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ENDOCRINE FUNCTION AND ENDOCRINE FUNCTION AND OPIATE THERAPYOPIATE THERAPY
Focus on Gonadal HormonesFocus on Gonadal Hormones
Harvey S. Bartnof, M.D.Harvey S. Bartnof, M.D.Founder and Medical DirectorFounder and Medical Director
California Longevity and Vitality Medical InstituteCalifornia Longevity and Vitality Medical Institute, , San FranciscoSan Francisco
Visiting Professor of Medicine, Visiting Professor of Medicine, Liaoning Medical College and Shenyang Medical College, Liaoning Medical College and Shenyang Medical College,
PeoplesPeoples Republic of ChinaRepublic of China
PAIN AND ADDICTION WORKSHOPPAIN AND ADDICTION WORKSHOPOctober 7, 2009October 7, 2009--San FranciscoSan Francisco
FINANCIAL DISCLOSUREFINANCIAL DISCLOSURE
Proprietor, California Longevity and Vitality Proprietor, California Longevity and Vitality Medical InstituteMedical Institute
[email protected]@DrBartnof.com 415415--986986--13001300
www.LongevityMD.netwww.LongevityMD.net
mailto:[email protected]
ENDOCRINE FUNCTION AND ENDOCRINE FUNCTION AND OPIATE THERAPYOPIATE THERAPY
OutlineOutline
Hormone declines (Hormone declines (pausespauses) with aging) with aging Hormone declines & morbidity/mortalityHormone declines & morbidity/mortality Sex hormone changes, libido, erectile Sex hormone changes, libido, erectile function, menstrual changesfunction, menstrual changes Heroin, Methadone, BuprenorphineHeroin, Methadone, Buprenorphine
Bone Density changes and opiatesBone Density changes and opiates ProlactinProlactin Testosterone Treatment (men) Testosterone Treatment (men)
LONGEVITYLONGEVITYHumanHuman
Americans Are Living Americans Are Living Longer, But Not Longer, But Not Necessarily HealthierNecessarily Healthier
Elliott VS, Elliott VS, American Medical News, American Medical News, Oct. 27, 2003. Oct. 27, 2003. http://www.amahttp://www.ama--assn.org/amednews/2003/10/27/hll11027.htmassn.org/amednews/2003/10/27/hll11027.htm
ASCENT OF HUMANS
United States: 1/3 Obese (Body Mass Index > 30 kg/m2); 1/3 Overweight (BMI 25-29.9)
US Department of Health and Human Services, Centers for Disease Control and Prevention, 2006
GONADAL HORMONE GONADAL HORMONE REGULATIONREGULATION
HORMONES DECLINEHORMONES DECLINEWITH AGINGWITH AGING--MenMen
Lamberts SW et al. The endocrinology of aging. Science. 1997
N=131 N=233
N=114 N=163
Free Testosterone Index
DHEA-S
IGF-I
DHEA-S= dehydroepiandrosterone-sulfate
IGF-1= insulin-like growth factor-1 or somatomedin)
HORMONES DECLINEHORMONES DECLINEWITH AGINGWITH AGING--WomenWomen
Lamberts SW et al. The endocrinology of aging. Science. 1997 Oct 17;278(5337):419-24.
N=131 N=233
N=114 N=163
Levels of Estradiol (and Progesterone) Are Low in Menopause
IGF-1(somatomedin; insulin-like growth factor-1)
DHEA-S(dehydroepiandrosterone-sulfate)
Estrogens
MENOPAUSE SYMPTOMSMENOPAUSE SYMPTOMS
Hot FlashesHot Flashes Excess SweatsExcess Sweats InsomniaInsomnia HeadacheHeadache DepressionDepression Other: Irritability, Lack of Concentration, Other: Irritability, Lack of Concentration,
Nervousness, Dizziness, Joint Pain, TremorNervousness, Dizziness, Joint Pain, Tremor
Kupperman HS, Contemporary therapy of the menopausal syndrome. JAMA 1959.
FEMALE MENOPAUSEFEMALE MENOPAUSEBenefits of BioBenefits of Bio--Identical Hormone Identical Hormone ReplacementReplacementLIFE EXPECTANCY LIFE EXPECTANCY BRAINBRAINcognition, memory, mood, libido cognition, memory, mood, libido HEART, BLOOD VESSELS HEART, BLOOD VESSELS BONE BONE (including teeth)(including teeth)WAIST CIRCUMFERENCEWAIST CIRCUMFERENCESKIN, HAIRSKIN, HAIRBREASTBREASTUTERUSUTERUS--VAGINAVAGINA--BLADDERBLADDERMUSCLEMUSCLE--ADIPOSE (FAT)ADIPOSE (FAT)
TESTOSTERONETESTOSTERONELife ExpectancyLife Expectancy--EPICEPIC
Khaw, K.-T. et al. Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) Prospective Population Study. Circulation 2007.
Multivariate-adjusted P
ANDROPAUSEANDROPAUSESymptomsSymptoms && SignsSigns
PHYSICALPHYSICAL--METABOLICMETABOLIC
PSYCHOLOGICALPSYCHOLOGICAL SEXUALSEXUAL
muscle mass & muscle mass & strengthstrength
Depressed moodDepressed mood LibidoLibido
bone mineral bone mineral densitydensity
Diminished energy, sense Diminished energy, sense of vitality, wellof vitality, well--beingbeing
Erectile Erectile dysfunctiondysfunction
GynecomastiaGynecomastia Impaired cognition, Impaired cognition, memorymemory
spontaneous spontaneous erectionserections
Body Fat or Body Body Fat or Body Mass IndexMass Index
intensity of intensity of orgasmorgasm
FatigueFatigue
AnemiaAnemia
FrailtyFrailty
BhasinBhasin S. Endocrine Society Clinical Practice Guideline, S. Endocrine Society Clinical Practice Guideline, J J ClinClin EndocrinolEndocrinol MetabMetab 2006; Am. Assoc. 2006; Am. Assoc. ClinClin. Endo. . Endo. Hypogonadism Task Force, Hypogonadism Task Force, EndocrEndocr PractPract. . 2002; 2002; Amer. Urol. Assn. 2002 in Rhoden E et al. N Engl J Med 2004.
