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Victoria
Natural progesterone:
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Is it legal?:
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1) http://www.fda.gov/cder/warn/cyber/cyber2002.htm
Cyber letters issued from CFSAN are to Internet Website Operators promoting
dietary supplement products that claim to diagnose, mitigate, treat, cure, or
prevent a specific disease or class of diseases.
2) http://www.fda.gov/cder/warn/cyber/2002/CFSANnewhorizons.htm
In addition, only products that are intended for ingestion may be lawfully
marketed as dietary supplements. Topical products and products intended to enter
into the body directly through the skin or mucosal tissues, such as transdermal
or sublingual products, are not dietary supplements. For these products, both
disease and structure/function claims may cause them to be new drugs.
Canada's Health Products and Food Branch on progesterone creams.:
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http://hc-sc.gc.ca/english/protection/warnings/1999/99_134e.htm
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FDA letters to companies on progesterone cremes:
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1) http://forums.obgyn.net/endo/ENDO.0207/0472.html
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2) http://forums.obgyn.net/womens-health/WHF.0208/0104.html
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FDA comments on dietary supplements:
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1) http://www.cfsan.fda.gov/~dms/qa-top.html
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2) http://www.ftc.gov/bcp/conline/pubs/buspubs/dietsupp.htm Dietary Supplements
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3) http://www.cfsan.fda.gov/~dms/supplmnt.html U.S. FDA Food Safety & Applied
Nutrition Dietary Supplements
4) http://www.cfsan.fda.gov/~dms/ds-oview.html#getinfo
5) http://www.cfsan.fda.gov/~dms/ds-savvy.html (includes information on
evaluating research/health info online)
6) http://www.cfsan.fda.gov/~dms/hclaims.html Conventional Foods and Dietary
Supplements Claims list
7) Is it legal to market a dietary supplement product as a treatment or cure for
a specific disease or condition? No, a product sold as a dietary supplement and
promoted on its label or in labeling* as a treatment, prevention or cure for a
specific disease or condition would be considered an unapproved--and thus
illegal--drug. To maintain the product's status as a dietary supplement, the
label and labeling must be consistent with the provisions in the Dietary
Supplement Health and Education Act (DSHEA) of 1994.
What do doctors say about this?:
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1) http://forums.obgyn.net/ob-gyn-l/OBGYNL.0205/0317.html
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Topical progesterone can be wonderful. 95% is metabolized to
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hydroxyprogesterones with little protective effect. Yet, these metabolites can
bind to the Cl ion channel, like valium. Salivary and serum progesterone
correlations tend to be quite high. (Dr. Mark Perloe, http://www.ivf.com, reproductive
endocrinologist):
2) http://forums.obgyn.net/ob-gyn-l/OBGYNL.0207/0039.html
Giving topical progesterone is worthless plain and simple. There are very large
amounts of 5 alpha reductase in the skin which will metabolize up to 98% of any
P administered topically. But they will feel good, since the 5 alpha reduced
progesterone will bind to the Cl ion channel receptor, the same place valium
binds.
3) http://forums.obgyn.net/womens-health/WHF.0209/1286.html (Dr. William D.
McIntosh, MD, FACOG)
Just because a medication is prescribed does not mean that it is not a placebo,
and just because it is not prescribed does not mean it is not an active drug.
Placebos are prescribed routinely, though the prescriber may not always
recognize that it IS a placebo. Progesterone cream has about the same response
rate as placebo, so the inference is that its benefits are primarily those of a
placebo. This inference is not a necessarily a fact, just a probability.
4) http://forums.obgyn.net/womens-health/WHF.0209/1079.html (R.Daniel Braun, MD
FACOG)
The studies show an 85% success rate with NOTHING. AND an 85% success rate with
the cream.
5) http://www.obgyn.net/newsheadlines/womens_health-Gynecology-20020808-8.asp
(Dr. Michael Kettel's work)
Dr. Michael Kettle and others have found Mifepristone (an anti-progesterone) to
help with endometriosis. If this is true in science studies, then how can
endometriosis be helped by more progesterone? Please see: (or do a search on
'endometriosis mifepristone' or 'endometriosis ru486' or 'endometriosis ru-486'
at http://www.ncbi.nlm.nih.gov, Pubmed)
a) Fertil Steril 2002 May;77(5):995-1000, Effect of mifepristone on estrogen and
progesterone receptors in human endometrial and endometriotic cells in vitro.
b) Ann N Y Acad Sci 2002 Mar;955:159-73; discussion 199-200, 396-406, Regulation
and modulation of abnormal immune responses in endometriosis.
