PEAK TESTOSTERONE

High Estradiol and the Prostate

STEP 3C: Do you have high estradiol? Consider the evidence that it can make (or perhaps even fuel) prostate cancer and/or BPH (enlarged prostate):

I occasionally get some criticism for insisting that high estradiol levels are as potentially dangerous for men as low.  I also have seen many men on The Peak Testosterone Forum  whose doctors have told them that high estradiol levels were actually protective. I could not disagree with this more for many reasons, especially the fact that it accelerates arterial plaque according to a number of studies.  Considering that heart disease is the #1 killer of men, it should be obvious in my opinion that high estradiol is not a good idea for the great majority of men.  You can read more about it here: Estradiol and Arterial Plaque.

However, there are a number of other great reasons to avoid high estradiol and a couple of them have to do with the prostate.  Below I will present evidence that high estradiol levels often the most significant prostate problems, including cancer and BPH: 

1) Estradiol Likely Fuels Prostate Cancer.  Some researchers have long protested the idea that testosterone is the primary culprit in prostate cancer.  They have noted that prostate cancer risk increases in one's middle and senior years, right when testosterone is generally decreasing and estradiol is generally rising: [6]

"Paradoxically, the incidence of prostate disease increases with age when serum androgen levels are in decline and emerging evidence suggests that estrogens may also be important in the normal prostate, as well as in the etiology of prostate disease. Both estrogen receptor subtypes are present in the prostate, demonstrating that the gland responds directly to estrogens. Recent data suggests that estrogens play a role in prostate disease and has demonstrated that high doses of estrogens induce premalignant dysplasia and in combination with high doses of androgens, malignancy. "

Studies, however, have been somewhat mixed with regards to showing estradiol playing a role in prostate cancer development, that is until it was noticed that testosterone deprivation therapy resulted in GREATER incidence of aggressive, advanced prostate cancers.  In other words, something else was fueling the nastiest kind of prostate cancer when testosterone was taken out of the way:

"In recent years, there has been an increasing focus on chemoprevention with agents such as finasteride being employed to reduce the risk of developing CaP [prostate cancer]. Significantly, such chemoprevention strategies are also based on 5alpha-reductase inhibition thus reducing intraprostatic dihydrotestosterone levels. Although there may be an overall reduction in CaP incidence in cohorts using such chemoprevention, in a subset of users who do develop this pathology there results a more aggressive, higher-grade disease. There have also been suggestions regarding the protective role of androgens against high-grade CaP [prostate cancer]. This leads to the intriguing notion that 17beta-oestradiol (E2) may be an initiating driver of CaP; in fact, in old studies in which CaP [prostate cancer] was induced in rodents, E2 often accelerated the effect of the carcinogen." [7]

Potentially this means that the cure may be worse than the disease in some men.  A 2015 study attempted to look into this issue further and found the following:

  • "The mean molar ratio of testosterone: E2 was lowest among CaP patients (134:1) and highest among controls (166:1)."
  • "Significant positive correlation between PSA and 17ß-estradiol was observed in prostate disorders (BPH and CaP patients."
  • "Significant negative correlations between testosterone and PSA were also observed among BPH patients (r = -0.221, p = 0.049) and control subjects."
  • "No significant correlation existed between testosterone and PSA in CaP patients."
  • [8]

    Of course, PSA is not the perfect measurement of prostate cancer as many of us know.  Nevertheless, the results above seem reasonably clear and at the same time counterintuitive:  estradiol seems to be tied to prostate cancer and testosterone actually protective if anything!  (Discuss with your doctor:  that's their job is to explain research like this to you and correlate it to their actual practice.)

    NOTE:  See my pages on The Testosterone-to-Estrogen (Estradiol specifically) Ratio and my Header Page for Prostate Cancer for more information. I would also encourage you to read Dr. Morgentaler's stellar research summary on the subject, where he explains that testosterone does fuel cancer but only near castrate levels:  Destroying the Myth About Testosterone Replacement and Prostate Cancer. [5] (Again, talk to your urologist if you have existing prostate cancer.)

