INTRODUCTION TOENDOBIOGENY:AN INTEGRATIVEAPPROACH TOMEDICINEBy:Jean Claude Lapraz, MDKamyar M. Hedayat, MD
OBJECTIVES• Introduce Endobiogeny and its componentelements:• Detailed history• Detailed physical exam• Classical labs and imaging studies• Biology of Functions• Integrative assessment, then…• Therapeutic strategy• Example: application of the concepts ofEndobiogeny to the clinical condition ofPolycystic Ovarian Syndrome (PCOS)• Discuss opportunities to learn the Endobiogenicmethod
VIGNETTE• 23 year old female presents with 4 year history ofoligomenorrhea, hirsutism, acne, failure toconceive, 30 pounds weight gain.• Laboratory studies reveal low-normal TSH,normal T3, T4, estradiol, dihydro-testosterone,androstenedione, but elevated fasting bloodglucose.• Ultrasound of uterus, ovaries unremarkable• History suggests Polycystic Ovarian Disease, butendocrine, radiological studies are normal. Doesthis woman have an endocrine disorder or not?
INTRODUCTIONAn introduction to theEndobiogenic conceptA brief review of the historyof medicine and its schoolsof thought
ENDOBIOGENY• The integrative study of the functionalmechanisms of regulation of the organism in itsbasic structure during homeostasis as well as itsfunctional response to internal and externalstressors:• As a whole system• In its individual units of function• core metabolism• cell, tissue and organ• in and of themselves and in relationship to each other• Endobiogeny evaluates the qualitative andquantitative state of the human organism and itsinternal milieu.
EXAMPLE:QUANTITATIVE ASSESSMENT• Consider a car factory to be like the ovaries. Does thenumber of cars (amount of estrogen) produced tell you howefficiently the factory (ovaries) is functioning or how wellthe cars produced drive?• A quantitative assessment of productivity tells you howmany cars are being produced (serum estrogen levels), butnot how well those cars drive (endocrine and metabolicactivity of estrogen).• For example, if the output of cars meets demand, but thegear shifter is faulty (altered estrogen-receptor binding),each car carries fewer people than its normal capacity dueto decreased torque. In this case, more cars will be needed tocarry people.• “Normal” factory output for this company (body) isinsufficient to meet demand
EXAMPLE:QUALITATIVE ASSESSMENT• But what about a qualitative assessment? Theremay be supply issues—not enough steel available.The factory cannot produce cars without steel(cholesterol as a precursor to estrogen production)• Perhaps there are not enough workers on theassembly line (Follicle stimulating hormone) andthe workers present are over-worked and willsoon decline in productivity (pituitary stress).• Perhaps there are ample supplies and workers,but the manager is inefficient (hypothalamus) inmanaging the factory, not regulating supply anddemand issues.
EXAMPLE:QUALITATIVE ASSESSMENT• Perhaps the manager is efficient, but the workersdo not always follow his directives (alteredthresholds of responsiveness).• Thus, it is clear that both a quantitative andqualitative assessment of physiological andendocrine activity is necessary to properlyunderstand disease and health.
ENDOCRINE MANAGEMENT• Thus, Endobiogeny views the endocrine systemas the manager of the body, the controller ofanabolism and catabolism—which is what lifeitself is at every level from the cell to thestructure of the universe:• destruction and reconstruction• expansion and contraction• growth and apoptosis• birth and death
LEVELS OF MANAGEMENT IN THE BODYInternal terrainExternal TerrainNeuro-EndocrineCellreceptorsEnzymes,co-factors,vitaminsEndobiogenyStandardMedicineFunctionalMedicineEnvironmental MedicineMental-EmotionalMind-BodyToxins, Microbes, MetalsNeuro-transmitters
PHILOSOPHY• Endobiogeny integrates the rational and empiricalschools of medicine with philosophy to create asingle coherent system of medicine:• PHILOSOPHY: The Endobiogenic approachbegins with the ontology (reason for existence) ofstructures and physiology• This leads to a logical approach to understandingstructural weaknesses in the organism as well asdetermining the true cause of disease
RATIONALISM• The rational school of medicine has been thepredominant Western school of medicine:• Relies on deductive reasoning, anatomy andphysiology as the basis of its approach to illness.• Nosology: Patients are categorized by disease, anddiseases are categorized by symptoms• Medications are chosen based on biochemical orempirical effects on symptoms or physiological signssuch as blood pressure or laboratory measurements• Biomedicine (Allopathy) is the best-known form ofrational medicine• Modern herbalism has rationalist tendencies
RATIONALISM (CONT.)• Endobiogeny is based upon:• Modern physiology and contemporary understanding ofneuro-endocrinology• Consideration of role of genetic polymorphisms,environmental toxins, stress, cytokines, cells, organs,and their products of metabolism in the origins ofhealth and illness.• Consideration that the organism contains in itself afundamental auto-pathogenicity (potential for a specificdisorder) which implies a particular risk of disease.• Endobiogeny considers the mechanistic, reductionisticconcepts of life insufficient to explain the complexityof the human organism• Endobiogeny treats the person, not the disease, thusrejecting standardized treatment protocols
EMPIRICISM• Refers to a system of medicine where thepractitioner’s impression of illness andassessment of the individual’s expression ofdysfunction is the basis of treatment.• Empirical medicine considers the energetics ofthe individual as well as the energetics of thetreatment• Chinese medicine and Homeopathy are formsof empirical medicine.
