Growth hormone deficiency

A new paradigm for hormone replacement therapy (HRT) is that healthy aging represents balanced signaling within the neuroimmuno-endocrine system. That means for every hormone signal there is a balanced response by another hormone signal. An overly simplistic view states that HRT corrects a measurable deficiency and prevents well known, age-related disturbances such as heart disease, hypertension, liver disease, bone fragility, obesity, diabetes, cancer and excess body fluid retention. Naturopaths all too frequently use the same thinking model except they replace prescription only hormones with 'natural phytoestrogens.' It is time to re-think our logic and return to "Less is more" and "Do no harm." There is an increasing literature that supports the notion that it is the imbalances in hormone signaling that heighten the risk of cancer and toxicity. (1-3)

Conventional medical thought recommends that a person replace by injection an equivalent level or higher, of a specific hormone as when they were 20 or thirty years old to prevent the development of longer-term deficiencies. The first clue as to the overly simplistic perspective of HRT is that higher than physiological levels of exogenous hormone are often necessary. Higher levels are needed to provide biologically active hormone in sufficient bio-available quantities to induce a physiological response after passing through the liver which in turn metabolizes most of it. Exogenous hormones frequently fall to reach their target organ in a bio-available form. Small hormone metabolites fail to elicit desired effects. Furthermore, tissue responsiveness declines with age, making higher hormone levels necessary to overcome tissue resistance.

Typically, HRT involves multiple hormones such as growth hormone, thyroid hormones, cortisol, testosterone, estrogen, and progestin. One of the inducements in HRT is that it only involves one hormone, however within a short time other HRT regimes can become necessary. Hormones have counter-regulatory signals to maintain homeostasis, thus unopposed hormonal signaling leads to further complex problems. For example, unopposed estrogen therapy strongly correlates to endometrial cancer risk. (4) Cycling progestin with estrogen reduces this risk when it is used for at least 14 days per cycle. Interesting, a combined HRT approach of estrogen-progestin without cycling is associated with higher risk of breast cancer as compared to unopposed estrogen therapy. Practitioners may easily begin HRT in their patients, however it becomes increasingly difficult to manage and involves increased health risks and side effects with aging. The more hormones involved the more difficult to manage patient care. One fundamental Princi ple of Pharmacology is that a drug (hormone) affects the body and the body responds with beneficial and/or adverse events. The more hormones administered exogenously, the more reactivity in the body that needs to be managed.

Conventional Toxicity, Patient Compliance and Cancer Risks

The complexity of hormone therapy cannot be denied. Unbalanced hormone networks heighten cancer risk (5) and yet the side effects and risks from HRT are numerous. Side effects and cancer risks arise from aberrant hormone levels such that an imbalance becomes distorted in either direction. Side effects from HRT include breast, ovarian and endomentrial cancers, gallbladder disease, thrombo-embolism, edema, nausea, fevers, tenderness, headaches, bloating, unwanted cyclical bleeding and inflammation. (6,7) The liver extensively metabolizes blood-circulating hormones making them far less bio-available. Adverse side effects are predicted from inflammatory processes. Hormones that are not trapped by the liver during their first pass cause inflammatory immune responses when partially enzyme-digested hormonal subspecies circulate a second time in the bloodstream. Due to increased liver toxicity with aging side effects from HRT predictably increase with age. The more hormone, the greater the risk of liver burden and i nflammatory eliciting responses.

Compliance with HRT is also a huge problem. In a study in Hong Kong, 29% of women were non-compliant with long term HRT, giving as primary reason experiences of side effects and fear of cancer. (8) Breast cancer is moderately elevated in current and recent HRT users, increasing 2.3% per year with longer term BET. (4) Recent data suggest that an estrogen only replacement increases endometrial cancer risk and is only appropriate for hysterectomized women. (9) HRT has been inversely related to colorectal cancer. (10) One good example is that long term steroid therapy causes protein wasting, increasing the urea cycle liver enzymes. (11) This toxic effect was normalized after co-administration of hGH and insulin-like growth factor-1 (IGF-I).

Naturopaths frequently use the same paradigm of HRT cloaked in a 'natural phytoestrogen base.' Phytoestrogens are structurally and functionally similar to estradiol, yet there are questions as to bioequivalence. While changes in diet and use of phytoestrogens have much favor there is controversy over which food groups are healthy or which specific types, like genistein and enterolactone, provide the benefits. Phytoestrogens frequently have high levels of phytic acid that reduce assimilation of minerals and can contribute to "brain aging" ailments. (12) Phytoestrogens use the same receptors as estrogens, however the bio-availability is different due to other contents of the food, like phytic acid, which bind minerals and, make the bio-activity poorly characterized. Considerable research is needed for better understanding of cellular responses to foods.

