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.
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
prostatic carcinoma is 250 mg for three times a day while 125 mg twice daily
is needed for the treatment of hirsutism.
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.
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
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
a day. A leveling of the rhythmic changes in the concentration of
serum androgen receptor has been noted with menstrual cycles.
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
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.