Steroidal antiandrogen
Drug class
Cyproterone acetate, the most widely employed steroidal antiandrogen.
Class identifiers
SynonymsSteroidal androgen receptor antagonists
UseProstate cancer; Benign prostatic hyperplasia; Acne; Hirsutism; Seborrhea; Pattern hair loss; Hyperandrogenism; Transgender hormone therapy; Hypersexuality; Paraphilias; Male precocious puberty; Priapism
ATC codeG03HA
Biological targetAndrogen receptor
Chemical classSteroidal
Legal status
In Wikidata

A steroidal antiandrogen (SAA) is an antiandrogen with a steroidal chemical structure.[1][2][3] They are typically antagonists of the androgen receptor (AR) and act both by blocking the effects of androgens like testosterone and dihydrotestosterone (DHT) and by suppressing gonadal androgen production.[2][3] SAAs lower concentrations of testosterone through simulation of the negative feedback inhibition of the hypothalamus.[4] SAAs are used in the treatment of androgen-dependent conditions in men and women, and are also used in veterinary medicine for the same purpose.[2] They are the converse of nonsteroidal antiandrogens (NSAAs), which are antiandrogens that are not steroids and are structurally unrelated to testosterone.[2][3]

Medical uses

SAAs are used in clinical medicine for the following indications:[2]

Available forms

Antiandrogens marketed for clinical or veterinary use
Generic name Class Type Brand name(s) Route(s) Launch Status Hitsa
Abiraterone acetate Steroidal Androgen synthesis inhibitor Zytiga Oral 2011 Available 523,000
Allylestrenol Steroidal Progestin Gestanin, Perselin Oral 1961 Availableb 61,800
Chlormadinone acetate Steroidal Progestin; AR antagonist Belara, Prostal Oral 1965 Available 220,000
Cyproterone acetate Steroidal Progestin; AR antagonist Androcur, Diane Oral, IM 1973 Available 461,000
Delmadinone acetate Steroidal Progestin; AR antagonist Tardak Veterinary 1972 Veterinary 42,600
Gestonorone caproate Steroidal Progestin Depostat, Primostat IM 1973 Availableb 119,000
Hydroxyprogesterone caproate Steroidal Progestin Delalutin, Proluton IM 1954 Available 108,000
Medroxyprogesterone acetate Steroidal Progestin Provera, Depo-Provera Oral, IM, SC 1958 Available 1,250,000
Megestrol acetate Steroidal Progestin; AR antagonist Megace Oral 1963 Available 253,000
Osaterone acetate Steroidal Progestin; AR antagonist Ypozane Veterinary 2007 Veterinary 87,600
Oxendolone Steroidal Progestin; AR antagonist Prostetin, Roxenone IM 1981 Availableb 36,100
Spironolactone Steroidal AR antagonist Aldactone Oral, topical 1959 Available 3,010,000
Footnotes: a = Hits = Google Search hits (as of February 2018). b = Availability limited / mostly discontinued. Class: Steroidal = Steroidal antiandrogen. Nonsteroidal = Nonsteroidal antiandrogen. Sources: See individual articles.

Pharmacology

Unlike NSAAs, most SAAs show off-target hormonal activity such as progestogenic, glucocorticoid, or antimineralocorticoid activity, possess antigonadotropic effects, and are weak partial agonists of the AR with some capacity to activate the receptor.[2] Due to their antigonadotropic effects, SAAs lower androgen levels in addition to directly blocking the actions of androgens at the AR; at sufficiently high dosages, they are able to lower circulating testosterone levels by up to 70 to 80% in men, to just above the castrate range.[8][9][10] However, due to their other hormonal effects, suppression of estrogen levels alongside testosterone levels, and AR activation, SAAs have increased side effects and show lower efficacy in the treatment of prostate cancer relative to NSAAs.[2]

List of SAAs

Marketed

Used specifically as antiandrogens (major)

Used specifically as antiandrogens (minor)

Used as antiandrogens in veterinary medicine

Used exclusively as progestins in women

Miscellaneous

Steroidal androgen synthesis inhibitors like the CYP17A1 inhibitor abiraterone acetate (Zytiga) or the 5α-reductase inhibitors finasteride and dutasteride could also technically be described as "SAAs", but the term is usually reserved to describe AR antagonists (and sometimes progestogenic antigonadotropins).

