Andropause Hormone Balance for Men Rebecca L. Glaser M.D., FACS Rebecca L. Glaser M.D., FACS.

AndropauseAndropause Hormone Balance for Hormone Balance for

MenMen

Rebecca L. Glaser M.D., FACSRebecca L. Glaser M.D., FACS

AndropauseAndropause

Testosterone levels begin to decline in some Testosterone levels begin to decline in some men as early as 35 years of age, typically age men as early as 35 years of age, typically age 5050

Gradual onsetGradual onset Deterioration of the mental and physical Deterioration of the mental and physical

conditioncondition Testosterone therapy has been used for over Testosterone therapy has been used for over

60 years60 years Diet and lifestyle are extremely important to Diet and lifestyle are extremely important to

hormone balancehormone balance Every person is a unique individualEvery person is a unique individual

TestosteroneTestosterone

Anabolic hormone that improves Anabolic hormone that improves muscle mass and bone densitymuscle mass and bone density

Improves mental sharpness, Improves mental sharpness, concentration, and memoryconcentration, and memory

Increases energy levelIncreases energy level Improves flexibility and mobilityImproves flexibility and mobility Prevents aches and painsPrevents aches and pains Increases sex drive and libidoIncreases sex drive and libido

Testosterone (cont.)Testosterone (cont.) Normal levels are protective against Normal levels are protective against

Alzheimer’s dementia, Parkinson’s Alzheimer’s dementia, Parkinson’s disease, & cognitive declinedisease, & cognitive decline

Protects against diabetes Protects against diabetes Protects against abdominal obesityProtects against abdominal obesity Antidepressant Antidepressant Protects against bone lossProtects against bone loss Prevents inflammatory conditionsPrevents inflammatory conditions

Testosterone and the Testosterone and the HeartHeart

Muscle building hormoneMuscle building hormone A low testosterone is a risk factor for A low testosterone is a risk factor for

CHFCHF Prevents CAD (heart disease)Prevents CAD (heart disease) Dilates coronary arteriesDilates coronary arteries Helps maintain healthy cholesterol Helps maintain healthy cholesterol

levelslevels As testosterone declines BP risesAs testosterone declines BP rises

TestosteroneTestosterone Does Does notnot cause prostate cancer cause prostate cancer

Low testosterone levels correlate with more Low testosterone levels correlate with more aggressive disease and worse outcomesaggressive disease and worse outcomes

May stimulate an undiagnosed cancerMay stimulate an undiagnosed cancer Does Does notnot cause liver failure cause liver failure

(17(17αα) Methyltestosterone (synthetic)) Methyltestosterone (synthetic) Orally effectiveOrally effective Hepatotoxic, jaundice, cysts, hepatocellular adenomasHepatotoxic, jaundice, cysts, hepatocellular adenomas Increased LDL, suppressed HDL, Increased risk HDIncreased LDL, suppressed HDL, Increased risk HD

Moralis 01: Algarte-Genin 04: Imamoto 04: Gooren 04: Slater 00Moralis 01: Algarte-Genin 04: Imamoto 04: Gooren 04: Slater 00

DHEA DHEA ( dehydroepiandrosterone) ( dehydroepiandrosterone)

Precursor hormone for both Precursor hormone for both testosterone and the estrogenstestosterone and the estrogens

LowLow levels have been associated levels have been associated with depression, autoimmune with depression, autoimmune diseases, and other chronic diseases diseases, and other chronic diseases (heart disease & diabetes)(heart disease & diabetes)

Low levels and high levels have been Low levels and high levels have been associated with breast cancerassociated with breast cancer

Estradiol/TestosteroneEstradiol/Testosterone

Testosterone is converted to estradiol Testosterone is converted to estradiol (estrone) by aromatase (enzyme)(estrone) by aromatase (enzyme)

As men age the ratio of estradiol to As men age the ratio of estradiol to testosterone increases testosterone increases

Elevated estradiol/testosterone increases Elevated estradiol/testosterone increases the risk of BPH and prostate cancerthe risk of BPH and prostate cancer

