A read of the file, TRT: A Recipe for Success, is incorrect for a number of reasons. There are many inaccuracies in this opus but one strikes me as possibly causing the greatest harm. In this file a special note is given to monitoring FSH as the best indicator of HPTA suppression. This could not be farther from the truth. More troubling is the person who would look to the FSH level to determine HPTA functionality. Under no conditions except for fertility should one look to the FSH level as a measure of HPTA suppression or likewise HPTA functionality. Clinically, FSH has returned with minimal or absent LH return after AAS cessation. One only has to look at the literature where after AAS cessation a study has investigated the return of spermatogenesis. In fact, a very simple look at the HPTA feedback for LH and FSH explains this quite easily. It appears as if the author of this article has either forgotten or neglected this fact.
After AAS cessation the negative feedback inhibition of the hypothalamo-pituitary area by testosterone and estradiol would be gone or at the minimum dissipating. If these were the only factors inhibiting the gonadotropins their return in approximately the same timeline is expected. However, the feedback of FSH by Inhibin and its delay in returning after AAS cessation will often have a return of FSH prior to LH. The bottom line is one should not depend upon the FSH as a measure of HPTA functionality or for that matter HPTA suppression. I hope this fully explains the reasons why FSH is not to be used for HPTA normalization or functionality.
Studies of sex steroid regulation of gonadotropin secretion in the human male have focused primarily on the respective site(s) of negative feedback of testosterone (T) and estradiol (E2). Studies provide evidence of differential regulation of gonadotropin secretion by T in the human male. T exerts both direct and indirect feedback on LH secretion, whereas its effects on FSH appear to be mediated largely by aromatization to E2.
Because androgens can undergo aromatization to estrogens in a variety of tissues, including adipose tissue, brain, and testis, it is important to be able to distinguish T effects that are mediated directly by the androgen receptor as opposed to those indirect effects that only occur after aromatization to E2. If the hypothesis is correct that T has no direct negative feedback effects on FSH, it follows that administration of T in conjunction with an aromatase inhibitor or administration of nonaromatizable androgens should not inhibit FSH secretion.
Comparing the gonadotropin responses to selective E2 inhibition vs. complete castration demonstrates that T has both direct negative feedback effects on LH presumably mediated by the androgen receptor as well as indirect effects mediated by aromatization to E2. In contrast, Ts effects on FSH appear to be mediated exclusively by aromatization to E2.
Selective suppression of E2 secretion with an aromatase inhibitor results in a significant increase in both gonadotropins.
Administration of nonaromatizable androgens, such as DHT or fluoxymesterone, has been shown to have no impact on FSH secretion except at very high doses. It is possible that given the high affinity of DHT for sex hormone-binding globulin, such high doses of DHT may displace E2 and T from sex hormone-binding globulin, increasing free levels of these sex steroids and thus confounding the impact of what was presumed to be a pure DHT effect.
Studies that E2 is the major sex steroid negative feedback regulator of FSH are supported by experiments of nature that have resulted in models of unopposed T action (congenital estrogen deficiency) and unopposed E2 action (androgen insensitivity syndrome). Men with E2 receptor mutations and congenital aromatase deficiency have a 2- to 3-fold increase in FSH despite elevated T levels. Patients with congenital androgen insensitivity syndrome (AIS) provide further evidence for the differential regulation of gonadotropin secretion by T in men, with the demonstration of normal or minimally elevated FSH despite markedly elevated LH levels.
Mike
After AAS cessation the negative feedback inhibition of the hypothalamo-pituitary area by testosterone and estradiol would be gone or at the minimum dissipating. If these were the only factors inhibiting the gonadotropins their return in approximately the same timeline is expected. However, the feedback of FSH by Inhibin and its delay in returning after AAS cessation will often have a return of FSH prior to LH. The bottom line is one should not depend upon the FSH as a measure of HPTA functionality or for that matter HPTA suppression. I hope this fully explains the reasons why FSH is not to be used for HPTA normalization or functionality.
Studies of sex steroid regulation of gonadotropin secretion in the human male have focused primarily on the respective site(s) of negative feedback of testosterone (T) and estradiol (E2). Studies provide evidence of differential regulation of gonadotropin secretion by T in the human male. T exerts both direct and indirect feedback on LH secretion, whereas its effects on FSH appear to be mediated largely by aromatization to E2.
Because androgens can undergo aromatization to estrogens in a variety of tissues, including adipose tissue, brain, and testis, it is important to be able to distinguish T effects that are mediated directly by the androgen receptor as opposed to those indirect effects that only occur after aromatization to E2. If the hypothesis is correct that T has no direct negative feedback effects on FSH, it follows that administration of T in conjunction with an aromatase inhibitor or administration of nonaromatizable androgens should not inhibit FSH secretion.
Comparing the gonadotropin responses to selective E2 inhibition vs. complete castration demonstrates that T has both direct negative feedback effects on LH presumably mediated by the androgen receptor as well as indirect effects mediated by aromatization to E2. In contrast, Ts effects on FSH appear to be mediated exclusively by aromatization to E2.
Selective suppression of E2 secretion with an aromatase inhibitor results in a significant increase in both gonadotropins.
Administration of nonaromatizable androgens, such as DHT or fluoxymesterone, has been shown to have no impact on FSH secretion except at very high doses. It is possible that given the high affinity of DHT for sex hormone-binding globulin, such high doses of DHT may displace E2 and T from sex hormone-binding globulin, increasing free levels of these sex steroids and thus confounding the impact of what was presumed to be a pure DHT effect.
Studies that E2 is the major sex steroid negative feedback regulator of FSH are supported by experiments of nature that have resulted in models of unopposed T action (congenital estrogen deficiency) and unopposed E2 action (androgen insensitivity syndrome). Men with E2 receptor mutations and congenital aromatase deficiency have a 2- to 3-fold increase in FSH despite elevated T levels. Patients with congenital androgen insensitivity syndrome (AIS) provide further evidence for the differential regulation of gonadotropin secretion by T in men, with the demonstration of normal or minimally elevated FSH despite markedly elevated LH levels.
Mike
