Testosterone (DHT) and Prostate Enlargement

[broker]

Many men suffer from BPH, prostate enlargement. As we get older, our prostates grow and it starts to squeeze the urethra which is the tube that carries urine from the bladder through the penis. When this constriction happens, our urine stream gets weak, it takes longer to urinate, and we eventually cant fully empty our bladder.
Studies clearly show DHT is what causes the prostate to grow and higher levels of dht for extended periods can make matters worse. Some say its not dht but estrogen. Estrogen may play a part but dht is the big culprit here. Proof of this is how taking anti DHT drugs such as finasteride and durasteride( avodart) actually shrink the prostate. If dht wasnt the culprit, both avodart and finasteride( proscar) would not work. These two drugs prevent the conversion of testosterone to DHT.
When using testosterone, you dont want dht levels too high for extended periods of time in my opinion as well as many doctors. BPH is not fun !!!

 

[madman]

Many men suffer from BPH, prostate enlargement. As we get older, our prostates grow and it starts to squeeze the urethra which is the tube that carries urine from the bladder through the penis. When this constriction happens, our urine stream gets weak, it takes longer to urinate, and we eventually cant fully empty our bladder.
Studies clearly show DHT is what causes the prostate to grow and higher levels of dht for extended periods can make matters worse. Some say its not dht but estrogen. Estrogen may play a part but dht is the big culprit here. Proof of this is how taking anti DHT drugs such as finasteride and durasteride( avodart) actually shrink the prostate. If dht wasnt the culprit, both avodart and finasteride( proscar) would not work. These two drugs prevent the conversion of testosterone to DHT.
When using testosterone, you dont want dht levels too high for extended periods of time in my opinion as well as many doctors. BPH is not fun !!!

You need to look into this deeper?
Key Conclusions and Recommendations for Future Clinical Research
Circulating levels of DHT in response to TRT do not correlate with those found in androgen-sensitive tissue (e.g., prostate, adipose, muscle) due to local regulatory mechanisms that tightly control intracellular androgen homeostasis. Observations from numerous clinical studies are consistent with current knowledge that androgen-sensitive tissues can self-regulate tissue DHT levels by downregulating its synthesis and upregulating metabolism during DHT excess or, conversely, upregulating synthesis and downregulating metabolism under conditions of T or DHT deprivation. We are reminded of Horton's admonition some 25 years ago when he concluded that blood levels of DHT provide only a hint of tissue levels and that DHT should be regarded as a paracrine hormone formed and acting primarily within target tissues (39).

 

[broker]

I read that study before but it was not a large study and most medical experts dismiss those results.
Again, if DHT isnt the culprit, why does finasteride or avodart shrink the prostate???? Many men who use T report that their prostate feels “ swollen” after using higher dosages of T and sometimes small dosages even when estrogen levels are normal. Its the DHT.
Again, when you take a finsasteride or avodart, why would the prostate shrink and why do both drugs prevent the prostate from getting larger???? If DHT wasnt the reason, those two drugs would simply not work . They both prevent T from converting to DHT and both drugs shrink the prostate.

 

[madman]

I read that study before but it was not a large study and most medical experts dismiss those results.
Again, if DHT isnt the culprit, why does finasteride or avodart shrink the prostate???? Many men who use T report that their prostate feels “ swollen” after using higher dosages of T and sometimes small dosages even when estrogen levels are normal. Its the DHT.
Again, when you take a finsasteride or avodart, why would the prostate shrink and why do both drugs prevent the prostate from getting larger???? If DHT wasnt the reason, those two drugs would simply not work . They both prevent T from converting to DHT and both drugs shrink the prostate.

You stated above "Again, if DHT isnt the culprit,"

.....e2 (estradiol)

Ofcourse DHT plays a role but there is much more involved than simply DHT!

