This is a longer posting, but is actually just segments of the full article...
QUOTE:
Objective:
Although shown to be effective for their intended medical treatment,
AAS have been shown to induce hypogonadotropic hypogonadism in adult males. The medical literature is conflicting in the reports of spontaneous return and long-term suppression of gonadal suppression post
AAS usage. This observational study documents the treatment protocol of HCG, clomiphene citrate, and tamoxifen in returning hormonal function to normal post
AAS usage.
Design: Five HIV-negative males age 27-49, weighing 77-100 kg, with serum total testosterone levels below 240 ng/dL and luteinizing hormone (LH) levels below 1.5 mIU/mL were considered for this observational study. All five patients were administered the treatment protocol.
Methods: Treatment consisted of combination therapy which included concurrent administration of (a) Human Chorionic Gonadotropin, (b) Clomiphene Citrate and (c) Tamoxifen Citrate for a standard duration of 45 days. This protocol was repeated with every patient until serum LH and total testosterone values reached normal ranges.
Results: All five patients were considered eugonadal by normal laboratory reference ranges by the conclusion of treatment. Average serum total testosterone rose from 98.2 to 692.8 ng/dL (p<.001) while the average serum LH rose from an average undetectable value of less than 1.0 to 7.92 mIU/mL (p<.0008).
Conclusions: Although the treatment protocol of HCG, clomiphene citrate, and tamoxifen proved beneficial in reversing
AAS induced hypogonadotropic hypogonadism, future controlled studies need to be performed to confirm the beneficial effects of this combined pharmacotherapy in returning HPGA functioning to normal.
This condition typically results from an abnormality in the normal functioning of the hypothalamic-pituitary-gonadal axis (HPGA), usually from a negative feedback inhibition of one of the hormone secreting glands, causing a cascading unbalance in the rest of the axis. Possibly resulting from a physiological abnormality (i.e. mumps orchitis, Klinefelters syndrome, pituitary tumor) or as an acquired result of exogenous factors (i.e. androgen therapy,
AAS administration). Clerico et al (1981) found a dramatic suppression of serum gonadotropin levels in athletes given methandrostenelone, suggesting a direct action of
AAS on the hypothalamus.
One particular study administered 600 mg of nandrolone decanoate to 30 HIV-positive males over twelve weeks (Sattler et al, 1999). The results made no reference to LH or testosterone levels. The lack of gonadotropin measurement is puzzling as the data showed 12 of 30 subjects experienced testicular shrinkage, implying Leydig cell dysfunction and suppressed testosterone levels. Other studies using
AAS have also shown no reference to LH or FSH levels but suppressed values are expected in each case (Bagatell et al, 1994; Behre et al, 1997; Sheffield-Moore et al, 1999; Tricker et al, 1996).
Declining, or suppressed, circulating testosterone levels as a result of either pathophysiological or induced hypogonadal conditions can have many negative consequences in males. Declining levels of testosterone have been directly linked to a progressive decrease in muscle mass (Mauras et al, 1998), loss of libido (Schiavi et al, 1991), decrease in muscular strength (Balagopal et al, 1997; Mauras et al, 1998) impotence (Rakic et al, 1997), oligospermia or azoospermia (Vermeulen & Kaufman, 1995), increase in adiposity (Mauras et al, 1998) and an increased risk of osteoporosis (Wishart et al, 1995).
While some research suggests that the hormonal axis will spontaneously return to normal shortly after cessation of testosterone administration (Knuth et al, 1989), documented cases have taken up to 2 ½ years to return to normal (Jarow & Lipshultz, 1990). This case of a 39-year old male who previously used
AAS was found to have low serum testosterone levels (6nmol/L, range 14 to 28 nmol/L) 2 ½ years after his last administration of the drugs (Jarow & Lipshultz, 1990). For most men, suffering with diminished libido, impotence, depression, fatigue, muscle atrophy, and infertility for 2 ½ years is not a pleasant option. Other androgen or anabolic steroid induced cases of hypogonadotropic hypogonadism have taken 6 months (Gazvani et al, 1997; Wu et al, 1996), 8 months (Gazvani et al, 1997), 10 months (Boyadjiev et al, 2000), 12 months (Schurmeyer et al, 1984), and 18 months (Gazvani et al, 1997) to finally return to eugonadal status.
