PHYSIOLOGIC DOSING OF HORMONES IN FEMALES ......2016/02/22  · One year without periods or TAHBSO...

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PHYSIOLOGIC DOSING OF HORMONES IN FEMALES AND LABORATORY FINDINGS Paul Savage MD, FACEP, FAARM

Transcript of PHYSIOLOGIC DOSING OF HORMONES IN FEMALES ......2016/02/22  · One year without periods or TAHBSO...

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PHYSIOLOGICDOSINGOFHORMONESINFEMALESANDLABORATORY

FINDINGS

PaulSavageMD,FACEP,FAARM

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Objec8ves

1.  Explainphysiologicdosingoffemalehormoneswithregardstomenopause.

2.  CorrectmisinformaDonaboutlaboratory

tesDnginregardstotreatmentmodality.3.  Defineevidence-basedclinicalalgorithmsfor

femaleBHT.

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DailySerumLevelsofHormonesinWomen

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Follicular Luteal

Men

ses

Men

ses

OvulaDo

n

TestosteronePeakSerum:55pg/ml

ProgesteronePeakSerum12ng/ml

EstradiolPeakSerum:160pg/ml

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DailyEndogenousProduc8onofHormonesinWomen

Steroids Follicular Luteal

Progesterone 1mg/day 25mgs/day

DHEA 7mgs/day 7mgs/day

Testosterone 0.144mgs/day 0.126mgs/day

Estradiol 0.036mgs/day 0.25mgs/day

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BarreVKE,BBarmanSM,BoitanoS,BrooksHL.“Chapter25.TheGonads:Development&FuncDonoftheReproducDvesystem"Ganong’sReviewofMedicalPhysiology

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ThePower2Prac8ceStudy/ChartReviewPurpose

DeterminerangeofVariousLabValuesforasymptomaDcwomenonBHTInclusion

FemaleOneyearwithoutperiodsorTAHBSOOnBioidenDcalHormoneTherapyAsymptomaDc(MRS<4)

Study2008-2013598PaDentVisits1914labvalues

AverageAge 55.3

MethodsLabCorp-SerumZRT-SalivaZRT–CapillaryBloodSpotRheinLabs-Urine

PharmacyDiplomatCompoundingPharmacy

5UnpublishedData

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ThePower2Prac8ceStudy/ChartReview

DosingMethodsEvaluated•  Patches

–  Estradiolpatch•  TopicalCreams

–  EstradiolCream–  TestosteroneCream–  ProgesteroneCream

•  Oral–  ProgesteroneSR–  DHEA

•  Pellets–  Testosterone

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1.3-3.3pg/mL

00.51

1.52

2.53

3.5

SalivaE2

SalivaE2

2-5µg/24hrs

0123456

UrineE2

UrineE2

42-289pg/mL43-180pg/mL

EstradiolPatch

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PhysiologicLevel

-104090140190240290

SerumE2

SerumE2 050100150200250300350

BloodSpotE2

BloodSpotE2

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EstradiolPatchEstradiolPatch Contains

0.025mgs/dayofestradiol 0.39mgsofestradiol(0.11mgs/day)

0.0375mgs/dayofestradiol 0.585mgsofestradiol(0.17mgs/day)

0.05mgs/dayofestradiol 0.78mgsofestradiol(0.22mgs/day)

0.075mgs/dayofestradiol 1.17mgsofestradiol(0.33mgs/day)

0.1mgs/dayofestradiol 1.56mgsofestradiol(0.44mgs/day)

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Steroids Follicular Luteal

Estradiol 0.036mgs/day 0.25mgs/day

DailyEndogenousProduc8onofEstradiol

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Dr.Paul’sPearls

•  Estradiolpatchworkswellfortreatmentofestradioldeficiencysymptoms.

•  EstradiolpatchdosingeffecDverangeis0.025-0.1mgspatchtwiceweekly.

•  EstradiolpatchcanbemonitoredbyallmethodsoftesDng.

