Nonsteroidal estrogen explained

Width:	250px
Synonyms:	Nonsteroidal estrogen receptor agonists
Atc Prefix:	G03C
Biological Target:	Estrogen receptors (ERα, ERβ, mERs (e.g., GPER, others))
Chemical Class:	Nonsteroidal

A nonsteroidal estrogen is an estrogen with a nonsteroidal chemical structure.^[1] The most well-known example is the stilbestrol estrogen diethylstilbestrol (DES).^[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.^{[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 , 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

See also

• Selective estrogen receptor modulator
• Nonsteroidal antiandrogen

Further reading

• Hermkens PH, Kamp S, Lusher S, Veeneman GH . Non-steroidal steroid receptor modulators . IDrugs . 9 . 7 . 488–94 . 2006 . 16821162 . 10.2174/0929867053764671 .
• Mohler ML, Narayanan R, Coss CC, Hu K, He Y, Wu Z, Hong SS, Hwang DJ, Miller DD, Dalton JT . Estrogen receptor beta selective nonsteroidal estrogens: seeking clinical indications . Expert Opin Ther Pat . 20 . 4 . 507–34 . 2010 . 20302450 . 10.1517/13543771003657164 . 314347 .

Notes and References

1. Hermkens PH, Kamp S, Lusher S, Veeneman GH . Non-steroidal steroid receptor modulators . IDrugs . 9 . 7 . 488–94 . 2006 . 16821162 . 10.2174/0929867053764671.
2. Scherr DS, Pitts WR . 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 . 14532759 . 10.1097/01.ju.0000077558.48257.3d .
3. Hammes B, Laitman CJ . Diethylstilbestrol (DES) update: recommendations for the identification and management of DES-exposed individuals . J Midwifery Womens Health . 48 . 1 . 19–29 . 2003 . 12589302 . 10.1016/s1526-9523(02)00370-7.
4. Schrager S, Potter BE . Diethylstilbestrol exposure . Am Fam Physician . 69 . 10 . 2395–400 . 2004 . 15168959 .
5. Book: Philipp Y. Maximov. Russell E. McDaniel. V. Craig Jordan. Tamoxifen: Pioneering Medicine in Breast Cancer. 23 July 2013. Springer Science & Business Media. 978-3-0348-0664-0. 4–.
6. Book: Edward P. Gelmann. Charles L. Sawyers. Frank J. Rauscher, III. Molecular Oncology. 19 December 2013. Cambridge University Press. 978-0-521-87662-9. 885–.
7. Witorsch RJ . Endocrine disruptors: can biological effects and environmental risks be predicted? . Regul. Toxicol. Pharmacol. . 36 . 1 . 118–30 . 2002 . 12383724 . 10.1006/rtph.2002.1564.
8. Book: V. Craig Jordan. Estrogen Action, Selective Estrogen Receptor Modulators, and Women's Health: Progress and Promise. 2013. World Scientific. 978-1-84816-958-6. 362–365.