Rigi10™ Malleable Penile Prosthesis
Also Known As
Androgen receptor antagonists, androgen receptor blockers, testosterone blockers, AR inhibitors, androgen antagonists
Definition
Antiandrogens are medications that act by binding to intracellular androgen receptors, preventing the effects of endogenous androgens on target tissues such as testes, hair follicles, hypothalamus, pituitary, ovaries, and prostate gland.1 These drugs antagonize the action of androgens by prohibiting the binding of androgen with androgen receptor (AR), thereby blocking the androgen signal by inhibiting nuclear translocation.2 Antiandrogens are classified into steroidal (such as cyproterone acetate) and nonsteroidal (including flutamide, nilutamide, bicalutamide, enzalutamide, apalutamide, and darolutamide).3 The newer generation antiandrogens (enzalutamide, apalutamide, darolutamide) have a higher affinity to the AR, which optimizes the androgen blockade effect.4 Antiandrogens are primarily used in the treatment of prostate cancer, but are also employed in other conditions where reducing androgen effects is beneficial.5
Clinical Context
Antiandrogens are primarily used in the treatment of prostate cancer, where they play a major role in both castration-sensitive and castration-resistant disease.1 Since the discovery of androgen receptors in the late 1960s, it has been understood that their activation induces the translocation from the cytoplasm to the nucleus, leading to the expression of proliferation genes.2
In prostate cancer treatment, antiandrogens are often used in combination with androgen deprivation therapy (ADT) to achieve a complete androgen blockade.3 This combination both reduces androgen levels and prevents any remaining androgen from binding to androgen receptors. The first-generation antiandrogens (flutamide, nilutamide, bicalutamide) have shown clinical benefit by improving overall survival between 3 to 8 months and extending progression-free survival in metastatic castration-sensitive prostate cancer.4
The newer generation antiandrogens (enzalutamide, apalutamide, darolutamide) have demonstrated greater efficacy. For instance, enzalutamide has shown an overall survival improvement in metastatic castration-resistant prostate cancer, both before and after chemotherapy (PREVAIL and AFFIRM trials), and a metastatic-free survival improvement in non-metastatic castration-resistant prostate cancer (PROSPER trial).5 Similarly, apalutamide has demonstrated improved metastatic-free survival in men with non-metastatic castration-resistant prostate cancer who are at high risk of developing metastases (SPARTAN trial).6
Patient selection for antiandrogen therapy depends on the stage and characteristics of prostate cancer. According to international guidelines (EAU, NCCN, AUA), antiandrogens are recommended for patients with non-metastatic castration-resistant prostate cancer who are at high risk of metastases, as well as for various stages of metastatic disease.7
Beyond prostate cancer, antiandrogens are also used in the treatment of other conditions such as hirsutism, acne, and paraphilias, though these applications vary by specific agent and are sometimes off-label.8