David S wrote:
No, I want know to what extent testosterone helps people with reduced levels of DHT. Wikipedia says DHT is a "very poor anabolic agent", but doesn't say how testosterone affects people without it.
I was previously under the impression that Caster was unable to properly metabolize any testosterone in her system, but apparently it's more complicated than that.
Hope this helps answer those two questions:
Dihydrotestosterone or DHT is a form of testosterone that serves as a more potent androgen than T. DHT plays its most important role in male sex development in utero, primarily in the formation of the male external genitalia, seminal vessels, prostate and urethra. In males, DHT also plays a role, albeit a smaller one, in puberty - and an even smaller role in adulthood because in puberty and adulthood it is T, not DHT, that predominates and has the most effects on male physiology.
People who inherit a genetic mutation (in the SRD5A2 gene) from each parent lack the genetic instructions that enable them to make 5-alpha reductase 2, one of two forms of the particular enzyme responsible for converting testosterone to DHT, and the one that does the bulk of the work converting T to DHT. This condition is called 5-alpha reductase 2 deficiency, or 5-ARD for short.
Both males and females can have 5-ARD, but since DHT is not essential for female sex development the way it is for male sex development, only in males is 5-ARD classified as a DSD.
Males with 5-ARD are not entirely incapable of converting T into DHT; most can still able to make some DHT to varying degrees because they are only deficient in one of the two forms of 5-alpha reductase. (There are probably additional differences in the way 5-ARD is expressed, and the extent to which it blocks or limits DHT, due to slight alterations in the genetic mutation that causes 5-ARD; so far 80 different variations have been found.)
DHT and T compete for and utilize the same androgen receptors. So after birth, the androgen receptors in a male body that produces T but cannot convert it to DHT will take up and make use of the T instead.
Once outside the womb, the bodies of those with 5-ARD make use of the T their gonads produce in all the usual ways male bodies customarily do. Because 5-ARD is classified as a "XY DSD," and that is a broad category which includes complete androgen insensitivity (CAIS) and partial androgen insensitivity (PAIS), all these conditions tend to get conflated by the press and public alike, with the result that many people understandably have the mistaken impression that all XY DSDs involve some sort of androgen insensitivity (AIS).
But 5-ARD definitely does not involve androgen insensitivity. In fact, if you look at XY DSD subclasses, you'll see that AIS, PAIS and CAIS are all in one category - "46,XY DSD DUE TO DEFECTS IN ANDROGEN ACTION" - whereas 5-ARD has its own stand-alone category - 46,XY DSD DUE TO DEFECTS IN TESTOSTERONE METABOLISM. (C &P'd - hence the caps, sorry.)
"At puberty or in young adult men, the basal hormonal evaluation (of XY persons with 5-ARD) demonstrates normal male serum testosterone levels, low or low normal dihydrotestosterone levels, and elevated or normal serum testosterone to dihydrotestosterone ratio." (from Domenice, et al, "46,XY Disorders of Sexual Development," 2017; second link below)
From puberty on, males with 5-ARD make T in the normal male range, have normal sensitivity to T, and utilize T in the customary ways, which leads the following characteristics, most but not all of which are distinctively male, to be PRESENT:
Male Anabolic Activity
Male Muscle mass increase
Penis enlargement
Scrotum enlargement
Vocal cord enlargement
Male skeletal growth and maturation
Male growth spurt
Epiphyseal (long bone) closure
Spermatogenesis
Male sex drive, performance
Most aspects of male pituitary-gonadal feedback
By contrast, from puberty on, DHT in normal male bodies is responsible for these traits in males, which means that in males with 5-ARD the following characteristics, most but not all of which are distinctively male, will be ABSENT OR LARGELY ABSENT:
Male facial hair and body hair
Male scalp recession (receding hairline, and male-pattern baldness)
Prostate enlargement to normal/typical adult size
Acne
Some other aspects of male pituitary-gonadal feedback
The above two lists come from Table 1 in the first link below.
Testifying on behalf of the IAAF in the proceedings before the CAS, various expert witnesses said: "The only physical/biological difference between androgen-sensitive 46 XY DSD athletes and non-DSD male athletes are that their testicles are not descended and their external genitalia may be undervirilised." (p.89, para 353)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4031759/