Ингибиторы 5α-редуктазы: применение, побочные эффекты и риски.

Class of medications

5α Reductase inhibitors (5 ARIs), also known as dihydrotestosterone (DHT) blockers, are a class of medications with antiandrogenic effects which are used primarily in the treatment of enlarged prostate and scalp hair loss. They are also sometimes used to treat excess hair growth in women and as a component of hormone therapy for transgender women. These agents inhibit the enzyme 5α reductase, which is involved in the metabolic transformations of a variety of endogenous steroids. 5 ARIs are most known for preventing conversion of testosterone, the major androgen sex hormone, to the more potent androgen dihydrotestosterone (DHT), in certain androgen associated disorders.

Finasteride (brand names Proscar, Propecia) inhibits the function of two of the isoenzymes (types 2 and 3) of 5α reductase. It decreases circulating DHT levels by up to about 70%. Dutasteride (brand name Avodart) inhibits all three 5α reductase isoenzymes and can decrease DHT levels by 95%. It can also reduce DHT levels in the prostate by 97 to 99% in men with prostate cancer. Epristeride (brand names Aipuliete, Chuanliu) is marketed in China for the treatment of benign prostatic hyperplasia. However, it can only decrease circulating DHT levels by about 25 to 54%. Alfatradiol (brand names Ell Cranell Alpha, Pantostin) is a topical 5 ARI used to treat pattern hair loss in Europe. An extract of Serenoa repens, also known as saw palmetto extract, is a 5 ARI that is sold as an over the counter dietary supplement. It is also used under the brand name Permixon in Europe as a pharmaceutical drug for the treatment of benign prostatic hyperplasia.

5 ARIs are generally well tolerated in both men and women and produce few side effects. However, they have been found to have some risks in studies with men, including slightly increased risks of decreased libido, erectile dysfunction, ejaculatory dysfunction, infertility, breast tenderness, gynecomastia, depression, anxiety, self harm, and dementia. In addition, although 5 ARIs decrease the overall risk of developing prostate cancer, they have been found to increase the risk of developing certain rare but high grade forms of prostate cancer. Finasteride has also been associated with intraoperative floppy iris syndrome and cataract formation. Depressive symptoms and suicidality have been reported.

Sexual dysfunction, including erectile dysfunction, loss of libido, and reduced ejaculate, may occur in 3.4 to 15.8% of men treated with finasteride or dutasteride. This is linked to lower quality of life and can cause stress in relationships. There is also an association with lowered sexual desire. It has been reported that in a subset of men, these adverse sexual side effects may persist even after discontinuation of finasteride or dutasteride.

A 2017 population based, matched cohort study of 93,197 men aged 66 years and older with BPH found that finasteride and dutasteride were associated with a significantly increased risk of depression (, 1.94; 95% , 1.73–2.16) and self harm (HR, 1.88; 95% CI, 1.34–2.64) during the first 18 months of treatment, but were not associated with an increased risk of suicide (HR, 0.88; 95% CI, 0.53–1.45). As such, on the basis of these findings, it has been stated that cases of depression in patients that are attributable to 5 ARIs will be encountered on occasion, while cases of self harm attributable to 5 ARIs will be encountered very rarely.

Finasteride was the first 5 ARI to be introduced for medical use. It was marketed for the treatment of BPH in 1992 and was subsequently approved for the treatment of pattern hair loss in 1997. The patent protection on finasteride and dutasteride has expired and both drugs are available as generic medications.

5 ARIs have been studied in combination with the nonsteroidal antiandrogen bicalutamide for the treatment of prostate cancer.