Post on 09-Aug-2020
PHYSIOLOGICDOSINGOFHORMONESINFEMALESANDLABORATORY
FINDINGS
PaulSavageMD,FACEP,FAARM
Objec8ves
1. Explainphysiologicdosingoffemalehormoneswithregardstomenopause.
2. CorrectmisinformaDonaboutlaboratory
tesDnginregardstotreatmentmodality.3. Defineevidence-basedclinicalalgorithmsfor
femaleBHT.
2
DailySerumLevelsofHormonesinWomen
3
Follicular Luteal
Men
ses
Men
ses
OvulaDo
n
TestosteronePeakSerum:55pg/ml
ProgesteronePeakSerum12ng/ml
EstradiolPeakSerum:160pg/ml
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
4
BarreVKE,BBarmanSM,BoitanoS,BrooksHL.“Chapter25.TheGonads:Development&FuncDonoftheReproducDvesystem"Ganong’sReviewofMedicalPhysiology
ThePower2Prac8ceStudy/ChartReviewPurpose
DeterminerangeofVariousLabValuesforasymptomaDcwomenonBHTInclusion
FemaleOneyearwithoutperiodsorTAHBSOOnBioidenDcalHormoneTherapyAsymptomaDc(MRS<4)
Study2008-2013598PaDentVisits1914labvalues
AverageAge 55.3
MethodsLabCorp-SerumZRT-SalivaZRT–CapillaryBloodSpotRheinLabs-Urine
PharmacyDiplomatCompoundingPharmacy
5UnpublishedData
ThePower2Prac8ceStudy/ChartReview
DosingMethodsEvaluated• Patches
– Estradiolpatch• TopicalCreams
– EstradiolCream– TestosteroneCream– ProgesteroneCream
• Oral– ProgesteroneSR– DHEA
• Pellets– Testosterone
7
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
7
PhysiologicLevel
-104090140190240290
SerumE2
SerumE2 050100150200250300350
BloodSpotE2
BloodSpotE2
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)
8
Steroids Follicular Luteal
Estradiol 0.036mgs/day 0.25mgs/day
DailyEndogenousProduc8onofEstradiol
Dr.Paul’sPearls
• Estradiolpatchworkswellfortreatmentofestradioldeficiencysymptoms.
• EstradiolpatchdosingeffecDverangeis0.025-0.1mgspatchtwiceweekly.
• EstradiolpatchcanbemonitoredbyallmethodsoftesDng.
9
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
10
PhysiologicLevel
UrinaryLevelsofEstradiol
11
E2Oral
E2Cream
E2Patch
Dr.Paul’sPearls
• Estradiolcreamtopicalworkswellfortreatmentofestradioldeficiencysymptoms.
• EstradiolcreamtopicaldosingeffecDverangeis0.25-0.5mgsapplieddaily.
• EstradiolcreamtopicalcanbeonlymonitoredbyBloodSpotorSalivaTesDng:– NotmonitoredwellwithSerumorUrine
12
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
13
PhysiologicLevel
Dr.Paul’sPearls
• Progesteroneorallyworkswellfortreatmentofprogesteronedeficiencysymptoms.
• ProgesteroneorallydosingeffecDverangeis100-250mgsdaily.
• ProgesteroneorallycanbemonitoredbyallmethodsoftesDng:– AdjusDngrangeforUrineto5000-30,000µg/24hrs
14
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
15
PhysiologicLevel
0
20
40
60
80
100
120
140
160
BaselinePG PGCreamTD20-40mgs
PGCreamTD50-75mgs
PGCreamTD100mgs
BloodSpotPG
BloodSpotPG
UrinaryLevelsofProgesterone
16
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
Dr.Paul’sPearls
• Progesteronecreamtopicalworkswellfortreatmentofprogesteronedeficiencysymptoms.
• ProgesteronecreamtopicaldosingeffecDverangeis20-50mgsapplieddaily.
• ProgesteronecreamtopicalcanbeonlymonitoredbyBloodSpotorSalivaTesDng:– AdjusDngrangeforSalivato300-3000pg/mL– NotmonitoredwellwithSerumorUrine17
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
18
PhysiologicLevel
Dr.Paul’sPearls
• Testosteronecreamtopicalworkswellfortreatmentoftestosteronedeficiencysymptoms.
• TestosteronecreamtopicaldosingeffecDverangeis0.5-1.5mgsapplieddaily.
• TestosteronecreamtopicalcanbeonlymonitoredbySerum,BloodSpotorSalivaTesDng.– NotmonitoredwellwithUrine
19
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
20
PhysiologicLevel
UrinaryLevelsofTestosterone
21
TPellets
TCream
Dr.Paul’sPearls
• Testosteronepelletsworkswellfortreatmentoftestosteronedeficiencysymptoms.
• TestosteronepelletsdosingeffecDverangeis75-125mgsimplantedq4-6mo.
• TestosteronepelletscanbemonitoredbyallmethodsoftesDng:– AdjusDngrangeforserumto20-130ng/dLat90days
22
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
23
PhysiologicLevel
Dr.Paul’sPearls
• DHEAoralworkswellfortreatmentofDHEAdeficiencysymptoms.
• DHEAoraldosingeffecDverangeis5-15mgsdaily.
• DHEAoralcanbemonitoredbyallmethodsoftesDng.
24
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
25
PhysiologicLevel
Dr.Paul’sPearls
• DHEAcreamtopicalworkswellfortreatmentofDHEAdeficiencysymptoms.• DHEAcreamtopicaldosingeffecDverangeis5-15mgsdaily.• DHEAcreamtopicalCANNOTbemonitoredwellbyanymethodoftesDng.• DHEACreamTopicalmeasurementismisleadingbecausewhatmostlabsare
measuringisDHEAS.– DHEAgiventopicallywillnotincreaseDHEAS,whichiswhyBloodSpotDHEASdoesnotgo
up.– UrineactuallymeasuresDHEA,buttheyarereallymeasuringDHEAandDHEASbecausethe
DHEASisdesulfatedbydigesDonandthenmeasuredasDHEA.– SO,carefulabouttheinterpretaDon-itstricky.
26
GuidetoSteroidTes8ngonHormoneTherapy
27
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
Therapeu8cDosingofHormonesinWomen
28
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
Therapeu8cDosingMethodsofHormonesinWomen
29
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
ObservedTherapeu8cRangesofHormonesbyTes8ngMethod
30
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
Dr.Paul’sFinalPearls
• Treatsymptoms,notnumbers• TherapywithOral,TopicalCreams,Patches,andPellets– Everytreatmentmethodworkstoeliminatesymptoms
• LabbaselinetesDng– Everymethodworks
• Labmonitoringoftherapy– TreatmentwithOral,PatchesandPellets
• Everylabworks– TreatmentwithTopicalCreams
• BloodSpotandSalivaworkbest
31
ThankYouPaulSavageMD,FACEP,FFARM