Antiandrogens as a remedy for hair loss

In connection with the establishment of the key role of androgens in the development of normal baldness and manifestations of the syndrome of hyperandrogenism, in the treatment of these diseases substances with antiandrogenic properties are used. The mechanism of action of antiandrogens is different. The suppression of the androgen effect is achieved either by inhibiting the activity of the enzyme 5a-reductase, or by blockade of androgen receptors in target tissues, or by increasing the production of globulin binding sex hormones.

Antiandrogens of the steroid structure

1. Finasteride (Proscar, Propecia) is a synthetic 4-azosteroid, a specific type II 5α-reductase inhibitor; when administered orally reduces the level of DTS, without changing the levels of testosterone, cortisol, prolactin, thyroxine, estradiol and globulin, binding sex hormones

In a daily dose of 5 mg, finasteride (Proscar) is used in the treatment of prostatic adenoma.

For the treatment of common baldness in men finasteride is recommended in a dose of 1 mg per day (Propecia). Propecia prevents the progression of alopecia and promotes the growth of new hair. The drug is intended for long-term (12-24 months) use. The therapeutic effect is noticeable after 3-6 months of total treatment, but a significant clinical improvement is observed by the end of the first year of therapy in 48% of patients and by the end of the second year - in 80%. The drug is indicated for the treatment of androgenic baldness only in men: it is most effective at initial and moderately expressed baldness (I-III types according to J. Hamilton); does not affect the growth of hair in the region of the bitemporal bald patches.

Contraindications:

• Finasteride is contraindicated in pregnant women and women of childbearing age. Since the drug is a specific inhibitor of 5a-reductase type II, it is possible hypospadias (disorders of the external genital organs) in a male fetus. Pregnant women should not even touch capsules with broken capsules (crushed, broken tablets) because of the risk of absorption.
• Intolerance of the components of the drug.

Cautions - with caution, appoint patients with functional disorders of the liver, since it is in the liver that finasteride is most actively metabolized.

Side effects: 1.2% of patients develop impotence, decreased libido, decrease in ejaculate volume, gynecomastia. These complications occur when the drug is discontinued and do not need additional treatment.

Dosage: 1 mg (1 table) once a day, regardless of food intake. Long-term use is recommended. Termination of treatment returns the patient to the initial condition of baldness approximately one year after the drug was discontinued.

2. Cyproterone acetate (Androkur, Androkur Depot) is a derivative of hydroxyprogesterone. By its structure, cyproterone is a progestogen, but its progestational properties are poorly expressed. Possessing a powerful anti-androgenic effect, the drug is effective in treating common baldness and other skin diseases of androgenic genesis in women. Cyproperone replaces androgens in the cytoplasmic receptors of the hair follicles. Since the drug has an anti-estrogenic effect, Estrogen administration is necessary to maintain the regularity of the menstrual cycle. Combined treatment with cyproterone and ethinyl estradiol is carried out according to a scheme called "cyclic anti-androgen therapy."

The optimal dose of cyproterone acetate (CPA) for the treatment of normal baldness has not yet been worked out. Good results were obtained with the appointment of high doses of CPA (daily 50-100 mg from the 5th to the 14th days of the menstrual cycle) in combination with 0.050 mg of ethinyl estradiol from the 5th to the 25th days of the cycle. The control of efficiency, conducted a year later to avoid possible seasonal fluctuations, objectively showed an increase in the diameter of the hair and the amount of hair in the anagen phase. It was noted that the optimal result is achieved in women with normal serum levels of vitamin B12 and iron.

According to another point of view, low doses of CPA in normal baldness are more effective than high ones. In this connection, the contraceptive Diane-3 5 (Diane-3 5), whose 1 pills contains 2 mg of CPA and 0.035 mg of ethinylestradiol, deserves attention. The drug is taken 1 tablet a day from the 1st day of the menstrual cycle according to the scheme indicated on the package. Duration of treatment for usual baldness is 6-12 months.

In a dose of 100 mg per day and above, CPA is hepatotoxic. In recent years, there have been reports of an increased risk of malignant neoplasm of the liver against the background of CPA. The purpose of the drug should be agreed with the gynecologist - endocrinologist.

3. Estrogens and gestagens.

For many years, combined oral contraceptives containing estrogens and gestagens are used to treat women androgenic alopecia and other manifestations of hyperandrogenism syndrome. Estrogens increase the production of globulin, binding sex hormones; as a result, the testosterone levels in the blood serum decrease. The gestagens inhibit 5a-reductase, and bind the cytosolic androgen receptors. Currently, preference is given to third-generation progestins, which are devoid of the side-effects of anti-estrogen (desogestrel, norgestimate, gestadene). Good results have been achieved with the use of the preparation of silest, containing norgestimate and ethynylestra diol. Unfortunately, long-term (more than 5 years) use of these drugs causes dysmenorrhea. The appointment of oral contraceptives should be agreed with the gynecologist - endocrinologist.