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42-289pg/mL

2-5µg/24hrs

00.51

1.52

2.53

3.54

4.55

BaselineE2 E2Cream0.125mgs

E2Cream0.25mgs

E2Cream0.5-0.75mgs

UrineE2

UrineE2

-10

40

90

140

190

240

290

BaselineE2 E2Cream0.125mgs

E2Cream0.25mgs

E2Cream0.5-0.75mgs

SerumE2

SerumE243-180pg/mL

0

50

100

150

200

250

BaselineE2 E2Cream0.125mgs

E2Cream0.25mgs

E2Cream0.5-0.75mgs

BloodSpotE2

BloodSpotE2

1.3-3.3pg/mL

0

2

4

6

8

10

12

BaselineE2 E2Cream0.125mgs

E2Cream0.25mgs

E2Cream0.5-0.75mgs

SalivaE2

SalivaE2

EstradiolCreamTopical

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PhysiologicLevel

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UrinaryLevelsofEstradiol

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E2Oral

E2Cream

E2Patch

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Dr.Paul’sPearls

•  Estradiolcreamtopicalworkswellfortreatmentofestradioldeficiencysymptoms.

•  EstradiolcreamtopicaldosingeffecDverangeis0.25-0.5mgsapplieddaily.

•  EstradiolcreamtopicalcanbeonlymonitoredbyBloodSpotorSalivaTesDng:– NotmonitoredwellwithSerumorUrine

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100-3287µg/24hrs0

2000400060008000

1000012000140001600018000

BaselinePG PGOral100-150mgs

PGOral200-250mgs

UrinePreg

UrinePreg

5000

30000

3.3-22.5ng/mL

0

5

10

15

20

25

BaselinePG PGOral100-150mgs

PGOral200-250mgs

BloodSpotPG

BloodSpotPG

1.7-27.0ng/mL

0

5

10

15

20

25

30

BaselinePG PGOral100-150mgs

PGOral200-250mgs

SerumPG

SerumPG

30-300pg/mL

0

50

100

150

200

250

300

BaselinePG PGOral100-150mgs

PGOral200-250mgs

SalivaPG

SalivaPG

ProgesteroneOral

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PhysiologicLevel

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Dr.Paul’sPearls

•  Progesteroneorallyworkswellfortreatmentofprogesteronedeficiencysymptoms.

•  ProgesteroneorallydosingeffecDverangeis100-250mgsdaily.

•  ProgesteroneorallycanbemonitoredbyallmethodsoftesDng:– AdjusDngrangeforUrineto5000-30,000µg/24hrs

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300-3000pg/mL

050010001500200025003000350040004500

BaselinePG PGCreamTD20-40mgs

PGCreamTD50-75mgs

PGCreamTD100mgs

SalivaPG

SalivaPG

100-3287µg/24hrs

0

500

1000

1500

2000

2500

3000

BaselinePG PGCreamTD20-40mgs

PGCreamTD50-75mgs

PGCreamTD100mgs

UrinePreg

UrinePreg

1.7-27.0ng/mL

-3

2

7

12

17

22

27

BaselinePG PGCreamTD20-40mgs

PGCreamTD50-75mgs

PGCreamTD100mgs

SerumPG

SerumPG

3.3-22.5ng/mL

ProgesteroneCreamTopical

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PhysiologicLevel

0

20

40

60

80

100

120

140

160

BaselinePG PGCreamTD20-40mgs

PGCreamTD50-75mgs

PGCreamTD100mgs

BloodSpotPG

BloodSpotPG

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UrinaryLevelsofProgesterone

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GC/MS/MS Testing of Urinary Pregnanediol in Premenopausal Women at Different Phases of the Menstrual Cycle and on Hormonal Contraceptives, and in Postmenopausal Women Supplementing with Topical, Vaginal, and Oral Progesterone

PGCream

PGOral

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Dr.Paul’sPearls

•  Progesteronecreamtopicalworkswellfortreatmentofprogesteronedeficiencysymptoms.

•  ProgesteronecreamtopicaldosingeffecDverangeis20-50mgsapplieddaily.

