Mr Mark Newman - Anti-ageing Conference · 2014-09-16 · Urine testing adds value (metabolites...

Mr Mark Newman

Monitoring Hormone TherapyMark Newman, M.S.

President of Precision Analytical Inc.

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

OBJECTIVE• Discuss best options for monitoring

different types of HRT therapy

TESTINGMATRIX Sex Hormones Adrenal Oral Pg Oral (other) Sublingual Vaginal Pellet/Inj. Cream (skin) Gel (skin)

B D F B D C B D B

+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 under‐represent 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

Difficult analysis No metabolites

Contamination lasts longer than blood levels are

elevated

‐ 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)

metabolism from oral intake

+Works for Pg ‐ Estrogen/Test contamination

Hormones and metabolites

A A+ C B‐ C B+ A D BMass spectrometry

(accurate) Includes metabolites

Easy collection

IDEAL OPTION Diurnal Cortisol AND

Metabolites!

IDEAL OPTION free hormone contamination is removed

24‐Hour Urine

Precision Analytical

% Values are too variable, change dramatically with different application sites, and do not represent systemic exposure

No Supplementation With Hormone Replacement Therapy

Saliva

New Option

TESTINGMATRIX Sex Hormones Adrenal

C B+ Good for tracking levels thru cycle ‐ Difficult analysis No metabolites

"free"

A A+Mass spectrometry

Easy collection

Metabolites!

24‐Hour Urine

No Supplementation

Saliva

New Option

"free"

Easy collection

Metabolites!

24‐Hour Urine

No Supplementation

Saliva

New Option

"free"

Easy collection

Metabolites!

24‐Hour Urine

No Supplementation

Saliva

New Option

Puberty Menopause HRT

Young Healthy

There is not a simple equivalency between these with lab results

Which Route of Administration

• Oral• Sublingual• Vaginal and transmucosal • Injections and pellets• Transdermal

Administration

SublingualVaginal and transmucosalInjections andTransdermal

EACH ONE IS UNIQUE!

TESTINGMATRIX

24‐Hour Urine

Saliva

Oral Pg Oral (other)

‐ No metabolites

F B‐

C B‐

THERAPY

New Option

ORAL HORMONES

TESTINGMATRIX

24‐Hour Urine

Saliva

‐ No metabolites

F B‐

C B‐

THERAPY

New Option

ORAL PROGESTERONE

Oral Pg doesn’t increase Pg levels

>6ng/mL is considered consistent with ovulation

VAGINAL vs Oral Progesterone

ORAL PROGESTERONE

• Serum/Saliva• Return to baseline is too fast (2 hours)• Most tests are inaccurately high

LC‐MS MS = true value

EIA = False Positive

ORAL PROGESTERONE

• Urine• Small doses don’t raise serum levels, but lead

to very high urine metabolites (1st‐pass)• Marginally valuable information can be taken

from specific metabolism patterns

ORAL PROGESTERONE

• Testing is of limited value

TESTINGMATRIX

24‐Hour Urine

Saliva

‐ No metabolites

F B‐

C B‐

THERAPY

New Option

ORAL HORMONES

TESTINGMATRIX

24‐Hour Urine

Saliva

‐ No metabolites

F B‐

C B‐

THERAPY

New Option

ORAL HORMONES

Baseline (healthy)

Deficiency (induced)

H.R.T.

ORAL ESTROGENS

Rise and fall is slow, so serum or saliva testing can be effective

ORAL ESTROGENS and SERUMSerum E2(nm

Hours Since Dose

2525Oral Estrogen and Urine TestingOral Estrogen and Urine Testing

Postmenopausal RangePostmenopausal Range0.20.2--0.80.8

Estrogen Metabolites and CancerEstrogen Metabolites and Cancer

TESTINGMATRIX

24‐Hour Urine

Saliva

Sublingual

Too Fast* (back to baseline in <3hrs)

FContamination lasts longer than blood levels are

elevated

CDifficult to avoid

1st‐pass metabolism from

oral intake

With HormonTHERAPY

New Option

SUBLINGUAL HORMONES

NO GOOD TEST!

Why Not Serum with Sublingual

TOO FAST! Gone before you can measure

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

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

Urine with Sublingual Hormones

• Hormones get into circulation and urine gets its fair share

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!