LOW TESTOSTERONELOW TESTOSTERONEBy AgeBy Age--MenMen
Rhoden EL et al. Risks of testosterone-replacement therapy and recommendations for monitoring. New England Journal of Medicine 2004 January.
ANDROPAUSE ANDROPAUSE Testosterone: Potential BenefitsTestosterone: Potential Benefits
BRAINBRAIN--cognition, mood, libido cognition, mood, libido HEART HEART BLOOD VESSELSBLOOD VESSELSBONEBONEMUSCLEMUSCLE--ADIPOSEADIPOSEWAIST CIRCUMFERENCEWAIST CIRCUMFERENCESKINSKINDIABETES, METABOLIC SYNDROMEDIABETES, METABOLIC SYNDROMETRIGLYCERIDESTRIGLYCERIDESERECTILE FUNCTIONERECTILE FUNCTIONPROSTATEPROSTATE-- neutral (neutral (rule out baselinerule out baseline carcinomacarcinoma))LIFE EXPECTANCYLIFE EXPECTANCY
GONADAL FUNCTIONGONADAL FUNCTIONOpioidsOpioids
[Opium] has kept, and does now keep [Opium] has kept, and does now keep down the population: the women have down the population: the women have fewer children than those of other fewer children than those of other countriescountriesthe feeble opiumthe feeble opium--smokers smokers of Assamof Assamare more effeminate than are more effeminate than women.women. Charles Alexander Bruce, Charles Alexander Bruce, Report on the Report on the Manufacture of Tea and on the extent Manufacture of Tea and on the extent and produc[tion] of the tea plantations in and produc[tion] of the tea plantations in Assam,Assam, Calcutta,Calcutta, 18391839..
Katz, N. The Impact of Opioids on the Endocrine System.Pain Management Rounds, MGH Pain Center 2005(1)9.www.painmanagementrounds.org
GONADAL HORMONEGONADAL HORMONEREGULATIONREGULATION--OpioidsOpioids
OPIOIDSOPIOIDS
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OPIOIDSOPIOIDS
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GONADAL HORMONESGONADAL HORMONES& SEXUAL FUNCTION& SEXUAL FUNCTION
Heroin, MorphineHeroin, Morphine MenMen
Decreased testosterone and LHDecreased testosterone and LH Decreased libido & fertility; erectile dysfunctionDecreased libido & fertility; erectile dysfunction
WomenWomen Decreased LH, estradiol, progesterone (premenopause)Decreased LH, estradiol, progesterone (premenopause) Decreased LH and FSH (postmenopause)Decreased LH and FSH (postmenopause) Amenorrhea, oligomenorrhea, irregular menses, Amenorrhea, oligomenorrhea, irregular menses,
galactorrhea & decreased libidogalactorrhea & decreased libido Trend of menstrual cycle normalization with increasing Trend of menstrual cycle normalization with increasing
duration of methadone treatmentduration of methadone treatmentCicero 1975, 1980; Mendelson 1975; Khan 1990; Genazzani 1993; Abs 2000; Schmittner 2005
SEXUAL FUNCTION & SEXUAL FUNCTION & ADHERENCE TO DOSINGADHERENCE TO DOSING
Other TherapeuticsOther Therapeutics
Sexual Dysfunction has been Sexual Dysfunction has been shown to interfere with shown to interfere with therapeutic adherence among therapeutic adherence among patients with:patients with: Depression Depression (Koutouvidis 1999)(Koutouvidis 1999) HIVHIV--AIDS AIDS (Trotta 2003)(Trotta 2003) Hypertension Hypertension (Rosen 1997)(Rosen 1997)
GONADAL HORMONESGONADAL HORMONES& SEXUAL FUNCTION& SEXUAL FUNCTION
MethadoneMethadone Early studies: Mixed results regarding Early studies: Mixed results regarding
testosterone levels in men on methadonetestosterone levels in men on methadone NormalNormal (Cushman 1973, 1974; Ragni 1988)(Cushman 1973, 1974; Ragni 1988) LowLow (Azizi 1973; Cicero 1975, N Engl J Med(Azizi 1973; Cicero 1975, N Engl J Med )) LowLow with higher dosing with higher dosing (Mendelson 1975)(Mendelson 1975)
8080--100 mg daily; normal if 10100 mg daily; normal if 10--60 mg daily60 mg daily Sexual behavior inversely associated with Sexual behavior inversely associated with
methadone dose in men (ejaculation) & methadone dose in men (ejaculation) & women (genital contact, orgasm) women (genital contact, orgasm) (Crowley 1978)(Crowley 1978)
GONADAL HORMONESGONADAL HORMONES& SEXUAL FUNCTION& SEXUAL FUNCTION
Methadone & Buprenorphine Methadone & Buprenorphine (1)(1)MethadoneMethadone
N = 37N = 37Buprenorphine Buprenorphine
N = 17N = 17ControlsControls
N = 51N = 51Age, yearsAge, years 37.537.5 34.734.7 35.235.2
Daily dose, mgDaily dose, mg 88.4 88.