 

activity measurement provides 

information as to the potency of a 

steroid to bind to a receptor and either 

initiate or inhibit the transcription of 

the reporter gene. The androgen 

receptor binding assay and androgen 

receptor transactivation assay are highly 

valuable tools in assessing the potential 

activity of a steroid and comparing the 

activity to testosterone. 

Results of the Androgenic and 

Anabolic Activity Assays: DEA reviewed 

the published scientific literature, and 

pharmacological studies were 

undertaken to collect additional 

information on prostanozol and 

methasterone in several different 

androgenic and anabolic activity assays. 

Findings from these studies indicate 

that in addition to being structurally 

similar to testosterone, prostanozol and 

methasterone have similar 

pharmacological activity as testosterone. 

Prostanozol 

The chemical synthesis and anabolic 

and androgenic effects of prostanozol 

(17b-hydroxy-5a-androstano[3,2- 

c]pyrazole) were published in 1961 

(Clinton et al., 1961). Clinton and 

coworkers evaluated the anabolic 

activity by means of nitrogen balance 

and androgenic activity based on weight 

changes of the ventral prostrate of 

prostanozol upon subcutaneous 

administration to rats with the reference 


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Federal Register / Vol. 77, No. 146 / Monday, July 30, 2012 / Rules and Regulations 44459 

1The study by Bioqual, Inc., Rockville, MD, may 

be found at http://www.regulations.gov in the 

electronic docket associated with this rulemaking. 

standard testosterone propionate. The 

potency ratio of anabolic activity to 

androgenic activity for prostanozol was 

reported to be eight (Clinton et al., 

1961). In another study, prostanozol was 

reported to have approximately the 

same relative binding affinity for human 

sex steroid binding protein as 

testosterone (Cunningham et al., 1981). 

To build on these findings, a 

pharmacological study 1 was conducted 

to evaluate the anabolic and androgenic 

effects of prostanozol in castrated male 

rats. Results were compared to 

testosterone by a similar protocol. 

Administration of prostanozol to 

castrated male rats by subcutaneous 

injection prevented the atrophy (loss in 

weight) of the ventral prostate, seminal 

vesicles, and levator ani muscle.1 These 

testosterone sensitive tissues 

experienced increases in weight 

comparable to testosterone in castrated 

male rats. Results from this study 

support that prostanozol possesses both 

androgenic and anabolic activity. 

Additional studies were conducted to 

further assess prostanozol’s anabolic 

effect. In a competitive binding assay, 

prostanozol was found to possess 

affinity for the androgen receptor 

comparable to testosterone.1 In the 

androgen receptor transactivation assay, 

prostanozol displayed increased activity 

relative to testosterone.1 Effects elicited 

by prostanozol in this transactivation 

assay were consistent and comparable to 

those of testosterone. Taken together, 

data from in vitro and in vivo assays 

indicate the pharmacology of 

prostanozol to be similar to testosterone. 

Methasterone 

The synthesis of methasterone 

(2a,17a-dimethyl-5a-androstan-17b-ol3-one) was reported in 1956 and the 

anabolic activity in 1959 (Ringold and 

Rosenkranz, 1956; Ringold et al., 1959). 

Methasterone was described as a potent 

anabolic agent exhibiting weak 

androgenic activity in the castrated male 

rat (Ringold et al., 1959). Zaffaroni and 

coworkers reported methasterone 

possessed one-fifth the androgenic 

activity and four times the anabolic 

activity of the anabolic steroid 

methyltestosterone, when administered 

orally to the experimental animal 

(Zaffaroni et al., 1960). 

Additional pharmacological studies 

were undertaken to further evaluate the 

androgenic and anabolic effects of 

methasterone.1 Methasterone was 

administered subcutaneously and orally 

to castrated male rats. By both routes of 

administration, methasterone prevented 

the atrophy (loss in weight) of ventral 

prostate, seminal vesicles, and levator 

ani muscle. Tissue weight increases for 

the castrated methasterone-treated 

animals were comparable to the 

castrated rats treated with testosterone 

and methyltestosterone. These results 

were consistent with earlier findings 

that methasterone is anabolic and 

androgenic (Zaffaroni, 1960; Ringold et 

al., 1959). Functional assays were also 

undertaken to further evaluate 

methasterone.1 Methasterone displayed 

affinity for the androgen receptor 

comparable to testosterone in a 

competitive binding assay.1 In the 

androgen receptor transactivation assay, 

methasterone displayed increased 

activity relative to testosterone.1 Effects 

elicited by methasterone in the 

androgen transactivation assay were 

consistent and comparable to those of 

testosterone. Collectively, in vivo and in 

vitro results indicate that the 

pharmacology of methasterone is similar 

to testosterone. 