EMPIRICISM (CONT.)• Endobiogeny shares an emphasis on detailed historyand careful physical exam to understand the uniquephysical and emotional antecedents of disease and itsphysiognomic expressions in the individual• However, Endobiogeny seeks to find coherence in thisinformation through physiological explanations• In sum, Endobiogeny is an integration that takes intoaccount various levels of the individual: physical,emotional and mental, in their relationship with theendocrine management of the body and everythingunder its control with its regulatory mechanisms
INTEGRATION OF DATA• Endobiogeny integrates:• History• Physical Exam• Laboratory data and imaging• To reach a conclusion regarding the current,dynamic physiological state of the individual inorder to formulate a treatment strategy whichaddresses:• the identified imbalances individually• as well as in their relationship to other imbalances
TREATMENT OPTIONS• Endobiogenic treatments consist of varioustherapeutic elements based on their safety andefficacy with no prejudice to the origin of thetreatment:• Phytotherapeutic elements• Homeopathic elements• Pharmaceuticals elements: reasoned usage based onseverity of symptoms, of degree or lack ofcompensatory physiology.• Physical manipulations: craniosacral, myofascial, etc.• Diet and Nutrition• Trace elements• Stress modification, hydrotherapy, acupuncture, etc.
INDIVIDUALIZED MEDICINE• Endobiogeny is individualized medicine based on:• The patient’s symptomization of illness within thecontext of the global functioning of the organism• The physician’s determination of the signs ofphysiological and endocrine dysfunction• The physician’s objective assessment of endocrinerelationships• The particular physical, physiological, psychologicaland emotional realities of the individual.
CONCLUSION• Endobiogenic treatment is determined by thetotality of the person:• Static and dynamic aspects of the patient’sconstitution• Etiology, ontology, and integration of symptoms• Adaptive and maladaptive aspects of physiology
PATIENT HISTORY• HISTORY: A detailed history of antecedentevents, including perinatal history, childhoodpersonality, illnesses, vaccinations and importantemotional events is solicited to establish theconstitutional and functional endocrine state ofthe patient.• Dietary preferences, sleep habits, dreams,menstrual history, various aspects of behaviorand review of systems are explored to establishneuro-endocrine patterns• The trajectory of structural hormonal imbalancesis followed throughout life, not just with respectto the outward manifestation of illness anddysfunction
PHYSICAL EXAM• A detailed physical exam from head to toeevaluates the phenotypic expression of neuro-endocrine relationships• Because the endocrine system manages both thestructural integrity of the body as well as itsfunctional expression, one is able to look for thephenotypic expressions of endocrine activity andcorrelate it with the internal state of the patient• Many of these findings are easily explained byclassical endocrinological assessment of hormonalactivity
LABORATORY STUDIES• Classical lab data is based on binary considerations:• disease vs. no disease• normal vs. abnormal value• The patient in our vignette presented with normallevels of all the relevant hormones. Can we concludethat these hormones are functioning normally, or eventhat their relative levels are appropriate?• Of course not. The history, symptoms and physicalexam suggest otherwise.• Thus, it is self-evident that binary considerationscannot be applied with any real assurance of itsfunctional relevance to a system as complex as thehuman body.
