Mr Mark Newman
Monitoring Hormone Therapy Mark Newman, M.S. President of Precision Analytical Inc. 2
Avoiding Pitfalls in (B)HRT Monitoring and Picking the Right Lab Test Objectives: Outline how expected lab results change for different routes of administration of exogenous hormones Review data to assist is avoiding common HRT lab test combinations that can be clinically misleading Discuss case studies with serum, urine and saliva results 3
TESTING No Supplementation With Hormone Replacement Therapy MATRIX Sex Hormones Adrenal Oral Pg Oral (other) Sublingual Vaginal Pellet/Inj. Cream (skin) Gel (skin) B D F B D C B D B Serum Saliva 24 Hour Urine +Well accepted and reliable methods No metabolites No diurnal free cortisol Inaccurate# and too Fast* +Works for DHEA, estrogens No metabolites Too Fast* (back to baseline in <3hrs) Rise and fall is unpredictable, so timing is difficult +Well accepted and reliable methods No metabolites Values underrepresent some tissue levels Increases are more significant than with creams C B F B F D B D D + Good for tracking levels thru cycle Difficult analysis No metabolites +Diurnal free cortisol No metabolites Inaccurate# and too Fast* Difficult analysis No metabolites Contamination lasts longer than blood levels are elevated Rise and fall is unpredictable, so timing is difficult Difficult analysis No metabolites A C C B C D A D B +Mass spectrometry (accurate) Includes metabolites Difficult collection +Metabolites No diurnal cortisol Often "total" not "free" Metabolites of marginal value Difficult to avoid 1st pass metabolism (skip dose day of test) Difficult to avoid 1st pass metabolism from oral intake +Works for Pg Estrogen/Test contamination Hormones and metabolites % Values are too variable, change dramatically with different application sites, and do not represent systemic exposure Values underrepresent some tissue levels Increases are more significant than with creams New Precision Analytical Option A A+ C B C B+ A D B Mass spectrometry (accurate) Includes metabolites Easy collection IDEAL OPTION Diurnal Cortisol AND Metabolites! Metabolites of marginal value Difficult to avoid 1st pass metabolism (skip dose day of test) Difficult to avoid 1st pass metabolism from oral intake IDEAL OPTION free hormone contamination is removed Hormones and metabolites Values underrepresent some tissue levels Increases are more significant than with creams OBJECTIVE Discuss best options for monitoring different types of HRT therapy 4
TESTING No Supplementation MATRIX Sex Hormones Adrenal B D Serum Saliva 24 Hour Urine +Well accepted and reliable methods No metabolites C + Good for tracking levels thru cycle Difficult analysis No metabolites A +Mass spectrometry (accurate) Includes metabolites Difficult collection No diurnal free cortisol B +Diurnal free cortisol No metabolites C +Metabolites No diurnal cortisol Often "total" not "free" 5 New Precision Analytical Option A A+ Mass spectrometry (accurate) Includes metabolites Easy collection IDEAL OPTION Diurnal Cortisol AND Metabolites!
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TESTING No Supplementation MATRIX Sex Hormones Adrenal B D Serum Saliva 24 Hour Urine +Well accepted and reliable methods No metabolites C + Good for tracking levels thru cycle Difficult analysis No metabolites A +Mass spectrometry (accurate) Includes metabolites Difficult collection No diurnal free cortisol B +Diurnal free cortisol No metabolites C +Metabolites No diurnal cortisol Often "total" not "free" 7 New Precision Analytical Option A A+ Mass spectrometry (accurate) Includes metabolites Easy collection IDEAL OPTION Diurnal Cortisol AND Metabolites!
TESTING No Supplementation MATRIX Sex Hormones Adrenal B D Serum Saliva 24 Hour Urine +Well accepted and reliable methods No metabolites C + Good for tracking levels thru cycle Difficult analysis No metabolites A +Mass spectrometry (accurate) Includes metabolites Difficult collection No diurnal free cortisol B +Diurnal free cortisol No metabolites C +Metabolites No diurnal cortisol Often "total" not "free" 8 New Precision Analytical Option A A+ Mass spectrometry (accurate) Includes metabolites Easy collection IDEAL OPTION Diurnal Cortisol AND Metabolites!
