Breast Cancer and Natural Progesterone Part Two
Natural Progesterone and Breast Cancer Part One
PROGESTERONE DECREASES CELL PROLIFERATION NATIONAL CANCER INSTITUTE'S SYMPOSIUM ON ESTROGEN AS A- MAJOR CAUSE OF CANCER
The Fertility and Sterility Journal article was particularly interesting, as it was the first double blind, placebo controlled, randomized study using transdermal progesterone and transdermal estrogen (estradiol) on real women (40 of them) who were having breast biopsies. They had one at the beginning of the study and another biopsy 13 days later, and were able to check on several interesting things. The first thing of note was that even though the estrogen and the progesterone did not show up in the serum, it showed up in the breast tissue at over 100% increased levels above the placebo cream. The most interesting finding was what happened to cell proliferation during this 13 day test. The following chart shows two ways of measuring cell proliferation. The PCNA (proliferating cell nuclear antigen) is the most accurate, but both methods were used. Based on PCNA numbers (these tend to be the most accurate measurement) the numbers in the above chart showing increase or decrease of cell proliferation showed up in only 13 days. Translated into percentages the following 3 sentences summarize it.
Method of Measuring cell Proliferation Placebo, Progesterone, Estrogen, Estrogen & Progesterone
Mitosis per 1000 Cells
0.51
0.17
0.83
0.52
PCNA
7.8
1.9
17.4
6.5
Topical Progesterone reduced cell proliferation by 410%
Topical Estrogen increased cell proliferation by 223%
Topical Estrogen/Progesterone combination reduced cell proliferation by 16%
The numbers on this chart were excerpted from the Fertility and Sterility Journal, Vol. 63, No. 4, April, 1995. The exact reference is: Chang KJ, Lee TTY , Linares-Cruz G, Fournier S, de Lignieres B. Influences of percutaneous administration of estradiol on human breast epithelial cell cycle in vivo. Fertility and Sterility 1995; 63; 7865-7891.
If You Want To Increase Cell Proliferation Use Estrogen If You Want To Decrease Cell Proliferation Use Progesterone
The conclusion seems to be: if you want increased cell proliferation use estrogen. If you want decreased cell proliferation use progesterone. The entire study is worth reading, and is an excellent affirmation that what Dr. John Lee has been saying and writing is correct. This is not secret information, but it is being denied to the typical doctor of conventional medicine, even though similar information is in the AMA journal.
It is Dr. John Lee's contention that progesterone prevents breast cancer, and if you already have breast cancer progesterone protects you against reoccurrence or late metastases. In his medical practice he treated many women who had had mastectomies. In the 20 years since he started recommending the use of progesterone, not one of the hundreds of women he treated has died of breast cancer. Think about what the odds are on that number when you compare it to normal post mastectomy figures.
Progesterone Levels At Time of Breast Cancer Surgery Affect Survival Rates
In 1976 Dr. Mohr started a test at two major hospitals in London that did breast surgery. He requested that every time they had a breast surgery that they take a blood test and save it so that he could test the progesterone level at the time of surgery. He tested testosterone, progesterone and estrogen. He found that progesterone level at the time of surgery was correlated with better survival. The survival record was reviewed 18 years after breast cancer surgery in node positive patients: this means that the cancer had already spread, was already metastasizing.
Summary of Dr. Mohr's findings
Progesterone Level at The Time of Surgery
Survival percentage after 18 year
Adequate Progesterone (4ng/ml or more) 62%
Low Progesterone (less than 4 ng/ml) 30%
This was written up in the British Journal of Cancer in 1996. The title of the article is: “Serum Progesterone and Prognosis in Operable Breast Cancer.” This is over a 100% improvement just by having adequate progesterone level at the time of surgery. There is no treatment that provides that degree of benefits. Progesterone is the treatment.
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Estrogen a Major Cause of Cancer
Dr. Ercole Cavalieri, the head of cancer research at the University of Nebraska Medical Center (also one of the speakers at the NCI program shown below). He calls estrogen the angel of life, the angel of death. It is necessary at the beginning to create a successful pregnancy, and if you have estrogen dominance later in your life it is the angel of death. When the body tries to metabolize estradiol and estrone it is possible to end up in this pathway which ends up in cancer. This is real human estrogen, and the body is trying to get rid of it. If the body does it correctly it methylates it, and it is safely excreted. But if the person has been eating margarine or transfatty acids, things that are not real and are missing the essential fatty acids it falls into another pathway. If the same person is not getting the sulfated amino acids like methionine and cysteine that is in garlic and beans, it continues on in this pathway and binds to DNA, causes a mutation, and creates cancer and kills the person.
