5 Alpha Reductase inhibitor benefit and
risk, side effects, herbal natural alterative
January 20 2016 by Ray Sahelian, M.D.
The enzyme 5 alpha-reductase catalyses the reduction of testosterone into the more potent androgen dihydrotestosterone (DHT). The abnormal production of DHT is associated with pathologies of the main target organs of this hormone: the prostate and the skin. Benign prostatic hyperplasia (BPH), prostate cancer, acne, androgenetic alopecia in men, and hirsutism in women appear related to excess DHT production. Two isozymes have been cloned, expressed and characterized (5 alpha R-1 and 5 alpha R-2). They share a poor homology, have different chromosomal localization, enzyme kinetic parameters, and tissue expression patterns. Since 5 alpha R-1 and 5 alpha R-2 are differently distributed in the androgen target organs, a different involvement of the two isozymes in the pathogenesis of prostate and skin disorders can be expected.
Risks, safety, danger, side effects of 5 alpha reductase Inhibitors
Reduced libido and impotence can be a concern with the use of finasteride and dutasteride. The 5alpha-reductase inhibitors, finasteride and dutasteride, are associated with erectile dysfunction (ED), ejaculatory dysfunction and decreased libido. Prostate enlargement is a common problem in middle-aged and elderly men. First-line medical therapy includes alpha 1blockers and 5alpha-reductase inhibitors (5ARIs), such as finasteride and dutasteride. 5ARI use has been associated with adverse sexual outcomes. These effects occur early in therapy. A proposed mechanism for sexual dysfunction involves decreased nitric oxide synthase activity due to decreased dihydrotestosterone. Though theories have been proposed, more needs to be known about the exact mechanisms behind 5ARI-related sexual dysfunction. Many men report lower vitality, lower mood, and easier abdominal weight gain. Many herbal aphrodisiacs can reverse some of the decline in libido.
Curr Opin Endocrinol Diabetes Obes. 2015. Safety concerns regarding 5α reductase inhibitors for the treatment of androgenetic alopecia. To examine the clinical and basic studies regarding persistent adverse effects associated with 5α reductase inhibitor treatment for androgenetic alopecia. Recent postmarketing reports and a US Food and Drug Administration analysis have documented uncommon persistent sexual and nonsexual side-effects in a subset of younger men who have taken finasteride 1 mg for androgenic alopecia. While the mechanisms of the sexual side-effects in humans is incompletely understood, one study found lower cerebrospinal fluid concentrations of dihydrotestosterone, progesterone, dihydroprogesterone and allopregnanolone, and higher levels of testosterone, 5α-androstane-3α,17β-diol and pregnenolone. Another study found up-regulation of the androgen receptor in the human foreskin with a mean of 5 years after finasteride discontinuation. Studies of erectile dysfunction in finasteride-treated rats showed fewer autophagosomes in smooth muscle on transmission electron microscopy, increased apoptosis, decreased smooth muscle, increased collagen deposition and decreased endothelial nitric oxide synthase. Finally, 5α reductase inhibitors have also been found to alter semen parameters in healthy men. Multiple animal studies provide a biological basis for many of the persistent effects seen in humans such as erectile dysfunction, depression and decreased alcohol consumption. Prescribers of 5α reductase inhibitors should discuss the potential risks with their patients seeking treatment for androgenetic alopecia.
Clinical trials with 5ARI report reveal decreased circulating dihydrotestosterone (DHT) resulting in diminished sexual desire and/or orgasm. The presence of adverse sexual effects is associated with decreased self-esteem, quality of life and ability to maintain an intimate relationship. Inhibition of 5ARI additionally influences progesterone and deoxycorticosterone levels and may alter psychological functions, including increased depression, melancholy and loss of general well being.
Korean J Urol. 2014. The dark side of 5α-reductase inhibitors' therapy: sexual dysfunction, high Gleason grade prostate cancer and depression.
Q. I read that 5-alpha-reductase inhibitor dutasteride helps
in reducing hair loss. However studies also show that it causes sexual side
effects like erectile dysfunction. Can you please advise me on this if I should
take supplement of dutasteride to fight hair loss. Will the natural ways of
taking 5ARIs still cause sexual side effects? Is there some I can externally
apply dutasteride to my scalp so that it will fighting thinning of my hair.
A. Dutasteride does help reduce hair loss but the downside is impotence and loss of libido. This is a decision you have to make. I am not aware yet of topically applied dutasteride availability.