It is not only the decline in testosterone It is not only the decline in testosterone but also the increase in estradiol that but also the increase in estradiol that cause the symptoms of Andropausecause the symptoms of Andropause

Symptoms of AndropauseSymptoms of Andropause

Mental fatigue, feeling burned out, Mental fatigue, feeling burned out, inability to concentrate, insomniainability to concentrate, insomnia

Decreased mental sharpnessDecreased mental sharpness Increased forgetfulnessIncreased forgetfulness Depression, irritability, anger, anxietyDepression, irritability, anger, anxiety Physical fatigue, tiredness in the Physical fatigue, tiredness in the

afternoonafternoon Aches, joint and muscle painAches, joint and muscle pain Decreased muscle massDecreased muscle mass

Symptoms of Andropause Symptoms of Andropause cont.cont.

Shortness of breath with activitiesShortness of breath with activities Development of chest pain, dx. of heart Development of chest pain, dx. of heart

disease, blockage of arteries, rising BPdisease, blockage of arteries, rising BP Swelling of ankles, varicose veinsSwelling of ankles, varicose veins Lightheadedness, dizzy spellsLightheadedness, dizzy spells Increased sweating, hot flashesIncreased sweating, hot flashes Rising blood sugar, worsening diabetesRising blood sugar, worsening diabetes IncontinenceIncontinence Erectile dysfunction and decreased libidoErectile dysfunction and decreased libido

Factors that Contribute to Factors that Contribute to Testosterone DeficiencyTestosterone Deficiency

MumpsMumps Alcohol, stress, obesityAlcohol, stress, obesity Drugs that affect the liver Drugs that affect the liver

NSAIDs (ibuprofen), Tylenol, ASANSAIDs (ibuprofen), Tylenol, ASA Statins (cholesterol lowering drugs)Statins (cholesterol lowering drugs) Many heart and BP medicationsMany heart and BP medications AntidepressantsAntidepressants H2 blockersH2 blockers ChemotherapyChemotherapy

Raise Testosterone Raise Testosterone NaturallyNaturally

Exercise, weight loss, eliminating Exercise, weight loss, eliminating processed foods (lowers insulin processed foods (lowers insulin levels), reducing stress, and limiting levels), reducing stress, and limiting alcohol will raise testosterone levelsalcohol will raise testosterone levels

Fruits, vegetables, nuts, seeds, and Fruits, vegetables, nuts, seeds, and fiber will offer protection to the fiber will offer protection to the prostate glandprostate gland

SupplementsSupplementsRaise testosterone and protect Raise testosterone and protect

prostateprostate Zinc 25-50mg, Vitamin C (1000mg) Zinc 25-50mg, Vitamin C (1000mg) Chrysin (with piperine), flavones, Rx. arimidexChrysin (with piperine), flavones, Rx. arimidex Saw Palmetto 350mg, Nettle RootSaw Palmetto 350mg, Nettle Root Vitamin E (400mg), B Complex (folate, B6, Vitamin E (400mg), B Complex (folate, B6,

B12)B12) Magnesium 500mg Magnesium 500mg Omega 3 Fatty Acids (flaxseed, fish oil)Omega 3 Fatty Acids (flaxseed, fish oil) Whole soy foods 2-3 times weeklyWhole soy foods 2-3 times weekly Pygeum, pumpkin seed, lycopenePygeum, pumpkin seed, lycopene I3C (Indole-3-carbinol)I3C (Indole-3-carbinol)

www.hormonebalance.orgwww.hormonebalance.org …Topics…Prostate Protection …Topics…Prostate Protection

ProgesteroneProgesterone

Levels decline after 60Levels decline after 60 Protects the prostate gland and Protects the prostate gland and

lowers PSAlowers PSA Inhibits aromatase and 5 alpha Inhibits aromatase and 5 alpha

reductase, raising testosterone levelsreductase, raising testosterone levels Antagonizes the stimulatory effect of Antagonizes the stimulatory effect of

estrogen on the prostate glandestrogen on the prostate gland Stimulates p53 (antitumor antigen)Stimulates p53 (antitumor antigen)

