17-Methyltestosterone Chemical Properties

Melting point:

162-168 °C(lit.)

Boiling point:

383.47°C (rough estimate)

alpha 

79 º (c=1, alcohol)

Density 

1.0434 (rough estimate)

refractive index 

1.4800 (estimate)

Flash point:

5 °C

storage temp. 

2-8°C

solubility 

H₂O: ≤0.5 mg/mL

pka

15.13±0.60(Predicted)

form 

solid (photosensitive)

color 

white

Water Solubility 

33.88mg/L(25 ºC)

Merck 

13,6148

BRN 

2057425

InChIKey

GCKMFJBGXUYNAG-HLXURNFRSA-N

CAS DataBase Reference

58-18-4(CAS DataBase Reference)

NIST Chemistry Reference

17(Alpha)-methyl-delta4-androsten-17-(beta)-ol-3-one(58-18-4)

EPA Substance Registry System

Methyltestosterone (58-18-4)

Safety Information

Hazard Codes 

T,Xn,F,Xi

Risk Statements 

45-63-22-20-19-11-61-60-36/37/38-38-10

Safety Statements 

53-36/37-45-24/25-22

RIDADR 

3249

WGK Germany 

3

RTECS 

BV8400000

HazardClass 

6.1(b)

PackingGroup 

III

HS Code 

29372900

Hazardous Substances Data

58-18-4(Hazardous Substances Data)

Toxicity

man,TDLo,oral,39mg/kg/33W-I (39mg/kg),LIVER: "JAUNDICE, CHOLESTATIC",American Journal of Gastroenterology. Vol. 82, Pg. 461, 1987.

MSDS

• Language:English Provider:17-Methyltestosterone
• Language:English Provider:ACROS
• Language:English Provider:SigmaAldrich

17-Methyltestosterone Usage And Synthesis

Overview

17-Methyltestosterone, a synthetic derivative of testosterone, is an androgen and anabolic steroid (AAS) medication. It is mainly used in the treatment of low testosterone levels in men, delayed puberty in boys, at low doses as a component of menopausal hormone therapy for menopausal symptoms like hot flashes, osteoporosis, and low sexual desire in women, and to treat breast cancer in women (1-3). It appears as white or creamy white crystals or powder, which is soluble in various organic sol vents but is practically insoluble in water. It should be subject to oral administration.
Methyltestosterone was first discovered in 1935 and was introduced for medical use in 1936. It was synthesized shortly after the discovery of testosterone, being one of the first synthetic AAS drug. 17-Methyltestosterone, beyond its medical function, can also be used to improve physique and performance, although it is not as commonly used as other AAS for such purposes due to its androgenic effects, estrogenic effects, and risk of liver damage. The drug is a controlled substance in many countries and so non-medical use is generally illicit.

Indication and administration

It has been used in the treatment of various symptoms such as hypogonadism, cryptorchidism, delayed puberty, and erectile dysfunction in males, and in low doses to treat menopausal symptoms (specifically for osteoporosis, hot flashes, and to increase libido and energy), postpartum breast pain and engorgement.
In US, 17-Methyltestosterone is an anabolic steroid hormone that majorly used to treat men with a testosterone deficiency, hypogonadism and delayed puberty. Hypogonadism include both primary type and hypogonadotropic type: the former one can be caused by cryptorchidism, bilateral torsions, orchitis, vanishing testis syndrome; or orchidectomy. The later one includes idiopathic gonadotropin or LHRH deficiency, or pituitary hypothalamic injury from tumors, trauma, or radiation. It is also used in women to treat breast cancer, breast pain, swelling due to pregnancy, and with the addition of estrogen it can treat symptoms of menopause. It has also been used in combination with esterified estrogens for the treatment of moderate to severe vasomotor symptoms associated with menopause in females.
17-Methyltestosterone is administered orally. The suggested dosage varies depending on the age, sex, and diagnosis of the individual patient. Dosage is adjusted according to the patient's response and the appearance of adverse reactions. Replacement therapy in androgen-deficient males usually demands 10 to 50 mg of 17-Methyltestosterone daily. However, the chronological and skeletal ages must be taken into consideration both in determining the initial dose and in adjusting the dose. Doses used in the treatment of the delayed puberty generally are in the lower range of that given above, and for a limited duration, for example 4 to 6 months. For the treatment of women breast cancer, the dosage of 17-Methyltestosterone in females is from 50-200 mg daily.