c) Tidsskr Nor Laegeforen 2001 Nov 20;121(28):3286-91 Mifepristone--a
controversial drug with great potential
d) Zhonghua Fu Chan Ke Za Zhi 2001 Apr;36(4):218-21 Effects of mifepristone on
expression of estrogen receptor and progesterone receptor in cultured human
eutopic and ectopic endometria.
e) Orv Hetil 2001 Apr 22;142(16):827-31 Effect of antigestagens on human
reproduction
f) J Med Chem 2000 Dec 28;43(26):5010-6 Synthesis and biological activity of a
novel, highly potent progesterone receptor antagonist.
g) Steroids 2000 Oct-Nov;65(10-11):807-15 Progesterone receptor modulators and
progesterone antagonists in women's health.
h) Presse Med 1999 Dec 4;28(38):2123-31 [Anti-progesterones] Hum Reprod Update
1998 Sep-Oct;4(5):584-93
Mechanism of action and clinical effects of antiprogestins on the non-pregnant
uterus.
i) J Reprod Med 1998 Jul;43(7):551-60 Mifepristone. Auxiliary therapeutic use in
cancer and related disorders.
j) Am J Obstet Gynecol 1998 Jun;178(6):1151-6 Preliminary report on the
treatment of endometriosis with low-dose mifepristone (RU 486).
Medline data (medical research results), Sept. 15, 2002 search on 'progesterone
cream':
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1) It doesn't appear effective in changing the endometrium
2) Absorption is low
3) Salivary levels had contradicting outcomes: one said it wasn't any good,
another said that it did show it was absorbed, a small increase but with wide
variation. What was absorbed though, does not come to the same levels as that of
the oral/vaginal medications.
4) Short term treatment in one study was free of side effects, it had little
effect on menopausal symptoms
5) The one study on breast pain showed major side effects, no improvement in
breast nodularity, but pain was reduced. (According to Dr. Mark Perloe, the
binding of these molecules is done in the same way as Valium. I'd be interested
to know if that might be the effect seen in that study, since there was no
change in the breast tissue composition.)
a) Hammarback S, Backstrom T, Holst J, von Schoultz B, Lyrenas S. Cyclical mood
changes as in the premenstrual tension syndrome during sequential
estrogen-progestagen postmenopausal replacement therapy. Acta Obstet Gynecol
Scand. 1985;64(5):393-7.
b) Climacteric 2000 Sep;3(3):155-60, Climacteric 2000 Sep;3(3):153-4. Effect of
sequential transdermal progesterone cream on endometrium, bleeding pattern, and
plasma progesterone and salivary progesterone levels in postmenopausal women.
Wren BG, McFarland K, Edwards L, O'Shea P, Sufi S, Gross B, Eden JA. Sydney
Menopause Centre, Royal Hospital for Women, Barker Street, Randwick, New South
Wales 2031, Australia.
INTERPRETATION: Pro-Feme transdermal progesterone administered in a 16-, 32- or
64-mg daily dose for 14 days in a sequential regimen does not appear to be
effective in inducing a secretory change in a proliferative endometrium.
Salivary progesterone levels were not of value in managing the therapy of
postmenopausal women.
c) Maturitas 2002 Jan 30;41(1):1-6, Caution on the use of saliva measurements to
monitor absorption of progesterone from transdermal creams in postmenopausal
women. Lewis JG, McGill H, Patton VM, Elder PA., Steroid and Immunobiochemistry
Laboratory, Canterbury Health Laboratories, P.O. Box 151, Christchurch, New
Zealand. john.lewis@cdhb.govt.nz
CONCLUSION: The absorption of progesterone from transdermal creams is low and we
caution against the use of saliva measurements to monitor progesterone
absorption. The low systemic absorption of progesterone may not be due to
peripheral conversion by 5 alpha-reductase(s). We also conclude that the low
level of progesterone associated with red cells suggests they are not important
in the delivery of progesterone to target tissues.
d) Climacteric 2001 Jun;4(2):144-50, Effects of wild yam extract on menopausal
symptoms, lipids and sex hormones in healthy menopausal women. Komesaroff PA,
Black CV, Cable V, Sudhir K., Baker Medical Research Institute, PO Box 6492, St
Kilda Central, Melbourne 8008, Victoria, Australia.
