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Influence on prostate gland and cancer

Testosterone is locally converted by 5alpha-reductase to 5alpha-dihydrotestosterone (5alpha-DHT) which is the major androgenic principle in prostates and seminal vesicles.

5ARI reduce prostate cancer risk but may increase the risk of high-grade disease in men who are undergoing regular screening for prostate cancer using prostate specific antigen and digital rectal examination. Effects are consistent across race, family history and age and possibly 5ARI but are limited to men with baseline PSA values <4.0 ng/mL. The impact of 5ARI on absolute or relative rates of prostate cancer in men who are not being regularly screened is not clear. Information is inadequate to assess the impact of 5ARI on mortality. Therefore, it is not clear whether men who take  5 alpha-reductase inhibitors will live longer or shorter as a result of lower overall risk for prostate cancer but higher risk for high-grade prostate cancer.

5 Alpha Reductase Inhibitors and BPH

By inhibiting the production of dihydrotestosterone (DHT) locally within the prostate gland, 5alpha-reductase inhibitors have the effect of reducing prostate volume, improving lower urinary tract symptoms, increasing peak urinary flow, and decreasing the risk of acute urinary retention and need for surgical intervention. The combination of a 5alpha-reductase inhibitor and an alpha1-adrenergic antagonist significantly reduces the clinical progression of BPH over either drug class alone.

5-ARIs have impacted the medical treatment of urologic disease, in particular BPH, and prostatic hematuria. Their use in the secondary treatment of prostate cancer is currently under investigation.

PSA test influence

A reduction of approximately 50% in PSA by 12 months is expected in men taking a 5-ARI.

5 Alpha Reductase Inhibitors and hair growth

The two 5alpha-reductase inhibitors currently available in pharmacies are finasteride and dutasteride. Finasteride is approved for the treatment of male pattern hair loss. Originally approved for the treatment of benign prostatic hypertrophy in 1992, its approval was expanded in 1997 to include the treatment of androgenetic alopecia in men at a dose of 1 mg/day. Finasteride prohibits the conversion of testosterone to dihydrotestosterone (DHT), which is implicated in the development of hair loss in some men.

In  a study titled “The importance of dual 5alpha-reductase inhibition in the treatment of male pattern hair loss: results of a randomized placebo-controlled study of dutasteride versus finasteride published in the journal J Am Acad Dermatology. 2006. Olsen EA, Hordinsky M, Whiting D, Stough D; Dutasteride Alopecia Research Team. Duke University Medical Center, Durham, North Carolina, USA.

The study involved Four hundred sixteen men, 21 to 45 years old, were randomized to receive dutasteride 0.05, 0.1, 0.5 or 2.5 mg, finasteride 5 mg, or placebo daily for 24 weeks. Dutasteride increased target area hair count versus placebo in a dose-dependent fashion and dutasteride 2.5 mg was superior to finasteride at 12 and 24 weeks. Scalp and serum dihydrotestosterone levels decreased, and testosterone levels increased, in a dose-dependent fashion with dutasteride medication. Dutasteride increases scalp hair growth in men with male pattern hair loss. Type 1 and type 2 5alpha-reductase may be important in the pathogenesis and treatment of male pattern hair loss.

Effect on blood studies and bone mineral density

The effect of 5alpha-reductase inhibition with dutasteride and finasteride on bone mineral density, serum lipoproteins, hemoglobin, prostate specific antigen and sexual function in healthy young men was published in the J Urol. 2008; Amory JK, Anawalt BD, Matsumoto AM, Page ST. Department of Medicine, University of Washington, Seattle, Washington, USA. Because androgens affect bone, lipids, hematopoiesis, prostate and sexual function, the study investigators determined the impact of 5alpha-reductase inhibitors on these end points. They conducted a randomized, double-blinded, placebo controlled trial of 99 men 18 to 55 years old randomly assigned to receive 0.5 mg dutasteride, 5 mg finasteride or placebo daily for 1 year. Bone mineral density was measured at baseline, after 1 year of treatment and 6 months after drug discontinuation.

In addition, markers of bone turnover, fasting serum lipoprotein concentrations, hemoglobin and prostate specific antigen were measured. Significant suppression of circulating dihydrotestosterone levels with the administration of dutasteride or finasteride did not significantly affect bone mineral density or markers of bone metabolism. Similarly serum lipoproteins and hemoglobin were unaffected. Serum prostate specific antigen and self-assessed sexual function decreased slightly during treatment with both 5alpha-reductase inhibitors but returned to baseline during followup. Suppression of circulating serum dihydrotestosterone induced by 5alpha-reductase inhibitors during 1 year does not adversely impact bone, serum lipoproteins or hemoglobin, and has a minimal, reversible effect on serum prostate specific antigen. Circulating dihydrotestosterone does not appear to have a clinically significant role in modulating bone mass, hematopoiesis or lipid metabolism in normal men.

Deficiency in male pseudohermaphrodites

Male pseudohermaphroditism involves 5alpha-reductase deficiency. This is an autosomal recessive form of partial male pseudohermaphroditism where there is a deficiency of the type 2 form of the enzyme 5 alpha-reductase.

Hirsute women and 5alpha-reductase

Hirsute women often have increased activity of 5alpha-reductase, the enzyme that converts the androgen testosterone to its active metabolite, in hair follicles.

Acne and alopecia in women

A study titled “ Effect of finasteride 5 mg Proscar on acne and alopecia in female patients with normal serum levels of free testosterone was published in Gynecol Endocrinol. 2007.

In some women with acne or alopecia who have normal serum levels of free testosterone, no clinical improvement can be reached by the classical treatment with antiandrogens, isotretinoids or corticosteroids.  The study authors’ hypothesis was that some of these women have an excessive activity of the enzyme 5alpha-reductase. They evaluated the subjective benefit of the treatment with finasteride (5 mg/day) in women with normal serum levels of free testosterone suffering from acne or alopecia.

Nine of the 12 patients benefited from the finasteride treatment, their symptoms decreased significantly and they felt better psychologically than before the administration of finasteride. The other three patients did not benefit at all from finasteride and reported no change in the extent of the acne or alopecia. Nine of the 12 patients benefited from the finasteride treatment. This supports their hypothesis of an excessive activity of 5alpha-reductase enzyme in peripheral tissue in these patients. The fact that three of the patients did not realize any change in their symptom severity implies that there must also be other pathways in the genesis of acne and alopecia in women with normal levels of free testosterone.

Source: Dr. Raphael Nyarkotey Obu