Hormone TestingHormone Testing

Saliva, Urine, BloodSaliva, Urine, Blood www.hormonebalance.orgwww.hormonebalance.org

Featured reference sitesFeatured reference sites Hormone TestingHormone Testing

Bio-available (free) testosteroneBio-available (free) testosterone SalivaSaliva 24 hour Urine24 hour Urine Free testosterone in blood (vs. total Free testosterone in blood (vs. total

Testosterone)Testosterone)

TestingTesting Saliva: Saliva: Profile IProfile I (estradiol, DHEA-S, (estradiol, DHEA-S,

progesterone, progesterone, testosterone, testosterone, and cortisol) and cortisol)

24 hour Urine 24 hour Urine

Blood : Testosterone , free testosterone Blood : Testosterone , free testosterone (non-SHBG (non-SHBG

bound)bound), , estradiol, estrone, and PSA estradiol, estrone, and PSA Blood : Thyroid Panel (T4, free T3, TSH), IGF-1Blood : Thyroid Panel (T4, free T3, TSH), IGF-1

ZRT laboratory ZRT laboratory www.salivatest.comwww.salivatest.com 503-466-2445 503-466-2445

Rhein Consulting (Urine Testing) Rhein Consulting (Urine Testing) www.rheinlabs.comwww.rheinlabs.com 503-292-1988 503-292-1988

Options for HRT Options for HRT menmen

Testosterone (bio-identical)Testosterone (bio-identical) Oral capsule (40-120 mg)Oral capsule (40-120 mg) Sublingual tablet or lozenge (5-10 mg)Sublingual tablet or lozenge (5-10 mg) TDD (Patch 5mg-10mg)TDD (Patch 5mg-10mg) Skin Cream/Gel (Patented 50-100 mg/5gm)Skin Cream/Gel (Patented 50-100 mg/5gm) (Compounded 20-100 mg/gm)(Compounded 20-100 mg/gm) Injections (T cypionate 100-200 mg IM)Injections (T cypionate 100-200 mg IM) Pellets (four 200 mg./4-6 months)Pellets (four 200 mg./4-6 months)

DHEA 25-50 mg/dayDHEA 25-50 mg/day ProgesteroneProgesterone (5-10 mg/d) (5-10 mg/d)

Oral TestosteroneOral Testosterone Testosterone is absorbed well from the gut but Testosterone is absorbed well from the gut but

is metabolized and inactivated in the liver is metabolized and inactivated in the liver ‘‘Micronized in oil’ shifts the absorption to the Micronized in oil’ shifts the absorption to the

lymphatics and thus to the systemic circulation lymphatics and thus to the systemic circulation via the thoracic duct to the subclavian vein via the thoracic duct to the subclavian vein

Testosterone undecanoate (esterified) also Testosterone undecanoate (esterified) also attempts to shift absorption to the lymphaticsattempts to shift absorption to the lymphatics

Alkylated testosterones (methyltestosterone) Alkylated testosterones (methyltestosterone) are metabolized more slowly but cause are metabolized more slowly but cause problems with lipid metabolism and liver problems with lipid metabolism and liver toxicitytoxicity

Sublingual Testosterone Sublingual Testosterone Lozenge/TabletLozenge/Tablet

Avoids intestinal absorption and hepatic Avoids intestinal absorption and hepatic inactivationinactivation

Dose is 5-10 mg. three times dailyDose is 5-10 mg. three times daily Serum levels peak in 30 minutes and return Serum levels peak in 30 minutes and return

to baseline in 4-6 hoursto baseline in 4-6 hours Increase in serum estradiol and DHTIncrease in serum estradiol and DHT

Patented 30 mg buccal mucoadhesive Patented 30 mg buccal mucoadhesive system applied twice dailysystem applied twice daily

Avoid swallowing salivaAvoid swallowing saliva Variability in absorptionVariability in absorption

