Epitiostanol Explained

Epitiostanol, sold under the brand name Thiodrol, is an injected antiestrogen and anabolic–androgenic steroid (AAS) of the dihydrotestosterone (DHT) group which was described in the literature in 1965 and has been marketed in Japan as an antineoplastic agent for the treatment of breast cancer since 1977.^{[1] [2] [3] [4] [5]}

Medical uses

Epitiostanol is used as an antiestrogen and antineoplastic agent in the treatment of breast cancer. It has also been found to be effective in the treatment of gynecomastia.^{[6] [7]}

Side effects

A prodrug of epitiostanol, mepitiostane, which is also marketed for the treatment of breast cancer, is reported to show a high rate of virilizing side effects such as acne, hirsutism, and voice changes in women.^[8]

Pharmacology

Pharmacodynamics

Epitiostanol binds directly to the androgen receptor (AR) and estrogen receptor (ER), where it acts as an agonist and antagonist, respectively.^{[9] [10]} It is described as potent in its activity as an antiestrogen and comparatively weak as an AAS. In any case, in terms of AAS potency, epitiostanol has been found to have 11 times the anabolic activity and approximately equal androgenic activity relative to that of the reference AAS methyltestosterone.^[11] The mechanism of action of epitiostanol in breast cancer is multimodal; it directly suppresses tumor growth through activation of the AR and inhibition of the ER, and, in premenopausal women, it additionally acts as an antigonadotropin and reducing systemic estrogen levels via AR activation and consequent suppression of the hypothalamic-pituitary-gonadal axis. Epitiostanol is unique among AAS in acting as an antagonist of the ER.

Pharmacokinetics

Similarly to the case of testosterone, epitiostanol shows poor bioavailability and weak therapeutic efficacy when taken orally due to extensive first-pass metabolism.^[12] As such, it must instead be administered via intramuscular injection.

Chemistry

See also: List of androgens/anabolic steroids.

Epitiostanol, also known as 2α,3α-epithio-4,5α-dihydrotestosterone (2α,3α-epithio-DHT) or as 2α,3α-epithio-5α-androstan-17β-ol, is a synthetic androstane steroid and a derivative of DHT. Mepitiostane, a derivative of epitiostanol with a C17α methoxycyclopentane ether substitution, is an orally active prodrug of epitiostanol.^{[13] [14]} Another derivative, methylepitiostanol (2α,3α-epithio-17α-methyl-5α-androstan-17β-ol), has a methyl group at the C17α position and is similarly an orally active variant of epitiostanol; it has surfaced as a novel designer steroid.^[15]

Society and culture

Generic names

Epitiostanol is the generic name of the drug and its and .

Notes and References

1. Book: Elks J . The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. 14 November 2014. Springer. 978-1-4757-2085-3. 492–.
2. Book: Index Nominum 2000: International Drug Directory. January 2000. Taylor & Francis. 978-3-88763-075-1. 394–.
3. Book: Timmerman H . QSAR and Drug Design: New Developments and Applications. 20 November 1995. Elsevier. 978-0-08-054500-4. 125, 145.
4. Book: William Andrew Publishing. Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. 22 October 2013. Elsevier. 978-0-8155-1856-3. 1455–.
5. Matsuzawa A, Yamamoto T . Antitumor effect of two oral steroids, mepitiostane and fluoxymesterone, on a pregnancy-dependent mouse mammary tumor (TPDMT-4) . Cancer Research . 37 . 12 . 4408–4415 . December 1977 . 922732 .
6. Kurachi K, Aono T, Tomoyama J, Matsumoto K, Nakasima A . Effects of 2alpha, 3alpha-epithio-5alpha-androstan-17beta-ol (epitiostanol) on hypothalamo-pituitary-gonadal axis in humans . Acta Obstetrica et Gynaecologica Japonica . 22 . 1 . 42–8 . January 1975 . 1224948 . Japanese Obstetrical and Gynecological Society .
7. Abe O, Kumaoka S, Yamamoto H . Japanese Journal of Clinical Oncology. 3 . 2 . 99–104 . 2α 3α-Epithio-5α-androstan-17β-ol in Treatment of Gynecomastia . December 1973 . 1465-3621. 10.1093/oxfordjournals.jjco.a039832.
8. Inoue K, Okazaki K, Morimoto T, Hayashi M, Uyama S, Sonoo H, Koshiba Y, Takihara T, Nomura Y, Yamagata J, Kondo H, Kanda K, Takenaka K . Therapeutic value of mepitiostane in the treatment of advanced breast cancer . Cancer Treatment Reports . 62 . 5 . 743–745 . May 1978 . 657160 .
9. Book: Matsuzawa A . Hormone Dependence and Independence in Mammary Tumors in Mice . Bourne GH, Heon KW, Friedlander M . International Review of Cytology . 103 . https://books.google.com/books?id=8SuUZFjkGpwC&pg=PA319 . 27 June 1986. Academic Press. 978-0-08-058640-3. 319–.
10. Croll RP, Wang C . Possible roles of sex steroids in the control of reproduction in bivalve molluscs. Aquaculture. 272. 1–4. 2007. 76–86. 0044-8486. 10.1016/j.aquaculture.2007.06.031. 2007Aquac.272...76C .
11. Book: Brueggemeier RW . Encyclopedia of Molecular Cell Biology and Molecular Medicine. Sex Hormones (Male): Analogs and Antagonists. 2006. Wiley-VCH Verlag GmbH & Co. KGaA . 10.1002/3527600906.mcb.200500066. 3-527-60090-6.
12. Ichihashi T, Kinoshita H, Yamada H . Absorption and disposition of epithiosteroids in rats (2): Avoidance of first-pass metabolism of mepitiostane by lymphatic absorption . Xenobiotica; the Fate of Foreign Compounds in Biological Systems . 21 . 7 . 873–880 . July 1991 . 1776263 . 10.3109/00498259109039527 .
13. Ichihashi T, Kinoshita H, Takagishi Y, Yamada H . Intrinsic lymphatic partition rate of mepitiostane, epitiostanol, and oleic acid absorbed from rat intestine . Pharmaceutical Research . 8 . 10 . 1302–1306 . October 1991 . 1796049 . 10.1023/A:1015864131681 . 31203405 .
14. Ichihashi T, Takagishi Y, Yamada H . Factors determining the intrinsic lymphatic partition rate of epitiostanol and mepitiostane . Pharmaceutical Research . 9 . 12 . 1617–1621 . December 1992 . 1488406 . 10.1023/A:1015824710957 . 2881279 .
15. Rahnema CD, Crosnoe LE, Kim ED . Designer steroids - over-the-counter supplements and their androgenic component: review of an increasing problem . Andrology . 3 . 2 . 150–155 . March 2015 . 25684733 . 10.1111/andr.307 . 6999218 . free .