CONCLUSIONS: This study suggests that short-term treatment with topical wild yam
extract in women suffering from menopausal symptoms is free of side-effects, but
appears to have little effect on menopausal symptoms. It emphasizes the
importance of careful study of treatments for menopausal symptoms if women are
to be adequately informed about the choices available to them.
e) Clin Endocrinol (Oxf) 2000 Nov;53(5):615-20, Salivary, but not serum or
urinary levels of progesterone are elevated after topical application of
progesterone cream to pre-and postmenopausal women. O'Leary P, Feddema P, Chan
K, Taranto M, Smith M, Evans S., Biochemistry Department, Royal Perth Hospital,
Western Australia, Australia. peteolea@rph.health.wa.gov.au
CONCLUSIONS: Salivary progesterone measurements confirm that topically applied
progesterone is absorbed, despite the lack of change in serum progesterone
concentrations. However, at the dose administered, serum progesterone levels do
not reach those observed after oral or vaginally delivered progesterone
preparations. Higher doses may be required to induce biological responses within
the endometrium.
f) BJOG 2000 Jun;107(6):722-6, A study to evaluate serum and urinary hormone
levels following short and long
term administration of two regimens of progesterone cream in postmenopausal
women. Carey BJ, Carey AH, Patel S, Carter G, Studd JW. Department of Obstetrics
and Gynaecology, Chelsea and Westminster Hospital, London, UK.
CONCLUSIONS: Transdermal progesterone (40 mg) per day for 42 days causes a small
increase in serum progesterone concentration, although there is wide variation.
Whether such levels are of clinical benefit remains to be seen.
g) Harv Womens Health Watch 1999 Oct;7(2):7, Scant evidence for progesterone
cream., Micronised transdermal progesterone and endometrial response, Barry G
Wren, Kathy McFarland, Lyndall Edwards. Sequential transdermal progesterone
administered with continuous transdermal oestrogen was insufficient to increase
circulating blood progesterone concentrations or induce a secretory response in
proliferating endometrium.
h) J Endocrinol Invest 1992 Dec;15(11):801-6, Double-blind controlled trial of
progesterone vaginal cream treatment for cyclical mastodynia in women with
benign breast disease. Nappi C, Affinito P, Di Carlo C, Esposito G, Montemagno
U., Cattedra di Endocrinologia Ginecologica, Universita di Torino, Italy.
Vaginal progesterone resulted significantly more efficacious than placebo in
reducing mean ratings of breast pain on VAS and mean scores of breast tenderness
to touch. Success of treatment, defined as reduction greater than 50% of basal
mean score of breast pain on VAS, was achieved in the 64.9% of patients treated
with progesterone and in the 22.2% of patients receiving placebo (p < 0.01).
Conversely, at the end of treatment, the improvement in breast nodularity showed
a not statistically significant difference between the two groups. No major
side-effects were detected.
i) Systemic absorption of progesterone from Pro-GestŪ cream in postmenopausal
women by A Cooper, C Spencer, M I Whitehead, D Ross, G J R Barnard, W P Collins,
The Lancet Volume 351, Number 9111 25 April 1998.
Your post is a very timely one, The Lancet has just published a study comparing
Pro-GestŪ to placebo and also comparing both to Uterogestan, an oral natural
progesterone known as Prometrium in Canada. The findings were that progesterone
levels from Pro-GestŪ were much much lower than the levels from the oral
progesterone, though they were higher than placebo. The levels found were not
high enough to use to oppose estrogen and protect the endometrium as a part of
HRT nor were they considered high enough to conserve bone density.
Medline data, Sept. 16, 2002 search on 'lee jr':
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1) Out of the 8 pages with 146 entries, I found 2 entries that I could associate
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with Dr. John Lee.
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2) The first was a response to 'Use of Pro-Gest cream in postmenopausal women'
in the Lancet, 1998 Sep 12;352(9131):905; discussion 906. No abstract was
available to see what Dr. Lee sent in, but this would have been in the form of
an opinion.
3) The second was an erratum in Medical Hypothesis in 1991 Oct;36(2):178. This
is where his original hypothesis was made concering progesterone being
clinically tested and was 'extraordinarily effective' in reversing osteoporosis.
I clicked on the related articles, and of the 6 pages of 108 items, none of this
was corroborated by any other study. I have listed only a few of those articles
that were done around the time that Dr. Lee's abstract was listed and after.
Note that the 1994 Calcium, estrogen, and progestin in the treatment of
osteoporosis study stated that "Progesterone, often given with estrogen to
prevent endometrial carcinoma, may itself have a trophic influence on bone."
a) Erratum in: Med Hypotheses 1991 Oct;36(2):178 (see also Med Hypotheses 1991
Aug;35(4):316-8), Is natural progesterone the missing link in osteoporosis
prevention and treatment? Lee JR.
Conventional treatment with vitamin D, calcium, and estrogen will delay but not
reverse osteoporosis. The addition of fluoride may increase bone mass but fails
to increase bone strength; fracture incidence is actually increased in
non-vertebral bone by fluoride. Clearly, successful treatment of osteoporosis
remains an unsolved problem. In women, osteoporosis coincides with menopause.
