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

DrBartnof@DrBartnof.comDrBartnof@DrBartnof.com 415415--986986--13001300

www.LongevityMD.netwww.LongevityMD.net

mailto:DrBartnof@DrBartnof.com

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

---

---

---

OPIOIDSOPIOIDS

---

---

---

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.