National Cancer Institute's Symposium on Estrogen as a Cause of Cancer
Estrogen is the cause of the cancer that women fear, and yet there are many doctors still giving them unopposed estrogen. The recent National Cancer Institute symposium March 16-17, 1998 basically states that estrogen is the cause of the cancer that is killing women. If you look at the following program to see some of the major medical research organizations stating this in their presentations, it sort of make you wonder why we didn't hear any of this on the news in any of the major media. It makes you wonder why unopposed estrogen is still being so widely used. Look at the following program:
The following symposium sponsored by the National Cancer Institute March 16-17,1998 was referred to by Dr. John R. Lee in his two tape series: "Progesterone Update
<https://www.vxn.com/springboard4health/forms/tape_order.html> ".
The content of the seminar fully supports Dr. Lee's assertion of the link between cancer and estrogen. Read the information below on their program, and you will find both the introduction and the titles of the presentations enough to make you pause before taking estrogen. Also listening to Dr. Lee's tapes will give you a good insight into some of the material presented at this symposium.
Estrogens as Endogenous Carcinogens in the Breast and Prostate
This symposium has been planned to explore the role of endogenous estrogens in the etiology of human breast and prostate cancer. An international group of scientists will share viewpoints and construct a more holistic understanding of the way estrogens induce cancer. Topics will include metabolic activations of estrogens to carcinogenic forms, deactivation of carcinogenic metabolites, and the role of estrogen receptor-mediated processes in tumor induction. One of the goals of this symposium is to provide the attendees with an overview of the direction of research on estrogen-induced cancer. Another goal is to identify biomarkers that can be useful in studies of cancer risk among humans and in the future development of preventive strategies. The overview of the role of estrogens in cancer obtained from this symposium will be useful for scientists engaged in a variety of cancer-related studies, as well as for epidemiologists, health planners, journalists and members of advocacy groups for breast and other human cancers.
The Program
Welcoming Remarks
Dr. David Longfellow
Chemical and Physical Carcinogenesis Branch
Division of Cancer Biology, NCI
Overview of Estrogens as Endogenous Carcinogens Introduction and Remarks
Co-Chairs:
Dr. David Longfellow
Dr. Richard Santen, University of Virginia Health Science Center
Cellular and Molecular Interactions in Breast Cancer: Role of Estrogen and Its Receptors
Dr. Joe Russo, Fox Chase Cancer Center
Endogenous Estrogens as Carcinogens Through Metabolic Activity
Dr. James Yager, The Johns Hopkins University
Estrogens as Endogenous Genotoxic Agents: DNA Adducts and Mutations Remarks:
Dr. Joachim Liehr, Stehlin Foundation for Cancer Research
Dr. Ercole Cavalieri, University of Nebraska Medical Center
Catechol Estrogen -3,4-Quinones and Apurinic Sites in Cancer Initiation
Dr. Ercole Cavalieri <#ercole> , University of Nebraska Medical Center
Endogenous Oxidants and DNA Damage
Dr. Krystyna Frenkel, New York University Medical Center
Estrogen-induced Gene Mutations
Dr. Deodutta Roy, University of Alabama at Birmingham
Tissue-Specific Synthesis and Oxidative Metabolism of Estrogens
Co-Chairs:
Dr. James Yager Dr. Colin Jefcoate, University of Wisconsin-Madison
Estrogen Formation by Aromatase in Breast Tissue
Dr. Richard Santen Metabolic Activation of Estrogens by 4-Hydroxylation
Dr. Joachim Liehr
Estrogen 4-Hydroxylation by Cytochrome P4501B1
Dr. Thomas Sutter, The Johns Hopkins University
Estrogen Metabolism by Conjugation
Co-Chairs:
Dr. Richard Weinshilboum, Mayo Medical School
Dr. Julius Axelrod, National Institute of Mental Health, Emeritus
Methylation of Catechol Estrogens by Catechol-O-methyltransferase (COMT)
Dr. Cyrus Creveling, National Institute of Diabetes and Digestive and Kidney Diseases
COMT Genetic Polymorphism and Breast Cancer
Dr. Patricia Thompson, National Center for Toxicological Research, FDA
COMT, CYP17, SRD5A Polymorphisms in Breast and Prostate Cancer
Dr. Douglas Bell, National Institute of Environmental Health Sciences
Estrogen Receptor-Mediated Processes in Normal and Cancer Cells
Co-Chairs:
Dr. George Stancel, University of Texas Medical School
