Progesterone and Breast health

Bioidentical Hormones

A lie repeated often
enough becomes
"the truth."

Fact: Bioidentical
hormone studies do
exist.
Click here for a
review and
bibliography.

Estrogen is the "proliferative" hormone. One of its functions is to make
things grow such as when the endometrial lining builds up in preparation
for conception. Progesterone is the "antiproliferative" hormone. It
opposes/constrains estrogen in very specific ways. See the links below.

As we age, our progesterone begins waning first, a decade or more
before estrogen wanes. Here is where the so-called estrogen
dominance concept comes in. Our bodies make too little progesterone in
relationship to estrogen. This is when we become most vulnerable to
breast cancer. But women may have life long progesterone deficiencies
as well: irregular periods, PMS, miscarriage, mood swings, blood sugar
problems and other symptoms may reflect too little progesterone.

Information to get started researching progesterone

Start with

an overview and introduction:

ideo

of Steven Hotze

, MD

2. Read

What Your Doctor May Not Tell you About Breast Cancer

by John

Lee, MD,

and David Zava, PhD.

Watch

Henry Linder, MD's

Powerpoint

--you may want to skim until you

get to

the progesterone parts around slide 22.

. Th

annotated bibliography

below of progesterone research

goes

into

deeper

detail

and will document the workings of progesterone

provide

a broader

understanding

and scientific documentation.

********
For Advanced Reading: Medical studies on progesterone

Acknowledgement

for annotations

to: http://www.cabecahealth.

com/media/sites/36/files/ProgesteronandBreastbibliography.pdf

Campagnoli C, Abba C, Ambroggio S, Peris C.
Pregnancy, progesterone and progestins in relation to breast cancer risk.
J Steroid Biochem Mol Biol 2005; 97(5):441-50.
The authors review recent findings that show that the production of progesterone
during pregnancy and the use of bioidentical progesterone in hormone therapy do
not increase breast cancer risk, and can even protect against the development of
breast cancer.

Kaaks R, et al.
Serum sex steroids in premenopausal women and breast cancer risk within
the European Prospective Investigation into Cancer and Nutrition (EPIC).
J Natl Cancer Inst 2005; 97:755-65.
In this large multicenter study, higher serum progesterone levels were associated
with a significant reduction in breast cancer risk.

Fournier A, Berrino F, Riboli E, Avenel V, Clavel-Chapelon F.
Breast cancer risk in relation to different types of hormone replacement
therapy in the E3N-EPIC cohort. Int J Cancer 2005; 114(3):448-54.
Combined HRT with estrogen (either oral or transdermal) and synthetic progestins
was found to carry a significantly increased risk of breast cancer compared with
estrogens plus oral micronized progesterone. In fact, no increase in breast
cancer risk was seen in the estrogen plus oral micronized progesterone group
compared with estrogen alone. This large multicenter study therefore suggests
that there is a dramatic difference between the effects of bioidentical
progesterone versus synthetic progestins on breast cancer risk.

Missmer SA, Eliassen AH, Barbieri RL, Hankinson SE.
Endogenous estrogen, androgen, and progesterone concentrations and
breast cancer risk among postmenopausal women. J Natl Cancer Inst 2004; 96
(24):1856-65.
Blood progesterone levels were found not to be related to breast cancer risk in
this first study to investigate this in postmenopausal women. The occurrence of
progesterone receptor positive tumors was the tumor type most strongly affected
by all the circulating steroid hormones measured except for progesterone. Higher
levels of endogenous estrogens and androgens were significantly correlated with
increasing breast cancer incidence. This suggests that circulating natural
progesterone does not increase breast cancer risk.

Malet C, Spritzer P, Guillaumin D, Kuttenn F.
Progesterone effect on cell growth, ultrastructural aspect and estradiol
receptors of normal human breast epithelial (HBE) cells in culture. J Ster
Biochem Mol Biol 2002; 73: 171-181.
In a culture system, progesterone was found to have an inhibitory effect on breast
cell growth. When given following estradiol (E2), it limited the stimulatory effect of
E2 on cell growth.

Desreux J, Kebers F, Noel A, Francart D, Van Cauwenberge H, Heinen V,
Thomas JL, Bernard AM, Paris J, Delansorne R, Foidart JM.
Progesterone receptor activation- an alternative to SERMs in breast cancer.
Eur J Cancer 2000 Sep;36 Suppl 4:S90-1.
This review emphasizes progesterone's role in supporting healthy breast
homeostasis and opposing the proliferative effects of estradiol in the breast,
unlike synthetic progestins.