(C) Not Estrogens, Progestins, and 

Corticosteroids 

DEA has determined that prostanozol 

and methasterone 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, since 

chemical structure can be related to its 

pharmacological and biological activity. 

DEA found that these two substances 

lack 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., 17b-alkyl group) (Williams and 

Stancel, 1996), or corticosteroidal 

activity (e.g., 17b-ketone group or 11bhydroxyl group) (Miller et al., 2002). 

Furthermore, methasterone was 

reported to display anti-estrogenic 

activity in mouse assay to assess 

estrogen stimulated uterine growth 

(Dorfman et al., 1961). To assess the 

estrogenic, progestational, and 

corticosteroid activity of prostanozol 

and methasterone, these substances 

were evaluated in receptor binding and 

functional transactivation assays. 

Prostanozol and methasterone showed 

low binding affinity for the estrogen, 

progesterone, and glucocorticoid 

receptors. Furthermore, these steroids 

displayed low to no transactivation 

mediated by the estrogen receptors, 

progesterone receptors, or 

glucocorticoid receptors. Therefore, 

based on these data, prostanozol and 

methasterone are not estrogens, 

progestins, or corticosteroids and these 

anabolic steroids are not exempt from 

control on this basis. 

(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)). Prostanozol and 

methasterone are not 

dehydroepiandrosterone and therefore, 

are not exempt from control on this 

basis. 

Comments Received 

On November 23, 2011, DEA 

published a NPRM (76 FR 72355) to 

classify prostanozol and methasterone 

as Schedule III anabolic steroids. The 

proposed rule provided an opportunity 

for all interested persons to submit their 

comments on or before January 23, 

2012. In response to the request, DEA 

received three comments. 

Comment: One commenter disagreed 

that anabolic steroids, and in particular 

those encountered in dietary 

supplements, should be placed in 

Schedule III of the CSA. He indicated 

that classifying these substances as 

Schedule III anabolic steroids would 

force the public to procure other, nonregulated and unsafe substitutes from 

illicit sources in the future, and that 

DEA should employ an alternate 

method of regulation. 

DEA Response: DEA disagrees with 

this comment. As stated in the NPRM 

and this Final Rule, these substances 

were found to be similar in structure 

and pharmacology to testosterone 

through substantive scientific 

evaluation and investigation. Further, 

the United States Food and Drug 

Administration has issued multiple 

warnings regarding dietary 

supplements, especially concerning 

contamination through novel synthetic 

steroids that do not qualify as dietary 

ingredients. 

Regarding the commenter’s request for 

alternative regulation of these 

substances. DEA regulates the 

manufacture, importation, export, 

distribution, and sale of controlled 

substances for medical, scientific, or 

other legitimate uses pursuant to the 

CSA. These substances have not been 

approved as safe for human 

consumption and, despite the 

commenter’s unsubstantiated and 

factually inaccurate claims of their 

benefits, should neither be consumed 

nor should other unapproved 

substances ever be sought from any 

source, illicit or otherwise. 

The additional remarks this 

commenter made regarding a perceived 


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disparity between men and women in 

access to hormonal products, and other 

perceived problems with the regulation 

of substances by the government, are not 

germane to this rulemaking. 

Comment: Two separate commenters 

agreed placement of these two 

substances under the CSA was 

appropriate as provided per the 

Anabolic Steroid Control Act of 2004. 

DEA Response: DEA appreciates the 

support for this rulemaking. As 

discussed above, prostanozol and 

methasterone are similar in structure 

and pharmacology to testosterone and 

are not approved for human 

consumption. DEA believes their 

placement into Schedule III as anabolic 

steroids will provide the appropriate 

safeguards to limit their availability to 

and prevent their abuse by the public. 

