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Using A Trans-dermal Growth Hormone Releasing Hormone Peptide Combination (TD-GHRH-A) For Prevention of Aging Fifth International Congress on Aging Skin May 17 – 20, 2001 Session Loews Coronado Bay Resort, San Diego, CA. Lecture Objectives:.

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slide1
Using A Trans-dermal Growth Hormone Releasing Hormone Peptide Combination (TD-GHRH-A) For Prevention of Aging

Fifth International Congress on Aging Skin

May 17 – 20, 2001 Session

Loews Coronado Bay Resort, San Diego, CA

Rashid A. Buttar, DO, FAAPM, FACAM

lecture objectives
Lecture Objectives:

1.) Explain the hypothalamic-pituitary axis clearly

2.) Understand why GHRH is a better treatment option than GH injections to increase GH levels

3.) Present research data on a highly effective and only transdermal longevity medical therapeutic

4.) Explain the IGF-1 myth and support with clinical data, published research & physiologic concepts

5.) Present initial findings of multi-centered, double blind, placebo controlled, cross over study

6.) Review protocols & compare to GH injection tx

Rashid A. Buttar, DO, FAAPM, FACAM

human growth hormone hgh has many beneficial effects such as
Human Growth Hormone (hGH) Has Many Beneficial Effects Such As:
  • Increase in lean body (muscle) mass
  • Decrease in body fat
  • Improved cognitive function
  • Increase in sexual vigor
  • Increase in energy
  • Increase in stamina
  • Improved endurance
  • Increased immune system response
  • Faster resolution of acute injuries

Rashid A. Buttar, DO, FAAPM, FACAM

slide4
Dietary

Protein

Dietary

Carbohydrates

Hypothalamus

Exercise

GHRH

Somatostatin

Sex Hormones

Adrenal

Output

Pituitary

Liver

hGH

Stress

Multi Organ Influence

IGF-1

Rashid A. Buttar, DO, FAAPM, FACAM

hgh injections vs ghrh treatments
hGH Injections vs GHRH Treatments

……long-term stimulation of pituitary cells with GHRH will shift the GHRH/somatostatin tone by exogenous [injection] therapy to increase GHRH responsivity and pituitary GH stores. It is predicted that this therapy will reverse the chronic inhibitory state induced by long-term somatostatin domination and create an environment now responsive to the endogenous GHRH tone….and allow for the normal [physiological] pulsatile GH release to reappear. This would produce a greater therapeutic benefit and a better safety profile compared with once daily injections of a bolus of recombinant GH …..[the need for] repeated stimulation of GHRH receptors is required in a patient friendly format….efforts are ongoing…..

Scott Chappel, PhD

Clinical Endocrinology Serono Laboratories, Norwell, MA

(1999) 50, 547-556

Rashid A. Buttar, DO, FAAPM, FACAM

only two ghrh products available on the market
Only Two GHRH ProductsAvailable on the Market

1.) Geref ® by Serono® (Depot Injection Delivery)

2.) Trans-D Tropin® by Balance Dermaceuticals® (Transdermal Delivery)

Rashid A. Buttar, DO, FAAPM, FACAM

delivery system of the future
"Delivery System of the Future"

Doctors around the world are calling trans-dermal delivery the 'delivery system of the future….high absorption rate of many supplements is achieved when delivered through the skin…the physical size of the supplement’s molecule plays an important role…when delivered trans-dermally, they directly enter the vascular system, initially bypassing the liver ….The result can mean as much as 95% of the supplements get to the cellular level where they are needed.. Conversely, studies show as little as 5% of supplements taken orally, make it to the cellular level….because the GI and hepatic systems are degrading and eliminating the majority of the active substances. A 95% absorption v.s. 5% absorption is why we believe trans-dermals to be a far more effective method of drug/supplement delivery. *

.

* Source: Dept. of Pharmacology, Univ. of Dublin

Rashid A. Buttar, DO, FAAPM, FACAM

trans d tropin ndc 65448 2115 1
Trans-D Tropin®NDC # 65448-2115-1

A Transdermal

Growth Hormone Releasing Hormone Analog

Rashid A. Buttar, DO, FAAPM, FACAM

slide9
Hypothalamus

GHRH

Somatostatin

Trans-D Tropin / Geraf

Pituitary

Endogenous hGH

V.S.

Recombinant hGH

Rashid A. Buttar, DO, FAAPM, FACAM

endogenous hgh levels 2 weeks apart per hgh radio immunoassay ng ml
Endogenous hGH Levels (2 weeks apart)per hGH Radio-Immunoassay (ng/ml)

Rashid A. Buttar, DO, FAAPM, FACAM

what level of hgh increase is necessary in order to achieve therapeutic benefit
What Level of hGH Increase Is Necessary In Order To Achieve Therapeutic Benefit?