Plu-Bureau G, Le MG, Thalabard JC, Sitruk-Ware R, Mauvais-Jarvis P.
Percutaneous progesterone use and risk of breast cancer: results from a
French cohort study of premenopausal women with benign breast disease.
Cancer Detect Prev 1999;23(4):290-6.
This cohort study followed 1150 premenopausal French women diagnosed with
benign breast disease. Topical progesterone cream, a common treatment for
mastalgia in Europe, had been prescribed to 58% of the women. Follow-up
accumulated 12,462 person-years. There was no association noted between
progesterone cream use and breast cancer risk. Furthermore, women who had
used both progesterone cream and an oral progestogen had a significant
decrease in breast cancer risk (RR= 0.5) as compared to women who did not use
progesterone cream. There was no significant difference in the risk of breast
cancer in percutaneous progesterone users versus nonusers among oral
progestogen users. These results suggest there are no deleterious effects caused
by percutaneous progesterone use in women with benign breast disease.

Formby B, Wiley TS.
Bcl-2, survivin and variant CD44 v7-v10 are downregulated and p53 is
upregulated in breast cancer cells by progesterone: inhibition of cell growth
and induction of apoptosis. Mol Cell Biochem 1999 Dec;202(1-2):53-61.
This study sought to elucidate the mechanism by which progesterone inhibits the
proliferation of breast cancer cells. Utilizing breast cancer cell lines with and
without progesterone receptors (T47-D and MDA-231, respectively) in vitro, the
authors looked at apoptosis (programmed cell death) in response to progesterone
exposure as a possible mechanism. The genetic markers for apoptosis - p53, bcl-2
and surviving, were utilized to determine whether or not the cells underwent
apoptosis. The results demonstrated that progesterone does produce a strong
antiproliferative effect on breast cancer cell lines containing progesterone
receptors, and induced apoptosis. The relatively high levels of progesterone
utilized were similar to those seen during the third trimester of human pregnancy.

Lin VC, Ng EH, Aw SE, Tan MG, Ng EH, Chan VS, Ho GH.
Progestins inhibit the growth of MDA-MB-231 cells transfected with
progesterone receptor complementary DNA. Clin Cancer Res 1999 Feb;5(2):395-
403.
Progesterone is mainly thought to exert its effects via the estrogen-dependent
progesterone receptor (PR), the effects of which may be overshadowed by the
presence of estrogen. In order to study the independent effects of progesterone
on breast cancer cell lines, PR expression vectors were transfected into a PR and
ER negative cell line (MDA-MB-231). The growth of these cells was then studied in
response to progesterone and several progestins. Progesterone was found to
significantly inhibit DNA synthesis and cell growth in a dose-dependant fashion.
The results of this study indicate that progesterone and progestins independent of
estrogen have an antiproliferative effect on breast cancer cells via the
progesterone receptor. This suggests a possible role in the treatment of PR
negative breast cancer via re-activation of the PR receptor.

Formby B, Wiley TS.
Progesterone inhibits growth and induces apoptosis in breast cancer cells:
inverse effects on Bcl-2 and p53. Ann Clin Lab Sci 1998 Nov-Dec;28(6):360-9.
This study explored the mechanism by which progesterone inhibits breast cancer
cell proliferation (growth). In progesterone receptor positive T47-D breast cancer
cells, the mechanism of apoptosis appeared to be through the regulation of the
genes p53 and bcl-2 by progesterone. These genes control the apoptotic process.
It was demonstrated that at progesterone levels that approximate the third
trimester of pregnancy, there was a strong antiproliferative effect in at least 2
breast cancer cell lines.

Foidart JM, Colin C, Denoo X, Desreux J, Beliard A, Fournier S, de Lignieres B.
Estradiol and progesterone regulate the proliferation of human breast
epithelial cells. Fertil Steril 1998 May;69(5):963-9.
In this double-blind randomized study, to evaluate the effects of estrogen and
progesterone on normal breast cells, 40 postmenopausal women received daily
topical application of a gel containing either placebo, estradiol, progesterone, or
estradiol + progesterone for two weeks prior to esthetic breast surgery or the
excision of a benign breast lesion. The results showed that increased estrogen
concentration increased the number of cycling epithelial cells, whereas exposure
to progesterone for 14 days reduced the estrogen-induced proliferation of normal
breast epithelial cells.

