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Retrospective Analysis of the Effects of Low Dose,
By, Edmund Y. Chein, M.D.,J.D.
Daniel G. Vogt, M.D.
Michael J. Gonzalez, D.Sc., Ph.D.,FACN Neil H. Riordan, PA-C ABSTRACT Methods. A retrospective analysis of IGF-1, TG, TC and PSA data from our patient population was performed to test our hypothesis that positive objective responses of IGF-1, TG, and TC occur and that elevation of PSA does not occur in response to LDHF dosing regimen of GH. The mean duration of treatment of the analyzed data ranged from 181 to 259 days. Results. The mean plasma IGF-1 level rose significantly (p<.00001) to a level 37% greater than baseline with treatment. TC and TG decreased significantly (p<.001) in those patients with elevated baseline values, and did not change significantly in those with normal baseline values. PSA concentrations decreased non-significantly during treatment, and few cases of edema, joint pain, or carpal tunnel were reported. Conclusions. Treatment of AGHD using the LDHF dosing regimen of Total Hormone Replacement Therapy resulted in significant increases in IGF-1, significant reductions in TC and TG levels in patients with elevated baseline values, no increase in PSA concentrations, and fewer side effects than other dosing regimens. INTRODUCTION Adult growth hormone deficiency (AGHD) appears to be associated with a lipid profile known to be related to premature atherosclerosis and cardiovascular disease2. Elevated total cholesterol (TC), and low density lipoprotein have been observed in a substantial proportion of patients with AGHD compared with the predicted range or to age- and sex-matched controls,3-5 and triglyceride (TG) levels are higher compared to healthy controls5-7. A reduction in TC has been reported in six double blind placebo controlled trials of growth hormone replacement (GHR),3-5,8-11 while no reduction was reported in one double placebo contolled,12 and one non-placebo controlled trial.13 None of these trials reported a significant reduction in TG levels, however there was a tendency for lower TG with GHR in patients with elevated baseline TG in one study.12 The dose of GH in the above trails was 0.25 IU/kg·week with the exceptions of the third study,8 in which patients were treated with 0.5 IU/kg·week, and the eighth study13 in which the dose was guided by insulin-like growth factor 1 (IGF-1, also known as somatomedin C is an indirect measurement of growth hormone secretion) plasma levels and averaged 0.23 IU/kg·week. The dosing frequency of the above studies was three times per week. Since 1994, one of us (EC) has administered lower doses of GH to AGHD patients in a manner that more closely mimics the normal daily pulsed pituitary secretion of GH. Typically 0.06 to 0.12 IU/kg·week was self-administered subcutaneousley in 12 divided doses, injected once upon rising, and once at bedtime, six days per week. Previously published clinical observations of over 1000 patients using this low-dose, high frequency GH regimen included increased IGF-1 levels, and many subjective improvements including increase in muscle strength, exercise endurance, sexual drive and performance, energy levels, emotions, memory, and loss of body fat.14 Following that publication, it was noticed that normalization of hypercholesterolemia and hypertriglyceridemia occurred in patients following this regimen. We therefore retrospectively analyzed our latest objective TC, TG, and IGF-1 data from our >2200 patient pool, and present the results herein. A recent study concluded that there was a strong positive association between IGF-1 levels and prostate cancer risk.15 Our study of our patients we also observed that serum prostate specific antigen (PSA) levels remained the same, and in some cases decreased in our patient population, PSA data were also analyzed and are presented. MATERIALS AND METHODS Data Analysis P values based on two-tailed, matched pair t-tests were calculated for the comparisions betweenans the intr- or post-therapy values using Microsoft Excel software. Measurements During routine clinical follow up, plasma IGF-1, TC, TG, and PSA levels were determined by Pinnacle Labs, Inc., Salt Lake City, Utah. Non-age/sex-specific reference values were 71-290 ng/mL for IGF-1, 30-150 mg/dL for TG, 120-240 mg/dL for TC, and 0-4 mcg/L for PSA. Other hormones as described by The Total Hormone Replacement Therapy patent were checked and balanced per patented procedures. RESULTS Laboratory Data A significant 37% increase in IGF-1 levels was seen compared to baseline levels (Table 1). Fasting serum TG and TC levels were significantly lower after treatment compared to baseline values. When subsets of normal and abnormal baseline TG and TC values were analyzed, it was found that there was a significant reduction in both TG and TC in the patients with abnormally high baseline levels and a non-significant increase in both TG and TC values in the normal baseline subsets (Table 2,3). Stratification of the IGF-1, TG, and TC data into groups treated for different durations (30-120, 121-210, 211-300, and >301 days) revealed: 1) a significant increase in IGF-1 levels in all groups (Table 4); 2) a significant decrease in Tg levels in all groups (Table 5); 3) a significant reduction in TC levels in the two groups treated for 30-120, and 121-210 days, and 4) a non-significant reduction in TC levels for the groups treated for longer than 211 days (Table 6). There was a non-significant trend toward decreases PSA values (Table 7). Only one out of twenty patients with an elevated PSA baseline value had an increase on treatment, while 18 had a reduction, and one remained the same. Interestingly, one patient, previously diagnosed with intracapsular carcinoma of the prostate experienced a dramatic decrease in PSA (33-0.2) after 11 months of treatment with GH without any other treatment for the prostate cancer. DISCUSSION The analysis of these data revealed that treatment using LDHF GH regimen resulted in a significant increase of IGF-1, an indirect indicator of circulating GH levels. The analysis also demonstrated that this treatment schedule resulted in a reduction of TG and TC in patients with elevated baseline values, and that there was not an unwanted decrease in TG and TC levels in patients with normal baseline values. We do not know whether the growth hormone itself, or another secondary factor, such as increased exercise was the prime force in reducing TC and TG in this pool of patients. The not result however, was a significant reduction in serum concentrations of two major indicators of IHD and atherosclerosis in patients with elevated TG and TC. We believe this is the first report of GH lowering Tg levels in AGHD patients. We also demonstrated that there was no increase in PSA associated with long term (mean 256 days, range to 752 days) usage of GH, indicating no association for risk of prostate cancer with the use of GH. These data, on the surface may appear to contradict the recent report of a strong positive association between IGF-1 levels and prostate cancer risk.15 However, IGF-1 parallels GH levels in the blood, but the two molecules do not behave similarly. GH exerts immunostimulatory effects,16 while IGF-1 possesses mitogenic and anti-apoptotic qualities. An elevated IGF-1 plasma level without concomitant elevation of plasma GH level, as was the case in study 15, allows for the negative effects of IGF-1 to be manifest without the positive immunostimulatory effects of GH. In this study, the IGF-1 and Gh levels rose together, and may explain why there was no increase in PSA in our data. Although this study was not double-blinded, or placebo controlled, it does contribute valuable information to those treating AGHD in the clinical setting. Author to whom reprint requests should be addressed: |
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