Endocrinology and Physiology Texts indicate that an absolute level of hGH above 5 ng/ml is needed before efficacy can be attained.

This “efficacy” referred to, is a DIAGNOSTIC response (for purposes of diagnosis), not a THERAPEUTIC response.

  • Diagnostic – To elicit a response far beyond the normal physiological range by taxing and overloading the system.
  • Therapeutic – To elicit a subtle response well within the normal physiological range to achieve therapeutic effects.

Rashid A. Buttar, DO, FAAPM, FACAM

endogenous hgh means change 53 specimens via hgh radio immunoassay ng ml
Endogenous hGH Means & % Change 53 Specimens via hGH Radio-Immunoassay (ng/ml)

Rashid A. Buttar, DO, FAAPM, FACAM

statistical analysis of data
Baseline mean

0.295918367

90 minute mean

2.213636364

P < 0.001

Baseline standard deviation

0.464112

90 minute standard deviation

2.673173

Statistical Analysis of Data

Rashid A. Buttar, DO, FAAPM, FACAM

specific changes noted with use of trans d tropin
Specific Changes Noted With Use of Trans-D Tropin®:
  • Change in facial/body contour
  • Decreased serum glucose levels
  • Increase in energy, stamina, endurance
  • Healing of old injuries with an increase in ROM
  • Increase in strength within 24 to 36 hours
  • Improved sleep patterns with increase in REM sleep
  • Improved mental focus and concentration
  • Decrease in depression with improved coping ability
  • Increased force of ejaculation and quality of erection
  • Improvement in LFT’s & other blood chemistries
  • Marked improvement in CHF patientsand some MS patients

Rashid A. Buttar, DO, FAAPM, FACAM

response in serum glucose levels
Response in Serum Glucose Levels
  • Trans-D Tropin® appears to have a distinct “euglycemic” effect on serum glucose.
  • Glucose level modulation was evidenced by glucose levels below 75 mg/dl  to ~100 mg/dl levels and above 150 mg/dl  to ~110 mg/dl levels.
  • Pt’s with IDDM had 50 to 70 mg/dl  in glucose, 90 minutes after Trans-D Tropin® usage.

Rashid A. Buttar, DO, FAAPM, FACAM

case report 2 patients with iddm
2 brittle insulin dependent diabetic patients showed the following response :

Baseline Pre Trans-D Tx - Glucose - 247 mg/dl - 190 mg/dl

90 Min Post Trans-D Tx - Glucose - 160 mg/dl

- 116 mg/dl

Both diabetic patients did NOT show response in hGH levels during the first blood draw (first day of Trans-D Tropin® use) or the second blood draw (after 2 weeks of Trans-D Tropin® usage).

However, at the 5 week blood draw, there was an average of over 400 % increase in levels of ENDOGENOUS hGH in both IDDM patients.

Case Report - 2 Patients with IDDM

Rashid A. Buttar, DO, FAAPM, FACAM

response in serum igf 1 levels
Response in Serum IGF-1 Levels
  • Trans-D Tropin® causes a measurable DECREASE in IGF-1 levels (ng/ml) on a consistent basis.
  • Efficacious hGH therapy DOES NOT increase IGF-1.
  • An inverse correlation of IGF-1 and hGH efficacy has clearly been established in our previous studies, in published literature, current research and in clinical observation.

Rashid A. Buttar, DO, FAAPM, FACAM

response in serum igf 1 levels18
Response in Serum IGF-1 Levels

Rashid A. Buttar, DO, FAAPM, FACAM

evidence of unreliable relationship between hgh and igf 1 levels
Evidence of Unreliable Relationship between hGH and IGF-1 levels
  • Jorgensen JO, Pedersen SB, Borglum J, Frystyk J, Ho KK, Christiansen JS, et al: Serum concentrations of insulin-like growth factors (IGFs), IGF binding proteins 1 and 3 and growth hormone binding protein in obese women and the effects of growth hormone administration: a double-blind, placebo- controlled study. European Journal of Endocrinology 1995 July; 133(1): 65-70.
  • Chapman IM, Hartman ML, Pieper KS, Skiles EH, Pezzoli SS, Hintz RL, et al: Recovery of growth hormone release from suppression by exogenous insulin-like growth factor I (IGF-I): evidence for a suppressive action of free rather than bound IGF-I.Journal of Clinical Endocrinology and Metabolism 1998 August; 83(8): 2836-42.

