Antiestrogen


Antiestrogens, also known as estrogen antagonists or estrogen blockers, are a class of drugs which prevent estrogens like estradiol from mediating their biological effects in the body. They act by blocking the estrogen receptor and/or inhibiting or suppressing estrogen production. Antiestrogens are one of three types of sex hormone antagonists, the others being antiandrogens and antiprogestogens. Antiestrogens are commonly used to stop estrogens from binding to the estrogen receptors, leading to a decrease of the effects of estrogens. Decreased levels of estrogen can lead to complications in sexual development.

Types and examples

Antiestrogens include selective estrogen receptor modulators like tamoxifen, clomifene, and raloxifene, the ER silent antagonist and selective estrogen receptor degrader fulvestrant, aromatase inhibitors like anastrozole, and antigonadotropins including androgens/anabolic steroids, progestogens, and GnRH analogues.
Estrogen receptors like ERα and ERβ include activation function 1 domain and activation function 2 domain in which SERMS act as antagonists for the AF2 domain, while "pure" antiestrogens like ICI 182,780 and ICI 164,384 are antagonists for the AF1 and AF2 domains.
Although aromatase inhibitors and antigonadotropins can be considered antiestrogens by some definitions, they are often treated as distinct classes. Aromatase inhibitors and antigonadotropins reduce the production of estrogen, while the term "antiestrogen" is often reserved for agents reducing the response to estrogen.

Medical uses

Antiestrogens are used for:
In women, the side effects of antiestrogens include hot flashes, osteoporosis, breast atrophy, vaginal dryness, and vaginal atrophy. In addition, they may cause depression and reduced libido.

Pharmacology

Antiestrogens act as antagonists of the estrogen receptors, ERα and ERβ.

History

The first nonsteroidal antiestrogen was discovered by Lerner and coworkers in 1958. Ethamoxytriphetol was the first antagonist of the ER to be discovered, followed by clomifene and tamoxifen.