There is not a simple equivalency between these with lab results Young Healthy HRT Puberty Menopause HRT 9
Which Route of Administration Oral Sublingual Vaginal and transmucosal Injections and pellets Transdermal EACH ONE IS UNIQUE! 10
TESTING MATRIX Serum Oral Pg F Inaccurate# and too Fast* THERAPY Oral (other) B +Works for DHEA, estrogens No metabolites F B ORAL HORMONES Saliva Inaccurate# and too Fast* Difficult analysis No metabolites 11 24 Hour Urine Precision New Analytical Option C B Metabolites of marginal value Difficult to avoid 1st pass metabolism (skip dose day of test) C B Metabolites of marginal value Difficult to avoid 1st pass metabolism (skip dose day of test)
TESTING MATRIX Serum Oral Pg F Inaccurate# and too Fast* THERAPY Oral (other) B +Works for DHEA, estrogens No metabolites ORAL PROGESTERONE F B Saliva Inaccurate# and too Fast* Difficult analysis No metabolites 12 24 Hour Urine Precision New Analytical Option C B Metabolites of marginal value Difficult to avoid 1st pass metabolism (skip dose day of test) C B Metabolites of marginal value Difficult to avoid 1st pass metabolism (skip dose day of test)
Oral Pg doesn t increase Pg levels >6ng/mL is considered consistent with ovulation 13
14 VAGINAL vs Oral Progesterone
ORAL PROGESTERONE Serum/Saliva Return to baseline is too fast (2 hours) Most tests are inaccurately high 15
EIA = False Positive LC MS MS = true value 16
ORAL PROGESTERONE Urine Small doses don t raise serum levels, but lead to very high urine metabolites (1 st pass) Marginally valuable information can be taken from specific metabolism patterns 17
ORAL PROGESTERONE Testing is of limited value 18
TESTING MATRIX Serum Oral Pg F Inaccurate# and too Fast* THERAPY Oral (other) B +Works for DHEA, estrogens No metabolites F B ORAL HORMONES Saliva Inaccurate# and too Fast* Difficult analysis No metabolites 19 24 Hour Urine New Precision Analytical Option C B Metabolites of marginal value Difficult to avoid 1st pass metabolism (skip dose day of test) C B Metabolites of marginal value Difficult to avoid 1st pass metabolism (skip dose day of test)
TESTING MATRIX Serum Oral Pg F Inaccurate# and too Fast* THERAPY Oral (other) B +Works for DHEA, estrogens No metabolites F B ORAL HORMONES Saliva Inaccurate# and too Fast* Difficult analysis No metabolites 20 24 Hour Urine Precision New Analytical Option C B Metabolites of marginal value Difficult to avoid 1st pass metabolism (skip dose day of test) C B Metabolites of marginal value Difficult to avoid 1st pass metabolism (skip dose day of test)
Baseline (healthy) 21 Deficiency (induced) H.R.T.
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ORAL ESTROGENS Rise and fall is slow, so serum or saliva testing can be effective 23
ORAL ESTROGENS and SERUM Serum E2(nmol) Hours Since Dose 24
Oral Estrogen and Urine Testing 25
Oral Estrogen and Urine Testing 26 Postmenopausal Range 0.2-0.8 0.8
27 Estrogen Metabolites and Cancer
Oral Estrogen and Urine Testing 28
Oral Estrogen and Urine Testing 29
Oral Estrogen and Urine Testing 30
TESTING MATRIX Serum Saliva 24 Hour Urine With THERAPY Hormon Sublingual D Too Fast* (back to baseline in <3hrs) F Contamination lasts longer than blood levels are elevated C Difficult to avoid 1st pass metabolism from oral intake SUBLINGUAL HORMONES NO GOOD TEST! 31 Precision New Analytical Option C Difficult to avoid 1st pass metabolism from oral intake
Why Not Serum with Sublingual TOO FAST! Gone before you can measure 32
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Why Not Saliva with Sublingual Hormones are in mg in supplements Hormones are in pg in saliva There are 1 Billion pg in 1 mg 34
Why Not Saliva with Sublingual Contamination of the mouth lasts longer than increased blood levels Personal levels T<100 (unfortunately) at baseline Personal levels peaked at >100,000,000 with troche Results are of no value Waiting 30 hours is not an option 35
Urine with Sublingual Hormones Hormones get into circulation and urine gets its fair share 36
Urine with Sublingual Hormones Hormones get into circulation and urine gets its fair share This should work But it Doesn t...if you swallow it! 37