Rashid A. Buttar, DO, FAAPM, FACAM

evidence of unreliable relationship between hgh and igf 1 levels20
Evidence of Unreliable Relationship between hGH and IGF-1 levels

3. Juul A, Andersson AM, Pedersen SA, Jorgensen JO, Christiansen JS, Groome NP, et al: Effects of growth hormone replacement therapy on IGF-related parameters and on the pituitary-gonadal axis in GH-deficient males. A double- blind, placebo-controlled crossover study. Hormonal Research 1998; 49(6): 269-78.

4. Yohay D, Lunenfeld E, Giat Y, Levy J, Sharoni Y, Potashnik G, et al: Do changes in growth hormone levels correlate with IGF-I levels in patients undergoing IVF-ET?Gynecological Endocrinology 1997 August; 11(4): 269-74.

5. Aimaretti G, Corneli G, Razzore P, et al: Usefulness of IGF-1 assay for the diagnosis of GH deficiency in adults. Journal of Endocrinology Investigation 1998 September; 21(8): 506-511.

Rashid A. Buttar, DO, FAAPM, FACAM

evidence of unreliable relationship between hgh and igf 1 levels21
Evidence of Unreliable Relationship between hGH and IGF-1 levels

6. Murphy LJ, Seneviratne C, Moreira P, Reid RE, et al: Enhanced expression of IGF binding protein-I in the fasted rat: the effects of insulin and growth hormone administration. Endocrinology 1991 February; 128(2): 689-96.

7. Norrelund H, Fisker S, Vahl N, Borglum J, Richelsen B, Christiansen, JS, et al: Evidence supporting a direct suppressive effect of GH on serum IGFBP-1 levels. Growth Hormone IGF Research (Denmark) 1999 February; 9(1): 52-60.

8. Borges MH, Pinto AC, DiNinno FB, Camacho-Hubner C, Grossman A, Kater CE, et. al: IGF-I levels rise and GH responses to GHRH decrease during long-term prednisone treatment in man. Journal of Endocrinological Investigation 1999 January; 22(1): 12-7.

Rashid A. Buttar, DO, FAAPM, FACAM

evidence of unreliable relationship between hgh and igf 1 levels22
Evidence of Unreliable Relationship between hGH and IGF-1 levels

9. Mazzoccoli G, Giuliani A, Bianco G, De Cata A, Balzanelli M, Carella AM, et al: Decreased serum levels of insulin-like growth factor (IGF)-I in patients with lung cancer: temporal relationship with growth hormone (GH) levels.Anticancer Research (Italy) 1999 March-April; 19(2B): 1397-9.

10. Furlanetto RW: Insulin-like growth factor measurements in the evaluation of growth hormone secretion.Hormonal Research 1990; 33 Suppl 4:25-30.

Rashid A. Buttar, DO, FAAPM, FACAM

possible explanation of igf 1 levels basic physiology questions
Possible Explanation of  IGF-1 Levels(Basic Physiology Questions)

IGF-1 = InsulinLike Growth Factor, Type I

Question # 1: Do sedentary people or athletes have lower glucose levels?

Question # 2: Are people who exercise, biologically (physiologically) younger or older?

Rashid A. Buttar, DO, FAAPM, FACAM

exercise insulin sensitivity or insulin levels
Exercise  Insulin Sensitivity(or  Insulin Levels)

Exercise sensitizes cells to the effects of insulin.

- Body needs less insulin to accomplish same effect.

Efficient use of glucose in patients who exercise.

Higher metabolism,  lean body mass + more activity lead to  levels of circulating glucose, in turn reducing insulin requirements =  Insulin Levels.

Rashid A. Buttar, DO, FAAPM, FACAM

exercise younger physiology
Exercise  Younger Physiology

Exercise has always been considered a natural form of anti-aging therapy.

  • Exercise  hGH,  Testosterone, and improves overall hormonal response in the entire system.
  • Exercise  BP, heart rate, respiratory rate, and peripheral vascular resistance, making the system more efficient.
  • Exercise  Endorphins, Lean Body Mass, Immunity, Range of Motion, Endurance, Stamina, Libido, etc.

Rashid A. Buttar, DO, FAAPM, FACAM

possible explanation of igf 1 levels basic physiology continued
What is IGF-1? Insulin Like Growth Factor Type 1 is one of many growth factors.

Why "Insulin Like” GF-1? The poly-peptide sequence is very similar to Insulin.

IGF-1 and Insulin also appear to share many of the same properties & characteristics.

Answer # 1:

Athletes have lower serum glucose levels 2o to insulin sensitivity.