Dr. Robert Dickson, Lombardi Cancer Center Dissection of the ER Signaling Pathway: Insights into the Mechanism of Tamoxifen Resistance
Dr. Donald McDonnell, Duke University Medical Center
Investigating the Role of ER-Alpha in Carcinogenesis Through the Use of Transgenic Mouse Models with Altered Levels of Receptor Expression
Dr. John Couse, National Institute of Environmental Health Sciences
Structure and Function of Estrogen Receptor-Beta
Dr. Jan-Ake Gustafsson, Karolinska Institute
Estrogen Receptor Structure, Modulators, and Targets in Hormone Responsive Tissues and Cancers
Dr. Geoffry Green, University of Chicago
Regulation of the Cell Cycle and Cell Death in Mammary Cancer
Dr. Robert Dickson
Estrogens and Cancer in Human Populations
Co-Chairs:
Dr. Louise Brinton, Environmental Epidemiology Branch Division of Cancer Epidemiology and Genetics, NCI
Dr. Shukmei Ho, Tufts University
Estrogen Levels and Breast Cancer Risk
Dr. Paolo Toniolo, New York University School of Medicine
Study Design Considerations in the Assessment of Cancer Risk in Relation to Genetic Polymorphisms
Dr. Montserrat Garcia-Closas, Environmental Epidemiology Branch, DCEG, NCI
Estrogens and Estrogen Metabolites: Technical Hurdles in Population Studies
Dr. Susan Hankinson, Brigham and Women's Hospital
DNA Biomarkers for Predicting Human Breast, Ovarian, and Prostate Cancer
Dr. Donald Malins, Pacific Northwest Research Foundation
Virginia Hopkins Health Watch - Vol 3, Issue 3
Progesterone Vs. Progestins in Monkeys
Wood CE, Register TC,
“Effects of estradiol with micronized progesterone or medroxyprogesterone acetate on risk markers for breast cancer in postmenopausal monkeys,”
Breast Cancer Res Treat (2007) 101:125-134
This is an important, even landmark study, not in the sense of bringing us new information, but in confirming what's already known but not substantially proven in published research to the satisfaction of those who don't quite grasp yet how safe and effective progesterone is in hormone replacement therapy.
Macaque monkeys are about as close as it can get to reproducing in animal research what will happen in humans. The goal of this study was to compare the effects of different types of HRT. Twenty-six macaque monkeys without ovaries were divided into groups and rotated through four HRT regimens lasting two months each, with a one-month washout period in-between. The four groups received either: 1) placebo, 2) estradiol, 3) estradiol and oral micronized progesterone (natural progesterone in a pill, 200 mg daily) or 4) estradiol and medroxyprogesterone acetate (MPA also known as Provera).
Breast epithelial proliferation, a type of cell growth that's a marker for breast cancer risk, was measured in each group after each type of treatment. Compared to placebo, treatment with estradiol and MPA resulted in significantly greater breast proliferation; treatment with estradiol and progesterone did not.
The conclusion of the authors: “These findings suggest that oral micronized progesterone has a more favorable effect on risk biomarkers for postmenopausal breast cancer than medroxyprogesterone acetate.”
http://www.virginiahopkinstestkits.com/vol3issue3.html#pgnewsv3i3
Journal of Steroid Biochemistry & Molecular Biology 97 (2005) 441-450
Pregnancy, progesterone and progestins in relation to breast cancer risk
Carlo Campagnoli °Ø, Chiara Abb`a, Simona Ambroggio, Clementina Peris
Unit of Endocrinological Gynecology,“Sant'Anna” Gynecological Hospital, Corso Spezia 60, 10126 Torino, Italy
Abstract
In the last two decades the prevailing opinion, supported by the “estrogen augmented by progesterone” hypothesis, has been that progesterone contributes to the development of breast cancer (BC). Support for this opinion was provided by the finding that some synthetic progestins, when added to estrogen in hormone replacement therapy (HRT) for menopausal complaints, increase the BC risk more than estrogen alone.
However, recent findings suggest that both the production of progesterone during pregnancy and the progesterone endogenously produced or exogenously administered outside pregnancy, does not increase BC risk, and could even be protective. The increased BC risk found with the addition of synthetic progestins to estrogen in HRT seems in all likehood due to the fact that these progestins (medroxyprogesterone acetate and 19-nortestosterone-derivatives) are endowed with some non-progesterone-like effects which can potentiate the proliferative action of estrogens. The use of progestational agents in pregnancy, for example to prevent preterm birth, does not cause concern in relation to BC risk.