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

TESTINGMATRIX

24‐Hour Urine

Saliva

Vaginal

CRise and fall is unpredictable, so timing is difficult

DRise and fall is unpredictable, so timing is difficult

B+ IDEAL OPTION free hormone contamination is removed

ne ReplacemeTHERAPY

New Option

VAGINAL HORMONES

• What happens…

VAGINAL TESTOSTERONE & Serum

VAGINAL TESTOSTERONE

Person #1

Person #2

Placebos

VAGINAL PROGESTERONE

Vaginal Hormone – variables

• Hormone (E2, E3, Pg, T)• Delivery

• Size• Concentration• Base (oil, water)

• Timing• Inter‐individual variance

Vaginal Hormones and Urine

• Reduces the timing problem of blood/saliva…BUT…

• Testo/Estrogens contaminate urine• THERE IS A SOLUTION!

Vaginal Hormones and Urine

Testosterone (or estrogens) must be conjugated to be excreted in urine

Water Soluble Conjugate (Testo + sugar)

Vaginal Hormones Contaminate Urine

TESTINGMATRIX

24‐Hour Urine

Saliva

Vaginal

CRise and fall is unpredictable, so timing is difficult

DRise and fall is unpredictable, so timing is difficult

B+ IDEAL OPTION free hormone contamination is removed

ne ReplacemeTHERAPY

New Option

VAGINAL HORMONES

TESTINGMATRIX

24‐Hour Urine

Saliva

Pellet/Inj. Cream (skin) Gel (skin)

B D B+Well accepted and reliable methods

‐ No metabolites

B‐ D D

ent Therapy THERAPY

New Option

PELLETS / INJECTIONS

USE YOUR FAVORITE TEST

TESTINGMATRIX

24‐Hour Urine

Saliva

‐ No metabolites

B‐ D D

ent Therapy THERAPY

New Option

Salivary Testing with Topical Hormones

• 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

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

• Testosterone –

50mg Transdermal Gel• Saliva goes up >15‐fold• Serum/Urine go up modestly• What happens to LH?

50mg partially suppresses LH

Swerdloff R S et al. JCEM 2000;85:4500-4510

• Testosterone• LH suppression implies a modest dose,

agreeing more with serum/urine testing• Muscle increase only seen if serum goes up

TESTINGMATRIX

24‐Hour Urine

Saliva

‐ No metabolites

B‐ D D

ent Therapy THERAPY

New Option

Best Way to Test?TESTINGMATRIX Sex Hormones Adrenal Oral Pg Oral (other) Vaginal Pellet/Inj.

B D F B C B

‐ No metabolites

C B F B‐ D B‐+ Good for tracking levels thru cycle ‐ Difficult analysis No metabolites

A C C B‐ D A

"free"

A A+ C B‐ B+ AMass spectrometry

(accurate) Includes metaoblites

Easy collection

Metabolites!

Saliva

24‐Hour Urine

New Option

Best Way to Test?

Multiple “Spot”

Urine Samples (with improved methods)

6363 24‐Hour Value

4 Spot Sam

ple Value

(ng/mg cr.)

Best Way to Test?

Multiple “Spot”

Urine Samples (with improved methods)

•Easiest Collection

Dried Collections are Easier

Best Way to Test?Multiple “Spot”

Urine Samples

(with improved methods)

•Easiest Collection•Represents more than ½ of the day•More clinical information (metabolites)•Improved adrenal profile

• Diurnal free cortisol plus metabolism picture

Jerjes, (2005, 2006)

Urinary Free Cortisol

Salivary Free Cortisol

Problems with Cortisol Testing

High Free Cortisol Low Free Cortisol

Overactive HPA‐Axis

Underactive HPA‐Axis

Stage 1 Adrenal Fatigue

Stage 3 Adrenal Fatigue

A Tale of 2 Low Cortisols

Free Cortisol PatternFree Cortisol Pattern

Cortisol Metabolites Cortisol Metabolites

Best Way to Test?TESTINGMATRIX Sex Hormones Adrenal Oral Pg Oral (other) Vaginal Pellet/Inj.

B D F B C B

‐ No metabolites

C B F B‐ D B‐+ Good for tracking levels thru cycle ‐ Difficult analysis No metabolites

A C C B‐ D A

+Metabolites ‐ No diurnal cortisol Often "total" not "free" cortisol

A A+ C B‐ B+ AMass spectrometry

Easy collection

Metabolites!

Saliva

24‐Hour Urine

New Option

THANK YOU!!!

For more information email

mnewman@precisionhormones.com

or visit

www.precisionhormones.com

(video library)

Mr Mark Newman - Anti-ageing Conference · 2014-09-16 · Urine testing adds value (metabolites...

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