Monitoring Sublingual HRT No solution can help with dosing Urine testing adds value (metabolites help in estrogen, progesterone evaluation) and can work if not swallowed 38
TESTING MATRIX Serum Saliva 24 Hour Urine ne THERAPY Replaceme Vaginal C Rise and fall is unpredictable, so timing is difficult D Rise and fall is unpredictable, so timing is difficult D +Works for Pg Estrogen/Test contamination VAGINAL HORMONES 39 New Precision Analytical Option B+ IDEAL OPTION free hormone contamination is removed
VAGINAL HORMONES What happens 40
VAGINAL TESTOSTERONE & Serum 41
VAGINAL TESTOSTERONE Person #2 Person #1 Placebos 42
43 VAGINAL PROGESTERONE
Vaginal Hormone variables Hormone (E2, E3, Pg, T) Delivery Size Concentration Base (oil, water) Timing Inter individual variance 44
Vaginal Hormones and Urine Reduces the timing problem of blood/saliva BUT Testo/Estrogens contaminate urine THERE IS A SOLUTION! 45
Vaginal Hormones and Urine Testosterone (or estrogens) must be conjugated to be excreted in urine Water Soluble Conjugate (Testo + sugar) 46
Vaginal Hormones Contaminate Urine 47
Vaginal Hormones Contaminate Urine 48
TESTING MATRIX Serum Saliva 24 Hour Urine ne THERAPY Replaceme Vaginal C Rise and fall is unpredictable, so timing is difficult D Rise and fall is unpredictable, so timing is difficult D +Works for Pg Estrogen/Test contamination VAGINAL HORMONES 49 Precision New Analytical Option B+ IDEAL OPTION free hormone contamination is removed
50 TESTING MATRIX Serum Saliva 24 Hour Urine Precision New Analytical Option ent Therapy Pellet/Inj. Cream (skin) Gel (skin) B D B +Well accepted and reliable methods No metabolites Values underrepresent some tissue levels Increases are more significant than with creams B D D Difficult analysis No metabolites A D B Hormones and metabolites Values underrepresent some tissue levels Increases are more significant than with creams A D B Hormones and metabolites THERAPY PELLETS / INJECTIONS % Values are too variable, change dramatically USE YOUR with different application sites, and do not represent systemic exposure FAVORITE TEST Values underrepresent some tissue levels Increases are more significant than with creams
51 TESTING MATRIX Serum Saliva 24 Hour Urine Precision New Analytical Option ent Therapy Pellet/Inj. Cream (skin) Gel (skin) B D B +Well accepted and reliable methods No metabolites Values underrepresent some tissue levels Increases are more significant than with creams B D D Difficult analysis No metabolites A D B Hormones and metabolites Values underrepresent some tissue levels Increases are more significant than with creams A D B Hormones and metabolites THERAPY % Values are too variable, change dramatically with different application sites, and do not represent systemic exposure Values underrepresent some tissue levels Increases are more significant than with creams
Salivary Testing with Topical Hormones 52 Saliva testing teaches us that some tissue get more hormone than is reflected in urine or serum testing when topical hormones are used. Salivary levels (with topical hormones) are too variable Levels change dramatically with: Different application sites Different base Levels do NOT reflect systemic exposure
Monitoring Transdermal Hormones 53
Monitoring Transdermal Hormones 54
Monitoring Transdermal Hormones 55
Let s Get Clinical!...with Transdermal Testosterone Too much T results in negative feedback and LH goes down (that s why testicles shrink) 100mg weekly injections suppress LH entirely 56
Let s Get Clinical!...with Transdermal Testosterone 50mg Transdermal Gel Saliva goes up >15 fold Serum/Urine go up modestly What happens to LH? 57
50mg partially suppresses LH 58 Swerdloff R S et al. JCEM 2000;85:4500-4510
Let s Get Clinical!...with Transdermal Testosterone LH suppression implies a modest dose, agreeing more with serum/urine testing Muscle increase only seen if serum goes up 59
60 TESTING MATRIX Serum Saliva 24 Hour Urine Precision New Analytical Option ent Therapy Pellet/Inj. Cream (skin) Gel (skin) B D B +Well accepted and reliable methods No metabolites Values underrepresent some tissue levels Increases are more significant than with creams B D D Difficult analysis No metabolites A D B Hormones and metabolites Values underrepresent some tissue levels Increases are more significant than with creams A D B Hormones and metabolites THERAPY % Values are too variable, change dramatically with different application sites, and do not represent systemic exposure Values underrepresent some tissue levels Increases are more significant than with creams