Healthy Aging with Homeopathic Cell to Cell Communication

Part of the aging process involves a progressive loss of regulation over cell-to-cell signaling within the neuroimmuno-endocrine system. (13) It may be more logical to strengthen cell signaling within the neuroimmuno-endocrine system rather than try to replace complex hormones. Instead of using high concentrations of prescription-only hormones or phytoestrogens with aging people, homeopathy strives to bring the body into homeostasis gently and steadily. The body is designed for self-regulatory processes and it makes more sense that practitioners and researchers focus on healthy aging within the confines of the patient's own self-regulatory processes. The best of the two worlds of HRT may be to use easily accessed pure bio-available signals in non-toxic, easy-to-use oral and homeopathic forms. Homeopathy assures safety and continual support of the body's natural processes.

Human growth hormone (hGH) and insulin-like growth factor-1 (IGF-l) are well recognized for their significance during the aging process. (14) The dual role of hGH and IGF-1 as hormones and as growth factors may underlie their signaling significance during the physical, mental aging process. The neuroimmuno-endocrine system uses the common language of hGH and IGF-1 to regulate many activities. Additionally, HGH and IGF-1 regulate each other and both have regulatory controls over the cell cycle. Both hGH and IGF-1 decline during aging. (15) Loss of control over the hGH/IGF-1 feedback decreases adaptation to internal and external environmental stress factors decreasing the odds of survival. Unbalanced feedback loops and abnormal signaling between hGH and IGF-1 are found in cancer patients. (16)

Homeopathic hGH was clinically proven in short term, randomized and double-blinded studies to benefit physical and physiological areas that are known to decline with aging. (17) The symptoms that improved in the randomized, double-blinded studies match the organs that decline with aging. Study participants decreased fat, aches and pains, headaches, anxiety, anger, edema, coughing, and shortness of breath while increasing lean mass, energy; sleep quality, skin moisture, and improved physical appearance. Longer-term studies are needed in comparison to HRT benefits. The most interesting finding of these oral homeopathic hGH studies was that lean mass increased over that measured with injectable hGH. (18-20) Thus, less concentration in an oral homeopathic hGH yielded stronger physical, hormone related responses compared to a pharmacological injectable delivery. The cause of this may be due to improved tissue sensitivity and improved cell to cell signaling g of a homeopathic delivery method.

Homeopathic IGF-1 also demonstrated in clinical studies powerful effects on balancing blood glucose and also improving mental and metabolic functions. (21) In the bo y, IGF-1 works as a multi-purposeful signaling growth factor enhancing cell to cell communication, thus harmonizing the neuroimmuno-endocrine systems. (22) IGF-1 signals orchestrate health in muscles, growth hormone levels, reproductive organs, skin, brain, nervous sys m, and metabolism. IGF-1 also regulates normal cell growth, den h and differentiation (specialization) with major influence on cell cycle events related to DNA synthesis. IGF-1 signals profoundly affect mental and physical capacities. (23) Since IGF-1 and hGH never need enter the cell in order to evoke a response, even a homeopathic signal can lead to huge physical and mental changes. High affinity cell receptors can activate signal transduction pathways via G-proteins just as occurs with electro-magnetic stimulus. (24)

In summary, natural health practitioners face an increasing population of aging clients, yet the simple HRT method of last century requires reevaluation due to complex feedback loops, side effects and cancer risks. The naturopathic approach of using phytoestrogens is more of the same logic of 'replacement' yet may not have bioequivalence and may disturb an individual's inner regulatory control processes. Homeopaths recognize that a drug is ideal for homeopathic delivery when it evokes positive and negative (biphasic) responses at various concentrations such as the case with hormones and phytoestrogens. Healthy aging results with the proper signaling between cells, especially along the hGH-IGF-1 endocrine axis. Homeopathic rhGH and IGF-1 may be the only logical and safe methods for supporting cell-to-cell communication and regulatory processes. Signaling support using homeopathic hGH and IGF-1 may go a long way in preventing the common problems of aging. Further research will be required to determine the valu e of the hGH-IGF-1 axis with regard to the sex steroids. Early clinical evidence suggests that balance in the hGH-IGF1 axis will sustain healthy aging. (17, 21)

