2α-メチル-17β-ヒドロキシ-5α-アンドロスタン-3-オン

Anticoagulant effects of coumarin- or indandione-derivative or anti-inflammatory analgesics, nonsteroidal or salicylates, in therapeutic doses may be increased during concurrent use with anabolic steroids, especially 17-alpha-alkylated compounds, because of decreased procoagulant factor concentration caused by alteration of procoagulant factor synthesis or catabolism and increased receptor affinity for the anticoagulant; anticoagulant dosage adjustment based on prothrombin time determinations may be required during and following concurrent use with anabolic steroids. /Anabolic Steroids/

Concurrent use of antidiabetic agents, sulfonylurea or insulin with anabolic steroids may decrease blood glucose concentration; diabetic patients should be closely monitored for signs of hypoglycemia ... /Anabolic Steroids/

Concurrent use of corticosteroids, glucocorticoid, especially with significant mineralocorticoid activity, prolonged therapeutic corticotropin or sodium-containing medications or foods with anabolic steroids may increase the possibility of edema; in addition, concurrent use of glucocorticoids or corticotropin with anabolic steroids may promote development of severe acne. /Anabolic Steroids/

Concurrent use of hepatotoxic medications with anabolic steroids may result in an increased incidence of hepatotoxicity; patients, especially those on prolonged administration or those with a history of liver disease, should be carefully monitored. /Anabolic Steroids/

Concurrent use of anabolic steroids with somatrem or somatropin may accelerate epiphyseal maturation. /Anabolic Steroids/

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3,500(SRC), determined from a log Kow of 3.99(2) and a regression-derived equation(3), indicates that dromostanolone is expected to have slight mobility in soil(SRC). Volatilization of dromostanolone from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 8.5X10-9 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Dromostanolone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.7X10-8 mm Hg(SRC), determined from a fragment constant method(5). No biodegradation data were available(SRC, 2005).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 3,500(SRC), determined from a log Kow of 3.99(2) and a regression-derived equation(3), indicates that dromostanolone is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 8.5X10-9 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 240(SRC), derived from its log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is high, provided the compound is not metabolized by the organism(SRC). No biodegradation data were available(SRC, 2005).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), dromostanolone, which has an estimated vapor pressure of 1.7X10-8 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the atmosphere. Particulate-phase dromostanolone may be removed from the air by wet and dry deposition(SRC). Dromostanolone does not contain chromophores that absorb at wavelengths >290nm and therefore is not expected to be susceptible to direct photolysis(SRC).

