Nelson Vergel
Founder, ExcelMale.com
By Dr Mauro Di Pasquale
For Part 1
For Part 2
For Part 3
While there are several measures that can be taken to minimize the effects of anabolic steroids on the HPTA, perhaps the most important precaution is that the athlete take sufficient time off anabolic steroids so that the bodies endocrine system can return to normal, and any testicular atrophy reversed. This rest phase should be at least as long as the period of time that anabolic steroids are used. For example, a cycle of 12 weeks on and 12 weeks off would prevent some of the long term sequelae of anabolic steroid use on the HPTA. It would appear that the more time spent drug free, the less long term suppression there is.
Secondly, the athlete should use low to moderate doses of those compounds which have less of a suppressive effect on the HPTA, although there is no anabolic steroid, even at low to moderate doses, that does not lead to some suppression. At high doses all anabolic steroids have a severe suppressive effect on the HTPA.
Since it appears that the production of testosterone is affected at several levels, minimizing the effect of anabolic steroids must take all these levels into account. It is especially important to minimize the direct effect of anabolic steroids on testicular steroidogenesis, the pituitary gonadotropins (LH and FSH) and hypothalamic GnRH.
Human chorionic gonadotropin (HCG) is used by athletes to prevent testicular atrophy during anabolic steroid usage, and to augment the exogenous intake of anabolic steroids by increasing endogenous production of testosterone (many studies have documented the plasma testosterone response to injections of HCG. However, using HCG at the same time as anabolic steroids will not maintain full testicular function, since the testicular response to HCG is diminished when anabolic steroids are used concomitantly. As well, the chronic use of HCG may eventually inhibit testicular steroidogenesis by decreasing the LH/HCG receptors on Leydig cells, thus making them refractory to stimulation from both HCG and exogenous and endogenous LH.
HCG is also used by athletes to try to decrease the negative effects which occur once off anabolic steroids. These athletes believe that by using the HCG after a cycle of anabolic steroid use, they can stimulate their own testes to produce testosterone, thereby returning to normal faster. This reasoning, however, is somewhat faulty, and the use of HCG may even compound the problem (see below).
HCG, however, may be useful in preventing primary testicular dysfunction, a factor in most cases of persistent low testosterone after going off anabolic steroid compounds. It appears that in cases of prolonged anabolic steroid use, testicular tissue may not regain its ability to produce normal levels of testosterone. The testicles remain somewhat atrophied, with inadequate testosterone production, even when stimulated by supraphysiological levels of LH and HCG. The intermittent use of HCG while on anabolic steroids may prevent this testicular dysfunction.
Some athletes are attempting to use GnRH to prevent the suppression of the HPTA. Unfortunately the effect of GnRH is blunted when anabolic steroids are used concomitantly. It appears that anabolic steroids and testosterone (and or their metabolites) directly inhibit LH and FSH secretion independent of GnRH , as well as their effect on the hypothalamic GnRH pulse generator.
However, this method may have some advantages over the use of HCG because all aspects of the HPTA are stimulated except for the hypothalamic component. It is not known if the hypothalamic suppression of endogenous GnRH caused by the exogenous GnRH leads to long term suppression of the HPTA and thus to testicular atrophy once the GnRH and the anabolic steroids are discontinued. In any case the pulsatile use of exogenous GnRH has proven effective in some cases of HPTA dysfunction secondary to the prolonged use of anabolic steroids.
Treating Residual HPTA Dysfunction
Residual HPTA dysfunction manifests itselfby a low serum testosterone and its symptoms (such as fatigue, depression, low sex drive and poor sexual performance). However, athletes with low serum testosterone secondary to anabolic steroid induced HPTA suppression may well represent with dysfunction at more than one level.
The first step in treating the dysfunction is determining where the problem is. In most athletes with residual suppression of the HPTA, I have found problems both at the testicular and the hypothalamic-pituitary level. Pituitary dysfunction, shown by the low normal LH response to GnRH, low hypothalamic-pituitary reserve, shown by a blunted response to clomiphene, and testicular dysfunction, shown by a blunted response to HCG, are often seen together.
Low serum testosterone levels with normal or low serum LH levels generally points to a hypothalamic-pituitary dysfunction, although not necessarily. Athletes with low serum testosterone but normal serum LH, may also have some degree of testicular failure secondary to their anabolic steroid use.
In athletes who continue to show significant suppression of the HPTA after cessation of the anabolic steroids, the suppression seems to affect all three areas of the axis and perhaps some suprahypophyseal areas. In these cases the treatment must be aimed at as many of the levels as possible often necessitating the use of the anti-estrogens, HCG and GnRH. However, care must be taken when using HCG and GnRH together since studies have shown that the simultaneous administration of an GnRH agonist and HCG blunts the plasma testosterone response observed after LHRH alpha alone, and decreases the testosterone production as compared to using HCG alone.