•  ProgesteronecreamtopicalcanbeonlymonitoredbyBloodSpotorSalivaTesDng:– AdjusDngrangeforSalivato300-3000pg/mL– NotmonitoredwellwithSerumorUrine17

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16-55pg/mL

10-55ng/dL 20-130ng/dL

020406080

100120140

BloodSpotTest

BloodSpotTest

4-18µg/24hrs

02468

1012141618

BaselineTestosterone

TestTD0.5-0.75mgs

TestTD1-1.5mgs

TestTD2mgs

UrineTest

UrineTest

0

20

40

60

80

100

120

140

160

BaselineTestosterone

TestTD0.5-0.75mgs

TestTD1-1.5mgs

TestTD2mgs

SalivaTest

SalivaTest

0

10

20

30

40

50

60

70

BaselineTestosterone

TestTD0.5-0.75mgs

TestTD1-1.5mgs

TestTD2mgs

SerumTest

SerumTest

TestosteroneCreamTopical

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PhysiologicLevel

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Dr.Paul’sPearls

•  Testosteronecreamtopicalworkswellfortreatmentoftestosteronedeficiencysymptoms.

•  TestosteronecreamtopicaldosingeffecDverangeis0.5-1.5mgsapplieddaily.

•  TestosteronecreamtopicalcanbeonlymonitoredbySerum,BloodSpotorSalivaTesDng.– NotmonitoredwellwithUrine

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10-55ng/dL0

50

100

150

200

250

SerumTest

SerumTest

16-55pg/mL

01020304050607080

SalivaTest

SalivaTest

20-130ng/dL

020406080100120140160180

BloodSpotTest

BloodSpotTest

UrineTesDngDataNotSufficient

TestosteronePellet–90days

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PhysiologicLevel

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UrinaryLevelsofTestosterone

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TPellets

TCream

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Dr.Paul’sPearls

•  Testosteronepelletsworkswellfortreatmentoftestosteronedeficiencysymptoms.

•  TestosteronepelletsdosingeffecDverangeis75-125mgsimplantedq4-6mo.

•  TestosteronepelletscanbemonitoredbyallmethodsoftesDng:– AdjusDngrangeforserumto20-130ng/dLat90days

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35-256µg/dL

0

50

100

150

200

250

BaselineDHEA DHEAOral5-7.5mgs

DHEAOral10-15mgs

SerumDHEAS

SerumDHEA

0

5

10

15

20

25

BaselineDHEA DHEAOral5-7.5mgs

DHEAOral10-15mgs

SalivaDHEA-S

SalivaDHEA 20-1139µg/24hrs

0

200

400

600

800

1000

1200

BaselineDHEA DHEAOral5-7.5mgs

DHEAOral10-15mgs

UrineDHEA(S)

UrineDHEA

40-290µg/dL

0

50

100

150

200

250

300

BaselineDHEA DHEAOral5-7.5mgs

DHEAOral10-15mgs

BloodSpotDHEAS

BloodSpotDHEA

2-23ng/mL

DHEAOral

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PhysiologicLevel

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Dr.Paul’sPearls

•  DHEAoralworkswellfortreatmentofDHEAdeficiencysymptoms.

•  DHEAoraldosingeffecDverangeis5-15mgsdaily.

•  DHEAoralcanbemonitoredbyallmethodsoftesDng.

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20-1139µg/24hrs

0

200

400

600

800

1000

1200

BaselineDHEA

DHEACream5-7.5mgs

DHEACream10-15mgs

DHEACream20-25mgs

UrineDHEA(S)

UrineDHEA

2-23ng/mL

0

5

10

15

20

25

BaselineDHEA

DHEACream5-7.5mgs

DHEACream10-15mgs

DHEACream20-25mgs

SalivaDHEA-S

SalivaDHEA

40-290µg/dL

0

50

100

150

200

250

300

BaselineDHEA

DHEACream

5-7.5mgs

DHEACream

10-15mgs

DHEACream

20-25mgs

BloodSpotDHEAS

BloodSpotDHEA35-256µg/dL

0

50

100

150

200

250

300

BaselineDHEA

DHEACream5-7.5mgs

DHEACream10-15mgs

DHEACream20-25mgs

SerumDHEAS

SerumDHEA

DHEACreamTopical

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PhysiologicLevel

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Dr.Paul’sPearls

•  DHEAcreamtopicalworkswellfortreatmentofDHEAdeficiencysymptoms.•  DHEAcreamtopicaldosingeffecDverangeis5-15mgsdaily.•  DHEAcreamtopicalCANNOTbemonitoredwellbyanymethodoftesDng.•  DHEACreamTopicalmeasurementismisleadingbecausewhatmostlabsare

