Prostate Cancer & Hormones - Estrogen [1] - (& Androgen Ratio)

[pjoshea13]

This is fmy irst post on estrogen in the "Prostate Cancer & Hormones" series. It is a review of how a shifting androgen/estrogen ratio affects the health of men. The second post will be specific to PCa.

While it is useful to focus on individual hormones, there are hormones that work together (such as hormonal vitamin D [calcitriol] & testosterone [T] in the prostate, via the VDR & AR receptors), & hormones that pull in different directions via their receptors.

The presence of estrogen in the male body is often viewed as a curiosity, just like T in the female body, & mostly ignored. Men begin to experience a 1-2% annual drop in T in their early 30's, & by the time one's wife has entered the meopause, a man might have a higher level of estradiol [E2] than she does.

My contention is that the change in the E2:T ratio is of greater significance than the change in either hormone. And indeed, the male body reponds to high E2 by reducing the production of T (the putative source of E2).

[1] Prostate Cancer.

[1.1] Aromatase.

[1.1a] "Although androgens and estrogens both play significant roles in the prostate, it is their combined action--and specifically their balance--that is critically important in maintaining prostate health and tissue homeostasis in adulthood. In men, serum testosterone levels drop by about 35% between the ages of 21 and 85 while estradiol levels remain constant or increase. This changing androgen:estrogen (T:E) ratio has been implicated in the development of benign and malignant prostate disease. The production of estrogens from androgens is mediated by the aromatase enzyme, the aberrant expression of which plays a critical role in the development of malignancy in a number of tissues."

[1.1b] "The estrogen signaling plays a pivotal role not only in female reproduction but also in recent years its emerging importance in the males has been shown too. As estrogens and androgens seem to be the two sides of one coin, the better understanding of this physiological and pathophysiological role of androgen/estrogen balance is becoming more crucial. Aromatase is the key enzyme to synthesize estrogens from androgens."

[2] Male breast.

[2.1] Male breast cancer.

"... conditions that alter the estrogen/androgen ratio ... are proven risk factors ..."

[2.2] Gynecomastia.

"Gynecomastia is a common finding in men ..."

"In most cases, the breast enlargement can be explained by an increased effective estrogen/androgen ratio acting at the breast itself."

[3] Sex steroid receptors in male human bladder.

"In male, lower urinary tract symptoms (LUTS) have been associated, beside benign prostatic hyperplasia, to some unexpected comorbidities (hypogonadism, obesity, metabolic syndrome), which are essentially characterized by an unbalance between circulating androgens/estrogens."

[4] Atherosclerosis.

[4.1] Hemodialysis.

"We conclude that in hemodialysis patients absolute estrogen levels are lower than normal, but that the estrogen/androgen ratio is shifted in favor of estrogen because of the coexistence of androgen deficiency. These findings suggest that an elevation in the estrogen/androgen ratio, rather than an increase in estrogen per se, may be a risk factor for atherosclerosis."

[4.2] Coronary atherosclerosis.

"Men with coronary artery disease had lower ... testosterone/estradiol ratio (228.5 ... vs. 289.8 ...)"

[5] Acquired cystic kidney disease.

"Based on the reported sex difference in the incidence of acquired cystic kidney disease (ACKD) in patients with chronic renal failure, it is hypothesized that the hormonal derangement, well documented in male and female uremic patients on long-term dialysis, could be responsible for the pathogenesis of ACKD. The decreased androgen/estrogen ratio, and the increased estrogen value could be responsible for an estrogen receptor mediated effect on the tubular epithelial cell proliferation, an event further potentiated by the action of regulatory peptides like epidermal growth factor (EGF). The epithelial stimulation is more pronounced in men because male tissues are less adapted than female tissues to high estrogen values. Furthermore the androgen reduction, more remarkable in male than female patients, is responsible for an up-regulation of EGF-R."

[6] Varicose veins.

[6a] "The serum E2:fT (estradiol:free testosterone) ratio ({varicose men} 2.83 ... and {healthy men} 2.32 ...) was significantly different ... between the two groups."

"In summary, our results demonstrate a changed serum E2:fT ratio among men with varicose veins compared to healthy men."

[6b] "Elevated serum E2/fT ratio is a precipitating factor for recurrent varicose veins in male patients."

[7] Metabolic syndrome [MetS].

"... a lower E2/T ratio was associated with a lower risk of incident MetS (OR = 0.38 ...)"

"A lower E2/T ratio may be protective against developing MetS."

[8] Pulmonary Arterial Hypertension (PAH)

[8a] "Higher ... E2/testosterone levels were associated with the risk of PAH ..."

[9] Atrial Fibrillation [A-Fib]

"In men aged 55 to 69 years, each 1 SD decrease in testosterone was associated with hazard ratio (HR) 1.30 ... for incident AF...

"In men≥80 years, a 1 SD decrease in testosterone was associated with HR 3.53 ... for AF risk...

"Estradiol was associated with incident AF (HR, 1.12 ...)"

[10] Left ventricular remodelling and function.

"Testosterone was inversely associated with ejection fraction (EF) and with more sensitive systolic tissue Doppler imaging indices. Oestradiol was positively associated with EF."

"The study suggests an opposite link, albeit modestly, of testosterone and oestradiol with left ventricle systolic function in healthy middle-aged men."

-Patrick

[1.1a] ncbi.nlm.nih.gov/pubmed/198...

[1.1b] ncbi.nlm.nih.gov/pubmed/187...

[2.1] ncbi.nlm.nih.gov/pubmed/234...

[2.2] ncbi.nlm.nih.gov/pubmed/770...

[3] ncbi.nlm.nih.gov/pubmed/204...

[4.1] ncbi.nlm.nih.gov/pubmed/326...

[4.2] ncbi.nlm.nih.gov/pubmed/156...

[5] ncbi.nlm.nih.gov/pubmed/849...

[6a] ncbi.nlm.nih.gov/pubmed/188...

[6b] ncbi.nlm.nih.gov/pubmed/257...

[7] ncbi.nlm.nih.gov/pubmed/256...

[8a] ncbi.nlm.nih.gov/pubmed/266...

[9] ncbi.nlm.nih.gov/pubmed/246...

[10] ncbi.nlm.nih.gov/pubmed/216...

[Dan59]

Great Research Patrick, If you had to summarize the way estrogen affect prostate cancer what would you say. Thanks, Dan

[pjoshea13 in reply to Dan59]

Thanks Dan!

Wait for the follow-up post.

-Patrick

[Hidden]

I guess my atrial fibrillation must be pretty well controlled with the meds I am on. My T was knocked way down on ADT yet I haven't had an a-fib episode in the six months I've been on eligard. Of course, the stress of working at a horrible and dysfunctional corporation was not there either.