In women, antiandrogens are used to treat acne, seborrhea, excessive hair growth, scalp hair loss, and high androgen levels, such as those which occur in polycystic ovary syndrome (PCOS).
These side effects include breast pain/tenderness and gynecomastia (breast development/enlargement), reduced body hair growth/density, decreased muscle mass and strength, feminine changes in fat mass and distribution, and reduced penile length and testicular size.
In addition, antiandrogens can cause infertility, osteoporosis, hot flashes, sexual dysfunction (including loss of libido and erectile dysfunction), depression, fatigue, anemia, and decreased semen/ejaculate volume in males.
Although the term antiandrogen is generally used to refer specifically to AR antagonists, it may also be used to describe functional antiandrogens like androgen synthesis inhibitors and antigonadotropins, including even estrogens and progestogens.
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.
The side effects of antiandrogens vary depending on the type of antiandrogen – namely whether it is a selective AR antagonist or lowers androgen levels – as well as the presence of off-target activity in the antiandrogen in question.
For instance, whereas antigonadotropic antiandrogens like Gn RH analogues and cyproterone acetate are associated with pronounced sexual dysfunction and osteoporosis in men, selective AR antagonists like bicalutamide are not associated with osteoporosis and have been associated with only minimal sexual dysfunction.
AR antagonists act by directly binding to and competitively displacing androgens like testosterone and DHT from the AR, thereby preventing them from activating the receptor and mediating their biological effects.
Steroidal AR antagonists are structurally related to steroid hormones like testosterone and progesterone, whereas nonsteroidal AR antagonists are not steroids and are structurally distinct.
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.