Mode of action

17-Methyltestosterone take effects through two main mechanisms: activation of the androgen receptor (directly or as DHT), and by conversion to estradiol and activation of certain estrogen receptors.
17-Methyltestosterone can enter into the target tissue cells, binding to the androgen receptor, or being reduced to 5α-dihydrotestosterone (DHT) by the cytoplasmic enzyme 5α-reductase. DHT binds to the same androgen receptor even more strongly, yielding a even stronger androgenic potency. The T-receptor or DHT-receptor complex undergoes a structural change that allows it to move into the cell nucleus and bind directly to specific nucleotide sequences of the chromosomal DNA, which is called hormone response elements (HREs). This process regulates the transcriptional activity of various genes, further producing the androgen effects.

Adverse reactions

17-methyltestosterone can cause various kinds of adverse reactions. Common side effects include increased facial/body hair growth, scalp hair loss, increased aggressiveness, skin, acne, seborrhea, and sex drive and spontaneous erections. There are also some kinds of estrogenic side effects such as breast tenderness, gynecomastia, fluid retention, and edema. Men can suffer hypogonadism, testicular atrophy, and reversible infertility. Women can sometimes suffer partially irreversible virilization including clitoromegaly, breast atrophy, voice deepening, hirsutism and muscle hypertrophy, as well as menstrual disturbances and reversible infertility.
17-methyltestosterone may also cause hepatotoxicity including elevated liver enzymes, cholestatic jaundice, peliosis hepatis, hepatomas, and hepatocellular carcinoma. It can also have adverse effect on the cardiovascular system such as causing erythropoiesis, increase hematocrit levels or even polycythemia, further leading to even thrombic events such as embolism and stroke. Finally, long-term treatment increase the risk of cancer. Some extreme cases also include hypomania/mania, depression, delusions, suicidality and psychosis.

Warning and precaution

People of the following cases should not use it: allergy; prostate cancer; male breast cancer, pregnant.
People with liver or kidney disease, an enlarged prostate, heart disease, congestive heart failure should use with caution.

References

• Alexandre Hohl (6 April 2017). Testosterone: From Basic to Clinical Aspects. Springer. pp. 204–. ISBN 978-3-319-46086-4.
• Shahidi NT (2001). "A review of the chemistry, biological action, and clinical applications of anabolic-androgenic steroids". Clin Ther. 23 (9): 1355–90.
• Shi, Y., et al. "Molecular identification of an androgen receptor and its changes in mRNA levels during 17α-methyltestosterone-induced sex reversal in the orange-spotted grouper Epinephelus coioides. " Comp Biochem Physiol B Biochem Mol Biol 163.1(2012):43-50.
• Zheng, Z., B. A. Armfield, and M. J. Cohn. "Timing of androgen receptor disruption and estrogen exposure underlies a spectrum of congenital penile anomalies." PNAS 112.52(2015):201515981.
• Komada, S., et al. "Side gland of Suncus murinus, as a new model of sebaceous gland: 5α-reductase, androgen receptor, and nuclear androgen content in male and female animals." Archives of Dermatological Research 280.8(1989):487-493.
• Kicman, A T (2008). "Pharmacology of anabolic steroids". British Journal of Pharmacology. 154 (3): 502–521.
• Jeffrey K. Aronson (21 February 2009). Meyler's Side Effects of Endocrine and Metabolic Drugs. Elsevier. pp. 141–. ISBN 978-0-08-093292-7.
• Benjamin J. Sadock; Virginia A. Sadock (26 December 2011). Kaplan and Sadock's Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry. Lippincott Williams & Wilkins. ISBN 978-1-4511-7861-6.
• Bird, D. R., and K. D. Vowles. "Liver damage from long-term methyltestosterone. " Inpharma 310.8032(1977):261-263.

