Antiestrogen

Types and examples

Antiestrogens include selective estrogen receptor modulators (SERMs) like tamoxifen, clomifene, and raloxifene, the ER silent antagonist and selective estrogen receptor degrader (SERD) fulvestrant, aromatase inhibitors (AIs) like anastrozole, and antigonadotropins including androgens/anabolic steroids, progestogens, and GnRH analogues.

Estrogen receptors (ER) like ERα and ERβ include activation function 1 (AF1) domain and activation function 2 (AF2) 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:

• Estrogen deprivation therapy in the treatment of ER-positive breast cancer
• Ovulation induction in infertility due to anovulation
• Male hypogonadism
• Gynecomastia (breast development in men)
• A component of hormone replacement therapy for transgender men

Side effects

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 (MER-25) was the first antagonist of the ER to be discovered, followed by clomifene and tamoxifen.

References

References

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