At first it may be worthwhile to use one of the anti-estrogens and see if this has a normalizing effect of the HPTA dysfunction. Anti-estrogens are compounds which are competitive inhibitors of estrogens, both endogenous and exogenous. Tamoxifen (Nolvadex) is a potent nonsteroidal, oral, anti-estrogen which competes with estrogen at binding sites and has no estrogenic activity. Clomiphene (Clomid) is an analog of chlorotrianisene (Tace), a synthetic estrogen. It is mildly estrogenic and acts as an antiestrogen. Cyclofenil, a non-steroidal compound, is a weak estrogen related to stilbestrol. It has structural analogies with both stilbene and triphenylethylene with a higher central than peripheral estrogenic activity. It acts as an anti-estrogen by effectively displacing the stronger estrogenic compounds.
All three compounds elevate endogenous gonadotropin production (both FSH and LH), which in turn stimulates the testes to produce more testosterone. Tamoxifen is thought to increase the release of GnRH as well. Clomiphene is also useful in the testing of hypothalamic-pituitary reserve in athletes whose serum testosterone remains depressed after the discontinuation of anabolic steroids.
These compounds are used by many athletes in an attempt to decrease the feminizing effects of the aromatizable anabolic steroids, and by some to increase HDL cholesterol and thus partially protect themselves from adverse cardiovascular problems. However these compounds seem to have little effect on preventing the suppression of the HPTA while anabolic steroids are being used, perhaps because of an overriding direct suppression exerted by the anabolic steroids on the HPTA.
Tamoxifen is the anti-estrogen of choice among most athletes. Tamoxifen, however, may be counterproductive in that it has been shown to decrease testicular steroidogenesis. A recent study reported that tamoxifen reduced the synthesis of testosterone through an inhibition of the 17 alpha-hydroxylase and l7,20-desmolase enzyme systems together with an increased 20 alpha-hydroxysteroid dehydrogenase activity. Thus the common use of tamoxifen by athletes using anabolic steroids may increase HPTA suppression.
However in the treatment ofHPTA dysfunction, tamoxifen's overall effect (perhaps due to it's ability to increase the release of GnRH as well as the gonadotropins) may make it the anti-estrogen of choice in the treatment of HPTA dysfunction.
In cases of prolonged hypogonadotropic hypogonadism subsequent to the use of androgenic/anabolic steroids, the response to the anti-estrogens is often disappointing. On the other hand, the response to HCG can be quite marked. However, the indiscriminate frequent use oflarge amounts ofHCG, rather than helping the testicular dysfunction, can often compound the problem. Recent studies have show that when HCG is used in cases of deficient testicular steroidogenesis, smaller doses used less frequently may be more effective and does not lead to Leydig cell steroidogenic desensitization.
If the main region affected is the testicles, that is their prolonged suppression has resulted in their inability to respond to physiological levels of LH, then the use of HCG (perhaps followed by the use of pulsatile GnRH if some degree of hypothalamic pituitary dysfunction is present) for several weeks to months to increase testicular steroidogenesis and size might prove effective. However, although HCG does stimulate endogenous testosterone production in those athletes who are in a transient hypogonadotropic hypogonadic state secondary to the use of anabolic steroids, it does not help in re* establishing a normal HPTA in cases where there is hypothalamic-pituitary dysfunction.
In this type of dysfunction the hypothalamus and pituitary are still in a refractory state after prolonged anabolic steroid use, and remain this way while HCG is being used since the endogenous testosterone produced as a result of the exogenous HCG suppresses endogenous LH production. Once the HCG is discontinued, the athlete must still go through a readjustment period. This is merely delayed by the HCG use.
Once the athlete discontinues the HCG (either at the same time or some time after the use of anabolic steroids), because of the lack of endogenous stimulation by LH, the testicles will tend to atrophy leading to possible gonadal impairment if the hypothalamic- pituitary-gonadal axis remains suppressed for any length of time. In these cases HCG (to stimulate testicular steroidogenesis), followed by the use of long term use of GnRH (by way of an intermittent infusion pump or by the intermittent use of one of the GnRH agonists), has proven to be more effective in re-establishing the HPTA in my more refractory patients.
Studies have shown that in some men with hypogonadotropic hypogonadism, normal pituitary-gonadal function can be maintained after discontinuation of long term pulsatile GnRH administration. Long term exogenous GnRH administration induces pituitary and gonadal priming, which subsequently enables them to sustain normal pituitary and gonadal function in response to their own GnRH secretion.
I have found that athletes with deficient testicular steroidogenesis and persistent depression ofthe HPTA often respond to this regimen. Occasionally, when there is a failure to respond to HCG, the menotropins, GnRH, and the anti-estrogens, the only alternative may be long term testosterone replacement therapy.