Local use of estrogens and progestogens, separately or in combination, has been ineffective in both women and men.

4. Spironolactone (Aldactone, Veroshpiron) is a mineral corticoid, has a diuretic and antihypertensive effect. The drug: is also a competitive antagonist of aldosterone. When administered orally at a dose of 100-200 mg / day has a pronounced antiandrogenic effect, due to the ability to inhibit the production of testosterone by the adrenal glands and block the TPA receptors at the site of translocation of the complex into the nucleus of the cell of the hair follicle.

It is prescribed for women over 30 years old for 6 months. In a daily dose of 200 mg, spironolactone is approved as a treatment for common baldness in 6 women; achieved a good cosmetic result. As side effects swelling of the mammary glands, dysmenorrhea was noted. Since the drug causes feminization of the male fetus, it is necessary to administer oral contraceptives. Long-term use of spironolactone increases the risk of developing breast tumors.

In men, spironolactone causes a decrease in libido and gynecomastia. The drug is contraindicated in acute renal failure, the nephrotic stage of chronic nephritis. Caution should be exercised when prescribing the drug to patients with incomplete atrioventricular blockade.

Antiandrogens of non-steroidal structure

• Bicalutamide (Casodex)
• Nimutamide (Anandron)
• Flutamide (Flulom, flucin)

Drugs with a very strong anti-androgenic effect; block the androgen receptor of target cells, preventing the development of biological effects of endogenous androgens. They are used for palliative treatment of prostate cancer. Information about the systemic application for the treatment of normal alopecia there. The experience of topical application of flutamide in small doses in combination with minoxidil has been reported. This combination gave more noticeable results than monoxidil monotherapy.

Antiandrogens of plant origin.

1. Fruits of dwarf palm (Serenoa repens)

The fruit of the dwarf palm contains a number of fatty acids (capric, caprylic, lauric, oleic and palmitic), a large number of phytosterols (beta-sitosterol, cyclotharenol, stigmasterol, lupeol, etc.), as well as tar and tannins. Red dwarf palm berries have long been used in alternative medicine for the treatment of prostatitis, enuresis, testicular atrophy, impotence.

Serenoa repens extract is an active substance of Prostarene preparations, Permixon, Prostamol-uno, Trikoxen. The mechanism of antiandrogenic action of the extract is not yet fully understood. Its inhibitory effect on the level of estrogenic and androgenic receptors in the nucleus was revealed. The drugs are recommended for the treatment of benign prostatic hyperplasia, do not affect the levels of T, FSH and LH in blood plasma in men. Data on the effect of the extract of dwarf palm fruits on the process of alopecia is not sufficient to be recommended for the treatment of androgenetic alopecia, although positive results have already been published, and in women. When used in recommended doses, the drugs are well tolerated by patients, do not affect sexual activity, appetite, body weight, blood pressure, heart rate; no cases of overdose have been reported. Until now, no clinically significant interactions of these drugs with other drugs have been identified.

2. Fruits of palm sabal (Sabal serrulata).

Lipophilic extract from palm sapal fruits inhibits enzymes 5a-reductase and aromatase, thereby inhibiting the formation of dihydrotestosterone and 17-estradiol from testosterone; is an active substance of phytopreparation Prostaplant. The drug is used to treat benign prostatic hyperplasia in adult men, has no contraindications. No cases of overdose of the drug Prostaplant have been reported, no drug interaction has been described.

Information about the use of the prostate for the treatment of androgenetic alopecia is not present at this time, however in the future Prostaplant, like other phytopreparations, can be a serious competitor to finasteride, which has a number of serious side effects.

Thus, the systemic use of antiandrogens is effective in preventing and treating normal alopecia, but the need for a prolonged (perhaps lifelong) intake of these drugs is disappointing.

Other drugs

1. Simvastin is used for obesity to reduce body weight. The drug lowers the level of cholesterol in the blood, as a result of which the testosterone level also decreases (T is synthesized from cholesterol). Anti-androgenic effect of Simvastin is assessed as weak.
2. Cimetidine (Tagamet, Belomet, etc.)

Cimetidine belongs to the first generation of histamine H2 receptor blockers, it is used in the treatment of peptic ulcer; is also an inhibitor of DTS. As a remedy for the treatment of normal baldness, the drug was tested on 10 women who received 300 mg of cimetidine 5 times a day for 9 months. The results of therapy are evaluated as good and excellent. At the same time, there is a publication describing alopecia caused by the use of cimetidine.

When using cimetidine, there may be various side effects: diarrhea, muscle pain, headache, dizziness, depression. With prolonged use of high doses of the drug, gynecomastia may develop, which is due to its ability to stimulate the secretion of prolactin. The use of cimetidine in men can lead to impotence and loss of libido.

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