Mr Mark Newman - Anti-ageing Conference · 2014-09-16 · Urine testing adds value (metabolites help in estrogen, ... hormone than is reflected in urine or serum testing when topical

Mr Mark Newman

2222

Monitoring Hormone TherapyMark Newman, M.S.

President of Precision Analytical Inc.

33

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

44

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

Serum

Saliva

New Option

55

TESTINGMATRIX Sex Hormones Adrenal

B D



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


A C




"free"

A A+Mass spectrometry


Easy collection


Metabolites!

24‐Hour Urine


No Supplementation

Serum

Saliva

New Option

66

77


B D





A C




"free"



Easy collection


Metabolites!

24‐Hour Urine


No Supplementation

Serum

Saliva

New Option

88


B D





A C




"free"



Easy collection


Metabolites!

24‐Hour Urine


No Supplementation

Serum

Saliva

New Option

99

Puberty Menopause HRT

Young Healthy

HRT

There is not a simple equivalency between these with lab results

1010

Which Route of Administration

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

Administration

SublingualVaginal and transmucosalInjections andTransdermal

EACH ONE IS UNIQUE!

1111

TESTINGMATRIX

24‐Hour Urine


Serum

Saliva

Oral Pg Oral (other)

F B



‐ No metabolites

F B‐



C B‐




C B‐




THERAPY

New Option

ORAL HORMONES

1212

TESTINGMATRIX

24‐Hour Urine


Serum

Saliva


F B



‐ No metabolites

F B‐



C B‐




C B‐




THERAPY

New Option

ORAL PROGESTERONE

1313

Oral Pg doesn’t increase Pg levels

>6ng/mL is considered consistent with ovulation

1414

VAGINAL vs Oral Progesterone

1515

ORAL PROGESTERONE

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

1616

LC‐MS MS = true value

EIA = False Positive

1717

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

1818

ORAL PROGESTERONE

• Testing is of limited value

1919

TESTINGMATRIX

24‐Hour Urine


Serum

Saliva


F B



‐ No metabolites

F B‐



C B‐




C B‐




THERAPY

New Option

ORAL HORMONES

2020

TESTINGMATRIX

24‐Hour Urine


Serum

Saliva


F B



‐ No metabolites

F B‐



C B‐




C B‐




THERAPY

New Option

ORAL HORMONES

2121

Baseline (healthy)

Deficiency (induced)

H.R.T.

2222

2323

ORAL ESTROGENS

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

2424

ORAL ESTROGENS and SERUMSerum E2(nm

ol)

Hours Since Dose

2525Oral Estrogen and Urine TestingOral Estrogen and Urine Testing


Postmenopausal RangePostmenopausal Range0.20.2--0.80.8

2727

Estrogen Metabolites and CancerEstrogen Metabolites and Cancer




3131

TESTINGMATRIX

24‐Hour Urine


Serum

Saliva

Sublingual

D

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

FContamination lasts longer than blood levels are

elevated

C



CDifficult to avoid

1st‐pass metabolism from

oral intake

With HormonTHERAPY

New Option

SUBLINGUAL HORMONES

NO GOOD TEST!

3232

Why Not Serum with Sublingual

TOO FAST! Gone before you can measure

3333

3434

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

3535

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

3636

Urine with Sublingual Hormones

• Hormones get into circulation and urine gets its fair share

3737

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!

3838

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

3939

TESTINGMATRIX

24‐Hour Urine


Serum

Saliva

Vaginal

CRise and fall is unpredictable, so timing is difficult

DRise and fall is unpredictable, so timing is difficult

D


B+ IDEAL OPTION free hormone contamination is removed

ne ReplacemeTHERAPY

New Option

VAGINAL HORMONES

4040

VAGINAL HORMONES

• What happens…

4141

VAGINAL TESTOSTERONE & Serum

4242

VAGINAL TESTOSTERONE

Person #1

Person #2

Placebos

4343

VAGINAL PROGESTERONE

4444

Vaginal Hormone – variables

• Hormone (E2, E3, Pg, T)• Delivery

• Size• Concentration• Base (oil, water)

• Timing• Inter‐individual variance

4545

Vaginal Hormones and Urine

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

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

4646

Vaginal Hormones and Urine

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

Water Soluble Conjugate (Testo + sugar)

4747

Vaginal Hormones Contaminate Urine

4848

Vaginal Hormones Contaminate Urine

4949

TESTINGMATRIX

24‐Hour Urine


Serum

Saliva

Vaginal

CRise and fall is unpredictable, so timing is difficult

DRise and fall is unpredictable, so timing is difficult

D


B+ IDEAL OPTION free hormone contamination is removed

ne ReplacemeTHERAPY

New Option

VAGINAL HORMONES

5050

TESTINGMATRIX

24‐Hour Urine


Serum

Saliva

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

B D B+Well accepted and reliable methods

‐ No metabolites



B‐ D D


A D B




A D B





ent Therapy THERAPY

New Option

PELLETS / INJECTIONS

USE YOUR FAVORITE TEST

5151

TESTINGMATRIX

24‐Hour Urine


Serum

Saliva



‐ No metabolites



B‐ D D


A D B




A D B





ent Therapy THERAPY

New Option

5252

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

5353

Monitoring Transdermal Hormones

5454


5555


5656

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

5757


• Testosterone –

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

5858

50mg partially suppresses LH

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

5959


• Testosterone• LH suppression implies a modest dose,

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

6060

TESTINGMATRIX

24‐Hour Urine


Serum

Saliva



‐ No metabolites



B‐ D D


A D B




A D B





ent Therapy THERAPY

New Option

6161

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

B D F B C B





‐ No metabolites



‐ 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!








Serum

Saliva

24‐Hour Urine

New Option

6262

Best Way to Test?

Multiple “Spot”

Urine Samples (with improved methods)

6363 24‐Hour Value

4 Spot Sam

ple Value

(ng/mg cr.)

6464

Best Way to Test?

Multiple “Spot”

Urine Samples (with improved methods)

•Easiest Collection

6565

6666

Dried Collections are Easier

6767

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

6868

Jerjes, (2005, 2006)

Urinary Free Cortisol

Salivary Free Cortisol

6969

Problems with Cortisol Testing

High Free Cortisol Low Free Cortisol

Overactive HPA‐Axis

Underactive HPA‐Axis

Stage 1 Adrenal Fatigue

Stage 3 Adrenal Fatigue

7070

A Tale of 2 Low Cortisols

Free Cortisol PatternFree Cortisol Pattern

7171



Cortisol Metabolites Cortisol Metabolites

7272



Cortisol Metabolites Cortisol Metabolites

7373

7474

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

B D F B C B





‐ No metabolites



‐ 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!








Serum

Saliva

24‐Hour Urine

New Option

7575

THANK YOU!!!

For more information email

[email protected]

or visit

www.precisionhormones.com

(video library)

Documents

Mr Mark Newman - Anti-ageing Conference · 2014-09-16 · Urine testing adds value (metabolites help in estrogen, ... hormone than is reflected in urine or serum testing when topical