Conclusion
BPH is a non-malignant enlargement of the prostate that affects a significant population of men above 50 years with substantial effect on quality of life. The actions of estrogens, as mediated by estrogen receptors, appear to contribute to the development of BPH in men through an intricate molecular process that is yet to be fully elucidated. Although surgery remains the gold standard in the treatment of BPH, understanding the elusive role of estrogen in BPH, in addition to the established role of androgens, would enhance the current therapeutic options and perhaps lead to the development of new therapies. Therapeutic use of phytoestrogens could be further explored to better harness phytoestrogens in the prevention and management of BPH.

 

[madman]

Discussion

This finding reinforces the interpretation that age has a greater effect on late-life prostate growth in healthy men than androgen exposure (46 – 49) does. Neither central prostate volume growth nor serum PSA level was significantly increased by DHT treatment, although both increased with study treatment duration, which we presume is also an age effect of evolving undiagnosed BPH.

 

[madman]

Is Dihyrotestosterone a Classic Hormone

A primary concern about supraphysiological serum DHT concentrations is the potential risks of prostatic disease (benign prostatic hyperplasia and prostate cancer). A lesser concern is androgenic alopecia. These concerns stem principally from the fact that 5a-reductase inhibitors are used to treat benign prostate hyperplasia and androgenic alopecia and (more controversially) might be effective in chemoprevention of prostate cancer. The syllogism is the following: “if 5a-reductase inhibitors that reduce serum DHT are useful in the treatment (or prevention) of these diseases, then supraphysiological serum DHT concentrations would increase the incidence of these diseases.”

In healthy, eugonadal men, the prostate synthesizes DHT from circulating testosterone (that diffuses into the prostate as a substrate). However, the prostate also produces DHT directly (via the “backdoor pathway”) from progestins (17-hydroxypregnenolone and 17-hydroxyprogesterone) in serial steps to several intermediates to 5a-androstane-3a, 17b-diol and eventually DHT (Figure 3 of Swerdloff review). In a third pathway, dehydroepiandrosterone (DHEA) and DHEA sulfate from the adrenal glands can be converted to serial steps directly to DHT or to testosterone and then to DHT (8). In normal men, local prostatic production of DHT results in concentrations that are ~10-fold higher than serum concentrations. Pharmacological suppression of serum testosterone concentrations to levels associated with castration results decreased prostatic DHT concentrations, but prostatic DHT concentrations remain 20-fold higher than serum DHT concentrations (9).

As a result of the prostatic pathways for DHT production, modest decreases in serum testosterone result in no change in normal prostatic DHT concentration. In a study of healthy eugonadal men who were medically castrated for 12 weeks and then divided into groups treated with variable dosages of testosterone gel (1.25 to 15 g 1% daily), prostatic DHT concentrations were similar across groups even in the group treated with the lowest dosage (1.25 g 1% daily) that resulted in a very low average serum testosterone concentration (~190 ng/dL) (10).

Two studies of eugonadal men have demonstrated that exogenous testosterone gel administration (at normal to high-normal dosages for treatment of hypogonadism) raises serum DHT concentrations significantly (about threefold to fivefold), but these increases in serum DHT concentrations do not affect prostatic DHT concentrations (10, 11). Administration of DHT sufficient to increase serum DHT concentrations sevenfold also does not affect prostatic DHT concentrations (12).

Collectively, these data indicate that the prostate self-regulates DHT concentrations independently of serum DHT concentrations. Within a broad range from low to high-normal serum testosterone concentrations, prostatic DHT concentrations remain stable. It is likely that even high dosages of testosterone would not affect prostatic DHT concentrations through passive diffusion; serum DHT concentrations would have to exceed normal prostatic DHT concentrations that are typically 10-fold higher than circulating DHT concentrations. However, very high dosages of testosterone could elevate prostatic DHT concentrations by providing more substrate (testosterone) for prostatic synthesis of DHT. For the prostate, DHT is a paracrine and intracrine hormone, not a classic circulating hormone.