Transdermal Testosterone Transdermal Testosterone (TDD)(TDD)PatchesPatches

Patented Products 1990’sPatented Products 1990’s Testoderm scrotal patch (4 to 6 mg/d), rapid Testoderm scrotal patch (4 to 6 mg/d), rapid

absorption, applied daily, elevated DHTabsorption, applied daily, elevated DHT Andropatch Andropatch Applied dailyApplied daily

Androderm Androderm Applied daily, rotating sites, delivers 5 mg Applied daily, rotating sites, delivers 5 mg T/dT/d

Alcohol base to enhance absorptionAlcohol base to enhance absorption Skin irritation (50%) or contact dermatitis Skin irritation (50%) or contact dermatitis

(12%)(12%) Problems with hair and sweatingProblems with hair and sweating

Percutaneous TestosteronePercutaneous TestosteroneCreams and GelsCreams and Gels

BaseBase Natural Cream Natural Cream Non alcoholic gelNon alcoholic gel Hydro-alcoholic gel (9-14% bioavailable)Hydro-alcoholic gel (9-14% bioavailable)

AndroGel, Testim, Testogel AndroGel, Testim, Testogel DoseDose 50-100 mg (delivers 5-10 mg of Testosterone) 50-100 mg (delivers 5-10 mg of Testosterone) Can combine testosterone with progesterone 5-10 Can combine testosterone with progesterone 5-10

mgmg Apply cream/gel to inner arms, abdomen, chest, neckApply cream/gel to inner arms, abdomen, chest, neck Rotate sites, rub vigorously, wash hands if handling Rotate sites, rub vigorously, wash hands if handling

infantinfant Variability in absorptionVariability in absorption

Swerdloff 00: Wang 00: Wang 01: McNicholas 03: Gooren 04: Ebert 05: Meikle 04: Rolf 02: Nieschlag 04:Swerdloff 00: Wang 00: Wang 01: McNicholas 03: Gooren 04: Ebert 05: Meikle 04: Rolf 02: Nieschlag 04:

Testosterone InjectionsTestosterone Injections Widely used in Europe, low cost, consistent Widely used in Europe, low cost, consistent

absorptionabsorption Well tolerated, intramuscular injectionWell tolerated, intramuscular injection Esterification of the 17Esterification of the 17ββ –hydroxyl group –hydroxyl group

Lipid solubleLipid soluble DepotDepot

Hydrolyzed in vivo to release TestosteroneHydrolyzed in vivo to release Testosterone Long acting estersLong acting esters

Testosterone Cypionate Testosterone Cypionate (every 2 weeks, weekly)(every 2 weeks, weekly)

Testosterone Propionate Testosterone Propionate (every 2 weeks)(every 2 weeks) Testosterone Undecanoate Testosterone Undecanoate (every 12 weeks)(every 12 weeks)

Testosterone PelletsTestosterone Pellets Have been used since 1940Have been used since 1940 Implanted in the subcutaneous tissue of the Implanted in the subcutaneous tissue of the

lower abdominal walllower abdominal wall Requires a minor procedureRequires a minor procedure 3-6 200 mg pellets provide a physiologic 3-6 200 mg pellets provide a physiologic

dose of testosterone for 4-6 monthsdose of testosterone for 4-6 months Effective form of therapy with complete Effective form of therapy with complete

bioavailabilitybioavailability No elevation of DHT or estradiolNo elevation of DHT or estradiol Transient accelerated release rate 1-2 d onlyTransient accelerated release rate 1-2 d only Extrusion 5%, minor bleeding 2%, infection Extrusion 5%, minor bleeding 2%, infection

<1%<1%

Compounding PharmacyCompounding Pharmacy

Oral CapsulesOral Capsules Sublingual lozenges or tabletsSublingual lozenges or tablets Creams and GelsCreams and Gels PelletsPellets Injectable testosterone estersInjectable testosterone esters

www.hormonebalance.orgwww.hormonebalance.org Topics…Compounding PharmaciesTopics…Compounding Pharmacies Featured Reference Sites…Find a compounding pharmacyFeatured Reference Sites…Find a compounding pharmacy

