Estrogen Metabolism
Patrick Hanaway, MD
====================================================================================
A4M :: Conference Library
GS02m - Estrogen Metabolism: Modifying Risk in Clinical Practice
$20.00 Speaker: Patrick Hanaway, MD
April 9, 2006 5:00 pm - 5:40 pm
=====================================
My take home (due to many discussions):
Brassica, I3C and DIM are important, in this order, I3C should not be missed.
I am staying with DualAction.
rosemary, turmeric, kudzu (Dr Delgado supplement contains kudzu)
======================================
RPHMark
please refresh your memory, you are probably well qualified to provide executive summary of:
testing, what to test, how blood urine, how read report
corrective actions, list of supplemets, doses, details
____________________________________________
DIM hinders 16-OHE formation. 16-OHE is prohormone for Estriol.
This is a BIG question when considering use of I-3-C/DIM, along with issues of possible androgen receptor antagonism (anyone seen anythng more about that?).
But, as you have pointed out,
iodine favors conversion of 16-OHE to E3.
Hey, wait a minute! I wonder if low iodine--DEFINITELY linked to cancers--is what induces elevated 16-OHE (also linked to cancers), since it then does not flow downstream to protective Estriol???
=====================================================================
=====================================================================
Dr. Hanaway spoke at a conference I atttended, and let me say, the dude can go DEEP into estrogen metabolism and genetic polymorphisms leading to cancer. I am virtually certain I remember him making that low iodine to increased 16OHE connection. So Dr. John, does it make sense to use DIM/I3C to block some 16OHE conversion and supply exogenous Estriol for a protective effect (in addition to the previously mentioned arimidex)?
========================================================================
2/16 Estrogen Metabolism:
Modifying Risk
in Clinical Practice
Patrick Hanaway, MD
-----------------------------------------------------------------------------------
page 10
Estrone(E1) -->2-hydroxyestrone (protective page12)
promote-Indole 3C, excercise, flax, ligams, soy, EPA
inhibit-Pesticide, ETOH (what is that)
---
Estrone(E1) ---> 16-alpha-Hydroxyestrone (carcinogenic page 12)
inhibit-obesity, hypothyroidism, pesticide, cimetidine (Taganent)
Estrone---> 4-OHE1
4-OHE1---- can be neutralized (good) or convert to Quinones (carcinogenic)
-----------------------------------------------------------------------------------
Modification of 2:16 OHE1 Ratio
16 OH-estrone (confers risk)
increased by:
• pesticides
• obesity
• cimetidine
• hypothyroidism
Generally, it is the
2OH-Estrone
that is more modifiable
----------------------------
Modification of 2:16 OHE1 Ratio
2 OH-estrone (protective)
increased by:
• flaxseed
• omega-3 fatty acids
• soy isoflavones
• indole 3-carbinol (I3C)
• diindolylmethane (DIM)
• rosemary, turmeric, kudzu (Dr Delgado supplement contains kudzu)
• strenuous exercise
• weight loss
-------------------------------------------------------------------------
Testing Considerations
• Measure in serum or urine; and stay
with same specimen type for followup
monitoring of risk!
• For women on Hormone Therapy
collect specimen 8-10 hrs after last
dose
• 2-OHE1 clears more rapidly in urine
than the 16α-OHE1
• First morning urine for greater
concentration
-----------------------------------------------------------------------------
page 50
The apparent induction of CYP1A1 was mirrored by a
66% increase in the urinary 2-hydroxyestrone/ 16α-
hydroxyestrone ratio in response to I3C.
The maximal
increase was observed with the 400 mg daily dose of I3C,
with no further increase found at 800 mg daily.
----------------------------------------------------------------------------
page 49
Cytochrome P-450
1A1 & 1B1
Intervention:
• Red wine extract (resveratrol)
• DHEA: Inhibits induced expression of
CYP1B1 (in vitro study)
• Increase 2-hydroxylation of estrogen
• I3C and DIM inhibit CYP1B1
• Antioxidants
• Minimize exposure to xenoestrogens
------------------------------------------------------------------------------
page 58
COMT– Intervention
• Limit alcohol intake
• Support methionine metabolism (+/+
women with breast CA have higher Hcy)
with SAMe supplementation; B-Vitamins
• Anti-oxidants (reduce quinones)
• Avoid excess weight, stress
• Avoid oral HRT (E2 levels higher in
supplemented women with SNP; which
is associated with increased breast
density on ERT)
--------------------------------------------------------------------------------
page 60
GST – Intervention
• Glutathione precursors and cofactors (NAC, Lglutamine,
glycine, Mg, methionine or SAMe)
• Minimize GSH depletion (e.g., alpha lipoic acid,
silymarin, ginkgo biloba, whey protein)
• Anti-oxidants
• Brassica based diets (stimulates GSTs and
provides chemoprotective isothiocyanates to
GSTM1-nulls)
• Allium diet increases GST activity, even in
GSTM1-null individuals
--------------------------------------------------------------------------------
In Summary. . .
Support Healthy metabolic pathways:
• Increase Production of 2-OH Estrone (E1)
• CYP450 1A1
• Decrease Production of 4- and 16-OH E1
• CYP450 1B1
• Increase Production of 2-Me Estrone (E1)
• COMT
• Decrease Production of 4- Quinones
• GST
---------------------------------------------------------------------------------
In Summary. . .
Women using Hormone Therapy should
be offered Genomic testing:
CYP450 1A1
CYP450 1B
COMT
GST
-----------------------------------------------------------------------------------
• Estrone Sulfate (E1S)
• Estrone (E1)
• Estradiol (E2)
• Estriol (E3)