Answer # 2 :

Exercise  Younger physiological age ( lean body mass, insulin sensitivity, hGH, etc.)

Possible Explanation of  IGF-1 Levels(Basic Physiology Continued)

Rashid A. Buttar, DO, FAAPM, FACAM

general physiological principals
Thus, athletes have lower insulin levels and are biologically younger than non-exercisers.

Example:

A 79 year-old who exercises is biologically younger than a 79 year-old who rocks in a rocking chair all day.

So, Exercise = Anti-Aging

Exercise/Anti-Aging causes:

 in Lean Body Mass

 in Hormonal levels

 in hGH levels

 in Insulin Sensitivity

 in Physiological Age

 in Insulin levels

And since Insulin is very similar to IGF-1, then …..

IGF-1 should in Athletes

General Physiological Principals

Rashid A. Buttar, DO, FAAPM, FACAM

igf 1 in athletes v s sedentary patients 3 week 38 patient outcome based study
21 Sedentary ♂ & ♀ patients (with no previous history of regular exercise)

Age Range 30 to 84 yr

Mean Age 55.3 yr

Median Age 57.0 yr

IGF-1 Range 61 to 304

IGF-1 Mean 153.0 ng/ml

IGF-1 Median 182.5 ng/ml

17 Athletic ♂ & ♀ patients (regularly exercising for a minimum of 2 years)

Age Range 25 to 42 yr

Mean Age 34.1 yr

Median Age 33.5 yr

IGF-1 Range 88 to 196

IGF-1 Mean 149.4 ng/ml

IGF-1 Median 142.0 ng/ml

IGF-1 in Athletes v.s. Sedentary Patients(3 Week, 38 Patient, Outcome Based Study)

Rashid A. Buttar, DO, FAAPM, FACAM

igf 1 in athletes v s sedentary patients 3 week 38 patient outcome based study29
21 Sedentary ♂ & ♀

Older Group

Age Range 30 to 84 yr

Mean Age 55.3 yr

Higher IGF-1

IGF-1 Range 61 to 304

IGF-1 Mean 153.0 ng/ml

17 Athletic ♂ & ♀

Younger Group

Age Range 25 to 42 yr

Mean Age 34.1 yr

Lower IGF-1

IGF-1 Range 88 to 196

IGF-1 Mean 149.4 ng/ml

IGF-1 in Athletes v.s. Sedentary Patients(3 Week, 38 Patient, Outcome Based Study)

Rashid A. Buttar, DO, FAAPM, FACAM

growing consensus that igf 1 levels are not related to hgh levels
Growing Consensus that IGF-1 Levels are NOT Related to hGH Levels

Janssen YJ, Helmerhorst F, Frolich M, Roelfsema F, et al: A switch from oral (2 mg/day) to trans-dermal (50 micro/day) 17 beta-estradiol therapy increases serum IGF-I levels in recombinant hGH substituted women with GH deficiency.Journal of Clinical Endocrinology and Metabolism. 2000January;85(1):464-6..…found direct relationship between serum levels of estradiol and IGF-1 levels, independent of hGH levels.

Inuki T, Takanashi K, Takebayashi K, Fuiwara Y, Tayama K, Takemura Y, et al: Thyroid hormone modulates insulin-like growth factor-1(IGF-1) and IGF-binding protein-3, without mediation by growth hormone, in patients with autoimmune thyroid disease. Metabolism Research 1999 October;31 (10):576-9.……..found that thyroid hormone modulates IGF-1 and IGF-BP3, without mediation by hGH.

Rashid A. Buttar, DO, FAAPM, FACAM

growing consensus that igf 1 levels are not related to hgh levels31
Growing Consensus that IGF-1 Levels are NOT Related to hGH Levels

Furlanetto RW: Insulin-like growth factor measurements in the evaluation of growth hormone secretion.Hormonal Research 1990; 33 Suppl 4:25-30. …..found that IGF-I levels are age dependent and subject to regulation by other hormones and nutritional variables; these features complicate the interpretation of IGF-I levels in individual patients and greatly limit the usefulness of these measurements, especially in establishing GH deficiency or [assessing GH replacement efficacy] …...Circulating IGF-II levels are not GH dependent and, therefore, their measurement is of little clinical utility in assessing GH secretion.

Department of Pediatrics, University of Rochester Medical Center, N.Y.

Rashid A. Buttar, DO, FAAPM, FACAM

igf 1 s seen in hgh injection tx
IGF-1 Δ’s Seen in hGH Injection Tx

Current Theory:

IGF-1 results from hepatic conversion of hGH. The more hGH injected into the body, the higher the IGF-1 levels accumulated. As the limited number of IGF receptor sites become saturated from the  hGH levels being injected (and being converted to IGF-1), IGF-1 serum levels start rising. Thus, assumption is  hGH =  IGF-1= Desired Result.

