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Silent Method
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I ran across several abstracts with some relevance regarding this topic. I've boldfaced some statements that lead me to believe that lowering DHT levels with finasteride is probably irrelevant (or close to irrelevant) regarding skeletal muscle development, but I think these are worth reading all the way through.
Finasteride: a clinical review.
Gormley GJ
Biomed Pharmacother 1995 49:319-24
Biomed Pharmacother • Volume 49 • Issue 7-8
VIEW
Abstract
Finasteride is the first of a new class of 5 alpha-reductase inhibitors which allows selective androgen deprivation affecting dihydrotestosterone (DHT) levels in target organs such as the prostate and scalp hair without effecting circulating levels of testosterone thus preserving the desired androgen mediated effects on muscle strength, bone density and sexual function. Finasteride has been demonstrated to produce significant effects in men with an enlarged prostate gland.
Androgen treatment of middle-aged, obese men: effects on metabolism, muscle and adipose tissues.
Mårin P, Krotkiewski M, Björntorp P
Eur J Med 1992 Oct 1:329-36
Eur J Med • Volume 1 • Issue 6
Abstract
OBJECTIVES: This pilot investigation was conducted to explore the relationship between androgens and glucose tolerance in obese men and to select an optimal mode for androgen treatment. METHODS: For exploratory purposes, testosterone (T) or dihydrotestosterone (DHT) were given in different doses and preparations for different periods of time to obese, middle-aged men. The administration forms were selected in order to by-pass the liver. In the first two studies T was given as a single intramuscular injection of 250 or 500 mg and the results evaluated after 1 week. In two subsequent studies testosterone was administered in moderate doses either as oral T undecanoate or a T and DHT in preparations applied on the skin for transdermal absorption for 6 weeks and 3 months respectively. Before and after treatment the following examinations were performed: glucose tolerance tests with insulin determinations or euglycemic clamps at submaximal insulin levels. Anthropometric measurements including the waist/hip circumference ratio and estimations of body fat and lean body mass (from measurements of whole body potassium content) were performed. Plasma triglyceride and cholesterol concentrations, liver function tests and blood pressure were followed. Physical examination including the prostate was performed before and after study. Muscle function, glycogen synthase and morphology were examined in the 3-month study. RESULTS: Administration of T was followed by moderate increases of circulating T concentrations in all studies, except after injection of 500 mg, where large increases were seen. <Note: I highlighted this statment as a benchmark for our own "therapeutic" use of test> Follicle stimulating hormone and luteinizing hormone levels decreased consistently. Injection of 500 mg T resulted in a decreased glucose tolerance. In the other treatment groups, plasma insulin decreased or glucose disappearance rate increased in clamp measurements, suggesting improved insulin sensitivity. This was most pronounced in men with relative hypogonadism from the outset. In the study of 3 months duration, a decrease in the waist/hip ratio, without a change in body fat mass, was also seen. Plasma lipids, liver function tests and blood pressure did not change. Muscle strength, the fractional velocity of glycogen synthase as well as the percentage and diameter of type IIB fibres increased after T treatment. No adverse effects were seen. 17 -beta oestradiol concentrations were unaltered and DHT administration was less effective than T, suggesting that T rather than derivatives of this hormone was mainly responsible for the effects observed. CONCLUSION: The results suggest that T administration to middle-aged, obese man may have beneficial effects.
Role of 5 alpha-reductase in health and disease.