LABORATORY STUDIES• Biological systems are complex, multi-tiered,dynamic interrelated and integrated systemsYeast Protein Interaction NetworkBader and Hogue (2002) NatureIntegrated, inter-related system
INTEGRATED SYSTEMS• Objective quantitative data (laboratory values)are required to assess the organism• However, one must be able to provide functionaldescriptions of quantitative and qualitativeactivity both within a particular unit of activity,from one unit to another, as well as within thesystem as a whole• Only then can a truly dynamic andindividualized assessment of the patient occur
LABORATORY STUDIES• The endocrine system, as the manager of themetabolic activity of the body, is the idealobject of evaluation.• Serum levels of hormones reflect neither thedegree of stimulation needed nor themetabolic costs incurred in producing aparticular hormone.1) Raison CL, Miller AH. When not enough is too much: the role of insufficientglucocorticoid signaling in the pathophysiology of stress-related disorders. Am JPsychiatry. Sep 2003;160(9):1554-15652) Chiam K, Tilley WD, Butler LM, Bianco-Miotto T. The dynamic and staticmodification of the epigenome by hormones: A role in the developmental originof hormone related cancers. Biochem Biophys Acta. Apr 2009;1795(2):104-109.3) Gerhard I, Waibel S, Daniel V, Runnebaum B. Impact of heavy metals onhormonal and immunological factors in women with repeated miscarriages.Hum Reprod Update. May-Jun 1998;4(3):301-309.
LABORATORY STUDIES• Serum levels of hormones only reflect quantitativeorgan output, not functional activity, which can beaffected by:• Hormone receptor binding (affected by over- or under-expression of other hormones)1• Intracellular messenger activity1• Epigenetic changes2• Heavy metal toxicity3, etc.1) Raison CL, Miller AH. When not enough is too much: the role of insufficientglucocorticoid signaling in the pathophysiology of stress-related disorders. AmJ Psychiatry. Sep 2003;160(9):1554-1565 Chiam K, Tilley WD, Butler LM, Bianco-Miotto T. The dynamic and staticmodification of the epigenome by hormones: A role in the developmental originof hormone related cancers. Biochem Biophys Acta. Apr 2009;1795(2):104-109. Gerhard I, Waibel S, Daniel V, Runnebaum B. Impact of heavy metals onhormonal and immunological factors in women with repeated miscarriages.Hum Reprod Update. May-Jun 1998;4(3):301-309
LABORATORY STUDIES• The ideal system of measurement of biologicalprocesses thus should examine the metabolicproducts of hormonal management of cellularactivity• Thus, the ideal laboratory system must• Reflect the complex, integrated and dynamic natureof biological systems• Describe the functionality of the system in its• Qualitative function• Quantitative function• Individual unit, relative to other units and as a whole• Assess the organism at the metabolic and interstitiallevel
BIOLOGY OF FUNCTIONS• The Biology of Functions (BoF) quantifies functionalabilities of the organism, before and after the effects ofadaptation to stressors. Because functionality isdynamic, a dynamic, integrated and evolutionarymethodology must be used instead of static lab values• BoF is based on a number of specific indices defined bymathematical relations between commonly used bloodanalysis data• The algorithms that permit the calculation of theseindices are based on the physiological relations thatexist between the direct or indirect products ofhormonal activity: cells, hormones or enzymes(eosinophils, TSH and LDH, for example).
BIOLOGY OF FUNCTIONS• These relations allow one to visualize thefunctioning of the organism at every level:maintenance of homeostasis, adaptation, recoveryafter aggression, immunity, etc.• Each function is quantified by an index, specifiedby a level of activity. The index expresses theactual activity of that function, both in and ofitself and in relation to the metabolic and tissueneeds of the organism.• The whole set of indices gives an evolutionaryassessment of an individual body’s functionality,system by system, organ by organ.
BIOLOGY OF FUNCTIONS• SUMMARY: Biology of Functions:• Allows one to determine:• Pathogenic tendencies of the organism• The stage of development and the degree ofseverity of a potential pathology (i.e. cancer,cardiac disease, degenerative neurologicaldisease)• Can be used as a tool to track• the natural development of pathology• To derive a rational therapeutic treatment• To evaluate the efficacy of the treatmentover time
BEYOND BINARY RELATIONSHIPS• PCOS is a good example of how allopathicmedicine is beginning to realize the importance ofthe qualitative relationship of hormones ratherthan quantitative ones in and of themselves. Thefollowing ratios have been found to be helpful indiagnosing PCOS:• Estradiol to Dihydro-testosterone ratio (Endocr Regul.2008 Mar;42(1):13-6)• Glucose to Insulin ratio <4.5 (Endocrinol Metab ClinNorth Am. 1999 Jun; 28(2):397-408, vii.)• LH to FSH ratio >3 (Endocrinol Metab Clin North Am.1997 Dec; 26(4):893-912.)