Problem with Theory:

IGF-1 is similar to Insulin &  insulin levels = Bad (cancer & heart dz.)

Our Postulate – Solution to Problem

IGF-1 receptor sites should never be saturated to the point where excess serum IGF-1 ’s. Trans-D very effectively ’s number of IGF receptor sites but does not allows IGF-1 levels to exceed physiological limits.

Rashid A. Buttar, DO, FAAPM, FACAM

possible reasons for igf 1 levels
Possible Reasons for  IGF-1 Levels

University of Washington, School of Medicine, Seattle, WA

…....“GH exerts its effects by binding to its own receptor sites as well as by stimulating the synthesis of IGF-1. The liver is the primary contributor to levels of IGF-1 in the systemic circulation. But IGF-1 is generated in many GH target tissues [and as a result], local effects may be more important than those of circulating IGF-1 of hepatic origin.”

Merriam GR, Kletke M, Barsness S, et al: GHRH in Normal Aging: An Update.Todays Therapeutic Trends

Rashid A. Buttar, DO, FAAPM, FACAM

normal growth in absence of igf 1
Normal Growth in Absence of IGF-1

Two separate studies show normal growth in mice in which hepatic IGF-1 synthesis was eliminated.

Yaker S, et al: Normal growth and development in the absence of hepatic IGF-1.Proc. Natl. Acad. Sci. USA 96:7324-7329, 1999.

Ohlsson C, Sjogren K, Jansson JO and Isaksson OG: The relative importance of endocrine versus autocrine/paracrine IGF-1 in the regulation of body growth.Pediatr. Nephrol. 14: 541-543, 2000.

Rashid A. Buttar, DO, FAAPM, FACAM

postulate for igf 1 levels
Postulate for  IGF-1 Levels

Possible reasons for the consistent drop in IGF-1 levels seen while using Trans-D Tropin®

  • Increase IGF-1 utilization leading to a decrease in free IGF-1 levels =  circulating serum IGF-1

2. IGF-1 receptor site up regulation leading to an  in IGF-1 binding =  circulating serum IGF-1

IGF-BP3 instead may be better for assessing efficacy of hGH treatments. Further research to validate is necessary.

Rashid A. Buttar, DO, FAAPM, FACAM

possible correlation clinically observed between stress and igf 1 levels
Possible correlation clinically observed between stress and IGF-1 levels:

Significant mental/emotional stress

(due to life style, vocational, situational factors)

Higher level of physical stress

(due to training/caloric restrictions as in athletes)

Severe pain, chronic depression, chronic dz’s

(due to immuno suppresion, adrenal exhaustion, late stages of cancer, etc.)

Rashid A. Buttar, DO, FAAPM, FACAM

trans d tropin igf 1 and cancer
Trans-D Tropin®, IGF-1 and Cancer
  • Kiaris, Schalty, Varga, et al, from Tulane University demonstrated GHRH inhibitors (opposite effect of Trans-D Tropin®) to suppress growth of various cancers, including small cell lung carcinoma.
  • Authors state clearly however, that NO studies have yet been able to show that GHRH stimulates the proliferation of cancer cells.
  • Mechanism cited by these authors for suppression of cancer cells was by reducing the levels of IGF’s, “which are known cancer-causing agents secreted by the liver and by tumors themselves.”
  • Mechanism of cancer suppression 2o to ing IGF levels per authors.

Rashid A. Buttar, DO, FAAPM, FACAM

igf 1 and cancer
IGF-1 and Cancer
  • IGF-1’s are known to stimulate cancer cell proliferation

Cohen, Pinchas, et al. Insulin-like growth factors (IGFs), IGF receptors, and IGF-binding proteins in primary cultures of prostate epithelial cells.Journal of Clinical Endocrinology and Metabolism, Vol. 73, No. 2, 1991, pp. 401-07

Rosenfeld, R.G., et al. Insulin-like growth factor binding proteins in neoplasia (meeting abstract).Hormones and Growth Factors in Development and Neoplasia, Fogarty International Conference, June 26-28, 1995, Bethesda, MD, 1995, p. 24

Lippman, Marc E. The development of biological therapies for breast cancer.Science, Vol. 259, January 29, 1993, pp. 631-32

Papa, Vincenzo, et al. Insulin-like growth factor-I receptors are overexpressed and predict a low risk in human breast cancer.Cancer Research, Vol. 53, 1993, pp. 3736-40

