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 Flutamide for female baldness
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Flutamide is a non-steroid anti-androgen that has no hormonal activity. It was believed to act after it converts 2-hydroxyflutamide, the potent competitive inhibitor of dihydrotestosterone (DHT) binding to the androgen receptor. The current use of Flutamide is treatment of prostate cancer when combined with luteinizing hormone-releasing hormone (LHRH). Flutamide is also believed to inhibit the action of testosterone on cancer cells by blocking the receptor sites that testosterone uses in the cells.

Indications

Gonadotropin-releasing hormones or GnRH triggers the release of LHRH by stimulating the pituitary gland. Drugs known as GnRH antagonists are known to block these releases. Flutamide was found out to inhibit the action of adrenal androgens in castrated men or those who receive GnRH blockages. It is also when LH production is not predominantly controlled by androgen like in the case of women. Flutamide has been used together with contraceptive pills in treating hirsutism, and is indicated for prostate cancer.

Flutamide’s role in androgen mediated responses like pattern baldness makes the Flutamide anti-androgen activity and its affinities for the androgen receptor in the androgen-sensitive issues. Since Flutamide is potent enough to cause feminizing effect on men, its application on female pattern hair loss is controlled. Restoration of the terminal hair production on previously healthy follicles could never be achieved even though anti-androgen therapy has already been shown to prevent further degeneration of follicles into vellus-hair production.

Mechanism of Action

Flutamide shows potent anti-androgenic effects in animal studies. It enforces its anti-androgenic action when it inhibits androgen uptake and/or the nuclear binding of androgen target tissues or both. Studies conducted on mature rats showed that Flutamide causes regression of androgen target tissues like prostate and seminal vesicles through the blockage of the inhibitory feedback of testosterone on LH production, resulting in a significant increase in the plasmic concentrations.

Similar effects were seen on men treated daily with 750 mg of Flutamide. The LH secretion pulse frequency is enhanced – the predominant pituitary effect of Flutamide in human. Flutamide may be effective as anti-androgens in in-vitro but the noted rise in plasma testosterone levels during in-vivo may set limits to its anti-androgenic effects.

2-hydroxy-flutamide inhibits the tissue uptake, testosterone retention, and formation of the nuclear steroid-androgen receptor complex. Without steroidal structure, anti-androgens may inhibit the negative feedback of gonadal steroids at the hypothalamic-pituitary level to enhance the release of the pituitary of gonadotropins and enhance the production of gonads of more testosterone and estradiol. To prevent the increase in androgen load (which neutralizes the inherent anti-androgen effect), non-steroidal anti-androgens needs to be administered together with antigonadotropin. To suppress the biosynthesis of androgen, Flutamide decreases the cytochrome P450 content in the in the testicular microsomal fraction of the male rats as it inhibits the testicular 17 to 20- hydroxylase and 17 to 20- lyase activity in rats.

Eulexinis (and other brands with generic formulations) is a Flutamide that is available in the market under prescription. The dose of Flutamide needed for metastatic prostatic carcinoma is 250 mg for three times a day while 125 mg twice daily is needed for the treatment of hirsutism.

Side Effects

58% skin dryness had been reported after taking Flutamide although the documented side effects of oral Flutamide are diarrhea and primary gastrointestinal problems. One side effect that deserves caution in oral administration of Flutamide is hepatoxicity, which includes progressive liver failure that limits the capability of its efficiency in treating pattern baldness. Known cases of hepatic injury are elevated serum transaminase (liver enzyme) levels, jaundice, hepatic encephalopathy, and death related to acute hepatic failure. Before treating patient with Flutamide, the level of serum transminase should be measured and liver functions test must be obtained at first signs and symptoms suggesting liver dysfunction (like nausea, vomiting, abdominal pain, anorexia, jaundice, and a flu-like symptom).

Flutamide is absolutely discouraged on pregnant women and women planning to get pregnant. It was found that a great possibility of Flutamide crossing the placenta produces male psudohermaphroditism just like that of cyprotone acetate. Thus, it is advised that women taking Flutamide must also take an oral contraceptive pill to avoid the risk of pregnancy.

Clinical trials

Some of the reports highlighting the improvement in the female pattern hair loss in women with hair loss and treated with Flutamide are as follows:

  • A significant rapid reduction in the hirsutism of 17 out of 18 women with hirsutism treated with a combined therapy of contraceptive pills and 250 mg twice-a-day of Flutamide. Among the 17, one woman with pattern hair loss exhibited remarkable improvements.
  • One study showed a significant decrease of testosterone level in women with idiopathic hirsutism when treated with 125 mg Flutamide three times a day. A leveling of the rhythmic changes in the concentration of serum androgen receptor has been noted with menstrual cycles.
  • Flutamide alone was successful in producing a small but definite reduction in hair loss on hyper-androgenic pre-menopausal women having female pattern hair loss when they were treated with Flutamide, Cypoterone acetate or finasteride (250 mg a day) as shown in the study of Ross.

Still, there is a need for further studies to evaluate and affirm the efficiency and reliability of Topical Flutamide in treating pattern baldness.

 
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