WHERE TO PROCEED?• Despite a growing recognition that the binary nature oflaboratory evaluations in not sufficient to understand thespectrum of disease expression, Allopathic medicine lacksan integrated assessment of ontology, etiology andtreatment of physiological derangements• Case in point: Standard of care for PCOS is to treat eachendocrino-metabolic derangement separately from eachother without considering their inter-relationship• There is no explanation for why only 50% of PCOS patientsare obese or why serum hormone levels may be normaldespite physical exam findings suggesting otherwise, or whypolycystic ovaries are not a sine qua non of PCOS
REDUCTIONISTIC TREATMENTPLAN• The allopathic treatment of PCOS consists of apiecemeal approach to inhibiting individualhormones with no concern for how it may affectthe global functioning of the organism in itsanabolic and catabolic activity• Hirsutism: spironolactone , oral contraceptives 1• Menstrual irregularities: Oral contraceptives ,metformin,pioglitazone, spironolactone• Hyperglycemia, Hyperinsulinemia: Metformin;pioglitazone• Infertility: clomiphene, letrozol, metformin,pioglitazone1. Drug treatments for polycystic ovary syndrome.Radosh L . American Family Physician, April 15,2009
ENDOBIOGENIC APPROACH• The Endobiogenic approach considers theontological role of all these endocrino-metabolicand tissular derangements as being linked to thebody’s management of a fundamental structuralor functional problem• Prolactin can be elevated during chronic stress• Hyperestrogenism is often an attempt toovercome Prolactin’s suppression of LH secretionof progesterone for ovulation
ENDOBIOGENIC APPROACH• Hyperandrogenism: caused by DHEA from the adrenal gland,which is over-stimulated due to the stress state, and bytestosterone from the ovaries due to LH excess, insulin excess,and/or increased theca cell enzyme activity.1• Hypercholesterolemia with low HDL cholesterol: Cholesterol isthe source of all sex hormones and corticosteroids, which areneeded to make more and more testosterone, estrogen andprogesterone. HDL removes cholesterol from tissues whichwould be counterproductive to the demand of the tissues formore cholesterol.• Hyperglycemia and hyperinsulinism reflect an attempt tomeet the huge anabolic demands of the body with anappropriate amount of short term energy substrate1. The biochemical basis for increased testosterone production in theca cells propagated from patients with polycystic ovarysyndrome2. Nelson VL, Qin KN, Rosenfield RL, Wood JR, Penning TM, Legro RS, Strauss JF 3rd, McAllister JM. J Clin Endocrinol Metab.2001 Dec;86(12):5925-33.
BIOLOGY OF FUNCTIONS (BOF)• Endobiogenic approach to PCOS involvesunderstanding the totality of endocrinologic,neurologic and metabolic disturbances in relationshipto each other.• A few examples of the 157 indices of the biology offunctions are discussed as relevant to PCOS• When interpreting the BoF, the endocrine system isunderstood in its• classical vertical activity (i.e. CRHACTH Cortisol),• horizontal activity (i.e. Dopamine CRH TRHProlactin), and• radial activity (i.e. TRH Prolactin Insulin; Estrogen+ Cortisol Luteinizing Hormone)
CATEGORIES OF BOF• Hypothalamic and pituitary level assessment ofresponsiveness to stimulation and feedback:• β-MSH/α-MSH• FSH #1 index• LH #1 index• Index of Estrogen-Somatotropic axis:
BIOLOGY OF FUNCTIONS• Role of Adrenals vs. Gonads in producingandrogens (Androgenic index)• Efficiency of FSH and LH in producing estrogensand androgens, respectively (Gonadotropicindex)• Anabolic activity of estrogen (Quantativeorgano-tissular estrogen yield index)• Progesterone activity (Progesterone index)
BIOLOGY OF FUNCTIONS• The role of the Hypothalamic-Pituitary-Adrenalaxis can be examined in various ways tounderstand the role of each endocrine gland inadaptive and maladaptive responses to stress• Circulating Cortisol Index• Aromatization of Estrogen Index• Adrenal cortex index
BIOLOGY OF FUNCTIONS• Role of the Somatotropic axis in generaladaptation, maladaptation, and metabolicderangements can also be examined:• Prolactin index• Insulin index• Insulin resistance index• Growth Hormone (GH) growth score• Somatostatin index
BIOLOGY OF FUNCTIONS• Psychological factors contributing to stress canalso be quantified• Global mental activity: Ketonic index• Internal dialogue: Adaptogenic index• Emotional etiology of stress response: Thyroidrelaunching index adjusted
CLINICAL PHYTOTHERAPY• Endobiogeny has developed a rational system ofclinical phytotherapy based on clinical studies,empirical observations and traditional herbalism• Elevated Prolactin: Strawberry leaf (Fragariavesca) mother tincture reduces pituitary andadrenal stress response through reduction ofACTH, TSH and Prolactin and aromatization ofAdrenal androgens to estrogen• Elevated Androgens-Estrogen ratio: hops(Humulus lupulus) has estrogenic activity andinhibits LH, reducing total gonadal androgens11) Milligan SR, Kalita JC, Pocock V, et al. The endocrine activities of 8-prenylnaringenin and related hop (Humulus lupulus L.) flavonoids. J ClinEndocrinol Metab. Dec 2000;85(12):4912-4915.
