5AR (5α-Reductase)

5α-Reductase converts:

TESTOSTERONE ➔  DIHYDROTESTOSTERONE (DHT) (normally in males)

Mainly in peripheral tissue, but also in testes; DHT is significantly more potent than TESTOSTERONE, and thought to be involved in prostate enlargement, prostate cancer and PCOS.

There are two 5AR forms (isoenzymes)

-   5-alpha reductase 1 (SRD5A1) - used to create neurosteroids

-   5-alpha reductase 2 (SRD5A2) - converts TESTOSTERONE ➔ DHT

5AR Inhibited by:

•  PROGESTERONE

•  Drugs (E.g. Finasteride , Dutasteride) - used against prostate cancer and male pattern baldness

•  Saw Palmetto (Serenoa repens)

•  Willow herb - contains oenothein B, with 5AR inhibitor activity

•  Astaxanthin - this carotenoid has demonstrated some 5AR inhibitor activity

•  Black cohosh (Cimicifuga racemosa)

Maturitas. 2006.Department of Clinical and Experimental Endocrinology, University of Goettingen, Robert-Koch-Strasse, Gottingen, Germany

-   5AR Inhibitor (5ARI) drugs (E.g. Finasteride , Dutasteride) have been associated with adverse outcomes, which side-effects may also be experienced with any natural 5AR inhibitor:

•  Adverse sexual outcomes - such as lack of libido, erectile dysfunction (ED), and ejaculatory dysfunction (EjD). Since NO (nitric oxide) is required to maintain an erection, a suggested theory is that lack of DHT inhibits nitric oxide synthase (NOS) activity.

Nitric Oxide

•  Anxiety / Depression - common side effects of 5ARI s believed to be caused, in part, by the prevention of the endogenous production of the neurosteroid allopregnanolone from PROGESTERONE

•  Cancer

•   Finasteride - inhibits the function of only type 2 form of 5AR (SRD5A2); however, it was found in a study of 18,000 healthy men, that although the finasteride group had a lower incidence of cancer (18.4% vs. 24.4%) there were more cases of aggressive cancer with finasteride than with placebo group (37% vs. 22.2%, P<0.001).

Thompson IM, Goodman PJ, Tangen CM, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med 2003;349:215-224 ;

•   Dutasteride - inhibits both forms of 5AR (SRD5A2 and SRD5A2);