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Testosterone Replacement, Low T, HCG, & Beyond
Testosterone Basics & Questions
Testosterone (DHT) and Prostate Enlargement
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<blockquote data-quote="madman" data-source="post: 124256" data-attributes="member: 13851"><p><strong>Is Dihyrotestosterone a Classic Hormone</strong></p><p></p><p>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.”</p><p></p><p>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).</p><p></p><p>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).</p><p></p><p>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).</p><p></p><p><strong>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. </strong></p><p></p><p>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.</p></blockquote><p></p>
[QUOTE="madman, post: 124256, member: 13851"] [B]Is Dihyrotestosterone a Classic Hormone[/B] 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). [B]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. [/B] 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. [/QUOTE]
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Testosterone Replacement, Low T, HCG, & Beyond
Testosterone Basics & Questions
Testosterone (DHT) and Prostate Enlargement
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