In the meantime, the review by Swerdloff et al. (5) demonstrates that DHT is principally a paracrine hormone. Circulating DHT concentrations have little relationship to prostatic and skin DHT concentrations. In addition, within a broad range of serum testosterone concentrations, raising or lowering serum testosterone concentrations has little effect on prostatic DHT concentrations. It is unlikely that exogenous testosterone therapy used for treatment of male hypogonadism or for future development of androgen based male hormonal contraceptives will appreciably alter the prostate hormonal milieu and the potential risk of incident prostate cancer.

 

[DragonBits]

Discussion

This finding reinforces the interpretation that age has a greater effect on late-life prostate growth in healthy men than androgen exposure (46 – 49) does. Neither central prostate volume growth nor serum PSA level was significantly increased by DHT treatment, although both increased with study treatment duration, which we presume is also an age effect of evolving undiagnosed BPH.

Madman, as I read this study, DHT treatment strongly suppressed serum testosterone, estradiol.

In most men here, testosterone is artificially held at a high level, so estrogen is also higher than it would be without that. And likely DHT is also higher because of this.

I would be concerned that when DHT is high, TT is high, E2 is high, you get a lot different effect on the prostate and PSA scores. At the least, we just don't know from this study.

 

[madman]

Madman, as I read this study, DHT treatment strongly suppressed serum testosterone, estradiol.

In most men here, testosterone is artificially held at a high level, so estrogen is also higher than it would be without that. And likely DHT is also higher because of this.

I would be concerned that when DHT is high, TT is high, E2 is high, you get a lot different effect on the prostate and PSA scores. At the least, we just don't know from this study.

We need to keep this in mind regarding (serum/tissue) levels of DHT

Key Conclusions and Recommendations for Future Clinical Research
Circulating levels of DHT in response to TRT do not correlate with those found in androgen-sensitive tissue (e.g., prostate, adipose, muscle) due to local regulatory mechanisms that tightly control intracellular androgen homeostasis. Observations from numerous clinical studies are consistent with current knowledge that androgen-sensitive tissues can self-regulate tissue DHT levels by downregulating its synthesis and upregulating metabolism during DHT excess or, conversely, upregulating synthesis and downregulating metabolism under conditions of T or DHT deprivation. We are reminded of Horton's admonition some 25 years ago when he concluded that blood levels of DHT provide only a hint of tissue levels and that DHT should be regarded as a paracrine hormone formed and acting primarily within target tissues (39).

 

[DragonBits]

madman, it appears they are able to measure intraprostatic androgens, though I don't know how that is done.

I can see the prostate wants to maintain a tight intraprostatic range of DHT and does so by changing serum T levels.

But what happens went we provide exogenous testosterone, HCG and DHEA, and in some cases supply testosterone to the scrotum ?

Is the prostate still able to self-regulate DHT under these conditions?

 

[broker]

Madman, i appreciate the studies and i also find them very interesting. However, how do we explain the fact that both finasteride and Adovart which prevent the conversion of T to DHT shrink the prostate as well as prevent the prostate from getting larger???
If those studies regarding DHT are true, finasteride would not shrink the prostate.., problem is, finasteride ( proscar) does actually work and it does shrink the prostate. The fact that finasteride works kind of contradicts that study, does it not ??

 

[broker]

Another note, a big belly/ fat( lots of estrogen activity) can make the body more sensitive to dht in the prostate?
This is something to also look into. We also have a genetic component to bph as well. Some guys get bph at a very young age, 40-45.

 

[madman]

I read that study before but it was not a large study and most medical experts dismiss those results.
Again, if DHT isnt the culprit, why does finasteride or avodart shrink the prostate???? Many men who use T report that their prostate feels “ swollen” after using higher dosages of T and sometimes small dosages even when estrogen levels are normal. Its the DHT.
Again, when you take a finsasteride or avodart, why would the prostate shrink and why do both drugs prevent the prostate from getting larger???? If DHT wasnt the reason, those two drugs would simply not work . They both prevent T from converting to DHT and both drugs shrink the prostate.

