Antiestrogen Explained

Width:	250px
Synonyms:	Estrogen antagonists; Estrogen blockers; Estradiol antagonists
Use:	Breast cancer Infertility; Male hypogonadism; Gynecomastia; transgender men
Atc Prefix:	L02BA
Biological Target:	Estrogen receptor
Chemical Class:	Steroidal; Nonsteroidal (triphenylethylene, others)

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 (ER) and/or inhibiting or suppressing estrogen production.^[1] Antiestrogens are one of three types of sex hormone antagonists, the others being antiandrogens and antiprogestogens.^[2] Antiestrogens are commonly used to stop steroid hormones, estrogen, from binding to the estrogen receptors leading to the decrease of estrogen levels.^[3] Decreased levels of estrogen can lead to complications in sexual development.^[4] Antiandrogens are sex hormone antagonists which are able to lower the production and the effects that testosterone can have on female bodies.^[5]

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,^{[6] [7]} 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.^[8]

Although aromatase inhibitors and antigonadotropins can be considered antiestrogens by some definitions, they are often treated as distinct classes.^[9] Aromatase inhibitors and antigonadotropins reduce the production of estrogen, while the term "antiestrogen" is often reserved for agents reducing the response to estrogen.^[10]

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.^[11] Ethamoxytriphetol (MER-25) was the first antagonist of the ER to be discovered,^[12] followed by clomifene and tamoxifen.^{[13] [14]}

See also

• Antiestrogen withdrawal response
• Estrogen synthesis inhibitor

Notes and References

1. Web site: Definition of antiestrogen - NCI Dictionary of Cancer Terms, Definition of antiestrogen - NCI Dictionary of Cancer Terms .,
2. Book: Nath JL . Using Medical Terminology: A Practical Approach . registration . 2006 . Lippincott Williams & Wilkins. 978-0-7817-4868-1. 977–.
3. McKeage K, Curran MP, Plosker GL . Fulvestrant: a review of its use in hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy . Drugs . 64 . 6 . 633–48 . 2004-03-01 . 15018596 . 10.2165/00003495-200464060-00009 . 242916244 .
4. Amenyogbe E, Chen G, Wang Z, Lu X, Lin M, Lin AY . A Review on Sex Steroid Hormone Estrogen Receptors in Mammals and Fish . International Journal of Endocrinology . 2020 . 5386193 . 2020-02-07 . 32089683 . 7029290 . 10.1155/2020/5386193 . free .
5. Angus LM, Nolan BJ, Zajac JD, Cheung AS . A systematic review of antiandrogens and feminization in transgender women . Clinical Endocrinology . September 2020 . 94 . 5 . 743–752 . 32926454 . 10.1111/cen.14329 . free . 11343/276405 . free .
6. Book: Ottow E, Weinmann H . Nuclear Receptors as Drug Targets. 8 September 2008. John Wiley & Sons. 978-3-527-62330-3. 164–165.
7. Book: Chabner BA, Longo DL . Cancer Chemotherapy and Biotherapy: Principles and Practice. 8 November 2010. Lippincott Williams & Wilkins. 978-1-60547-431-1. 660–.
8. Pike. Ashley C.W.. Brzozowski. A.Marek. Walton. Julia. Hubbard. Roderick E.. Thorsell. Ann-Gerd. Li. Yi-Lin. Gustafsson. Jan-Åke. Carlquist. Mats. 2001-02-01. Structural Insights into the Mode of Action of a Pure Antiestrogen. Structure. en. 9. 2. 145–153. 10.1016/S0969-2126(01)00568-8. 11250199. 0969-2126. free.
9. Book: Riggins RB, Bouton AH, Liu MC, Clarke R . Antiestrogens, aromatase inhibitors, and apoptosis in breast cancer . 71 . 201–37 . 2005 . 16112269 . 10.1016/S0083-6729(05)71007-4 . 9780127098715 . Vitamins & Hormones .
10. Thiantanawat A, Long BJ, Brodie AM . Signaling pathways of apoptosis activated by aromatase inhibitors and antiestrogens . Cancer Research . 63 . 22 . 8037–50 . November 2003 . 14633737 .
11. MacGregor JI, Jordan VC . Basic guide to the mechanisms of antiestrogen action . Pharmacological Reviews . 50 . 2 . 151–96 . June 1998 . 9647865 .
12. Book: Maximov PY, McDaniel RE, Jordan VC . Tamoxifen: Pioneering Medicine in Breast Cancer. 23 July 2013. Springer Science & Business Media. 978-3-0348-0664-0. 7–.
13. Book: Jordan VC . Estrogen Action, Selective Estrogen Receptor Modulators and Women's Health: Progress and Promise. 27 May 2013. World Scientific. 978-1-84816-959-3. 7,112.
14. Book: Sneader W . Drug Discovery: A History. 23 June 2005. John Wiley & Sons. 978-0-471-89979-2. 198–199.