TESTING Best Way to Test? No Supplementation With Hormone Replacement Therapy MATRIX Sex Hormones Adrenal Oral Pg Oral (other) Vaginal Pellet/Inj. B D F B C B Serum Saliva 24 Hour Urine Precision New Analytical Option 61 +Well accepted and reliable methods No metabolites No diurnal free cortisol Inaccurate# and too Fast* +Works for DHEA, estrogens No metabolites Rise and fall is unpredictable, so timing is difficult +Well accepted and reliable methods No metabolites C B F B D B + Good for tracking levels thru cycle Difficult analysis No metabolites +Diurnal free cortisol No metabolites Inaccurate# and too Fast* Difficult analysis No metabolites Rise and fall is unpredictable, so timing is difficult Difficult analysis No metabolites A C C B D A +Mass spectrometry (accurate) Includes metabolites Difficult collection +Metabolites No diurnal cortisol Often "total" not "free" Metabolites of marginal value Difficult to avoid 1st pass metabolism (skip dose day of test) +Works for Pg Estrogen/Test contamination Hormones and metabolites A A+ C B B+ A Mass spectrometry (accurate) Includes metaoblites Easy collection IDEAL OPTION Diurnal Cortisol AND Metabolites! Metabolites of marginal value Difficult to avoid 1st pass metabolism (skip dose day of test) IDEAL OPTION free hormone contamination is removed Hormones and metabolites
Best Way to Test? Multiple Spot Urine Samples (with improved methods) 62
4 Spot Sample Value (ng/mg cr.) 63 24 Hour Value
Best Way to Test? Multiple Spot Urine Samples Easiest Collection (with improved methods) 64
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66 Dried Collections are Easier
Best Way to Test? Multiple Spot Urine Samples Easiest Collection (with improved methods) Represents more than ½of the day More clinical information (metabolites) Improved adrenal profile Diurnal free cortisol plus metabolism picture 67
Urinary Free Cortisol Salivary Free Cortisol Jerjes, (2005, 2006) 68
Problems with Cortisol Testing High Free Cortisol Low Free Cortisol Stage 1 Adrenal Fatigue Stage 3 Adrenal Fatigue 69 Overactive HPA Axis Underactive HPA Axis
A Tale of 2 Low Cortisols Free Cortisol Pattern Free Cortisol Pattern 70
A Tale of 2 Low Cortisols Cortisol Metabolites Free Cortisol Pattern Cortisol Metabolites Free Cortisol Pattern 71
A Tale of 2 Low Cortisols Cortisol Metabolites Free Cortisol Pattern Cortisol Metabolites Free Cortisol Pattern 72
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TESTING Best Way to Test? No Supplementation With Hormone Replacement Therapy MATRIX Sex Hormones Adrenal Oral Pg Oral (other) Vaginal Pellet/Inj. B D F B C B Serum Saliva 24 Hour Urine Precision New Analytical Option 74 +Well accepted and reliable methods No metabolites No diurnal free cortisol Inaccurate# and too Fast* +Works for DHEA, estrogens No metabolites Rise and fall is unpredictable, so timing is difficult +Well accepted and reliable methods No metabolites C B F B D B + Good for tracking levels thru cycle Difficult analysis No metabolites +Diurnal free cortisol No metabolites Inaccurate# and too Fast* Difficult analysis No metabolites Rise and fall is unpredictable, so timing is difficult Difficult analysis No metabolites A C C B D A +Mass spectrometry (accurate) Includes metabolites Difficult collection +Metabolites No diurnal cortisol Often "total" not "free" cortisol Metabolites of marginal value Difficult to avoid 1st pass metabolism (skip dose day of test) +Works for Pg Estrogen/Test contamination Hormones and metabolites A A+ C B B+ A Mass spectrometry (accurate) Includes metabolites Easy collection IDEAL OPTION Diurnal Cortisol AND Metabolites! Metabolites of marginal value Difficult to avoid 1st pass metabolism (skip dose day of test) IDEAL OPTION free hormone contamination is removed Hormones and metabolites
THANK YOU!!! For more information email mnewman@precisionhormones.com or visit www.precisionhormones.com (video library) 75