Cosmetic in Japan 美容医学への扉-東京大学美容外科-アンチエイジング
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Web Master -Kotaro Yoshimura, M.D.-

Anti-androgen Therapy

Kotaro Yoshimura

Anti-androgen treatment is generally used to treat symptoms arising from excessive androgen, or to prevent symptoms that are expected to be worsened by androgen, but it can be used in treatments for other purposes. For example, it is a male to female trans-sexual treatment in gender identity disorders.

Anti-androgen treatment is usually used for prostate cancer or prostatic hyperplasia in men. It is rarely used for uterine or breast cancer. When indication of the treatment expands, it can be applied to male baldness, female acne, hypertrichosis, gynopathy, and amenorrhea, etc. Of course, because hormone action is to be controlled, side effects of such treatment must be monitored. When administering it to women, patients have to prevent pregnancy, and it can be performed together with birth control pills. Synergism can be seen in some cases when used in combination with birth control pills.

Various action mechanisms are present in anti-androgen drugs as follows.
Even though we understand the effects to some extent, there are many actions which are not yet known, and there are many medicines whose entire action mechanisms are not yet understood.

@ Receptor inhibition with steroids
This inhibits receptors. Androgen acts on an intranuclear receptor in target cells, but we can attempt to inhibit it at the receptor level, as these drugs have a strong affinity for androgen receptors. This is effective for adrenal androgen in particular. Spironolactone and cyproterone acetate are two examples. They are primarily drug developed for other purposes. It is known that Megestrol has androgen receptor inhibition and production inhibition effects in the gonads.

It is a diuretic drug used for hypertension and edema generally, but it is known to have an androgen receptor inhibitive effect. It was originally developed as anti-aldosterone medicine, but when combined with other steroid hormones, seems to inhibit receptors. It is said to have an affinity of 67% of DHT for androgen receptors. Action is weak, but it is said to control ovarian and male adrenal hormone-production (cytochrome P-450 decrease) and inhibit activation of 5α-reductase. Androstendione in the blood seems to decrease, but DHEA and DHEAS do not seem to deteriorate very much. There may be an anti-progesterone effect as well as some antiestrogen action, too. It is contraindication for patients with renal disorder due to fear of high K blood disease.

Cyproterone acetate:
Hindering action takes place in androgen receptors. This seems to inhibit ovarian androgen production so that there is an inhibitory effect on gonadotrophin secretion from the pituitary gland too. Furthermore, if used together with estrogen, gonadotrophin secretion is even further suppressed, and synergy can be expected so that blood SHBG increases. It was used widely overseas, and also for prostate cancer in Japan, but a link to development of liver cancer was found, and it was removed from the Japanese market in 1999. In women, it is used from the fifth day until the 14th day of their menstruation cycle, and there seems to be many cases where estrogen is used in combination from the fifth until 25th day. There also seems to be a protocol administrating it during the first ten days of menstrual cycle.

AReceptor inhibition by non-steroid
Flutamide is well-known. Androgen and receptors are inhibited, and it is used for prostate cancer. Overseas, it is used for female hypertrichosis and acne, but monthly blood testing is necessary for Japanese because liver damage often occurs. There is a report that this is rarely seen in women. The use of Warfarin in combination is contraindication; in men feminism & gynecomastia are possibly seen, in women menoxenia and amenorrhea. Cimetidine also inhibits signaling of the androgen receptors.

BInhibition of androgen synthesis
It is not normal, but castration is one method to inhibit production of androgen. Ketoconazole and imidazone peperazine are antifungal agents, but it is known that they have androgen production inhibitory effect in the adrenal gland. In addition, we also know that aminoglutethimide inhibits androgen production in the gonads.

CGn-RH (gonadotrophin secretion hormone)
LH-RH analog indirectly controls androgen production and synthesis. Gn-RH literally promotes secretion of gonadotrophin at first, but we know that if the administration is continuous, then so does inhibition of gonadotrophin secretion; androgyny is not a problem, and can be used in treatment of malignant tumor and sex hormone dependency. Injection or collunarium methods are approved.

Administration of estrogen increases blood SHBG levels, and there is a secondary action of reducing free T (testosterone). In addition, with continuous use, secretion of gonadotrophin is restrained, and production/secretion of androgen from the ovaries is indirectly inhibited. It is said that Fosfestrol (internal use 100-400mg / day) acts on diencephalon, the pituitary gland, and testes with administration of a small amount, large doses inhibit 5α-reductase, so can be used to act directly on the prostate. Thrombosis is a side effect. Because there is a risk with long-term individual use, combination with progestin (or a Kaufmann treatment) is done for birth control.

EConversion inhibitor
Finasteride is well-known to inhibit 5α-reductase (type2), and it is assumed that T to HDT conversion is impeded. It is used for prostatic hypertrophy as well as hair loss prevention. So that 5α reductaseType1 (acts on sebaceous gland) is not hindered, the dosage is adjusted according to purpose. Serum DHT, 3α-diolG, and DHT/T are lowered. No major side effects seem to occur. Now clinical trials are underway in Japan. The new drug dutasteride, which inhibits 5α-reductase of type1 and type2, was recently approved in the U.S.A.

FAdrenal cortical hormone medicine
ACTH secretion from the pituitary gland is restrained, and androgen production from adrenal cortex is suppressed.

Medroxyprogesterone acetate (MPA) can inhibit LH secretion from the pituitary gland, and increased excretion of T by derivation of a metabolism enzyme in the liver can be expected.

Chlormadinone acetate
It is used to treat prostate cancer, prostatic hypertrophy, etc., but it is assumed that there is direct anti-prostate action. It is assumed that there is inhibition of uptake, action, and synthesis of T.