PSA increased more in men with prostate cancer compared to no disease in men on finasteride therapy. This supports the idea that finasteride has a greater PSA reduction in benign prostate disease compared to prostate cancer.
In this study we have shown that regulation of the levels of 3βAdiol by CYP7B1 is a key factor in regulation of prostatic
growth
We provide evidence that proliferating cells in the prostate epithelium have elevated levels of AR and that AR protein
but not mRNA levels are regulated by ERβ and its ligand 3βAdiol in the prostate epithelium.
because inhibition of 5α-reductase causes accumulation of testosterone
and removal of ERβ action increases the level of AR in the prostate, the overall effect of Finasteride would be to favor proliferation
of the prostate epithelium
studies show that ERβ tends to be lost in advanced prostate cancer.
DHEA is converted in the body to 5-androstene-3β,17β-diol, which is also a ligand for estrogen receptors (25, 39) and a substrate for CYP7B1
At the peak of proliferation, the proliferating
epithelial cells in the ventral prostate expressed high levels of CYP7B1 but had no detectable ERβ, whereas in nonproliferating
cells the level of ERβ was high and that of CYP7B1 was low.
3-beta androstanediola, a product of 3alpha-HSD from DHT binds to ER beta and down regulates AR in prostate cancer. This study proposes that the mechanism is via CYP7B1. CYP7B1 inactivates 3-beta androstanediol. Interesting, because 3-beta androstanediol is considered "inactive" when compared to 3-alpha androstanediol and its interaction with ER alpha.
Hypogonadism may be defined either as serum concentration of T (either total T, bioavailable T or free T) or as low T plus symptoms of hypogonadism
The Baltimore Longitudinal Study on Aging reported the incidence of total serum T < 325 ng/dL to be 20% for men in their 60s, 30% for men in their 70s and 50% for men over 80
The Massachusetts Aging Male Study reported that 12.3% of men aged 40 to 70 had a total serum T of < 200 ng/dL with 3 or more symptoms of hypogonadism
The Boston Area Community Health Study reported that 5.6% of men aged 30 to 70 were hypogonadal, as defined by total serum T < 300 ng/dL; or, free serum T < 5 ng/dL plus 3 or more symptoms of hypogonadism
In a health screening project among 819 men in Taiwan, the prevalence of hypogonadism (total serum T < 300 ng/dL) ranged from 16.5% for men in their 40s, 23.0% for men in their 50s, 28.9% for men in their 60s, and 37.2% for men older than 70 years of age
The prevalence of hypogonadism among men in Taiwan is higher than the prevalence reported in the Massachusetts Male Aging Study
CAG repeat sequence, within the androgen receptor (AR). Rajender et al[12] reviewed over 30 studies on the AR trinucleotide repeat and infertility
suggestion that CAG repeat length may determine androgen responsiveness, this issue is not clearly settled
reported prevalence of low T in older men range from 5.6% to 50%
Those in the hypogonadal group (n = 4269) had direct health care costs, that exceeded the eugonadal group (n = 4269) by an average of $7100 over the course of the observation window
higher economic burden and presence of co-morbidities for hypogonadism
minor to moderate improvements in lean mass and muscle strength
increased bone mineral density
modest enhancement in sexual function
reduced adiposity
lessening of depressive symptoms
Meta-analyses of clinical TRT trials as of 2010 have identified three major adverse events resulting from TRT: (1) polycythemia; (2) an increase in prostate-related events; and (3) and a slight reduction in serum high-density lipoprotein (HDL) cholesterol
polycythemia (> 3.5-fold increase in risk
TRT produced a 40% prostate enlargement in older hypogonadal male Veterans over 12 mo
no published analysis has reported measurable increases in prostate cancer risk or Gleason score in men undergoing TRT, or in hypogonadal men with a history of prostate cancer undergoing TRT
the prostate which highly expresses the type II 5α-reductase enzyme. Inhibition of this enzyme via finasteride (a type II 5α-reductase inhibitor) or dutasteride (a dual type I and II 5α-reductase inhibitor) reduces circulating DHT 50%-75% and > 90%, respectively[47], and reduces prostate mass[48] and prostate cancer risk
Normally estradiol partially regulates testosterone levels, at the hypothalamus, blunting LH and FSH release from the pituitary. As a selective estrogen receptor modulator, CC interrupts this pathway, and consequently there is a greater stimulation for the production of testosterone in Leydig cells
Testosterone found to provide small improvement in depression in men > 60 and starting serum Testosterone levels < 300. Small improvement in cognition also noted.