measuringisDHEAS.–  DHEAgiventopicallywillnotincreaseDHEAS,whichiswhyBloodSpotDHEASdoesnotgo

up.–  UrineactuallymeasuresDHEA,buttheyarereallymeasuringDHEAandDHEASbecausethe

DHEASisdesulfatedbydigesDonandthenmeasuredasDHEA.–  SO,carefulabouttheinterpretaDon-itstricky.

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GuidetoSteroidTes8ngonHormoneTherapy

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LabTes8ng

Baseline(noBHT) Oral Topical/

VaginalTroche/

Sublingual Patches Pellets

Serum Yes Yes No Yes Yes Yes

BloodSpot Yes Yes Yes Yes Yes Yes

Saliva Yes Yes Yes1 No Yes Yes

Urine Yes Yes2 No Yes Yes Yes

1  ProgesteroneSalivalevelsmustbeadjustedto200-3000pg/mL2  ProgesteroneUrinelevelsmustbeadjustedto5000-30,000µg/24hrs

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Therapeu8cDosingofHormonesinWomen

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Steroids Oral Topical Patch Pellet

Progesterone 50-250mgsdaily

20-50mgsdaily * *

DHEA 5-15mgsdaily

5-15mgsdaily * *

Testosterone1-2mgsdaily 0.5-1.5mgs

daily * 75-125mgsq4-6mo

Estradiol

* 0.25-0.75mgsdaily

0.025-0.1mgstwiceweekly

*

Dr.Paul’sPearls:1.  Treatsymptoms,notnumbers2.  BaselinetesDng:Everymethodworks3.  TreatmentwithOral,Patches,andPellets:Everymethodworks4.  TreatmentwithTopicalCreams:OnlyBloodSpotandSalivawork

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Therapeu8cDosingMethodsofHormonesinWomen

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BarreVKE,BBarmanSM,BoitanoS,BrooksHL.“Chapter25.TheGonads:Development&FuncDonoftheReproducDvesystem"Ganong’sReviewofMedicalPhysiology

Steroid Oral Topical/Vaginal Patches Pellets

Progesterone Yes Yes No No

DHEA Yes Yes No No

Testosterone Yes Yes No Yes

Estradiol Yes* Yes Yes Yes

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ObservedTherapeu8cRangesofHormonesbyTes8ngMethod

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Steroid Serum CapillaryBloodSpot Saliva Urine

EstradiolPatches 42-289pg/mL 43-180pg/mL 1.3-3.3pg/mL 2-5µg/24hrs

EstradiolCream * 43-180pg/mL 1.3-3.3pg/mL *

ProgesteroneOral 1.7-27ng/mL 3.3-22.5ng/mL 30-300pg/mL 5000-30,000µg/24hrs1

ProgesteroneCream * 3.3-22.5ng/mL 300-3000pg/mL2 *

TestosteroneCream 10-55ng/dL 20-130ng/dL 16-55pg/mL 4-18µg/24hrs

TestosteronePellets 20-130ng/dL3 20-130ng/dL 16-55pg/mL ?

DHEAOral 35-256µg/dL 40-290µg/dL 2-23ng/mL 20-1139µg/24hrs

DHEACream * * * *

*=Notwellmeasuredbytest?=Notstudied

1=Highervalue2=Highervalue3=Highervalue

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Dr.Paul’sFinalPearls

•  Treatsymptoms,notnumbers•  TherapywithOral,TopicalCreams,Patches,andPellets–  Everytreatmentmethodworkstoeliminatesymptoms

•  LabbaselinetesDng–  Everymethodworks

•  Labmonitoringoftherapy–  TreatmentwithOral,PatchesandPellets

•  Everylabworks–  TreatmentwithTopicalCreams

•  BloodSpotandSalivaworkbest

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ThankYouPaulSavageMD,FACEP,FFARM