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Risks, Safety, Danger, Side Effects Of 5 Alpha Reductase Inhibitors For Conventional Prostate Treatment (Part 1)

A person who has health has a hundred goals; a person who doesn't have health has but one goal. Every man has a prostate, but every prostate doesn't have to make every man miserable. This all-too commonly bothersome gland is the source of a lot of grief as men age. Still, there are steps that can be taken to help it last a lifetime

Prostate problems are common in men over 50 years of age. They can affect your daily routine adversely.

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.

A study in the Curr Opin Endocrinol Diabetes Obes. 2015 titled “Safety concerns regarding 5α reductase inhibitors for the treatment of androgenetic alopecia” 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. It is therefore necessary for Prescribers of 5α reductase inhibitors to 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.

In another study published in the Korean J Urology. 2014. “Clinical effects of discontinuing 5-alpha reductase inhibitor in patients with benign prostatic hyperplasia”. The study assesses 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 alternative to 5-alpha-reductase inhibitory activity

There are a number of substances in herbs that have 5-alpha-reductase inhibitory activity. Here I will list a few and will add to the list over time.

Astaxanthin carotenoid has activity and has been studied.

Black cohosh extract has potential. In a study titled “Inhibition of 5alpha-reductase in the rat prostate by Cimicifuga racemosa, black cohosh. Maturitas” published in the year 2006 at the Department of Clinical and Experimental Endocrinology, University of Goettingen, Robert-Koch-Strasse, Gottingen, Germany. The 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 is also excellent source.

Saw palmetto, also known as serenoa repens, is being studied to determine how potent it is in terms of being a 5alpha-reductase inhibitor. In a study also titled” Serenoa repens (Permixon, saw palmetto) inhibits the 5alpha-reductase activity of human prostate cancer cell lines without interfering with PSA expression” published in the journal Int J Cancer. 2005. The Prostate Research Group, University of Edinburgh, School of Molecular and Clinical Medicine, Western General Hospital, Edinburgh, Scotland, UK,

Results demonstrate that despite serenoa repens effective inhibition of 5alpha-reductase activity in the prostate; it did not suppress PSA secretion. Therefore, the investigators 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. In a study published in the journal

Andrologia. 2014, tittled” 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 (UD), Caesalpinia bonducella (CB), Tribulus terrestris (TT), Pedalium murex (PM), Sphaeranthus indicus (SI), Cuscuta reflexa (CR), Citrullus colocynthis, Benincasa hispida, Phyllanthus niruri (PN) and Echinops echinatus (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.

By Dr. Raphael Nyarkotey Obu
Tel:0541234556

Disclaimer: "The views/contents expressed in this article are the sole responsibility of the author(s) and do not neccessarily reflect those of Modern Ghana. Modern Ghana will not be responsible or liable for any inaccurate or incorrect statements contained in this article." © Raphael Nyarkotey Obu

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