References

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(2.) Lee SH, Kim SO, Kwon WS, Chung BC. Androgen imbalance in premenopausal women with benign breaot disease and breast cancer. Clin. Biochem. 1999; 32:375-380

(3.) Nilsson R. Endocrine modulators in the feed chain and environment. Tbxicol. Pathol 2000; 28:420-431

(4.) La veccbia C, brinten LA, MoTiernan A. Menopause, hormone replacement therapy and cancer. Maturitas 2001 39:97-115

(5.) Lee SH, Kim SO, Kwen SW, Chung BC. Androgen imbalance in premenopausal women with benign breast disease and breast cancer. Clin Biochem 1999; 32:375-380

(6.) Gambacciani M, Genazzani AR. Hormone replacement therapy: The benefits in tailoring the regimen and dose. Maturitas 2001; 40:195-201

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(8.) Leung, TN, Haines CJ, Chung TK Fiver-year compliance with hormone replacement therapy in pestmenopausal Chinese women in Hong Kong. Maturitas 2001 39:195.201

(9.) Genazzaani AK, Gadducci A, Gambacciani M. Controversial issues in climacteric medicine II. Hormone replacement therapy and cancer. Intl. Menopause Sec. Expert Workshop 9-12 June 2001, Opera del Duomo, Pies Italy, Climacteric 2001 4:181-193

(10.) La Vecchia C, Brinton LA, McTiernan A. Menopause, hormone replacement therapy and cancer. Maturitas 2001; 39:97-115.

(11.) Grofte T, Jensen DS, Greioen J, Tygstrup N, Vilstrup H. Growth hormone and insulin-like growth factor-I counteracte established steroid catabolism in rats by effects on hepatic amino-N degradation. J Hepatol 2001 35:700-706

(12.) Fallon S. More on Soy. The Washington Times, 1999; Dec 24

(13.) Semsei, I. On the nature of aging. Mech. Aging Dev. 2000 117(1-3):93-108

(14.) Ghigo E, Arvat E, Gianotti L, Ramunni J, DiVito L, Maccagne B, Grottoli S, Camanni F. Human aging and the GH-IGF-1, axis. J. Pediatr Endocrinol Metab 1996; 9 (Suppl 3):271-280

(15.) Rudman D. Growth hormone, body composition and aging. J Am Ger Soc 1985; 33:800-807.

(16.) Urdl W. Pelycyotic ovarian disease: endecrinelogical parameters with specific reference to growth hormone and somatomedin-C. Arch Gynecol Obstet 1988; 243:13-36

(17.) Brewitt B, Hughes J, Welsh EA, Jackson R. Homeepothic human growth hormone for physiologic and psychologic health. Altern. Compl.Ther. 1999; 6:373-385

(18.) Cuttica CM, Casteldi L, Gorrini GP, Peluffo F, Delitala G, Phillippa P, Fanciulli G, Giusti M. Effects of six-month administration of recombinant human growth hormone to healthy elderly subjects. Aging Clin. Exp. Res. 1997; 9:193-197

(19.) Toogood AA, Shalet SM Growth hormone replacement therapy in the elderly with hypothalamic pituitary disease: A dose-finding study. J. Clin. Endorinol. Metab. 1999; 94:131-136

(20.) Bramnert M, Bernterp E, Groop L., Manhem P. Effects of growth hormone replacement therapy on bleed pressure regulation and coagulation factors. Endocrinol. Metab. 1994; 1 (Suppl A):A57

(21.) Brewitt B. Homeopathic growth fetters: Understanding Like Cures Like from the scientific and medical literature. Altern. Ther. 1997; 3:92-93

(22.) Liu Tj. Lai Hc, Wu W, Chinn S, Wang PH. Developing a strategy to define the effects of insulin-like growth fetter-1 on gene expression profile in cardiomyocytes. Circ Res 2001 88:1231-1238

(23.) Kalmijn S, Janssen JA, Polo HA, Lamberts SW, Breteler MM.; A prospective study on circulating insulin-like growth factor I (IGF-I), IGF-binding proteins, and cognitive function in the elderly. J Clin Endocrinol Metab 2000; 85:4551-4555

(24.) Brewitt B Bioelectromagnetic medicine and HIV/AIDS treatment: Clinical data and hypotheses for mechanism of action. In AIDS and Complementary & Alternative Medicine: Current Science and Practice. Eds. LJ Standish, C Calabrese, ML Galantino, Churchill Livingstone, Philadelphia; PA 2002

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