The Science Behind “Anti-Androgens”

Dihydrotestosterone (DHT), a hormone produced naturally in the body, has been linked to both prostate cancer growth and androgenetic alopecia (AGA; male pattern hair loss).

Those of you who visit hair loss forums or websites promoting hair restoration treatments have most likely seen some of the following terms:
• “Anti-androgens”
• “DHT blockers”
• “DHT inhibitors”
• “Androgen blockers”
• “AR blockers”

These terms are frequently used interchangeably and/or incorrectly. In this Avacor® Hair Regrowth Blog post we will explain the difference, at the molecular and biochemical level, between an androgen receptor antagonist and an inhibitor of DHT synthesis.

DHT, 5-Alpha Reductase and the Androgen Receptor

The androgen receptor (AR) is a protein found in many tissues in both men and women, including the prostate (men), bone marrow, muscle, brain, and hair follicles. When DHT binds to AR it “activates” the receptor, leading to changes in gene expression and cellular behavior. In the scalp, these changes can include miniaturization (shrinking) of hair follicles and eventually male pattern hair loss.1

Testosterone is converted to DHT in the body by enzymes called steroid 5-alpha reductases (5-ARs). Humans possess two types of 5-alpha reductase enzymes: Type 1 (expressed in the skin/scalp and liver) and Type 2 (skin/scalp, prostate, and liver).2, 3

There are two main classes of molecules that prevent the action of DHT in the body:

5-alpha reductase inhibitors reduce the amount of DHT produced in the body

FDA-approved 5-ARIs:
Finasteride (Propecia®, Proscar®)
Dutasteride (Avodart®)

Natural/botanical sources reported to inhibit 5-alpha reductases:
Saw Palmetto (Serenoa Repens)4
African Pygeum (Pygeum Africanum)5
Stinging Nettle Root (Urtica Dioica)5

Finasteride (Propecia®) inhibits only Type 2 5-alpha reductase. Dutasteride (Avodart®) inhibits both Types 1 and 2.

AR antagonists bind to AR and prevent its ability to respond to DHT

Androgen receptor “antagonists”:
Flutamide (Eulexin®)
Bicalutamide (Casodex®)
Cyproterone acetate (Androcur®)
MDV3100 (in Phase III trials)
Spironolactone* (Aldactone®)

*Note – Although some websites6, 7 mention Spironolactone in conjunction with the word “natural,” it is in fact a synthetic drug. The NIH's MedlinePlus website8 states: “Important Warning: Spironolactone has caused tumors in laboratory animals. Talk to your doctor about the risks and benefits of using this medication for your condition.”

If you have questions about the science surrounding AR antagonists, 5-alpha reductase inhibitors, or any of the substances mentioned in this post, please leave a comment here on the Avacor Hair Regrowth Blog so everyone can benefit from the discussion!

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1. Zouboulis CC, Degitz K. Androgen action on human skin -- from basic research to clinical significance. Exp Dermatol. 2004;13 Suppl 4:5-10. Link to Pubmed

2. Thigpen AE, Silver RI, Guileyardo JM, Casey ML, McConnell JD, Russell DW. Tissue distribution and ontogeny of steroid 5 alpha-reductase isozyme expression. J Clin Invest. 1993 Aug;92(2):903-10. Link to Pubmed

3. Asada Y, Sonoda T, Ojiro M, Kurata S, Sato T, Ezaki T, Takayasu S. 5 alpha-reductase type 2 is constitutively expressed in the dermal papilla and connective tissue sheath of the hair follicle in vivo but not during culture in vitro. J Clin Endocrinol Metab. 2001 Jun;86(6):2875-80. Link to Pubmed

4. Bayne CW, Donnelly F, Ross M, Habib FK. Serenoa repens (Permixon): a 5alpha-reductase types I and II inhibitor-new evidence in a coculture model of BPH. Prostate. 1999 Sep 1;40(4):232-41. Link to Pubmed

5. Hartman RW, Mark M, Soldati F. Inhibition of 5a-reductase and aromatase by PHL-00801 (Prostatonin), a combination of PY 102 (Pygeum africanum) and UR 102 (Urtica dioica) extracts. Phytomedicine. 1996 3:121–128.

6. “Revivogen & Topical Spironolactone: Natural Alternative to Propecia?” HairLossTalk.com. (Accessed June 22, 2011)
http://www.hairlosstalk.com/hair-loss-treatments/revivogen/revivogen-spironolactone.php

7. “natural dht inhibitors?” HairLossHelp.com Forums. (Accessed June 22, 2011)
http://www.hairlosshelp.com/FORUMS/messageview.cfm?catid=10&threadid=34449

8. “Spironolactone.” MedlinePlus, U.S. National Library of Medicine, National Institutes of Health. (Accessed June 22, 2011)
http://www.nlm.nih.gov/medlineplus/druginfo/meds/a682627.html