CLINICAL PHYTOTHERAPY• Clinical phytotherapy (cont.)• Estrogen activity: Chaste tree (Vitex agnus castus)is highly efficacious in its ability to alter receptorsensitivity to estrogen and modulate prolactin activityallowing for increased progesterone activity, restoringprospects for fertility1,2• Insulin Resistance: Wolfberry (Lycium barbarum)as a fluid extract or bulk herb reduces insulinresistance3 Liu J, Burdette JE, Sun Y, et al. Isolation of linoleic acid as an estrogenic compoundfrom the fruits of Vitex agnus-castus L. (chaste-berry). Phytomedicine. Jan2004;11(1):18-23.; Loch EG, Selle H, Boblitz N. Treatment of premenstrual syndrome with aphytopharmaceutical formulation containing Vitex agnus castus. J Womens HealthGend Based Med. Apr 2000;9(3):315-320. Zhao R, Li Q, Xiao B. Effect of Lycium barbarum polysaccharide on the improvementof insulin resistance in NIDDM rats. Yakugaku Zasshi. Dec 2005;125(12):981-988.
OTHER TREATMENTS• Nutritional support• Omegas 3 and 6 (cell wall stability, decreasedinflammation, improved gonadotropic activity1)• Magnesium and Calcium (noradrenaline, acetylcholineproduction, activity and recycling)• B complex (management of stress)• Diet: low in inflammatory foods such as refined floursand sugar to reduce insulin secretion and insulinresistance, androgen activity2• Stress relief: cognitive behavioral therapy,meditation, yoga, massage therapy, acupuncture• 1) Sidani M, Campbell J. Gynecology: select topics. Prim Care. Jun2002;29(2):297-321, vi; 2) Smith R, Mann N, Makelainen H, Roper J,Braue A, Varigos G. A pilot study to determine the short-term effects of alow glycemic load diet on hormonal markers of acne: a nonrandomized,parallel, controlled feeding trial. Mol Nutr Food Res. Jun 2008;52(6):718-726.
CONCLUSIONS• Endobiogeny is the study of the internal milieu of theorganism within itself and in its relationship with itsenvironment, stressors, etc. from the standpoint of theendocrine system as the manager of human life• It combines in an integrative understanding:• a philosophical consideration of the ontology of structuresand functions of the body,• a rational approach to understanding physiology• an empirical assessment of history and symptoms• utilization of a dynamic, integrative and integratedmetabolic assessment of endocrine management of theorganism called the “Biology of Functions”• an integrated assessment of all clinical data to obtain aprecise understanding of maladaptive physiology• In order to create a rational, individualized treatment plan
CONCLUSIONS• The Biology of Functions is an algorithmicassessment of the qualitative and quantitativerelationships of hormones in terms of metabolicactivity from nuclear, cellular, tissue, organ andsystem-wide perspectives• The Biology of Functions allows for an objective,longitudinal assessment of the effects of therapy overtime• Endobiogeny relies on phytotherapy, oligotherapy,and diet as well as lifestyle modification as itspreferred methods of ameliorating physiologicalimbalances• It reserves the use of synthetic drugs for urgent cases,or when the body is not able to establish anequilibrium by the effects of functional regulation
RESOURCES• To learn more about Endobiogeny:• Web:• Genearal information:• www.endobiogeny.com• Biology of Functions demonstration:• http://extranet.endobiogenics.com/en/
CONTACT• Kamyar M. Hedayat, MD, President, American Societyfor Endobiogenic Medicine and Integrative Physiology• Contact: firstname.lastname@example.org• Web: www.endobiogeny.com