Pasqualini JR, Paris J, Sitruk-Ware R, Chetrite G, Botella J.
Progestins and breast cancer. J Steroid Biochem Mol Biol 1998 Apr;65(1-6):225-
35.
This review article outlines the many functions of progestogens in hormone-
dependent and independent breast cancer and suggests new clinical applications
for their use in the treatment of breast cancer.

Mohr PE, Wang DY, Gregory WM, Richards MA, Fentiman IS.
Serum progesterone and prognosis in operable breast cancer.
British Journal of Cancer 1996;73:1532-1533.
Higher blood levels of progesterone measured during surgical treatment of breast
cancers were associated with significantly better survival, especially in women
who were node-positive (P<0.01). There was no significant relationship between
estradiol levels and survival. This study demonstrated that a higher level of
progesterone at time of excision is associated with improved prognosis in women
with operable breast cancer.

Chang KJ, et al.
Influences of percutaneous administration of estradiol and progesterone on
human breast epithelial cell cycle in vivo. Fertil Steril 1995; 63(4):785-91.
The effect of transdermal estradiol (1.5 mg), transdermal progesterone (25 mg),
and combined transdermal estradiol and progesterone (1.5 mg and 25 mg) on
human breast epithelial cell cycles was evaluated in vivo. Results demonstrated
that estradiol significantly increases cell proliferation, while progesterone
significantly decreases cell replication below that observed with placebo.
Transdermal progesterone was also shown to reduce estradiol-induced
proliferation.

Laidlaw IJ, Clarke RB.
The proliferation of normal breast tissue implanted into athymic nude mice is
stimulated by estrogen, but not by progesterone. Endocrinology Jan 1995;136
(1):164-71.
Normal human breast tissue was implanted subcutaneously into athymic nude
mice. The mice were then treated with estradiol or progesterone such that serum
levels approximated those seen in normal menstruating women.
Immunocytochemical measures were made of proliferative activity and steroid
receptor expression of the tissue implants. It was found that physiologic levels of
estradiol significantly stimulated the proliferation of human breast epithelial cells
and increased progesterone receptor expression 10-20-fold. Progesterone failed to
affect proliferation alone or after estradiol priming.

Nappi C, Affinito P.
Double-blind controlled trial of progesterone vaginal cream treatment for
cyclical mastodynia in women with benign breast disease. J Endocrin Invest
1994;15(11):801-6.
Eighty regularly menstruating women with mastodynia were studied to evaluate
the clinical effectiveness of vaginally administered micronized progesterone.
Subjects were randomly assigned to one of two groups, with all participating in a
control cycle prior to treatment. One group received 4 grams of vaginal cream
containing 2.5% natural progesterone for six cycles from day 19 to day 25 of the
cycle. The other group was similarly treated with placebo. Both subjective
reporting on a daily basis and clinical examination revealed a significant
reduction in breast pain, defined as 50% reduction, in 64.9% of subjects receiving
progesterone and 22.2% of subjects receiving placebo. Effects of breast
nodularity were not significant. No side effects were detected.

Mauvais-Jarvis P, Kuttenn F, Gompel A.
Antiestrogen action of progesterone in breast tissue. Horm Res 1987;28(2-4):
212-8.
In a review of international literature on the cellular effects of progesterone on
both normal breast cells and breast cancer cell lines, the authors conclude that
most data indicate progesterone and progestins have an antiestrogenic effect on
the breast, as reflected in the decrease in estradiol receptor content, the
decrease in cell proliferation, and an increase in a marker of cell differentiation,
17 beta-hydroxysteroid activity, which is mediated by the progesterone receptor.

Cowan LD, Gordis L, Tonascia JA, et al.
Breast cancer incidence in women with a history of progesterone deficiency.
American Journal of Epidemiology 1981; 114:209. ,083.
Infertile women were followed for 14-34 years. Those who were deficient in
progesterone showed a fivefold greater incidence of premenopausal breast
cancer.

The purpose of patient
education is to equip
the patient to make
informed decisions for
her own treatment--
NOT to convince her
doctor of the validity of
her decisions. --MH

To understand natural progesterone's role in breast health,
patients often must out-read practitioners who have been
misinformed about progesterone.

Progesterone research emerged widely in the mid 90s although
it had been studied long before. Many integrative practitioners
familiar with the research have used progesterone widely in
their practices for many years.

Can progesterone help breast cancer patients?

Click here: Christine Northrup, MD, explains