Dosing Dosing Swerdloff 00: Wang 96, 00, 01: McNicholas 03: Gooren 04: Ebert 05: Meikle 04: Swerdloff 00: Wang 96, 00, 01: McNicholas 03: Gooren 04: Ebert 05: Meikle 04:

Rolf 02: Nieschlag 04: Marbury 03Rolf 02: Nieschlag 04: Marbury 03

TestosteroneTestosterone

Oral Capsule Oral Capsule not not recommendedrecommended

50-200 mg50-200 mg Variable Variable absorptionabsorption

Elevated estrogen levelsElevated estrogen levels

Sublingual Sublingual lozenge/tabletlozenge/tablet

5-10 mg three 5-10 mg three times dailytimes daily

Variable Variable absorptionabsorption

Rapid rise and fallRapid rise and fall

TDD PatchTDD Patch 5 or 10 mg 5 or 10 mg

Applied dailyApplied dailyPatented Patented

Delivers 5 to 10 mg ofDelivers 5 to 10 mg of T/dT/d

Percutaneous (skin) Percutaneous (skin) gel/creamgel/cream

50-100 mg daily50-100 mg daily Delivers 5 to 10 mg of Delivers 5 to 10 mg of T/dT/d

Doses as low as 20 mg/g Doses as low as 20 mg/g recrec

Pellets (implanted)Pellets (implanted) 800-1000 mg 800-1000 mg 4-6 4-6 mosmos

4 - 5 200 mg pellets4 - 5 200 mg pellets

Consistent Consistent absorptionabsorption

200mg releases 1.3 mg 200mg releases 1.3 mg T/dT/d

InjectionInjection Testosterone Testosterone CypionateCypionate

200 mg every 2 weeks 200 mg every 2 weeks

Peak at 42 h, Peak at 42 h, declinedecline

Weekly injections at Weekly injections at homehome

CostCost Patented Androgel $235.00/mo.Patented Androgel $235.00/mo. USP Testosterone Gel $30.00-$45.00/mo.USP Testosterone Gel $30.00-$45.00/mo. USP Testosterone SL lozenge (5-10 mg.)USP Testosterone SL lozenge (5-10 mg.) two or three times dailytwo or three times daily $30.00-$45.00/mo.$30.00-$45.00/mo. Pellets 200 mg pellets implanted/6 mos Pellets 200 mg pellets implanted/6 mos

$365$365

Injection $30 twice monthly or at homeInjection $30 twice monthly or at home

BHRT and the ProstateBHRT and the Prostate

PSA (<2.6) & digital rectal exam prior PSA (<2.6) & digital rectal exam prior to starting therapy to starting therapy

PSA at 3, 6, and 12 mos. following PSA at 3, 6, and 12 mos. following initiation of testosterone therapyinitiation of testosterone therapy

If PSA > 4.0 prostate biopsyIf PSA > 4.0 prostate biopsy FU estradiol, estrone, free testosterone, FU estradiol, estrone, free testosterone,

and testosterone levels at 3 monthsand testosterone levels at 3 months Testosterone does not cause prostate Testosterone does not cause prostate

cancer but may stimulate an existing cancer but may stimulate an existing cancercancer

ConclusionConclusion

BALANCEBALANCE IndividualIndividual LevelsLevels Biologically Identical HormonesBiologically Identical Hormones Disease PreventionDisease Prevention Active ParticipantActive Participant

Recommended ReadingRecommended Reading

www.lef.orgwww.lef.org Testosterone Protocol Testosterone Protocol www.salivatest.comwww.salivatest.com The Testosterone SyndromeThe Testosterone Syndrome

Shippen/FryerShippen/Fryer The Hormone SolutionThe Hormone Solution Thierry Thierry

HertogheHertoghe Adrenal FatigueAdrenal Fatigue James Wilson James Wilson The Miracle of Natural HormonesThe Miracle of Natural Hormones

BrownsteinBrownstein