Why are you so dead set on" Its the DHT."

Much more is involved than just DHT.

Epidemology and risk factors of lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction

The role of androgens in determining LUTS/BPH and the physiopathological ways that may lead to it are still a matter of debate. Although an increased androgen signaling is clearly implicated in the first two waves of prostate growth (the first one at birth, the second one at puberty – under the influence of increasing testosterone levels), its role in the third phase (starting at mid-late adulthood and involving selectively the periurethral zone), is not completely clear yet. In fact, a clear dose–response relationship between circulating androgen levels and BPH has never been demonstrated. In addition, during male senescence, androgens tend to decrease and not to increase. Several recent studies indicate that a low testosterone, more than a high one, might have a detrimental effect on prostate biology. In fact, LUTS can even be lessened by androgen supplementation in hypogonadal men [65].

Recent data indicate that not only low testosterone but also high estradiol can favor BPH/LUTS progression. It is important to note that circulating testosterone is actively metabolized to estrogens and part of testosterone hormonal activity depends upon its binding to the estrogen receptors (ERs) that are present in both the prostate and bladder. In addition, the enzyme P450 aromatase that converts androgens to estrogens is highly expressed not only in fat tissue but also in the urogenital tract. Marmorston et al. showed an increased estrogen/androgen ratio almost half a century ago [66] reporting that the estrogen/androgen ratio in 24-h urinary collections was elevated in men with BPH, as compared to normal controls. Many studies have reported a correlation between plasma 17b-estradiol levels and prostate volume or other features of LUTS/BPH, while others have not. The fear of clinicians to start a TRT on hypogonadal men with LUTS/ BPH must be redefined based on this upcoming evidence [65]. It is necessary to establish ways to determine which patients with LUTS/BPH, and even combined phenotype LUTS/BPH – ED, may benefit from TRT and in which terms; for this purpose, more studies are needed [61].

 

[madman]

madman, it appears they are able to measure intraprostatic androgens, though I don't know how that is done.

I can see the prostate wants to maintain a tight intraprostatic range of DHT and does so by changing serum T levels.

But what happens went we provide exogenous testosterone, HCG and DHEA, and in some cases supply testosterone to the scrotum ?

Is the prostate still able to self-regulate DHT under these conditions?

Collectively, these data indicate that the prostate self-regulates DHT concentrations independently of serum DHT concentrations. Within a broad range from low to high-normal serum testosterone concentrations, prostatic DHT concentrations remain stable. It is likely that even high dosages of testosterone would not affect prostatic DHT concentrations through passive diffusion; serum DHT concentrations would have to exceed normal prostatic DHT concentrations that are typically 10-fold higher than circulating DHT concentrations. However, very high dosages of testosterone could elevate prostatic DHT concentrations by providing more substrate (testosterone) for prostatic synthesis of DHT. For the prostate, DHT is a paracrine and intracrine hormone, not a classic circulating hormone

 

[Vince Carter]

I read that study before but it was not a large study and most medical experts dismiss those results.
Again, if DHT isnt the culprit, why does finasteride or avodart shrink the prostate???? Many men who use T report that their prostate feels “ swollen” after using higher dosages of T and sometimes small dosages even when estrogen levels are normal. Its the DHT.
Again, when you take a finsasteride or avodart, why would the prostate shrink and why do both drugs prevent the prostate from getting larger???? If DHT wasnt the reason, those two drugs would simply not work . They both prevent T from converting to DHT and both drugs shrink the prostate.

Because Finasteride and similar do that by chemically neutering a male.

You're really not on this forum going to find a supporting environment for what you're trying to do.

 

[broker]

Madman
This is interesting, i have never seen this before. Is this factual?
I wonder if clomid’s estrogenic actions could exacerbate bph through this.

“In addition, the enzyme P450 aromatase that converts androgens to estrogens is highly expressed not only in fat tissue but also in the urogenital tract.”