    2) Enlarged Prostate (BPH or Benign Prostatic Hyperplasia).  An enlarged prostate can bite men of almost any age but by the senior years, the great majority of senior men will struggle with it.  One research summary noted that "the histologic prevalence of BPH, which has been examined in several autopsy studies around the world, is approximately 10% for men in their 30s, 20% for men in their 40s, reaches 50% to 60% for men in their 60s, and is 80% to 90% for men in their 70s and 80s." [4]

    And just about everyone knows that DHT plays the primary role in any growth in the prostate, during puberty, during HRT (if applicable) and middle age. For example, "studies demonstrate that across a wide spectrum of racial and ethnic groups, prostate size increases from 25 g to 30 g for men in their 40s to 30 g to 40 g for men in their 50s and to 35 g to 45 g for men in their 60s. At the same time, the transition zone of the prostate, which is quite small at approximately 15 g in men in their 40s, increases to approximately 25 g for men in their 60s and 70s." [4]

    But is DHT really the only culprit?  As it turns out, there is a growing body of research that estradiol plays a significant role as well.  For example, one recent research summary wrote that "However, BPH is a multifactorial disease and not all men respond well to currently available treatments, suggesting factors other than androgens are involved. Testosterone, the primary circulating androgen in men, can also be metabolized via CYP19/aromatase into the potent estrogen, estradiol-17ß. The prostate is an estrogen target tissue and estrogens directly and indirectly affect growth and differentiation of prostate." [1] Researchers have even found the possible mechanism of action by which estradiol induces BPH. [2]

    This still has, as of yet, to be directly tested in humans.  However, it has been verifed in dogs where prostate growth was found to increase prostate volume in a dose dependent fashion. [3] Furthermore, this was done in the absence of androgens (DHT, testosterone, etc.) as the animals had been castrated. This study, though, was rather clear: they lowered testosterone down to the minimum and then gave the animals estradiol. The more estradiol they gave, the bigger the prostate. Again, higher estradiol levels are just hard on the prostate and likely a culprit in many issues for men.   I remember getting chewed out by a member on  The Peak Testosterone Forum for suggesting that estradiol could cause prostate growth. I didn't say much, because this poor guy had struggled with BPH and other medical issues.

    CONCLUSION:  There is a very good chance that high estradiol is very hard on the prostate and potentially dangerous for men.  Hopefully, more study work will be done to determine just what a "high estradiol" level may be.  (Considerable individual variation does occur however.)  What can you do to lower estradiol?  Of course, the number one thing is to lose weight.  Fat cells store aromatase, the enzyme that converts testosterone into estradiol.  So the more body fat you carry, the most aromatase and the higher your estradiol levels tend to be.  (It's actually a bit more complicated that that and you can read the discussion in my page on Testosterone and Weight Loss.

    So I encourage you to drop the pounds.  I like Clarence Bass' approach and how he encourages men to drop their body fat percentage below 15%.  He personally kept his body fat year round well below 10 percent and had considerable muscle mass as well.  See my pages on Challenge Yourself (Clarence Bass) and An Interview with Clarence Bass on Bodybuilding and Losing Weight.

    REFERENCES:

    1) Differentiation. 2011 Nov-Dec;82(4-5):184-99, "Androgens and estrogens in benign prostatic hyperplasia: past, present and future"

    2) Toxicol Appl Pharmacol, 1996 Feb, 136(2):211-9, "Possible mechanism of induction of benign prostatic hyperplasia by estradiol and dihydrotestosterone in dogs"

    3) The Prostate (Impact Factor: 3.57), 44(1):8-18. "Estradiol causes a dose-dependent stimulation of prostate growth in castrated beagle dogs."

    4) Rev Urol. 2005, 7(Suppl 9): S3–S14., "Benign Prostatic Hyperplasia: An Overview"

    5) Life Extension Magazine, Dec 2008, "Destroying the Myth About Testosterone Replacement and Prostate Cancer", By Abraham Morgentaler, MD, Facs

    6) Minerva Endocrinol. 2006 Mar;31(1):1-12, "Aromatase and prostate cancer"

    7) Eur J Cancer, 2008 May, 44(7):928-36, "A potential paradox in prostate adenocarcinoma progression: oestrogen as the initiating driver"

    8) Indian J Clin Biochem, 2015 Jan, 30(1):59-65, "Serum Testosterone, 17β-Estradiol and PSA Levels in Subjects with Prostate Disorders"