The individual use of human chorionic gonadotropin (HCG), clomiphene citrate, and tamoxifen citrate in the treatment of testicular sub-function and gonadotropin suppression, respectively, is well documented. HCG has been shown to significantly improve gonadal function in hypogonadotropic hypogonadal adult males (Barrio et al, 1999; Burgess & Calderon, 1997; Cisternino et al, 1998; D’Agata et al, 1982; 1984; Dunkel et al, 1985; Kelly et al, 1982; Ley & Leonard, 1985; Liu et al, 1988; Martikainen et al, 1986; Okuyama et al, 1986; Ulloa-Aguirre et al, 1985; Vicari et al, 1992). Studies using clomiphene citrate to induce endogenous gonadotropin production in males found significant improvements in LH and FSH values after treatment (Bjork et al, 1977; Burge et al, 1997; Guay et al, 1995; Landefeld et al, 1983; Lim & Fang, 1976; Ross et al, 1980; Spijkstra et al, 1988). Tamoxifen citrate has also been found to produce a profound increase in serum LH levels as well as improved semen and sperm quality (Gazvani et al, 1997; Krause et al, 1985; Lewis-Jones et al, 1987; Wu et al, 1996).
As HCG’s effect is centralized at the Leydig cells of the testicles, clomiphene citrate and tamoxifen citrate act upon the hypothalamic-pituitary region in stimulating gonadotropin production. Tamoxifen, a nonsteroidal antiestrogen, and clomiphene citrate, a nonsteroidal ovulatory stimulant, compete with estrogen for estrogen receptor binding sites, thus eliminating excess estrogen circulation at the level of the hypothalamus and pituitary and allowing gonadotropin production to resume normally. The normal operation of both the testicular and hypothalamic-pituitary regions is crucial in returning HPGA function to normal. Returning one component of the axis to normal without concurrently returning the other would sabotage and inhibit the operation of the entire HPG axis. It was with this understanding that HCG was eventually combined with clomiphene citrate and tamoxifen as attempted therapy to reverse gonada function in hypogonadotropic hypogonadal males.
In accordance with previous studies, each medication was used individually, and along with HCG, in initial trials. The simultaneous use of clomiphene citrate and tamoxifen was determined through preliminary use of clomiphene citrate and tamoxifen individually. It was discovered that although both clomiphene citrate and tamoxifen met with some success, when combined together they achieved a more significant increase in gonadotropin production. This clinical outcome resulted in the combination therapy of HCG, clomiphene citrate and tamoxifen.
With roughly 4 million men in the U.S. being considered hypogonadal (Lacayo R., 2000; Sheffield-Moore et al, 1999; Shelton DL, 2000), an estimated 200,000 men are currently receiving testosterone treatment for the condition (Shelton DL, 2000). As stated earlier,
AAS are being prescribed to HIV & AIDS sufferers to combat progressive muscle loss. The Centers for Disease Control and Prevention (CDC) reported an estimated 635,000+ men diagnosed with AIDS through December 2000 while an estimated 97,700 have been reported with HIV (Centers for Disease Control, vol.12, No. 2, table 5; Centers for Disease Control, vol. 12, No. 2, table 6). In 2000 alone over 31,000 men were diagnosed with the AIDS virus (Centers for Disease Control, vol. 12, No. 2, figure 3). Between hypogonadal, AIDS, & HIV males, potentially over 900,000 men are being administered
AAS therapy.
As described herein, a possible treatment modality may be the combined regimen of HCG, clomiphene citrate, and tamoxifen. Medical history has demonstrated examples of physician-induced complications resulting from treatment. Iatrogenic hyperthyroidism (Bartsch & Scheiber, 1981) and iatrogenic Cushing’s syndrome (Cihak & Beary, 1977; Kimmerle & Rolla, 1985; Smidt & Johnston, 1975; Tuel et al, 1990) are cases were administered medications or treatments provoked abnormalities in patients’ normal physiology. The administration of testosterone as a treatment for hypogonadotropic hypogonadism falls into this same category of causing endocrine related abnormalities (Bhasin et al, 1996; Marynick et al, 1979; Strawford et al, 1999; Tenover, 1992). Testosterone replacement therapy has proven to be very effective in reversing the symptoms of suppressed testosterone production, but does not treat the underlying cause of the deficiency....
