Nonsteroidal Estrogen

Nonsteroidal estrogen
	Drug class
	Diethylstilbestrol, one of the most well-known nonsteroidal estrogens.
Class identifiers
Synonyms	Nonsteroidal estrogen receptor agonists
ATC code	G03C
Biological target	Estrogen receptors (ERα, ERβ, mERs (e.g., GPER, others))
Chemical class	Nonsteroidal

Short description: Class of drugs

A nonsteroidal estrogen is an estrogen with a nonsteroidal chemical structure.^[1] The most well-known example is the stilbestrol estrogen diethylstilbestrol (DES).^[1]^[2] Although nonsteroidal estrogens formerly had an important place in medicine, they have gradually fallen out of favor following the discovery of toxicities associated with high-dose DES starting in the early 1970s, and are now almost never used.^[2]^[3]^[4] On the other hand, virtually all selective estrogen receptor modulators (SERMs) are nonsteroidal, with triphenylethylenes like tamoxifen and clomifene having been derived from DES,^[5] and these drugs remain widely used in medicine for the treatment of breast cancer among other indications.^[6] In addition to pharmaceutical drugs, many xenoestrogens, including phytoestrogens, mycoestrogens, and synthetic endocrine disruptors like bisphenol A, are nonsteroidal substances with estrogenic activity.^[7]

Pharmacology

Nonsteroidal estrogens act as agonists of the estrogen receptors, ERα and ERβ.

List of nonsteroidal estrogens

Synthetic

Pharmaceutical

Stilbestrols: benzestrol, bifluranol, dienestrol, diethylstilbestrol, dimestrol, fosfestrol, furostilbestrol, hexestrol, mestilbol, methestrol, pentafluranol, phenestrol, terfluranol, stilbestrol esters
Triphenylethylenes: chlorotrianisene, desmethylchlorotrianisene, estrobin (DBE), M2613, triphenylbromoethylene, triphenylchloroethylene, triphenyliodoethylene, triphenylmethylethylene
Secosteroids (open-ring steroids): allenestrol, allenolic acid, bisdehydrodoisynolic acid, carbestrol, doisynoestrol, doisynolic acid, fenestrel, methallenestril
Selective ERα or ERβ agonists: diarylpropionitrile, ERB-196, erteberel, FERb 033, GTx-758, prinaberel, propylpyrazoletriol, WAY-166818, WAY-214156
Others: 2,8-dihydroxyhexahydrochrysene (2,8-DHHHC), paroxypropione, quadrosilan, tetrahydrochrysene

SERMs like tamoxifen and raloxifene can also be considered to be nonsteroidal estrogens in some tissues.^[8]

Environmental

Synthetic xenoestrogens: alkylphenols, bisphenols (e.g., bisphenol A), parabens, phthalates, polyhalogenated compounds

Natural

Metalloestrogens: cadmium, others
Mycoestrogens: taleranol (β-zearalanol), α-zearalenol, β-zearalenol, zearalanone, zearalenone, zeranol (α-zearalanol)
Phytoestrogens: coumestrol, daidzein, deoxymiroestrol, equol, genistein, miroestrol, many others

References

↑ ^1.0 ^1.1 "Non-steroidal steroid receptor modulators". IDrugs 9 (7): 488–94. 2006. doi:10.2174/0929867053764671. PMID 16821162.
↑ ^2.0 ^2.1 "The nonsteroidal effects of diethylstilbestrol: the rationale for androgen deprivation therapy without estrogen deprivation in the treatment of prostate cancer". J. Urol. 170 (5): 1703–8. 2003. doi:10.1097/01.ju.0000077558.48257.3d. PMID 14532759.
↑ "Diethylstilbestrol (DES) update: recommendations for the identification and management of DES-exposed individuals". J Midwifery Womens Health 48 (1): 19–29. 2003. doi:10.1016/s1526-9523(02)00370-7. PMID 12589302.
↑ "Diethylstilbestrol exposure". Am Fam Physician 69 (10): 2395–400. 2004. PMID 15168959.
↑ Philipp Y. Maximov; Russell E. McDaniel; V. Craig Jordan (23 July 2013). Tamoxifen: Pioneering Medicine in Breast Cancer. Springer Science & Business Media. pp. 4–. ISBN 978-3-0348-0664-0. https://books.google.com/books?id=p-W5BAAAQBAJ&pg=PA4.
↑ Edward P. Gelmann; Charles L. Sawyers; Frank J. Rauscher, III (19 December 2013). Molecular Oncology. Cambridge University Press. pp. 885–. ISBN 978-0-521-87662-9. https://books.google.com/books?id=GrZEAgAAQBAJ&pg=PA885.
↑ "Endocrine disruptors: can biological effects and environmental risks be predicted?". Regul. Toxicol. Pharmacol. 36 (1): 118–30. 2002. doi:10.1006/rtph.2002.1564. PMID 12383724.
↑ V. Craig Jordan (2013). Estrogen Action, Selective Estrogen Receptor Modulators, and Women's Health: Progress and Promise. World Scientific. pp. 362–365. ISBN 978-1-84816-958-6. https://books.google.com/books?id=ejS6CgAAQBAJ&pg=PA362.