More on DHT:
I have seen some horror stories (rare) about finasteride and other 5 alpha reductase drugs, here and elsewhere. Permanent hormone system damage after ‘temporary’ DHT reduction. This drug was developed and the market established based on the premise that DHT causes BPH. Now it is known that E2 is the biggest thread to the prostate… but few in the medical community understand this. Some have been damaged using these drugs to combat hair loss. Loss of libido is a frequent result. Again, DHT is important for many reasons. Many aspects of DHTs actions are not well understood. With that ignorance, those who stand to profit by selling these drugs can hide safely behind what is not well understood, even though there are strong indications of adverse actions.
I agree that DHT is important generally, and that estradiol is underappreciated as a contributor to BPH. But I offer a contradictory observation, just for laughs:
There is a single gene mutation which causes the deficiency of 5 alpha reductase. The result is “pseudohermaphroditism,” in which genotypic males have ambiguous genitalia. When they reach puberty, funny changes happen to their genitalia, inside and out. But they retain only a rudimentary prostate, even though they have high T, low or no DHT and high or uneffected estrogens. This “natural history” experiment suggest that DHT is the dominant cause of prostate stromal and cellular mainteneance or hyperplasia, and physiologic estrogen is much less important.
In another thread, I posted a couple articles—among many–that confirm that AIs reduce estrogen in men but do not effect BPH; perhaps T and DHT rise enough to “undo” the effect or estrogen isn’t that important.
Further, in and non-castrated men with prostate cancer, estrogen at high doses decreases prostate volume; whether this is due to a direct effect or T/DHT remains a mystery to me. But because estrogens and progesterones, in high doses, work in castrated men, there is a direct effect on prostate cancer and tissue to reduce prostate volume.
Shutting down the HPTA with estrogen or progesterone will reduce LH, T and DHT. This is useful for testosterone receptor positive prostate cancer. With HPTA shutdown, pregnenolone and DHEA levels probably fall as well.
I think the situation with men on TRT is quite different. They have higher levels of TT, FT and DHT. When an AI is used, the TT, FT and DHT levels will not change significantly, but E levels drop. There can be positive results for BPH.
Men with syndrome X or metabolic disorder have a much higher incidence of prostate problems. As a group they have low TT, FT, DHT and high or elevated levels of E2.
It would require a long term study to show that AI reduction of E would reduce BPH or reduce its progression. Such a study may need to address reduction of E to different levels and perhaps reduction would have to be to less that some number like 25mg/ml to so benefits.
Yes the prostate and other genitalia require DHT to develop. I think that your reach to E not been important is a bit of a reach.[/quote]
Thanks for your thoughts!
- I attempted, and failed, to make a distinction between physiologic estrogen and pharmacologic estrogen. Physiologic E levels seem to contribute something, but my point was how difficult it is to separate the effects of T/DHT from E in the intact man under trial with AIs. (Some studies are indeed long enough; a year and more). E and Progesterones work in previously castrated men with hormone-sensitive prostate cancer, so at pharmacologic levels, the effect on prostate tissue cannot be dependent on LH action on absent testes.
- The points about metabolic syndrome are well taken; and hypogonadism is both cause and effect of the syndrome, which is at root, a form of insulin resistance and hyperinsulinemia. Epidemiologic studies are divided on some points on cancer risk, but do support a higher risk for BPH. It is plausible that higher E:T ratio is responsible for BPH in this cohort—and that would be a fairly simple longitudinal study, but it hasn’t been published yet.
- I respect your thoughts, but to be practical, I also emphasize that specific inhibitors of 5 alpha reductase do work to decrease BPH (a little); so far, specific AIs or SERMs do not work in statistically valid trials. (Toremifene is under trial and won’t work where tamoxifen doesn’t work). One study I found addresses your comment about T replacement along with AI: the AI raised T by 40%, lowered E dramatically, but there was no reduction of BPH. (If you have a reference for a study of combined TRT and AI effect on BPH, I would be grateful.)
But all that does not argue against a contribution of E to prostate problems; it just provokes more analysis…