Antiandrogen

Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking the androgen receptor (AR) and/or inhibiting or suppressing androgen production. They can be thought of as the functional opposites of AR agonists, for instance androgens and anabolic steroids (AAS) like testosterone, DHT, and nandrolone and selective androgen receptor modulators (SARMs) like enobosarm. Antiandrogens are one of three types of sex hormone antagonists, the others being antiestrogens and antiprogestogens.Antiandrogens are substances which prevent androgens from expressing their activity at target sites. The inhibitory effect of these substances, therefore, should be differentiated from compounds which decrease the synthesis and/or release of hypothalamic (releasing) factors, from anterior pituitary hormones (gonadotropins, particularly luteinizing hormone) and from material which acts directly on the gonads to inhibit biosynthesis and/or secretion of androgens. Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking the androgen receptor (AR) and/or inhibiting or suppressing androgen production. They can be thought of as the functional opposites of AR agonists, for instance androgens and anabolic steroids (AAS) like testosterone, DHT, and nandrolone and selective androgen receptor modulators (SARMs) like enobosarm. Antiandrogens are one of three types of sex hormone antagonists, the others being antiestrogens and antiprogestogens. Antiandrogens are used to treat an assortment of androgen-dependent conditions. In males, antiandrogens are used in the treatment of prostate cancer, enlarged prostate, scalp hair loss, overly high sex drive, unusual and problematic sexual urges, and early puberty. In women, antiandrogens are used to treat acne, seborrhea, excessive hair growth, scalp hair loss, and high androgen levels, such as those that occur in polycystic ovary syndrome (PCOS). Antiandrogens are also used as a component of feminizing hormone therapy for transgender women and as puberty blockers in transgender girls. Side effects of antiandrogens depend on the type of antiandrogen and the specific antiandrogen in question. In any case, common side effects of antiandrogens in men include breast tenderness, breast enlargement, feminization, hot flashes, sexual dysfunction, infertility, and osteoporosis. In women, antiandrogens are much better tolerated, and antiandrogens that work only by directly blocking androgens are associated with minimal side effects. However, because estrogens are made from androgens in the body, antiandrogens that suppress androgen production can cause low estrogen levels and associated symptoms like hot flashes, menstrual irregularities, and osteoporosis in premenopausal women. There are a few different major types of antiandrogens. These include AR antagonists, androgen synthesis inhibitors, and antigonadotropins. AR antagonists work by directly blocking the effects of androgens, while androgen synthesis inhibitors and antigonadotropins work by lowering androgen levels. AR antagonists can be further divided into steroidal antiandrogens and nonsteroidal antiandrogens; androgen synthesis inhibitors can be further divided mostly into CYP17A1 inhibitors and 5α-reductase inhibitors; and antigonadotropins can be further divided into gonadotropin-releasing hormone modulators (GnRH modulators), progestogens, and estrogens. Antiandrogens are used in the treatment of an assortment of androgen-dependent conditions in both males and females. They are used to treat men with prostate cancer, benign prostatic hyperplasia, pattern hair loss, hypersexuality, paraphilias, and priapism, as well as boys with precocious puberty. In women and girls, antiandrogens are used to treat acne, seborrhea, hidradenitis suppurativa, hirsutism, and hyperandrogenism. Antiandrogens are also used in transgender women as a component of feminizing hormone therapy and as puberty blockers in transgender girls. Androgens like testosterone and particularly DHT are importantly involved in the development and progression of prostate cancer. They act as growth factors in the prostate gland, stimulating cell division and tissue growth. In accordance, therapeutic modalities that reduce androgen signaling in the prostate gland, referred to collectively as androgen deprivation therapy, are able to significantly slow the course of prostate cancer and extend life in men with the disease. Although antiandrogens are effective in slowing the progression of prostate cancer, they are not generally curative, and with time, the disease adapts and androgen deprivation therapy eventually becomes ineffective. When this occurs, other treatment approaches, such as chemotherapy, may be considered. The most common methods of androgen deprivation therapy currently employed to treat prostate cancer are castration (with a GnRH modulator or orchiectomy), nonsteroidal antiandrogens, and the androgen synthesis inhibitor abiraterone acetate. Castration may be used alone or in combination with one of the other two treatments. When castration is combined with a nonsteroidal antiandrogen like bicalutamide, this strategy is referred to as combined androgen blockade (also known as complete or maximal androgen blockade). Enzalutamide, apalutamide, and abiraterone acetate are specifically approved for use in combination with castration to treat castration-resistant prostate cancer. Monotherapy with the nonsteroidal antiandrogen bicalutamide is also used in the treatment of prostate cancer as an alternative to castration with comparable effectiveness but with a different and potentially advantageous side effect profile. High-dose estrogen was the first functional antiandrogen used to treat prostate cancer. It was widely used, but has largely been abandoned for this indication in favor of newer agents with improved safety profiles and fewer feminizing side effects. Cyproterone acetate was developed subsequently to high-dose estrogen and is the only steroidal antiandrogen that has been widely used in the treatment of prostate cancer, but it has largely been replaced by nonsteroidal antiandrogens, which are newer and have greater effectiveness, tolerability, and safety. Bicalutamide, as well as enzalutamide, have largely replaced the earlier nonsteroidal antiandrogens flutamide and nilutamide, which are now little used. The earlier androgen synthesis inhibitors aminoglutethimide and ketoconazole have only limitedly been used in the treatment of prostate cancer due to toxicity concerns and have been replaced by abiraterone acetate. In addition to active treatment of prostate cancer, antiandrogens are effective as prophylaxis (preventatives) in reducing the risk of ever developing prostate cancer. Antiandrogens have only limitedly been assessed for this purpose, but the 5α-reductase inhibitors finasteride and dutasteride and the steroidal AR antagonist spironolactone have been associated with significantly reduced risk of prostate cancer. In addition, it is notable that prostate cancer is extremely rare in transgender women who have been on feminizing hormone therapy for an extended period of time.