For Part 1
For Part 2
For Part 3
While there are several measures that can be taken to minimize the effects of anabolic steroids on the HPTA, perhaps the most important precaution is that the athlete take sufficient time off anabolic steroids so that the bodies endocrine system can return to normal, and any testicular atrophy reversed. This rest phase should be at least as long as the period of time that anabolic steroids are used. For example, a cycle of 12 weeks on and 12 weeks off would prevent some of the long term sequelae of anabolic steroid use on the HPTA. It would appear that the more time spent drug free, the less long term suppression there is.
Secondly, the athlete should use low to moderate doses of those compounds which have less of a suppressive effect on the HPTA, although there is no anabolic steroid, even at low to moderate doses, that does not lead to some suppression. At high doses all anabolic steroids have a severe suppressive effect on the HTPA.
Since it appears that the production of testosterone is affected at several levels, minimizing the effect of anabolic steroids must take all these levels into account. It is especially important to minimize the direct effect of anabolic steroids on testicular steroidogenesis, the pituitary gonadotropins (LH and FSH) and hypothalamic GnRH.
Human chorionic gonadotropin (HCG) is used by athletes to prevent testicular atrophy during anabolic steroid usage, and to augment the exogenous intake of anabolic steroids by increasing endogenous production of testosterone (many studies have documented the plasma testosterone response to injections of HCG. However, using HCG at the same time as anabolic steroids will not maintain full testicular function, since the testicular response to HCG is diminished when anabolic steroids are used concomitantly. As well, the chronic use of HCG may eventually inhibit testicular steroidogenesis by decreasing the LH/HCG receptors on Leydig cells, thus making them refractory to stimulation from both HCG and exogenous and endogenous LH.
HCG is also used by athletes to try to decrease the negative effects which occur once off anabolic steroids. These athletes believe that by using the HCG after a cycle of anabolic steroid use, they can stimulate their own testes to produce testosterone, thereby returning to normal faster. This reasoning, however, is somewhat faulty, and the use of HCG may even compound the problem (see below).
HCG, however, may be useful in preventing primary testicular dysfunction, a factor in most cases of persistent low testosterone after going off anabolic steroid compounds. It appears that in cases of prolonged anabolic steroid use, testicular tissue may not regain its ability to produce normal levels of testosterone. The testicles remain somewhat atrophied, with inadequate testosterone production, even when stimulated by supraphysiological levels of LH and HCG. The intermittent use of HCG while on anabolic steroids may prevent this testicular dysfunction.
Some athletes are attempting to use GnRH to prevent the suppression of the HPTA. Unfortunately the effect of GnRH is blunted when anabolic steroids are used concomitantly. It appears that anabolic steroids and testosterone (and or their metabolites) directly inhibit LH and FSH secretion independent of GnRH , as well as their effect on the hypothalamic GnRH pulse generator.
However, this method may have some advantages over the use of HCG because all aspects of the HPTA are stimulated except for the hypothalamic component. It is not known if the hypothalamic suppression of endogenous GnRH caused by the exogenous GnRH leads to long term suppression of the HPTA and thus to testicular atrophy once the GnRH and the anabolic steroids are discontinued. In any case the pulsatile use of exogenous GnRH has proven effective in some cases of HPTA dysfunction secondary to the prolonged use of anabolic steroids.
Treating Residual HPTA Dysfunction
Residual HPTA dysfunction manifests itselfby a low serum testosterone and its symptoms (such as fatigue, depression, low sex drive and poor sexual performance). However, athletes with low serum testosterone secondary to anabolic steroid induced HPTA suppression may well represent with dysfunction at more than one level.
The first step in treating the dysfunction is determining where the problem is. In most athletes with residual suppression of the HPTA, I have found problems both at the testicular and the hypothalamic-pituitary level. Pituitary dysfunction, shown by the low normal LH response to GnRH, low hypothalamic-pituitary reserve, shown by a blunted response to clomiphene, and testicular dysfunction, shown by a blunted response to HCG, are often seen together.
Low serum testosterone levels with normal or low serum LH levels generally points to a hypothalamic-pituitary dysfunction, although not necessarily. Athletes with low serum testosterone but normal serum LH, may also have some degree of testicular failure secondary to their anabolic steroid use.
In athletes who continue to show significant suppression of the HPTA after cessation of the anabolic steroids, the suppression seems to affect all three areas of the axis and perhaps some suprahypophyseal areas. In these cases the treatment must be aimed at as many of the levels as possible often necessitating the use of the anti-estrogens, HCG and GnRH. However, care must be taken when using HCG and GnRH together since studies have shown that the simultaneous administration of an GnRH agonist and HCG blunts the plasma testosterone response observed after LHRH alpha alone, and decreases the testosterone production as compared to using HCG alone.
