The assumption that anti-androgen can be feasibly used to halt or even
reverse male pattern baldness resulted from observing castrated men. Hamilton
observed that castration prevented further progression of male pattern hair
loss among eunuchs; furthermore, the hair loss in eunuchs resulting from
induced exogenous testosterone halted when testosterone treatment was discontinued.
Anti-androgen therapy for androgen-induced baldness is a relatively new
concept, and only a topical anti-androgen would be plausible in men.
Anti-androgens are compounds (usually synthetic pharmaceuticals) that stops
or interferes with the normal action of androgens at cellular receptor sites.
There are two types of anti-androgen:
- Steroidal anti-androgens
- Non-steroidal anti-androgens
Anti-androgen drugs may be systemic or topical. Systemic anti-androgens
are currently only specified for women suffering from pattern baldness,
as it reduces circulating testosterone and may hamper normal male sexual
functioning. Topical anti-androgens can be applied directly to the skin
and are generally preferred by men.
Anti-androgen’s mechanism of action
The perception on the mechanism of action of anti-androgens is it prevents
the Dihydrotestosterone (DHT) from binding to the androgen receptor. Being
weak agonists, Anti-androgens compete less well than endogenous hormones
and dissociate rapidly from the androgen receptor, or potent agonists, which
form a complex bond with the receptor molecule and dissociate slowly. The
weak agonists are the true antagonists of the endogenous and exogenous androgens
that rely only on a continuous supply of the compound to achieve full inhibition.
Non-steroid anti-androgen cyoctol displays neither the estrogen (female
hormone estrogen) production nor progestogenic (female hormone progesterone)
production activity, acting by competitively binding to the androgen receptors
thus preventing dihydrotestosterone from binding and effectively inhibiting
the stimulatory effects of androgens. Cyoctol is completely metabolized
in the skin after topical application and it competitively inhibits DHT
receptor. During the American Academy of Dermatology presentation in 1989,
the use of cyoctol has been reported in only one; however, the dropout rate
of that study was greater than 50% thus the definitive results was ruled
Topical Progesterone Treatment
Progesterone is a compound that has high structural similarity to testosterone,
and can therefore use the enzyme 5a-Reductase, and can bind to the androgen
receptor. Some synthetic progesterone naturally has estrogenic as well as
androgenic effects. Progesterone has affinity to the androgen receptor that
allows it to act as androgen or anti-androgen; it also binds to its own
intracellular transcription receptor.
Aside from the inhibiting effect of progesterone to the androgen receptor
binding, it also inhibits the enzyme 5a-Reductase responsible for the metabolism
of testosterone to DHT. Compared to testosterone, however, the DHT binds
the androgen receptor with five times the tenacity of testosterone and is
more potent in its ability to cause downstream activation. Another inhibitory
effect of progesterone is towards the formation of the 5ametabolites from
androstenedione. Most tissues such as the skin rapidly metabolize progesterone
to relatively nonandrogenic substances. In women, one milliliter of a 2
percent solution applied topically twice daily appears to be well tolerated,
but higher doses lead to menstrual irregularities.
Although it has not been tested thoroughly in clinical studies, topical
progesterone has been utilized widely. To ascertain the efficacy of the
compound, a study using topical progesterone has been undertaken for 10
to 48 months in 12 men in the age group 18 to 39-year old with male pattern
baldness. However, the results were not that promising because none of the
subjects grew hair: 6 of them developed further thinning, and the other
6 had the same hair density.
However, 14 patients treated with 15 mL of a 0.5percent topical 11a-hydroxyprogesterone
applied twice daily to the scalp for 2.4 to 4 years documented a “positive” response.
Another study on 1% 11a-hydroxyprogesterone lotions in 18 young men for
12-month period found that the 11a-hydroxyprogesterone treated group had
increased numbers of anagen hairs in the treated scalp, and 9 of 10 had
improvement. In the controls, however, there was a decrease in anagen hairs
and worsening hair loss in 7 of the 8 subjects.
Topical Estrogen Treatment
Estrogens, as indirect anti-androgens, lead to a decrease in the bioactive
free testosterone by increasing the production of sex hormone binding globulin
(SHBG). Synthesized by the liver, SHBG is a glycoprotein most important
for androgen binding in which in the plasma, the more potent androgens and
estradiol are bound with different binding affinities. An increased activity
of 5a-Reductase – the enzyme responsible for the metabolism of testosterone
to DHT, and an increased testosterone level causes SHBG synthesis to decrease.
On the other hand, estrogen increases the Sex Hormone Binding Globulin (SHBG)
and thus decreasing further the amount of free testosterone.
There have been no extensive clinical trials regarding the use or topical
estrogen preparation in subjects with pattern baldness; however, there
has been one double-blind, controlled 6-month trial to topical 0.025% 17a-estradiol
conducted with 15 men and women who had pattern alopecia. The trial showed
that a significant reduction in the percentage of telogen hairs along with
stabilization of the hair loss. However, the absorption of topical estrogen
can lead to decreased libido in men even if more than 70 percent of a topically
applied preparation is metabolized to weak non-androgenic by-products.