Rashid A. Buttar, DO, FAAPM, FACAM

igf 1 and cancer39
IGF-1 and Cancer

Chan, June M., et al. Plasma insulin-like growth factor I and prostate cancer risk: a prospective study. Science, Vol. 279, January 23, 1998, pp. 563-66

Stoll, B.A. Breast cancer: further metabolic-endocrine risk markers?British Journal of Cancer, Vol. 76, No. 12, 1997, pp. 1652-54

LeRoith, Derek, et al. The role of the insulin-like growth factor-I receptor in cancer.Annals New York Academy of Sciences, Vol. 766, September 7, 1995, pp. 402-08

Mantzoros, C.S., et al. Insulin-like growth factor 1 in relation to prostate cancer and benign prostatic hyperplasia. British Journal of Cancer, Vol. 76, No. 9, 1997, pp. 1115-18

Cascinu, S., et al. Inhibition of tumor cell kinetics and serum insulin growth factor I levels by octreotide in colorectal cancer patients. Gastroenterology, Vol. 113, September 1997, pp. 767-72

Rashid A. Buttar, DO, FAAPM, FACAM

trans d tropin igf 1 and cancer40
Trans-D Tropin®, IGF-1 and Cancer
  • If cancer suppression is 2o to  IGF levels as per authors, then use of synthetic, recombinant GH injection therapy (which reportedly ’s IGF levels) may be carcinogenic and potentially dangerous.
  • Studies have shown possible correlations between GH injection therapy and cancer proliferation.
  • Trans-D Tropin® (GHRH analog)’s IGF levels as demonstrated in 3 separate studies. Thus, conclusion is Trans-D Tropin® may be beneficial in cancer patients. Pending a trial with Cancer patients.
  • Clinical evidence supports conclusion. Trans-D Tropin® usage is helpful in anorexia, insomnia, pain, fatigue, malaise, ambulation.

Rashid A. Buttar, DO, FAAPM, FACAM

igf 1 and cancer41
IGF-1 and Cancer

Yu, Herbert and Rohan, Thomas. Role of Insulin-Like Growth Factor Family in Cancer Development and Progression. Journal of the National Cancer Institute, Vol. 92, No. 18, September 20, 2000, pp. 1472- 1489 …………..

“Laboratory studies have shown that IFGs exert strong mitogenic and antiapoptotic actions on various cancer cells…………….IGF’s also act synergistically with other mitogenic growth factors and steroids and antagonize the effect of antiproliferative molecules on cancer growth….……..The role of IGFs in cancer is supported by epidemiologic studies, which have found that high levels of circulating IGF-1 and low levels of IGFBP-3 are associated with increased risk of [many] cancers ….….IGFs are related to increased cell proliferation, suppression of apoptosis and increased cancer risk.”

Rashid A. Buttar, DO, FAAPM, FACAM

multi centered double blind placebo controlled cross over study
Multi Centered, Double Blind, Placebo Controlled, Cross Over Study

Preliminary Results of Multi-Centered,

Double Blind, Placebo Controlled, Cross-Over

Study Evaluating Endogenous hGH Levels with

Serial hGH Radio-Immunoassay Levels

After Trans-Dermal GH Releasing Hormone Analog

(Trans-D Tropin) Administration

Rashid Buttar, DO, James Biddle, MD, Rajiv Chandra,MD,

Terry Grossman, MD, Clarence Norris, MD, James Smith, DO, Annette Stoesser, MD, Dean Viktora, PhD

Rashid A. Buttar, DO, FAAPM, FACAM

multi centered double blind placebo controlled cross over study43
Multi Centered, Double Blind, Placebo Controlled, Cross Over Study
  • Requirements were very stringent:
    • To insure accuracy of study due to transitory nature of hGH.
    • To insure quality of study for establishing future protocols.
  • Patient Selection Criteria: Over 30 years old, non-gravid.
  • Placebo indistinguishable from Trans-D Tropin® (same carrier, consistency, smell, color, appearance, and bottle).
  • If study patient did not present as scheduled for blood draw, the patient was eliminated from the study.
  • Out of 46 centers, 25 separate study sites were selected.
    • 14 sites dropped out of study due to various reasons.
    • 4 sites eliminated due to not following study protocol.

Rashid A. Buttar, DO, FAAPM, FACAM

multi centered double blind placebo controlled cross over study44
Blood Draw Intervals

All study patients had blood drawn at Baseline.

Trans-D Tropin®/ placebo administered immediately after baseline blood draw.

All study patients had repeat blood draws at 30, 60 and 90 minutes after treatment administration.