Randall VA
Baillieres Clin Endocrinol Metab 1994 Apr 8:405-31
Baillieres Clin Endocrinol Metab • Volume 8 • Issue 2
Abstract
The mechanism of androgen action varies in different tissues, but in the majority of androgen target tissues either testosterone or 5 alpha-dihydrotestosterone (DHT) binds to a specific androgen receptor to form a complex that can regulate gene expression. Testosterone is metabolized to DHT by the enzyme 5 alpha-reductase. The autosomal recessive genetic disorder of 5 alpha-reductase deficiency has clearly shown that the requirement for DHT formation varies with different tissues. In this syndrome genetic males contain normal male internal structures including testes, but exhibit ambiguous or female external genitalia at birth; at puberty they undergo partial virilization which includes development of a male gender identity even if brought up as females. Their development suggests that testosterone itself is able to stimulate psychosexual behaviour, development of the embryonic wolffian duct, muscle development, voice deepening, spermatogenesis, and axillary and pubic hair growth; DHT seems to be essential for prostate development and growth, the development of the external genitalia and male patterns of facial and body hair growth or male-pattern baldness. How different hormones operate to regulate genes via the same receptor is currently unknown, but appears to involve cell-specific factors. The 5-alpha-reductase enzyme has proved difficult to isolate biochemically, but recently at least two human isoenzymes have been identified using molecular biological methods. All the various 5 alpha-reductase-deficient kindreds have been shown to have mutations in 5 alpha-reductase 2, the predominant form in the prostate. The biological role of 5 alpha-reductase 1 has not yet been ascertained, but at present it cannot be ruled out that some of the actions ascribed to testosterone are indeed in cells producing DHT via this enzyme. The activity of 5 alpha-reductase is also implicated in benign prostatic hypertrophy, hirsutism and possibly male-pattern baldness; recent evidence discounts the role of 5 alpha reductase 2 in sebaceous glands and acne. Specific inhibitors of both enzymes are now available and finasteride, a 5 alpha-reductase 2 inhibitor, has been used successfully in clinical trials of benign prostatic hypertrophy. Knowledge of 5 alpha-reductase is expanding dramatically at the moment with the application of molecular biological methods. The advent of antibodies to the isoenzymes should herald further understanding of their biological and clinical roles.
Clinical pharmacokinetics and pharmacodynamics of finasteride.
Steiner JF
Clin Pharmacokinet 1996 Jan 30:16-27
Clin Pharmacokinet • Volume 30 • Issue 1
Abstract
Finasteride is a potent 5 alpha-reductase inhibitor that has shown limited success in men treated for benign prostatic hyperplasia (success is defined as a decrease in the symptoms associated with urinary tract obstruction, and as increases in the urinary flow rate). 5 alpha-reductase is necessary for the prostatic conversion of testosterone to dihydrotesterone (DHT), the specific steroid that stimulates prostate transitional zone growth. Finasteride reduces the size of the prostate gland by 20%, but this does not correlate well with improvement in symptoms. Finasteride is well absorbed after oral administration and, while the rate of absorption may be slowed postprandially, the presence of food has no effect on the total bioavailability. Finasteride is widely distributed, but since its pharmacological effects are very specific to inhibition of 5 alpha-reductase, and since only the prostate gland, the scalp, and the genital skin contain high concentrations of this enzyme, few adverse reactions will be seen in other organ systems. Finasteride undergoes extensive hepatic metabolism to essentially inactive metabolites, which are eliminated through the bile and urine. The terminal elimination half-life (t1/2z) is 4.7 to 7.1 hours; but despite this, slow accumulation occurs with multiple doses. Values of t1/2z are higher in elderly men, but no dosage adjustments are necessary. Likewise, no dosage adjustments are necessary for patients with renal dysfunction, since the metabolites which accumulate are relatively inactive and well tolerated, and because greater faecal excretion of the metabolites occurs in these patients. The effect of hepatic dysfunction on the metabolism of finasteride is unknown. Therapeutic doses of finasteride produce a rapid and pronounced effect in reducing both plasma and prostate tissue levels of DHT. Doses below 0.5 mg/day do not produce much suppression of DHT levels, and doses above 5 mg/day have little additional benefit. A single dose of finasteride suppresses serum DHT levels for up to 4 days, longer than would be expected from the serum terminal elimination half-life (t1/2z) of the drug: this is probably due to the high affinity that finasteride has for the 5 alpha-reductase enzyme. Serum testosterone levels increase in patients receiving finasteride, but are not normally outside the upper limits of the normal range. Serum prostate-specific antigen (PSA) levels decrease with finasteride administration; the baseline for investigation of prostate cancer with elevated PSA levels should be one-half of the normal range. In responders to finasteride, the prostate gland shrinks in volume by about 20%, urinary flow rate improves by approximately 3 ml/s, and symptoms are relieved. The response to finasteride appears to be maximal at doses of 5 mg/day. For most men receiving finasteride, these effects will persist for at least the 5 years that long term studies have been conducted. Serum DHT levels increase again when finasteride therapy is discontinued, probably resulting in the return of the hyperplasia, decreased urine flow and obstructive symptoms. Finasteride is well tolerated, with loss of libido and sexual potency being the most commonly reported adverse reactions. No drug interactions with finasteride have been reported.
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