From Standard of Care
5 mg of testosterone manufactured daily by the testicles.
Approximately 6-8% of testosterone is metabolized by 5 alpha-reductase to make a 0.3 mg of dihydroxytestosterone ( DHT).
Local conversion of testosterone to DHT by 5 alpha-reductase in the skin and prostate can create high concentrations at those sites.
DHT stimulates prostate health and may promote scalp hair loss.
5-alpha-reductase is the principal treatment for BPH.
In men treated with finasteride or dutasteride plasma DHT levels decline by 60-95% and testosterone levels increase by 15-22% .
In men treated with finasteride or dutasteride intra- prostatic concentrations of DHT and testosterone change by similar proportions as plasma levels.
Shrink the prostate and reduce prosthetic growth.
Reduced intra-prostatic DHT causes shrinkage of hyperplastic prostate tissue.
A PSA level of more than 1.5 ng/mL is a surrogate criteria for initiating therapy with five alpha-reductase inhibitors, this correlates with a prostate size of more than 30 g.
Sexual dysfunction is slightly more common among men using these agents.
Finasteride (Proscar) and dutasteride (Avodart) which are type 1 and type1/2 5 alpha-reductase inhibitors which block testosterone conversion to dihydrotestosterone, the androgen involved in BPH.
Finasteride slightly decreases body mass, particularly among men who have low testosterone levels before starting treatment.
Finasteride inhibits the type 2 5-alpha reductase isoenzyme leading to decrease in serum dihydrotestosterone levels by 70-90%.
Dutasteride blocks both type I and type 2 5-alpha-reductase isoenzymes, reducing dihydrotestosterone to levels that approach zero.
5alpha- reductase inhibitors finasteride and dudasteride reduce plasma DHT levels, whereas levels of testosterone and estradiol increase.
Finasteride and dutasteride reduce prostate size by as much as 25% and decrease lower urinary tract symptoms over 2 to 6 months.
In a direct comparison between finasteride and dutasteride, the results were similar.
Represent androgen suppressive treatment for BPH and have greatest effect in patients with prostates larger than 40 gm and when the treatment is maintained for 6 months or more.
The overall reduction in prostate cancer diagnoses in chemoprevention trials with finasteride and dutasteride resulted (23%) from a decreased incidence of only low-grade prostate cancer, Gleason's score 6 or below, and there was an absolute increase in the incidence of high-grade prostate cancers in the chemoprevention group.
The use of 5a-reductase inhibitors for chemoprevention of prostate cancer was studied in patients who did not have diagnosed prostate cancer but who were at risk.
An absolute increase of 0.5% in the incidence of tumors with modified Gleason scores of 8 to 10 was observed with dutasteride treatment, and a similar absolute increase of 0.7% in the incidence of such tumors with finasteride treatment: suggesting that one additional man would receive a diagnosis of high-grade prostate cancer for every 150 to 200 men treated long-term with 5-alpha reductase inhibitors.
Five alpha-reductase inhibitors reduce PSA values and any increase in the PSA level above the lowest value obtained may signal the presence of prostate cancer, even if the value remains in normal range for men not taking such an agent.
5a-reductase inhibitors do not affect bone, as bone turnover and bone mineral density did not change with the use of these agents.
Side effects include: decreased libido, erectile dysfunction, decreased ejaculation, and gynecomastia.
Finasteride and dutasteride use have an absolute reduction in the risk of prostate cancer by up to six percentage points, but both are associated with an increase of moderate to high-grade prostate cancer that is, a Gleason score of 7 or greater.
As five alpha-reductase inhibitors reduce PSA concentrations by approximately 50% after six months, this decrease must be taken into account in the interpretation of PSA tests performed for cancer detection.