Antiandrogens

Products

Antiandrogens are mainly commercially available in the form of tablets, capsules, and injectables. Among the first steroidal agents was cyproterone acetate, which was patented in the 1960s. Flutamide was the first non-steroidal agent to be approved in the 1980s.

Structure and properties

A distinction is made between antiandrogens with a steroidal structure (like the androgens themselves) and those with a nonsteroidal structure. The steroidal antiandrogens are derived from progesterone and are less selective than the newer agents: the nonsteroidal agents such as bicalutamide, with the exception of darolutamide, share a common structural element:

Effects

The agents (ATC L02BB) have antiandrogenic properties, meaning that they abolish the effects of male sex hormones, i.e., androgens such as testosterone and dihydrotestosterone, at their receptor. They are usually antagonists at the androgen receptor and they are therefore also called androgen receptor antagonists. The androgen receptor is a transcription factor that regulates the expression of numerous genes. Binding of androgens to the receptor in the cytoplasm leads to dimerization and activation, which allows interaction with DNA in the nucleus and transcription. Abiraterone (Zytiga) has a different mechanism of action. It inhibits CYP17 in the testes, adrenal glands, and prostate tumor tissue, leading to blockade of androgen synthesis.

Indications

Medical indications for antiandrogens include:

Not all drugs are approved for all indications. For example, cyproterone acetate is not suitable for prostate cancer therapy.

Dosage

According to the SmPC. Antiandrogens are usually administered perorally. Injectables are also available, and they are also applied topically for local treatment (e.g., acne).

Active ingredients

Nonsteroidal antiandrogens:

  • Apalutamide (Erleada).
  • Bicalutamide (Casodex, generic).
  • Darolutamide (Nubeqa)
  • Enzalutamide (Xtandi)
  • Flutamide (Flucinom, in many countries out of trade).
  • Nilutamide (Nilandron Anandron, in many countries out of trade).

Steroidal antiandrogens / progestins:

Androgen synthesis inhibitors:

Contraindications

  • Hypersensitivity
  • Pregnancy and lactation

Full precautions can be found in the drug label.

Interactions

Many antiandrogens interact with CYP450 isozymes and corresponding interactions are possible. They should not be combined with androgens.

Adverse effects

The most common potential adverse effects of antiandrogens include:

  • Fatigue, weakness
  • High blood pressure
  • Skin rash
  • Gastrointestinal disorders
  • Hot flashes
  • Peripheral edema
  • Pain: joint pain, back pain, muscle pain, headache.
  • Enlargement of the mammary gland, sensitivity to touch the breast.