Blood Analysis Schedule:

Control Group (on placebo)

Blood specimen analyzed at:

- 0 & 8 weeks

(2nd & 5th week blood specimens discarded)

Experimental Group

(on Trans-D Tropin®)

Blood specimen analyzed at:

- 0, 2, 5 & 8 weeks

Multi Centered, Double Blind, Placebo Controlled, Cross Over Study

Rashid A. Buttar, DO, FAAPM, FACAM

in endogenous hgh in 117 patients tested from baseline to 90 min after trans d tropin over 8 wks
% Δ in Endogenous hGH in 117 Patients Tested(Δ from Baseline to 90 Min. after Trans-D Tropin®Over 8 Wks)

Rashid A. Buttar, DO, FAAPM, FACAM

possible reasons for decrease in hgh levels during week 8 of trans d tropin study
Somatostatin Issues

Negative Inhibitory Feedback Loops become initiated……

Result is  in Somatostatin (hGH antagonist)…..

Result in decreased levels of endogenous hGH.

Pituitary Reserve Issues

Pituitary Gland holds hGH in store, releasing it in a pulsatile manner.

Due to effectiveness of Trans-D Tropin®, the pituitary reserves may become depleted and require time to replenish hGH stores.

Possible Reasons for Decrease in hGH Levels During Week # 8 of Trans-D Tropin® Study

Subjective improvements continue at 18 months post treatment initiation

Rashid A. Buttar, DO, FAAPM, FACAM

multi centered double blind placebo controlled cross over study47
Multi Centered, Double Blind, Placebo Controlled, Cross Over Study
  • 5 week increase in experimental group  1754 % but placebo was not drawn at 5 week interval.
  • Change in Endogenous hGH measured at 8 weeks:

Placebo group - 118.13%  in Endogenous hGH (attributed to life style modification, exercise, diet, etc.)

Experimental group - 609.04%  in Endogenous hGH (patients on Trans-D Tropin®)

  • All patients crossed over into experimental group at 8 weeks, subjectively followed for 8 more weeks

Rashid A. Buttar, DO, FAAPM, FACAM

response in serum cortisol levels
Response in Serum Cortisol Levels

Rashid A. Buttar, DO, FAAPM, FACAM

response in serum cortisol levels49
Response in Serum Cortisol Levels

Rashid A. Buttar, DO, FAAPM, FACAM

response in serum igf 1 levels50
Response in Serum IGF-1 Levels

Rashid A. Buttar, DO, FAAPM, FACAM

trans d tropin hgh injections
Trans-D Tropin® & hGH Injections

A study conducted by Roy Heerenveen, MD in the Dutch Antilles

(Cura’cao, Aruba, Saba, Bonaire and St. Maarten),

assessed concomitant hGH injection use with Trans-D Tropin® :

Pt’s treated with 2 iu hGH injectable q day experienced same objective changes as pt’s treated with 0.25 iu hGH injectable + 6 gtts Trans-D Tropin®

(0.25 iu hGH injectable q day) + (2 gtt Trans-D Tropin® tid) = 2 iu hGH q day

Conclusion based upon objective responses measured by

IGF-1, IGF-BP3, hGH radio-immunoassay and SMAC 26 results.

Synergism or does 1.75 iu hGH injection = 2 gtts Trans-D Tropin® tid?

Official recommendation: Do not use hGH injections with Trans-D Tropin®

Rashid A. Buttar, DO, FAAPM, FACAM

trans d tropin hgh injections52
Trans-D Tropin® & hGH Injections

Currently being studied at the

Life Extension Institute in the Dutch Antilles

and

University of Munich in Germany

Study conducted at these institutions is entitled

The Role of Trans-D Tropin® As An Adjunct To hGH Injections

And should be available within the next 12 months.

Rashid A. Buttar, DO, FAAPM, FACAM

residual effects responsivity
Residual Effects / Responsivity

Rene Martina MD, PhD and Arnold Segredo MD, PhD

conducted a study assessing residual effects of Trans D-Tropin®

Most people with idiopathic GH deficiency have an intact pituitary but one that does not release adequate GH. Trans D-Tropin® may be the answer in these cases.

Trans D-Tropin® acts directly on the pituitary to stimulate synthesis and release of GH, definitively increasing pituitary responsivity as demonstrated.

Trans-D Tropin® administered to 12 patients at 9am, noon, 3pm and 6pm. Residual effects were compared to 12 non-stimulated patients, monitored by hourly hGH radio-immunoassays drawn from 8pm to 8am next morning.