 

Description

Methyltestosterone is a synthetic analog of testosterone that possesses all of the properties of testosterone, exhibiting stimulatory action on the development of male sex organs and secondary sex characteristics, although it is not degraded by enzymes in the gastrointestinal tract, and therefore it can only be taken orally

Chemical Properties

white to slightly yellowish-white crystalline

Originator

Metandren ,Ciba,US,1941

Uses

It is used for the same indications as testosterone for sexual underdevelopment, functional problems of the reproductive system, and the vascular nerve disorders associated with climacteric problems in men. It is also used for dysfunctional uterine bleeding in premenopausal and menopausal women as well as for breast and ovarian cancer.

Uses

Androgen. It has been used as an androgenic agent. Controlled substance (anabolic steroid).

Definition

ChEBI: A 17beta-hydroxy steroid that is testosterone bearing a methyl group at the 17alpha position.

Manufacturing Process

0.6 g of 17-Methyl-?5,6-androstenediol-(3,17) is heated under reflux cooling during 20 hours in 50 cm3 of benzene and 12 cm3 of acetone with 3 g of tertiary chloromagnesium butylate, which may be prepared by conversion of acetone with methyl magnesium chloride. The magnesium is then removed by shaking out with dilute H2SO4; the benzene layer is washed with water, dried with sodium sulfate and then evaporated to dryness. Methyltestosterone (MP 160° to 162°C) is obtained in a yield of more than 75% of the theory, according to US Patent 2,384,335.

brand name

Android (Valeant);Metandren (Novartis); Oreton (Schering); Testred (Valeant); Virilon (Star).

Therapeutic Function

Androgen

Pharmacokinetics

The synthesis of 17α-methyltestosterone made available a compound that was orally active in daily doses between 10 and 50 mg, which is equivalent to a 400 mg oral dose of testosterone. The presence of a 17α alkyl group reduces susceptibility to hepatic oxidative metabolism, thereby increasing oral bioavailability by slowing metabolism. Following oral administration, methyltestosterone is well absorbed from the gastrointestinal tract, with a half-life of approximately 3 hours. This drug has the androgenic and anabolic activities of testosterone. Although orally active, it is more effective when administered sublingually. The alkylated oral androgens should be viewed as potentially hepatotoxic and should not be used.

Safety Profile

Poison by intraperitoneal route. Moderately toxic by ingestion. Human teratogenic effects by ingestion: developmental abnormalities of the urogenital system. Experimental teratogenic and reproductive effects. Human systemic effects: cholestatic jaundce, weight loss or decreased weight gain. Questionable human carcinogen producing liver tumors. A synthetic androgenic steroid. When heated to decomposition it emits acrid smoke and irritating fumes.

Synthesis

Methyltestosterone, 17|?-hydroxy-17|á-methylandrost-4-en-3-one (29.1.7), is also synthesized from androstenolone by reacting it with methylmagnesiumiodide, forming the corresponding tertiary alcohol (29.1.6), and subsequent oxidation of the hydroxyl group at C3 to a ketone using chromium (VI) oxide. Simultaneous isomerization of the double bond takes place under the reaction conditions, giving the desired methyltestosterone (29.1.7).

Purification Methods

This anabolic steroid is crystallised from hexane or hexane/*benzene. It has E1cm 1% 495-530 at 241nm (EtOH). The colour reaction with 2,4-dinitrophenyl hydrazine is used for assaying it. [Gornall & Macdonald J Biol Chem 201 279 1953.] In another colour reaction the sterone (1mg) in acetic acid (0.2ml) + 88% H3PO4 (2mL) is allowed to stand for 1hour when it becames fluorescent. After 1hour it is diluted with acetic acid (~3mL) and provides a strong yellow fluorescence with the intensity of 50-100 times that of estrone. [Stuart & Stuckey J Pharm Pharmacol 1 130 1949, Openauer Rec Trav Chim Pays-Bas 56 137 137, Beilstein 8 IV 1010.]

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