Not marketed

Under development

Development discontinued

See also

References

  1. ^ Schröder, Fritz H.; Radlmaier, Albert (2009). "Steroidal Antiandrogens". In V. Craig Jordan; Barrington J. A. Furr (eds.). Hormone Therapy in Breast and Prostate Cancer. Humana Press. pp. 325–346. doi:10.1007/978-1-59259-152-7_15. ISBN 978-1-60761-471-5.
  2. ^ a b c d e f g Singh SM, Gauthier S, Labrie F (2000). "Androgen receptor antagonists (antiandrogens): structure-activity relationships". Curr. Med. Chem. 7 (2): 211–47. doi:10.2174/0929867003375371. PMID 10637363.
  3. ^ a b c Migliari R, Muscas G, Murru M, Verdacchi T, De Benedetto G, De Angelis M (1999). "Antiandrogens: a summary review of pharmacodynamic properties and tolerability in prostate cancer therapy". Arch Ital Urol Androl. 71 (5): 293–302. PMID 10673793.
  4. ^ Akakura, K.; Furuya, Y.; Ito, H. (August 1998). "[Steroidal and nonsteroidal antiandrogens: chemical structures, mechanisms of action and clinical applications]". Nihon Rinsho. Japanese Journal of Clinical Medicine. 56 (8): 2124–2128. ISSN 0047-1852. PMID 9750520.
  5. ^ Erem C (2013). "Update on idiopathic hirsutism: diagnosis and treatment". Acta Clin Belg. 68 (4): 268–74. doi:10.2143/ACB.3267. PMID 24455796. S2CID 39120534.
  6. ^ Reisner SL, Radix A, Deutsch MB (August 2016). "Integrated and Gender-Affirming Transgender Clinical Care and Research". J. Acquir. Immune Defic. Syndr. 72 Suppl 3 (3): S235–42. doi:10.1097/QAI.0000000000001088. PMC 4969060. PMID 27429189. There are many different androgen blockers used for transition care. Spironolactone, an aldosterone receptor antagonist, is frequently used in the United States, whereas cyproterone acetate, a synthetic steroidal antiandrogen with prostogenic properties, is predominantly outside of the United States.
  7. ^ Gooren LJ (2011). "Clinical practice. Care of transsexual persons". N. Engl. J. Med. 364 (13): 1251–7. doi:10.1056/NEJMcp1008161. PMID 21449788. ... Hormone therapy is prescribed for male-to-female transsexuals to induce breast formation and ... To achieve these goals, the biologic action of androgens must be almost completely neutralized. ... combining this treatment [of administrating estrogens] with ... other medications that suppress androgen action (e.g., cyproterone acetate, ...) appears to be more effective. ...
  8. ^ Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA (25 August 2011). Campbell-Walsh Urology: Expert Consult Premium Edition: Enhanced Online Features and Print, 4-Volume Set. Elsevier Health Sciences. pp. 2938–. ISBN 978-1-4160-6911-9.
  9. ^ Kjeld JM, Puah CM, Kaufman B, Loizou S, Vlotides J, Gwee HM, Kahn F, Sood R, Joplin GF (1979). "Effects of norgestrel and ethinyloestradiol ingestion on serum levels of sex hormones and gonadotrophins in men". Clinical Endocrinology. 11 (5): 497–504. doi:10.1111/j.1365-2265.1979.tb03102.x. PMID 519881. S2CID 5836155.
  10. ^ Miyamoto H, Messing EM, Chang C (2004). "Androgen deprivation therapy for prostate cancer: current status and future prospects". The Prostate. 61 (4): 332–53. doi:10.1002/pros.20115. PMID 15389811. S2CID 22300358.
  11. ^ Jack H. Mydlo; Ciril J. Godec (11 July 2003). Prostate Cancer: Science and Clinical Practice. Academic Press. pp. 437–. ISBN 978-0-08-049789-1.
  12. ^ William D. Figg; Cindy H. Chau; Eric J. Small (14 September 2010). Drug Management of Prostate Cancer. Springer Science & Business Media. pp. 99–. ISBN 978-1-60327-829-4.

Further reading

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