Conclusion 

After evaluation of the statutory 

factors above and consideration of the 

comments to the NPRM, DEA concludes 

that prostanozol and methasterone 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)). Once a 

substance is determined to be an 

anabolic steroid, DEA has no discretion 

regarding the placement of these 

substances into Schedule III of the CSA. 

Impact of Classification as Anabolic 

Steroids 

With the publication of this Final 

Rule, DEA classifies prostanozol (17bhydroxy-5a-androstano[3,2-c]pyrazole) 

and methasterone (2a,17a-dimethyl-5aandrostan-17b-ol-3-one) as Schedule III 

anabolic steroids subject to the CSA. 

Any person who manufactures, 

distributes, dispenses, imports, or 

exports prostanozol or methasterone, or 

who engages in research or conducts 

instructional activities with respect to 

these two substances, will be required to 

obtain a Schedule III registration in 

accordance with the CSA and its 

implementing regulations. 

As of the effective date of this Final 

Rule, the manufacture, import, export, 

distribution, or sale of prostanozol or 

methasterone, except by DEA 

registrants, is a violation of the CSA that 

may result in imprisonment and fines 

(see, e.g., 21 U.S.C. 841 and 960). 

Possession of these two steroids, unless 

legally obtained, is also subject to 

criminal penalties pursuant to 21 U.S.C. 

844. 

Manufacturers and importers of these 

two substances will be required to 

register with DEA and will be permitted 

to distribute these substances only to 

other DEA registrants. Only persons 

registered as dispensers will be allowed 

to dispense these substances to end 

users. The CSA defines a practitioner as 

‘‘a physician, dentist, veterinarian, 

scientific investigator, pharmacy, 

hospital, or other person licensed, 

registered, or otherwise permitted, by 

the United States or the jurisdiction in 

which he practices or does research, to 

distribute, dispense, conduct research 

with respect to, administer, or use in 

teaching or chemical analysis, a 

controlled substance in the course of 

professional practice or research.’’ 21 

U.S.C. 802(21). At present, there are no 

approved medical uses for these two 

substances. Until a manufacturer 

applies to the FDA and gains approval 

for products containing these 

substances, no person may dispense 

them in response to a prescription. 

Additionally, these two substances 

may only be imported 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. Any 

individual who purchases either of 

these substances directly from foreign 

companies and has them shipped to the 

United States will be considered to be 

importing even if the steroids are 

intended for personal use. Illegal 

importation of these substances will be 

a violation of the CSA that may result 

in imprisonment and fines pursuant to 

21 U.S.C. 960. 

Requirements for Handling Substances 

Defined as Anabolic Steroids 

As of the effective date of this Final 

Rule, prostanozol and methasterone are 

subject to CSA regulatory controls and 

the 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, will be required to be 

registered to conduct such activities 

with Schedule III controlled substances 

in accordance with 21 CFR Part 1301. 

Security. Substances defined as 

anabolic steroids will be subject to 

Schedule III security requirements and 

will be required to 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 will be required to comply with 

the 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 will be required to keep 

an inventory of all stocks of the 

substances on hand pursuant to 21 

U.S.C. 827 and 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 will be required to conduct an 

inventory of all stocks of the substances 

on hand at the time of registration. 

Records. All registrants will be 

required to keep records, as generally 

provided in 21 U.S.C. 827(a) and 

specifically pursuant to 21 CFR 1304.03, 

1304.04, 1304.05, 1304.21, 1304.22, and 

1304.23. 

Prescriptions. All prescriptions for 

these Schedule III substances or for 

products containing these Schedule III 

substances, if approved in the future by 

FDA, will be required to be issued 

pursuant to 21 U.S.C. 829(b) and 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, will be limited 

to five refills within six months of the 

date of issuance of the prescription. 

Controlled substance dispensing via the 

Internet will have to comply with 21 

U.S.C. 829(e). 

Importation and Exportation. All 

importation and exportation of any 

substance defined as an anabolic steroid 

will be required to be in compliance 

with 21 U.S.C. 952(b), 953(e), and 21 

CFR Part 1312. 

Disposal. Persons who possess 

substances that become 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 pursuant to 21 

CFR 1307.21. The DEA Diversion field 

office will provide the person with 

instructions regarding the disposal. A 

list of local DEA Diversion field offices 

may be found at http:// 

www.deadiversion.usdoj.gov. 

