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
FDA: “Label Change – Increased Risk of Prostate Cancer” for the hair loss drug Propecia®
On June 9, 2011, the FDA issued a Drug Safety Communication1 about a class of drugs called 5-alpha reductase inhibitors, which includes the hair loss drug Propecia® (finasteride).
FDA Drug Safety Communication: 5-alpha reductase inhibitors (5-ARIs) may increase the risk of a more serious form of prostate cancer
[6-9-2011] The U.S. Food and Drug Administration (FDA) is informing healthcare professionals that the Warnings and Precautions section of the labels for the 5-alpha reductase inhibitor (5-ARI) class of drugs has been revised to include new safety information about the increased risk of being diagnosed with a more serious form of prostate cancer (high-grade prostate cancer). This risk appears to be low, but healthcare professionals should be aware of this safety information, and weigh the known benefits against the potential risks when deciding to start or continue treatment with 5-ARIs in men.
Two large clinical trials, known as PCPT and REDUCE, were conducted to assess the use of 5-ARIs for preventing prostate cancer. The PCPT trial raised concern at the FDA because patients being treated with finasteride had a slightly higher risk of developing high-grade prostate cancer than patients receiving placebo (1.8% versus 1.1%, respectively). It should be noted that although the title of the FDA's Safety Alert2 reads "Increased Risk of Prostate Cancer," the data on increased risk appear to relate only to the incidence of high-grade prostate cancer (Gleason Score 8-10).
While the “risk appears to be low,” the labels for drugs including Propecia®, Proscar® (finasteride) and Avodart® (dutasteride) are all being modified to warn patients of this potential risk. Propecia® is also associated with sexual side effects3 in some men, including less desire for sex and difficulty in achieving an erection.
The FDA has provided a page of Questions and Answers on the change in label information for 5-ARIs. Below are a few Q/A’s pertaining to the use of Propecia® for male pattern hair loss.
Q6. Does FDA believe the benefits of 5-alpha reductase inhibitors (5-ARIs) still outweigh their risks for the approved indications?
A. Yes. FDA believes that 5-ARIs remain safe and effective for their approved indications. Proscar and Avodart have been effective in controlling symptoms of benign prostatic hyperplasia (BPH), as well as in reducing the risks of acute urinary retention and the need for surgical intervention related to BPH. Healthcare professionals and patients are still encouraged to discuss the risks and benefits of 5-ARIs when deciding the best treatment for their disease.
FDA will continue its risk/benefit assessment of using 5-ARIs for the treatment for male pattern hair loss and will update the public when additional information is available.
Q9. Are there other medications to treat benign prostatic hyperplasia (BPH) or male pattern baldness?
A. Yes. Another class of medications called alpha-blockers is approved to treat the symptoms of BPH. Medications in the alpha-blocker class include tamsulosin (Flomax), doxazosin (Cardura), terazosin (Hytrin), alfuzosin (Uroxatral), and silodosin (Rapaflo). However, 5-ARIs are the only medications that have been shown to reduce the risk of urinary retention or surgery related to an enlarged prostate.
Minoxidil is a topical product that is available over the counter in various formulations to treat male pattern hair loss.
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1. FDA Drug Safety Communication: 5-alpha reductase inhibitors (5-ARIs) may increase the risk of a more serious form of prostate cancer. June 9, 2011.
http://www.fda.gov/Drugs/DrugSafety/ucm258314.htm
2. 5-alpha reductase inhibitors (5-ARIs): Label Change - Increased Risk of Prostate Cancer. June 9, 2011.
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm258529.htm
3. PROPECIA® labeling information, FDA website.
http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020788s018lbl.pdf
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