Withdrawal effects, risks, and consequences
Korean J Urol. 2014. Clinical effects of discontinuing 5-alpha reductase inhibitor in patients with benign prostatic hyperplasia. To assess changes in lower urinary tract symptoms (LUTS), prostate volume, and serum prostate-specific antigen (PSA) after discontinuation of 5-alpha reductase inhibitor (5ARI) combination therapy in patients with benign prostatic hyperplasia (BPH). Data were collected retrospectively from 81 men more than 40 years of age with moderate to severe BPH symptoms (International Prostate Symptom Score [IPSS]≥8). The men were classified into group 1 and group 2 according to the use of 5ARI therapy. A combination of dutasteride 0.5 mg with tamsulosin 0.2 mg was given daily to all patients for 1 year. For the next 1 year, group 1 received the combination therapy and group 2 received tamsulosin 0.2 mg monotherapy only. The IPSS, prostate volume, and PSA level were measured at baseline and at 12 and 24 months according to the use of dutasteride. Discontinuation of dutasteride led to significant deterioration of LUTS, increased prostate volume, and increased PSA level. The repeated-measures analysis of variance showed that the changes in IPSS, prostate volume, and PSA level over time also differed significantly between groups 1 and 2. Withdrawal of 5ARI during combination therapy resulted in prostate regrowth and deterioration of LUTS. The PSA level is also affected by the use of 5ARI. Therefore, regular check-up of the IPSS and PSA level may be helpful for all patients who either continue or discontinue the use of 5ARI.
Natural substances and herbs that have
5-alpha-reductase inhibitory activity
There are a number of substances in herbs that have 5-alpha-reductase inhibitory activity, however at this time we don't know how potent they are and how they compare to the active drugs finasteride and dutasteride which are quite specific. Here I will list a few and will add to the list over time.
has activity and has been studied.
Black cohosh extract has potential.
Inhibition of 5alpha-reductase in the rat prostate by Cimicifuga racemosa, black cohosh. Maturitas. 2006. Department of Clinical and Experimental Endocrinology, University of Goettingen, Robert-Koch-Strasse, Gottingen, Germany.
Results indicate that the black cohosh extract BNO 1055 contains one or more potent 5alpha-reductase inhibitors.
Camelia sinensis which is the plant from which various teas are made.
Saw palmetto, also known
as serenoa repens, is being studied to determine how potent it is in terms
of being a 5alpha-reductase inhibitor.
Serenoa repens (Permixon, saw palmetto) inhibits the 5alpha-reductase activity of human prostate cancer cell lines without interfering with PSA expression. Int J Cancer. 2005. . Prostate Research Group, University of Edinburgh, School of Molecular and Clinical Medicine, Western General Hospital, Edinburgh, Scotland, UK.
Our results demonstrate that despite serenoa repens effective inhibition of 5alpha-reductase activity in the prostate, it did not suppress PSA secretion. Therefore, we confirm the therapeutic advantage of serenoa repens over other 5alpha-reductase inhibitors as treatment with the phytotherapeutic agent will permit the continuous use of PSA measurements as a useful biomarker for prostate cancer screening and for evaluating tumour progression.
Willow herb has a substance called oenothein B, which appears to have 5-alpha-reductase inhibitory activity. For more oenothein information.
Andrologia. 2014. Evaluation of 5α-reductase inhibitory activity of certain herbs useful as antiandrogens This study demonstrates 5α-reductase inhibitory activity of certain herbs useful in the management of androgenic disorders. Ganoderma lucidum (Curtis) P. Karst (GL), Urtica dioica Linn. (UD), Caesalpinia bonducella Fleming. (CB), Tribulus terrestris (TT), Pedalium murex Linn. (PM), Sphaeranthus indicus Linn. (SI), Cuscuta reflexa Roxb. (CR), Citrullus colocynthis Schrad. (CC), Benincasa hispida Cogn. (BH), Phyllanthus niruri Linn. (PN) and Echinops echinatus Linn. (EE) were included in the study. Petroleum ether, ethanol and aqueous extracts of these herbs were tested for their 5α-reductase inhibitory activity against the standard 5α-reductase inhibitor, finasteride. A biochemical method to determine the activity of 5α-reductase was used to evaluate the inhibition of different extracts to the enzyme. The optical density (OD) value of each sample was measured continuously with ultraviolet spectrophotometer for the reason that the substrate NADPH has a specific absorbance at 340 nm. As the enzyme 5α-reductase uses NADPH as a substrate, so in the presence of 5α-reductase inhibitor, the NADPH concentration will increase with the function of time. This method thus implicates the activity of 5α-reductase. The method proved to be extremely useful to screen the herbs for their 5α-reductase inhibitory potential. GL, UD, BH, SI and CR came out to be promising candidates for further exploring their antiandrogenic properties.
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.
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.
J Am Acad Dermatol. 2006. Olsen EA, Hordinsky M, Whiting D, Stough D; Dutasteride Alopecia Research Team. Duke University Medical Center, Durham, North Carolina, USA.
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.
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, we determined the impact of 5alpha-reductase inhibitors on these end points. We 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
Effect of finasteride 5 mg Proscar on acne and alopecia in female patients with normal serum levels of free testosterone.
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. Our hypothesis is that some of these women have an excessive activity of the enzyme 5alpha-reductase. We 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 our 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.
I am curious if you are aware of any research -- specifically in men -- involving natural progesterone cream as a natural 5 alpha-reductase inhibitor. I have seen this suggestion elsewhere, and wonder if it is a sensible one.
I doubt natural progesterone cream has this effect.