Description
Fluoxymesterone(Halotestin) is a steroid with an androgenic property that is used in primary hypogonadism and testicular failure due to cryptorchidism, vanishing testes syndrome, or orchidectomy; and in hypogonadotrophic hypogonadism and luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary hypothalamic injury from tumors, trauma, or radiation. It mimics the actions of testosterone, which is responsible for normal growth and development of the male sex organs and for the maintenance of secondary sex characteristics. In female postmenopausal patients, fluoxymesterone may be indicated in the palliation of recurrent mammary cancer.
Chemical Properties
white to light yellow crystal powder
Originator
Halotestin, Upjohn, US,1957
Uses
Fluoxymesterone is an anabolic steroid with androgenic activity. It is used in the treatment of male hypogonadism. It showed antitumor effects on pregnancy-dependent mammary tumors TPDMT-4.
Indications
Fluoxymesterone promotes growth and development of male reproductive organs, maintains secondary sex characteristics, increases protein anabolism, and decreases protein catabolism. It is used to treat symptoms of low testosterone in adult men who have hypogonadism (a condition in which the body does not produce enough natural testosterone). It is also used for palliation of androgen-responsive recurrent mammary cancer in women who are more than 1 year but less than 5 years postmenopausal (women).
Definition
ChEBI: Fluoxymesterone is an anabolic androgenic steroid, a 17beta-hydroxy steroid, an 11beta-hydroxy steroid, a fluorinated steroid and a 3-oxo-Delta(4) steroid. It has a role as an antineoplastic agent and an anabolic agent.
brand name
Android (Valeant); Halotestin (Pharmacia & Upjohn); Ora-Testryl (Bristol-Myers Squibb).
Therapeutic Function
Androgen
General Description
Fluoxymesterone, 9α-fluoro-11β,17β-dihydroxy-17-methylandrost-4-en-3-one, is ahighly potent, orally active androgen, about 5 to 10 timesmore potent than testosterone. It can be used for all theindications discussed previously, but its great androgenicactivity has made it useful primarily for treatment of theandrogen-deficient male.
Mechanism of action
Fluoxymesterone is a synthetic androgenic anabolic steroid and is approximately 5 times as potent as natural methyltestosterone. Like testosterone and other androgenic hormones, fluoxymesterone binds to the androgen receptor. It produces retention of nitrogen, sodium, potassium, and phosphorus, increases protein anabolism, decreases amino acid catabolism and decreases urinary excretion of calcium. The antitumour activity of fluoxymesterone appears related to the reduction or competitive inhibition of prolactin receptors or estrogen receptors or production.
Pharmacokinetics
By substituting a 9α-fluoro group onto an analog of 17α-methyltestosterone, fluoxymesterone has 20
times the anabolic and 10 times the androgenic activity of 17α-methyltestosterone. It
has a mean half-life of 9 hours, and less than 5% of the drug is excreted unchanged. An adverse
effect of fluoxymesterone is sodium and water retention that could lead to edema.
Side effects
Fluoxymesterone is used as an androgen hormonal supplement. An adverse effect of fluoxymesterone is sodium and water retention that could lead to edema. Side effects associated with this agent include closing of the epiphyseal closures, hypercalcemia, and edema. This product should not be given to boys who are in puberty because of its effect on the epiphyseal closures.
Safety Profile
Fluoxymesterone is contraindicated in male subjects with known or suspected carcinoma of the prostate gland. Prolonged use of high-dosage 17-alpha-alkyl androgens is known to have caused hypercalcemia, hepatic adenoma, hepatocellular carcinoma, and hepatitis. Fluoxymesterone, which accelerates bone maturation without producing linear growth, should be used cautiously in males with delayed puberty. Edema and CHF may occur in patients with preexisting cardiovascular problems. Androgens cause virilization in female subjects.
Synthesis
Fluoxymesterone, 9-fluoro-11|?,17|?-dihydroxy-17|á-methylandrost-
4-en-3-one (29.3.8), is made from 11|?-hydroxy-4-androsten-3,17-dione, which is reacted
with pyrrolidine to give a dieneamine (29.3.4). This undergoes a reaction with methylmagnesiumiodide, which after hydrolysis forms 11|?,17|?-dihydroxy-17|á-methylandrost-
4-en-3-one (29.3.5). Dehydration of this compound by selective tosylation of the
secondary hydroxyl group at C11 using p-toluenesulfonyl chloride and subsequent reaction
with a base gives the diene (29.3.6), and the double bond at C9¨CC11 is transformed to an
epoxide (29.3.7) by subsequent reaction with N-bromoacetamide in a wet solvent (source
of HOBr), and a base. Further reaction with hydrogen fluoride results in an opening of the
epoxide ring and the formation of the desired fluoxymesterone (29.3.8).
Mode of action
Fluoxymesterone binds to androgen receptors, suppressing GnRH, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) through a negative feedback mechanism involving the hypothalamus and anterior pituitary. It antagonizes the estrogenic effects in estrogendependent target cells.