Criminal Liability. Any activity with 

any substance defined as an anabolic 


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Federal Register / Vol. 77, No. 146 / Monday, July 30, 2012 / Rules and Regulations 44461 

steroid not authorized by, or in violation 

of, the Controlled Substances Act or the 

Controlled Substances Import and 

Export Act will be unlawful. 

Regulatory Analyses 

Regulatory Flexibility Act 

The 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 March 

2010, DEA had identified approximately 

75 dietary supplements that were 

currently or had been promoted for 

building muscle and increasing strength 

that purported to contain prostanozol or 

methasterone. Thirteen dietary 

supplements were purported to contain 

prostanozol and 62 dietary supplements 

were purported to contain 

methasterone. These dietary 

supplements are marketed and sold over 

the Internet. 

The manufacturers and distributors of 

dietary supplements purported to 

contain prostanozol and methasterone 

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. Without 

information on the percentage of 

revenues derived from these dietary 

supplements, DEA is not able to 

determine the economic impact of the 

removal of these dietary supplements 

alone on the business of the firms. 

These steroids have been the focus of 

warning letters issued by the FDA. 

However, products continue to be 

marketed despite these warnings. DEA 

has not been able to identify any 

chemical manufacturers that are 

currently using these substances as 

intermediates in their manufacturing 

process(es). As of March 2010, DEA had 

identified 13 chemical manufacturers 

and distributors that sell at least one of 

the two steroids. Most of these 

companies are located in China and sell 

a variety of other anabolic 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. DEA has not identified 

any company based in the United States 

that manufactures or distributes these 

substances. 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 Orders 12866 and 13563 

This rulemaking has been drafted in 

accordance with the principles of 

Executive Order 12866, 1(b), as 

reaffirmed by Executive Order 13563. 

This rule is not a significant regulatory 

action but has been reviewed by the 

Office of Management and Budget. As 

discussed above, the effect of this rule 

will be to remove products containing 

these substances from the over-thecounter 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 

in 2009 was $5.9 million. These two 

substances would be a subset of those 

imports. The total market for products 

containing these substances, therefore, 

is probably quite small. Moreover, DEA 

believes that the importation of these 

two 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 

would 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 will bar the importation, 

exportation, and sale of these two 

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. 

Executive Order 13175 

This rule will not have tribal 

implications and will not impose 

substantial direct compliance costs on 

Indian tribal governments. 

Paperwork Reduction Act 

This rule regulates two anabolic 

steroids, which are neither approved for 

medical use in humans nor approved for 

administration to cattle or other nonhumans. Only chemical manufacturers 

who may use these substances as 

chemical intermediates for the synthesis 

of other steroids would be required to 

register with DEA under the CSA. 

However, DEA has not been able to 

identify any chemical manufacturers 

that are currently using these substances 

as intermediates in their manufacturing 

processes. 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 $136,000,000 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, 2 U.S.C. 

1532. 

List of Subjects in 21 CFR Part 1300 

Chemicals, Drug traffic control. 

For the reasons set out above, 21 CFR 

part 1300 is amended as follows: 

PART 1300—DEFINITIONS 

■ 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). 

■ 2. In § 1300.01, the definition of 

Anabolic steroid under paragraph (b) is 

amended by: 

■ A. Redesignating paragraphs (32) 

through (63) as (33) through (64), 

■ B. Adding a new paragraph (32), 

■ C. Further redesignating newly 

designated paragraphs (58) through (64) 

as (59) through (65), and 

■ D. Adding new paragraph (58). 

The additions read as follows: 

§ 1300.01 Definitions relating to controlled 

substances. 

* * * * * 

(b) * * * 

Anabolic steroid * * * 

(32) Methasterone (2a,17a-dimethyl5a-androstan-17b-ol-3-one) 

* * * * * 


tkelley on DSK3SPTVN1PROD with RULES
44462 Federal Register / Vol. 77, No. 146 / Monday, July 30, 2012 / Rules and Regulations 

(58) Prostanozol (17b-hydroxy-5aandrostano[3,2-c]pyrazole) 

* * * * * 

Dated: July 13, 2012. 

Michele M. Leonhart, 

Administrator. 

Note: The following appendix will not 

appear in the Code of Federal Regulations. 

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[FR Doc. 2012–18495 Filed 7–27–12; 8:45 am] 

BILLING CODE 4410–09–P 


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