Because of the negative impact of the hypogonadal state on physical and mental well- being, pharmacotherapy that restores HPGA function more rapidly than current modalities would greatly benefit men with hypogonadotropic hypogonadism.
While we believe that the treatment protocol was effective in returning normal hormonal function to these men, the lack of randomization or a control group leaves room for speculation. Although cases of spontaneous return to eugonadism with no medicinal intervention have been published, these reports documented durations anywhere from 6-18 months before normal hormone status was achieved (Gazvani et al, 1997; Wu et al, 1996). If the alternative treatment modality described herein can reverse suppressed gonadotropin production and
AAS associated side effects much sooner than non-treatment, further evaluation of this therapy should continue.
END QUOTE
The more complete article is at this site (only one where I could find it at):
http://www.basskilleronline.com/hpta_reversal.html
I found this section especially interesting:
QUOTE: The normal operation of both the testicular and hypothalamic-pituitary regions is crucial in returning HPGA function to normal. Returning one component of the axis to normal without concurrently returning the other would sabotage and inhibit the operation of the entire HPG axis. It was with this understanding that HCG was eventually combined with clomiphene citrate and tamoxifen as attempted therapy to reverse gonada function in hypogonadotropic hypogonadal males. END QUOTE
And even more so:
QUOTE: This condition typically results from an abnormality in the normal functioning of the hypothalamic-pituitary-gonadal axis (HPGA), usually from a negative feedback inhibition of one of the hormone secreting glands, causing a cascading unbalance in the rest of the axis. Possibly resulting from a physiological abnormality (i.e. mumps orchitis, Klinefelters syndrome, pituitary tumor) or as an acquired result of exogenous factors (i.e. androgen therapy,
AAS administration)... While some research suggests that the hormonal axis will spontaneously return to normal shortly after cessation of testosterone administration (Knuth et al, 1989), documented cases have taken up to 2 ½ years to return to normal (Jarow & Lipshultz, 1990)... The individual use of human chorionic gonadotropin (HCG), clomiphene citrate, and tamoxifen citrate in the treatment of testicular sub-function and gonadotropin suppression, respectively, is well documented... In accordance with previous studies, each medication was used individually, and along with HCG, in initial trials. The simultaneous use of clomiphene citrate and tamoxifen was determined through preliminary use of clomiphene citrate and tamoxifen individually. It was discovered that although both clomiphene citrate and tamoxifen met with some success, when combined together they achieved a more significant increase in gonadotropin production. This clinical outcome resulted in the combination therapy of HCG, clomiphene citrate and tamoxifen... Medical history has demonstrated examples of physician-induced complications resulting from treatment. I
atrogenic hyperthyroidism (Bartsch & Scheiber, 1981) and iatrogenic Cushing’s syndrome (Cihak & Beary, 1977; Kimmerle & Rolla, 1985; Smidt & Johnston, 1975; Tuel et al, 1990) are cases were administered medications or treatments provoked abnormalities in patients’ normal physiology. The administration of testosterone as a treatment for hypogonadotropic hypogonadism falls into this same category of causing endocrine related abnormalities (Bhasin et al, 1996; Marynick et al, 1979; Strawford et al, 1999; Tenover, 1992). Testosterone replacement therapy has proven to be very effective in reversing the symptoms of suppressed testosterone production, but does not treat the underlying cause of the deficiency... Because of the negative impact of the hypogonadal state on physical and mental well-being, pharmacotherapy that restores HPGA function more rapidly than current modalities would greatly benefit men with hypogonadotropic hypogonadism... END QUOTE
I wonder whatever happened with further examination of that protocol? From some of the language used it almost sounds like possibly a British study? It seems relatively recent (comparatively speaking) as it references clinical studies from 1999. I wonder if anyone would be interested in duplicating this study with a larger base (I for one would be willing to be a
test subject - at least once I get things cleared up with the Pheo tumor or whatever it is!).
) is my experience where my HCG dosage has decreased gradually by about 50% over 5 years of HCG administration.
Linear Mode