© 2005 Elsevier Ltd. All rights reserved.
Keywords: Breast cancer; Pregnancy; Progesterone; Progestins
International Journal of Cancer
Volume 114, Issue 3 , Pages 448 - 454
Published Online: 18 Nov 2004
Copyright © 2004 Wiley-Liss, Inc.
Breast cancer risk in relation to different types of hormone replacement therapy in the E3N-EPIC cohort
Agnès Fournier 1, Franco Berrino 3, Elio Riboli 2, Valérie Avenel 1, Françoise Clavel-Chapelon 1*
1Equipe E3N, Institut National de la Santé et de la Recherche Médicale (INSERM), Villejuif, France
2Unit of Nutrition and Cancer, International Agency for Research on Cancer (IARC-WHO), Lyon, France
3Department of Preventive and Predictive Medicine, Istituto Nazionale Tumori, Milan, Italy
email: Françoise Clavel-Chapelon ( clavel@igr.fr )
*Correspondence to Françoise Clavel-Chapelon, Equipe E3N, INSERM, Institut Gustave-Roussy, 94805, Villejuif, France
Fax: +33-1-42-11-40-00
Funded by:
French League against Cancer
European Community
3M Company
Mutuelle Générale de l'Education Nationale
Institut Gustave-Roussy
Institut National de la Santé et de la Recherche Médicale
Abstract
Most epidemiological studies have shown an increase in breast cancer risk related to hormone replacement therapy (HRT) use. A recent large cohort study showed effects of similar magnitude for different types of progestogens and for different routes of administration of estrogens evaluated. Further investigation of these issues is of importance. We assessed the risk of breast cancer associated with HRT use in 54,548 postmenopausal women who had never taken any HRT 1 year before entering the E3N-EPIC cohort study (mean age at inclusion: 52.8 years); 948 primary invasive breast cancers were diagnosed during follow-up (mean duration: 5.8 years). Data were analyzed using multivariate Cox proportional hazards models. In this cohort where the mean duration of HRT use was 2.8 years, an increased risk in HRT users compared to nonusers was found (relative risk (RR) 1.2 [95% confidence interval 1.1-1.4]). The RR was 1.1 [0.8-1.6] for estrogens used alone and 1.3 [1.1-1.5] when used in combination with oral progestogens. The risk was significantly greater ( p<0.001) with HRT containing synthetic progestins than with HRT containing micronized progesterone, the RRs being 1.4 [1.2-1.7] and 0.9 [0.7-1.2], respectively. When combined with synthetic progestins, both oral and transdermal/percutaneous estrogens use were associated with a significantly increased risk; for transdermal/percutaneous estrogens, this was the case even when exposure was less than 2 years. Our results suggest that, when combined with synthetic progestins, even short-term use of estrogens may increase breast cancer risk. Micronized progesterone may be preferred to synthetic progestins in short-term HRT. This finding needs further investigation. © 2004 Wiley-Liss, Inc.
Received: 12 May 2004; Accepted: 12 August 2004
Digital Object Identifier (DOI)
10.1002/ijc.20710 About DOI
http://www3.interscience.wiley.com/cgi-bin/abstract/109795649/ABSTRACT?CRETRY=1&SRETRY=0
Pregnancy, progesterone and progestins in relation to breast cancer risk
Carlo Campagnoli * , Chiara Abb `a, Simona Ambroggio, Clementina Peris
Unit of Endocrinological Gynecology,“Sant’Anna” Gynecological Hospital, Corso Spezia 60, 10126 Torino, Italy
Abstract
In the last two decades the prevailing opinion, supported by the “estrogen augmented by progesterone” hypothesis, has been that progesterone
contributes to the development of breast cancer (BC). Support for this opinion was provided by the finding that some synthetic progestins,
when added to estrogen in hormone replacement therapy (HRT) for menopausal complaints, increase the BC risk more than estrogen alone.
However, recent findings suggest that both the production of progesterone during pregnancy and the progesterone endogenously produced or
exogenously administered outside pregnancy, does not increase BC risk, and could even be protective. The increased BC risk found with the
addition of synthetic progestins to estrogen in HRT seems in all likehood due to the fact that these progestins (medroxyprogesterone acetate
and 19-nortestosterone-derivatives) are endowed with some non-progesterone-like effects which can potentiate the proliferative action of
estrogens. The use of progestational agents in pregnancy, for example to prevent preterm birth, does not cause concern in relation to BC risk.
© 2005 Elsevier Ltd. All rights reserved.