Rene Martina MD, PhD

Arnold Segredo MD, PhD

*Graphs reproduced by permission

Rashid A. Buttar, DO, FAAPM, FACAM

residual effects responsivity54
Non-Stimulated, Normal Physiology

Stimulated with Trans-D Tropin®

Residual Effects / Responsivity

Reproduced by permission from Dr. Martina and Dr. Segredo

Rashid A. Buttar, DO, FAAPM, FACAM

residual effects responsivity55
Residual Effects / Responsivity

Trans D-Tropin® works to stimulate the pituitary to restore the natural physiologic pulsatile release of endogenous GH and is the only physiologic choice to mimic the body's natural pattern of GH release.*

Rene Martina MD, PhD

Arnold Segredo MD, PhD

*Diagram reproduced by permission

Rashid A. Buttar, DO, FAAPM, FACAM

advantage of trans d tropin
Advantage of Trans-D Tropin®

Besides  endogenous GH, there is evidence that

Trans-D Tropin® also  receptor site activity:

1.) Either up-regulation of target tissue receptor sites or,

2.) Increase utilization of GH at local target tissue sites.

Evidence found during 24 hour urinary GH collection:

Urinary GH levels don’t measure total GH in body but rather,

indicate level of GH exceeding renal thresh hold.

(similar to glucose spilling over into urine of diabetic patients)

Rashid A. Buttar, DO, FAAPM, FACAM

evidence of receptor site up regulation
Evidence of Receptor Site Up-Regulation

Baseline to Wk 1:

All pts had a large drop in urinary GH representing an  in activity of receptor sites / up-regulation.

Wk 1 to Wk 3:

Despite receptor site activity ing, GH steadily ’s beyond baselines, showing  in GH production/release

Rashid A. Buttar, DO, FAAPM, FACAM

testing protocol for trans d tropin
Testing Protocol for Trans-D Tropin®

Safety goal is to rule out a hyper-functioning pituitary state or a salient pituitary tumor to prevent further stimulation.

- Obtain a serum/saliva IGF-1 or a prolactin level within 30 days.

- If level above 1 SD of normal, refer to endocrinologist to rule out pituitary adenoma and send for CT scan. STOP TX with TDT.

Medical goal is to establish objective proof that the hormonal balance is positively impacted in a physiological manner.

- If serum, measure hGH radio-immuno assays prior to TX (baseline) and again at 30, 60 and 90 minutes post TX.

- If urine, measure hGH 1 wk post TX and again at 3 wks post TX.

Consider CBC, Chem 21, Cortisol, C-reactive prot., IL-6, NFkB & hormonal profile

Rashid A. Buttar, DO, FAAPM, FACAM

use protocol for trans d tropin
Use Protocol for Trans-D Tropin®

Goal is to emulate natural physiology the way God designed:

Maintain natural physiological pulsatile release of hGH

Improve pituitary function instead of creating atrophy

Maintain natural physiological safety mechanisms (negative inhibitory feed back loops)

15 gtts – tid or 10-11 gtts – qid , 5 days on, 2 days off

(May want to cycle off every 6 to 8 weeks for 2 weeks)

Higher frequency, lower dose seems to get best response.

If patients do not see a response in 2 months, stop therapy.

Rashid A. Buttar, DO, FAAPM, FACAM

uniqueness of trans d tropin
Uniqueness of Trans-D Tropin®

Ingredients – Amino Acids and Fatty Acids

Uniqueness is NOT in constituents but rather, how those ingredients ARE COMBINED!

Technology utilized to manufacture Trans-D Tropin® as well as delivery mechanism utilized to administer Trans-D Tropin® are what allow for the unique efficacy of this transdermal GHRH analog.

Rashid A. Buttar, DO, FAAPM, FACAM

uniqueness of trans d tropin61
Uniqueness of Trans-D Tropin®

Best results obtained in patients who have been “optimized”, ie, GI dysbiosis resolved, liver detoxified, heavy metals removed, viral loads reduced, systemic candidiasis tx, etc.

You can only REBUILD a burning house…….

AFTER you’ve PUT OUT the FIRE!

Trans-D Tropin® efficacy  in smokers, with estrogen replacement therapy, as well as with anti-depressant and anxiolytic usage.

Rashid A. Buttar, DO, FAAPM, FACAM

anti aging therapy comparison
Anti-Aging Therapy Comparison

Rashid A. Buttar, DO, FAAPM, FACAM

trans d tropin
Trans-D Tropin®

The goal of therapy is

NOT ONLY to EXTEND LIFE,

But to

IMPROVE THE QUALITY

OF THATEXTENDED LIFE.

Rashid A. Buttar, DO, FAAPM, FACAM

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