IDENTIFICATION: Drostanolone is an anabolic steroid. Origin of the substance: Naturally occurring anabolic steroids are synthesized in the testis, ovary and adrenal gland from cholesterol via pregnenolone. Synthetic anabolic steroids are based on the principal male hormone testosterone, modified in one of three ways: alkylation of the 17-carbon; esterification of the 17-OH group; modification of the steroid nucleus. Indications: Anabolic agent for systemic use; veterinary anabolic steroid; veterinary estron derivative. Description: The only legitimate therapeutic indications for anabolic steroids are: Replacement of male sex steroids in men who have androgen deficiency, for example as a result of loss of both testes. The treatment of certain rare forms of aplastic anemia which are or may be responsive to anabolic androgens. The drugs have been used in certain countries to counteract catabolic states, for example after major trauma. HUMAN EXPOSURE: Main risks and target organs: There is no serious risk from acute poisoning, but chronic use can cause harm. The main risks are those of excessive androgens: menstrual irregularities and virilization in women and impotence, premature cardiovascular disease and prostatic hypertrophy in men. Both men and women can suffer liver damage with oral anabolic steroids containing a substituted 17-alpha-carbon. Psychiatric changes can occur during use or after cessation of these agents. Summary of clinical effects: Acute overdosage can produce nausea and gastrointestinal upset. Chronic usage is thought to cause an increase in muscle bulk, and can cause an exaggeration of male characteristics and effects related to male hormones. Anabolic steroids can influence sexual function. They can also cause cardiovascular and hepatic damage. Acne and male-pattern baldness occur in both sexes; irregular menses, atrophy of the breasts, and clitoromegaly in women; and testicular atrophy and prostatic hypertrophy in men. Contraindications: Known or suspected cancer of the prostate or (in men) breast; pregnancy or breast-feeding; known cardiovascular disease is a relative contraindication. Routes of exposure: Oral: Anabolic steroids can be absorbed from the gastrointestinal tract, but many compounds undergo such extensive first-pass metabolism in the liver that they are inactive. Those compounds in which substitution of the 17-carbon protects the compound from the rapid hepatic metabolism are active orally. There are preparations of testosterone that can be taken sublingually. Parenteral: Intramuscular or deep subcutaneous injection is the principal route of administration of all the anabolic steroids except the 17-alpha-substituted steroids which are active orally. Absorption by route of exposure: The absorption after oral dosing is rapid for testosterone and probably for other anabolic steroids, but there is extensive first-pass hepatic metabolism for all anabolic steroids except those that are substituted at the 17-alpha position. The rate of absorption from subcutaneous or intramuscular depots depends on the product and its formulation. Absorption is slow for the lipid-soluble esters such as the cypionate or enanthate, and for oily suspensions. Distribution by route of exposure: The anabolic steroids are highly protein bound, and is carried in plasma by a specific protein called sex-hormone binding globulin. Biological half-life by route of exposure: The metabolism of absorbed drug is rapid, and the elimination half-life from plasma is very short. The duration of the biological effects is therefore determined almost entirely by the rate of absorption from subcutaneous or intramuscular depots, and on the de-esterification which precedes it. Metabolism: Free (de-esterified) anabolic androgens are metabolized by hepatic mixed function oxidases. Elimination by route of exposure: After administration of radiolabelled testosterone, about 90% of the radioactivity appears in the urine, and 6% in the feces; there is some enterohepatic recirculation Pharmacodynamics: Anabolic steroids bind to specific receptors present especially in reproductive tissue, muscle and fat. The anabolic steroids reduce nitrogen excretion from tissue breakdown in androgen deficient men. They are also responsible for normal male sexual differentiation. The ratio of anabolic ("body-building") effects to androgenic (virilizing) effects may differ among the members of the class, but in practice all agents possess both properties to some degree. There is no clear evidence that anabolic steroids enhance overall athletic performance. Carcinogenicity: Anabolic steroids may be carcinogenic. They can stimulate growth of sex-hormone dependent tissue, primarily the prostate gland in men. Precocious prostatic cancer has been described after long-term anabolic steroid abuse. Cases where hepatic cancers have been associated with anabolic steroid abuse have been reported. Teratogenicity: Androgen ingestion by a pregnant mother can cause virilization of a female fetus. Main adverse effects: The adverse effects of anabolic steroids include weight gain, fluid retention, and abnormal liver function as measured by biochemical tests. Administration to children can cause premature closure of the epiphyses. Men can develop impotence and azoospermia. Women are at risk of virilization. Chronic poisoning: Ingestion: Hepatic damage, manifest as derangement of biochemical tests of liver function and sometimes severe enough to cause jaundice; prostatic hypertrophy, impotence and azoospermia in men; acne, abnormal lipids, premature cardiovascular disease (including stroke and myocardial infarction), abnormal glucose tolerance, and muscular hypertrophy in both sexes; psychiatric disturbances can occur during or after prolonged treatment. Parenteral exposure: Virilization in women; prostatic hypertrophy, impotence and azoospermia in men; acne, abnormal lipids, premature cardiovascular disease (including stroke and myocardial infarction), abnormal glucose tolerance, and muscular hypertrophy in both sexes. Psychiatric disturbances can occur during or after prolonged treatment. Hepatic damage is not expected from parenteral preparations. Systematic description of clinical effects: Cardiovascular: Chronic ingestion of high doses of anabolic steroids can cause elevations in blood pressure, left ventricular hypertrophy and premature coronary artery disease. Neurological: Central nervous system: Stroke has been described in a young anabolic steroid abuser. Mania and psychotic symptoms of hallucination and delusion has been described in anabolic steroid abusers. They also described depression after withdrawal from anabolic steroids. There is also considerable debate about the effects of anabolic steroids on aggressive behavior and on criminal behavior. Mood swings were significantly more common in normal volunteers during the active phase of a trial comparing methyltestosterone with placebo. Gastrointestinal: Acute ingestion of large doses can cause nausea and gastrointestinal upset. Hepatic: Orally active (17-alpha substituted) anabolic steroids can cause abnormalities of hepatic function, manifest as abnormally elevated hepatic enzyme activity in biochemical tests of liver function,and sometimes as overt jaundice. The histological abnormality of peliosis hepatis has been associated with anabolic steroid use. Angiosarcoma and a case of hepatocellular carcinoma in an anabolic steroid user has been reported. Urinary: Other: Men who take large doses of anabolic steroids can develop prostatic hypertrophy. Prostatic carcinoma has been described in young men who have abused anabolic steroids. Endocrine and reproductive systems: Small doses of anabolic steroids are said to increase libido, but larger doses lead to azoospermia and impotence. Testicular atrophy is a common clinical feature of long-term abuse of anabolic steroids, and gynecomastia can occur. Women develop signs of virilism, with increased facial hair, male pattern baldness, acne, deepening of the voice, irregular menses and clitoral enlargement. Dermatological: Acne occurs in both male and female anabolic steroids abusers. Women can develop signs of virilism, with increased facial hair and male pattern baldness. Eye, ear, nose, throat: local effects: Changes in the larynx in women caused by anabolic steroids can result in a hoarse, deep voice. The changes are irreversible. Hematological: Anabolic androgens stimulate erythropoiesis. Fluid and electrolyte disturbances: Sodium and water retention can occur, and result in edema; hypercalcemia is also reported. Others: Insulin resistance with a fall in glucose tolerance, and hypercholesterolemia with a fall in high density lipoprotein cholesterol, have been reported.

