madman
Super Moderator
In this issue of Endocrine Reviews, Swerdloff et al. (5) review the human and animal data regarding the physiological and clinical implications of elevated blood concentrations of DHT in men and women. All exogenous testosterone formulations increase serum DHT concentrations above physiologically normal serum concentrations. Because testosterone therapy is commonly prescribed to men, understanding the physiological effects (beneficial and adverse) of supranormal DHT concentrations is clinically important (6, 7). Although the focus of their review is on the physiological and clinical effects of supraphysiological serum DHT concentrations, they also review the effects of pharmacological suppression of DHT.
*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.
*there is little correlation between circulating and skin DHT concentrations in men or women.
*Although 5α-reductase inhibitors are effective in treating male androgenic alopecia, DHT does not appear to play a primary role in the pathogenesis of male or female androgenic alopecia or acne. Androgen receptor polymorphisms and differences in androgen receptor concentrations and steroid-converting enzymes are the principal contributors to male androgenic alopecia (5). There is no correlation between serum DHT concentrations and androgenic alopecia or acne.
* DHT acts as a paracrine independently of circulating DHT concentrations for the two principal target organs in adults: prostate and skin.
*Swerdloff et al. examine the modest literature on DHT and extraprostatic and extra dermal effects. Broadly speaking, the evidence suggests that DHT may directly modulate sexual function, but the evidence is insufficient to conclude that DHT has clinically significant specific effects (that are unique to DHT vs testosterone) on a variety of outcomes and functions, including cardiovascular health, cognitive function, immune function, erythropoiesis, and glucose and lipid metabolism.
*data from trials of 5α-reductase inhibitors have demonstrated that DHT does not appear to be necessary for the direct effects of testosterone on muscle function and erythropoiesis and the indirect effects of testosterone (via aromatization to estradiol) on bone and fat (4, 14,–17).
*Suppression of circulating and tissue DHT concentrations are associated with decreases in libido and erectile function in some men (<10%) and a small decrease in average sperm concentration (16, 18,–23).
*Administration of high-dosage DHT maintains most androgenic effects of exogenous testosterone in men with androgen insufficiency with the notable exception of libido and bone mineral density. A 2-year study of daily application of high-dosage DHT gel (that increased serum DHT by ~10-fold) in middle-aged to older healthy eugonadal men demonstrated that exogenous DHT markedly suppressed serum testosterone and estradiol concentrations, increased lean mass and erythropoiesis and decreased fat mass, but it did not affect prostate volume (13). Vertebral bone mass and overall sexual desire decreased modestly, but significantly, during the 2-year period (13, 24).
*DHT was the last major sex hormone to be described. There remain significant gaps in its role in human physiology. We need a more complete understanding of the physiological effects of DHT, including its specific role in cardiovascular health, sexual function, and bone health.
*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.
*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.
*there is little correlation between circulating and skin DHT concentrations in men or women.
*Although 5α-reductase inhibitors are effective in treating male androgenic alopecia, DHT does not appear to play a primary role in the pathogenesis of male or female androgenic alopecia or acne. Androgen receptor polymorphisms and differences in androgen receptor concentrations and steroid-converting enzymes are the principal contributors to male androgenic alopecia (5). There is no correlation between serum DHT concentrations and androgenic alopecia or acne.
* DHT acts as a paracrine independently of circulating DHT concentrations for the two principal target organs in adults: prostate and skin.
*Swerdloff et al. examine the modest literature on DHT and extraprostatic and extra dermal effects. Broadly speaking, the evidence suggests that DHT may directly modulate sexual function, but the evidence is insufficient to conclude that DHT has clinically significant specific effects (that are unique to DHT vs testosterone) on a variety of outcomes and functions, including cardiovascular health, cognitive function, immune function, erythropoiesis, and glucose and lipid metabolism.
*data from trials of 5α-reductase inhibitors have demonstrated that DHT does not appear to be necessary for the direct effects of testosterone on muscle function and erythropoiesis and the indirect effects of testosterone (via aromatization to estradiol) on bone and fat (4, 14,–17).
*Suppression of circulating and tissue DHT concentrations are associated with decreases in libido and erectile function in some men (<10%) and a small decrease in average sperm concentration (16, 18,–23).
*Administration of high-dosage DHT maintains most androgenic effects of exogenous testosterone in men with androgen insufficiency with the notable exception of libido and bone mineral density. A 2-year study of daily application of high-dosage DHT gel (that increased serum DHT by ~10-fold) in middle-aged to older healthy eugonadal men demonstrated that exogenous DHT markedly suppressed serum testosterone and estradiol concentrations, increased lean mass and erythropoiesis and decreased fat mass, but it did not affect prostate volume (13). Vertebral bone mass and overall sexual desire decreased modestly, but significantly, during the 2-year period (13, 24).
*DHT was the last major sex hormone to be described. There remain significant gaps in its role in human physiology. We need a more complete understanding of the physiological effects of DHT, including its specific role in cardiovascular health, sexual function, and bone health.
*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.