At first it may be worthwhile to use one of the anti-estrogens and see if this has a normalizing effect of the HPTA dysfunction. Anti-estrogens are compounds which are competitive inhibitors of estrogens, both endogenous and exogenous. Tamoxifen (Nolvadex) is a potent nonsteroidal, oral, anti-estrogen which competes with estrogen at binding sites and has no estrogenic activity. Clomiphene (Clomid) is an analog of chlorotrianisene (Tace), a synthetic estrogen. It is mildly estrogenic and acts as an antiestrogen. Cyclofenil, a non-steroidal compound, is a weak estrogen related to stilbestrol. It has structural analogies with both stilbene and triphenylethylene with a higher central than peripheral estrogenic activity. It acts as an anti-estrogen by effectively displacing the stronger estrogenic compounds.
All three compounds elevate endogenous gonadotropin production (both FSH and LH), which in turn stimulates the testes to produce more testosterone. Tamoxifen is thought to increase the release of GnRH as well. Clomiphene is also useful in the testing of hypothalamic-pituitary reserve in athletes whose serum testosterone remains depressed after the discontinuation of anabolic steroids.
These compounds are used by many athletes in an attempt to decrease the feminizing effects of the aromatizable anabolic steroids, and by some to increase HDL cholesterol and thus partially protect themselves from adverse cardiovascular problems. However these compounds seem to have little effect on preventing the suppression of the HPTA while anabolic steroids are being used, perhaps because of an overriding direct suppression exerted by the anabolic steroids on the HPTA.
Tamoxifen is the anti-estrogen of choice among most athletes. Tamoxifen, however, may be counterproductive in that it has been shown to decrease testicular steroidogenesis. A recent study reported that tamoxifen reduced the synthesis of testosterone through an inhibition of the 17 alpha-hydroxylase and l7,20-desmolase enzyme systems together with an increased 20 alpha-hydroxysteroid dehydrogenase activity. Thus the common use of tamoxifen by athletes using anabolic steroids may increase HPTA suppression.
However in the treatment ofHPTA dysfunction, tamoxifen's overall effect (perhaps due to it's ability to increase the release of GnRH as well as the gonadotropins) may make it the anti-estrogen of choice in the treatment of HPTA dysfunction.
In cases of prolonged hypogonadotropic hypogonadism subsequent to the use of androgenic/anabolic steroids, the response to the anti-estrogens is often disappointing. On the other hand, the response to HCG can be quite marked. However, the indiscriminate frequent use oflarge amounts ofHCG, rather than helping the testicular dysfunction, can often compound the problem. Recent studies have show that when HCG is used in cases of deficient testicular steroidogenesis, smaller doses used less frequently may be more effective and does not lead to Leydig cell steroidogenic desensitization.
If the main region affected is the testicles, that is their prolonged suppression has resulted in their inability to respond to physiological levels of LH, then the use of HCG (perhaps followed by the use of pulsatile GnRH if some degree of hypothalamic pituitary dysfunction is present) for several weeks to months to increase testicular steroidogenesis and size might prove effective. However, although HCG does stimulate endogenous testosterone production in those athletes who are in a transient hypogonadotropic hypogonadic state secondary to the use of anabolic steroids, it does not help in re* establishing a normal HPTA in cases where there is hypothalamic-pituitary dysfunction.
In this type of dysfunction the hypothalamus and pituitary are still in a refractory state after prolonged anabolic steroid use, and remain this way while HCG is being used since the endogenous testosterone produced as a result of the exogenous HCG suppresses endogenous LH production. Once the HCG is discontinued, the athlete must still go through a readjustment period. This is merely delayed by the HCG use.
Once the athlete discontinues the HCG (either at the same time or some time after the use of anabolic steroids), because of the lack of endogenous stimulation by LH, the testicles will tend to atrophy leading to possible gonadal impairment if the hypothalamic- pituitary-gonadal axis remains suppressed for any length of time. In these cases HCG (to stimulate testicular steroidogenesis), followed by the use of long term use of GnRH (by way of an intermittent infusion pump or by the intermittent use of one of the GnRH agonists), has proven to be more effective in re-establishing the HPTA in my more refractory patients.
Studies have shown that in some men with hypogonadotropic hypogonadism, normal pituitary-gonadal function can be maintained after discontinuation of long term pulsatile GnRH administration. Long term exogenous GnRH administration induces pituitary and gonadal priming, which subsequently enables them to sustain normal pituitary and gonadal function in response to their own GnRH secretion.
I have found that athletes with deficient testicular steroidogenesis and persistent depression ofthe HPTA often respond to this regimen. Occasionally, when there is a failure to respond to HCG, the menotropins, GnRH, and the anti-estrogens, the only alternative may be long term testosterone replacement therapy.