The Koc of dromostanolone is estimated as 3,500(SRC), using a log Kow of 3.99(1)and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that dromostanolone is expected to have slight mobility in soil.

An estimated BCF of 240 was calculated for dromostanolone (SRC), using a log Kow of 3.99(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is high, provided the compound is not metabolized by the organism(SRC).

The Henry's Law constant for dromostanolone is estimated as 8.5X10-9 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that dromostanolone is expected to be essentially nonvolatile from moist soil(SRC) and water surfaces(2). Dromostanolone is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.7X10-8 mm Hg(SRC), determined from a fragment constant method(3).

Anabolic steroids should be used with caution in children and adolescents and only by specialists who are aware of their effects on bone maturation because of possible premature epiphyseal closure, precocious sexual development in males, and virilization in females. The epiphyseal maturation may be accelerated more rapidly than linear growth in children, and the effect may continue for 6 months after the medication has been discontinued. /Anabolic Steroids/

Anabolic steroids are not recommended for use during pregnancy, since studies in animals have shown that anabolic steroids cause masculinization of the fetus. Risk-benefit must be carefully considered. /Anabolic steroids/

Anabolic steroids may decrease blood glucose concentrations; diabetic patients should be closely monitored for signs of hypoglycemia and dosage of hypoglycemic agent adjusted as necessary. /Anabolic steroids/

Concurrent use of antidiabetic agents, sulfonylurea or insulin with anabolic steroids may decrease blood glucose concentration; diabetic patients should be closely monitored for signs of hypoglycemia ... /Anabolic Steroids/

Dromostanolone is not expected to undergo hydrolysis in the environment due to the lack of hydrolyzable functional groups(1). Dromostanolone does not contain chromophores that absorb at wavelengths >290nm and therefore is not expected to be susceptible to direct photolysis(SRC).

Schedules of controlled substances are established by section 202 of the Controlled Substances Act (21 U.S.C. 812). Schedule III shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation containing any quantity of the following substances, including its salts, isomers, and salts of isomers whenever the existence of such salts of isomers is possible within the specific chemical designation. DEA Code #: 4000; Drug class: anabolic steroids.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies discontinued drug products, incl dromostanolone propionate. /Dromostanolone Propionate/