Antiandrogens as a treatment for hair loss

Due to the established key role of androgens in the development of common baldness and manifestations of hyperandrogenism syndrome, substances with antiandrogenic properties are used in the treatment of these diseases. The mechanism of action of antiandrogens is different. Suppression of the androgen effect is achieved either by inhibiting the activity of the enzyme 5a-reductase, or by blocking androgen receptors in target tissues, or by increasing the production of globulin that binds sex hormones.

Antiandrogens of steroid structure

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

At a daily dose of 5 mg, finasteride (Proscar) is used in the treatment of prostate enlargement.

For the treatment of common male pattern baldness, finasteride is recommended at a dose of 1 mg per day (Propecia). Propecia prevents the progression of baldness and promotes new hair growth. The drug is intended for long-term (12-24 months) use. The therapeutic effect is noticeable after 3-6 months of general treatment, but 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 alopecia only in men: it is most effective in initial and moderate baldness (types I-III according to J. Hamilton); does not affect hair growth in the area of bitemporal bald spots.

Contraindications:

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

Warnings: Use with caution in patients with functional liver disorders, as finasteride is most actively metabolized in the liver.

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

Dosage: 1 mg (1 tablet) once a day, regardless of food intake. Long-term use is recommended. Stopping treatment returns the patient to the initial state of baldness approximately one year after discontinuing the drug.

2. Cyproterone acetate (Androcur, Androcur-depot) is a derivative of hydroxyprogesterone. Cyproterone is a progestogen by its structure, but its gestagenic properties are weak. With a powerful antiandrogenic effect, the drug is effective in the treatment of common baldness and other skin diseases of androgenic genesis in women. Cyprogeron replaces androgens in the cytoplasmic receptors of hair follicles. Since the drug has an antiestrogenic effect, it is necessary to prescribe estrogens 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 common alopecia has not yet been established. Good results were obtained with high doses of CPA (50-100 mg daily from days 5 to 14 of the menstrual cycle) in combination with 0.050 mg ethinyl estradiol from days 5 to 25 of the cycle. Efficacy monitoring conducted after one year to avoid possible seasonal fluctuations objectively showed an increase in hair diameter and the number of hairs 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 are more effective than high doses for common baldness. In this regard, the contraceptive drug Diane-3 5 deserves attention; 1 tablet of it contains 2 mg of CPA and 0.035 mg of ethinyl estradiol. The drug is taken 1 tablet per day from the 1st day of the menstrual cycle according to the scheme indicated on the package. The duration of treatment for common baldness is 6-12 months.

At a dose of 100 mg per day and above, CPA is hepatotoxic. In recent years, there have been reports of an increased risk of developing malignant liver tumors while taking CPA. The prescription of the drug should be agreed upon with a gynecologist - endocrinologist.

3. Estrogens and gestagens.

For many years, combined oral contraceptives containing estrogens and gestagens have been used to treat androgenic alopecia and other manifestations of hyperandrogenism syndrome in women. Estrogens increase the production of sex hormone-binding globulin; as a result, the serum testosterone level decreases. Gestagens inhibit 5a-reductase and also bind cytosolic androgen receptors. Currently, preference is given to third-generation gestagens, which are devoid of the side antiestrogenic effect (desogestrel, norgestimate, gestaden). Good results have been achieved with the use of the drug Silest, which contains norgestimate and ethinyl estradiol. Unfortunately, long-term (more than 5 years) use of these drugs causes dysmenorrhea. The prescription of oral contraceptives should be agreed with a gynecologist - endocrinologist.

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

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

Prescribed to women over 30 for 6 months. In a daily dose of 200 mg, spironolactone has been tested as a treatment for common baldness in 6 women; a good cosmetic result was achieved. Side effects include swelling of the mammary glands and dysmenorrhea. Since the drug causes feminization of the male fetus, oral contraceptives must be prescribed. Long-term use of spironolactone increases the risk of breast tumors.

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

Non-steroidal antiandrogens

• Bicalutamide (Casodex)
• Nimutamide (Anandron)
• Flutamide (Flulem, flucinom)

Drugs with very strong antiandrogenic action; block androgen receptors of target cells, preventing the development of biological effects of endogenous androgens. Used for palliative treatment of prostate cancer. There is no information on systemic use for the treatment of common alopecia. Experience with local use of flutamide in small doses in combination with minoxidil is reported. This combination gave more noticeable results than monotherapy with minoxidil.

Antiandrogens of plant origin.

1. Fruits of the dwarf palm (Serenoa repens)

The fruits of the dwarf palm contain a number of fatty acids (capric, caprylic, lauric, oleic and palmitic), a large number of phytosterols (beta-sitosterol, cycloartenol, stigmasterol, lupeol, etc.), as well as resins and tannins. The red berries of the dwarf palm have long been used in folk medicine to treat prostatitis, enuresis, testicular atrophy, and impotence.

Serenoa repens extract is the active ingredient of Prostaserene, Permixon, Prostamol-uno, Tricoxen. The mechanism of antiandrogenic action of the extract has not yet been fully elucidated. Its inhibitory effect on the level of estrogen and androgen receptors of the nucleus has been revealed. The drugs are recommended for the treatment of benign prostatic hyperplasia, do not affect the levels of T, FSH and LH in the blood plasma in men. There is insufficient data on the effect of saw palmetto fruit extract on the baldness process for it to be recommended for the treatment of androgenetic alopecia, although positive results have already been published, including 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. To date, no clinically significant interactions of these drugs with other drugs have been identified.

2. Fruits of the Sabal palm (Sabal serrulata).

Lipophilic extract from the fruits of the saw palmetto inhibits the enzymes 5a-reductase and aromatase, thereby inhibiting the formation of dihydrotestosterone and 17-estradiol from testosterone; is the active substance of the herbal preparation Prostaplant. The drug is used to treat benign prostatic hyperplasia in adult men, has no contraindications. There have been no reports of overdose of Prostaplant, and drug interactions have not been described.

There is currently no information on the use of Prostaplant for the treatment of androgenic alopecia, but in the future Prostaplant, like other herbal preparations, may become a serious competitor to finasteride, which has a number of serious side effects.

Thus, systemic use of antiandrogens is effective in the prevention and treatment of common baldness, but the need for long-term (possibly lifelong) use 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 level of testosterone also decreases (T is synthesized from cholesterol). The antiandrogenic effect of Simvastin is assessed as weak.
2. Cimetidine (Tagamet, Belomet, etc.)

Cimetidine is a first-generation histamine H2 receptor blocker used to treat peptic ulcers; it is also a DTS inhibitor. As a treatment for common baldness, the drug was tested on 10 women who received 300 mg of cimetidine 5 times a day for 9 months. The results of the therapy were assessed as good and excellent. At the same time, there is a publication describing alopecia caused by taking cimetidine.

When using cimetidine, various side effects may be observed: diarrhea, muscle pain, headache, dizziness, depression. With prolonged use of high doses of the drug, gynecomastia may develop, which is associated with 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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