The hypothesis that progesterone and not estrogen is the missing factor was
tested in a clinical setting and was found to be extraordinarily effective in
reversing osteoporosis.
b) Lancet 1990 Nov 24;336(8726):1327, Osteoporosis reversal with transdermal
progesterone, Lee JR., Publication Types: Comment, Letter. Comment on: Lancet.
1990 Aug 4;336(8710):265-9.
c) Am J Pharmacogenomics 2001;1(1):11-9, Candidate genes for osteoporosis.
Therapeutic implications. Niu T, Xu X., Program for Population Genetics, Harvard
School of Public Health, Boston, Massachusetts, USA. xu@hohp.harvard.edu
d) Radiologe 1999 Mar;39(3):228-34, [Pathophysiology and therapy of
osteoporosis], [Article in German], Pietschmann P, Peterlik M., Institut fur
Allgemeine und Experimentelle Pathologie, Universitat Wien.
e) Rheum Dis Clin North Am 1994 Aug;20(3):691-716, Calcium, estrogen, and
progestin in the treatment of osteoporosis., Breslau NA., University of Texas
Southeastern Medical Center, Dallas.
Progesterone, often given with estrogen to prevent endometrial carcinoma, may
itself have a trophic influence on bone.
f) Curr Opin Rheumatol 1992 Jun;4(3):402-9, Treatment of osteoporosis,
Burckhardt P., Department of Internal Medicine, Centre Hospitalier Universitaire
Vaudois, Lausanne, Switzerland.
Estrogen replacement therapy is still the most effective prevention of
postmenopausal bone loss.
g) Prim Care 1990 Sep;17(3):647-66, Estrogen therapy during menopause and the
treatment of osteoporosis., Noyes MA, Demmler RW., College of Pharmacy,
University of Houston, Texas.
Estrogen remains the single most effective agent in the treatment of menopausal
symptoms and prevention of bone loss.
h) Drugs 1989 Feb;37(2):205-11, A rational approach to the prevention and
treatment of postmenopausal osteoporosis., Spector TD, Huskisson EC., Department
of Rheumatology, St Bartholomew's Hospital, London, England.
Combination therapy with oestrogens and progestogens is currently the treatment
of choice for prevention, in conjunction with calcium supplementation and
changes in lifestyle. Treatment of existing disease is less effective, although
oestrogens should be tried first, with calcitonin as a second choice. There is
no place at present for vitamin D, anabolic steroids or parathyroid hormone. The
use of fluoride or diphosphonates cannot be recommended outside research centres
until further long term studies are completed, which will enable a comparison of
the relative risks and benefits.
Investigating the claims (one website):
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Here is a progesterone cream product
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(http://www.mineralmagic.com/frames/inprcr.htm,
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http://www.wallach-colloidal.net/INVProgesterone.htm, and
http://www.american-nutrition.com/progesterone.html) and its marketing/sales
page.
1) Review some of the wording and the claims on the product.
2) Check the statements regarding skin absorption and how it is taken up into
the body, then the bloodstream and its final effects.
3) Read the section on what the pros are of using natural progesterone.
4) Read the section on the survey presented to the FDA almost 20 years ago.
5) Note the claims regarding hypoglycemia and obesity.
Now find the disclaimers under the section starting with 'Reason'. It states
that the information has NOT been checked out by the FDA and that the product
was not made to "diagnose, treat, or prevent any disease". So what is its
purpose? Doesn't the effect work the same as prescription drugs? What about the
comments just listed on teh webpage in regards to the claims? Review my
information on wild yam, one of the ingredients.
So if the product is not made to diagnose, treat, cure or prevent any disease,
what does it do?
Rumors:
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1) That Dr. John Lee owned Aviary Labs, a testing lab to measure progesterone
levels, before being sold to an 'ally'. Any reliable confirmation places? Please
let me know!
2) That Dr. John Lee sold or has recommended specific creams in which he
received compensation for. Any reliable confirmation places? Please let me know!
Regarding wild yam creams:
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1) http://www.quackwatch.com/04ConsumerEducation/QA/wyc.html
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2) http://www.quackwatch.com/01QuackeryRelatedTopics/wildyam.html
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3) General Comments from doctors, myself and others:
http://forums.obgyn.net/womens-health/WHF.0209/1079.html
http://forums.obgyn.net/womens-health/WHF.0208/2668.html
http://forums.obgyn.net/endo/ENDO.0207/0472.html
http://forums.obgyn.net/womens-health/WHF.0207/0786.html
http://forums.obgyn.net/womens-health/WHF.0207/0826.html
http://forums.obgyn.net/womens-health/WHF.0207/1966.html
http://forums.obgyn.net/womens-health/WHF.0207/2350.html
http://forums.obgyn.net/womens-health/WHF.0208/0205.html
http://www.foxnews.com/story/0,2933,58769,00.html
http://www.hc-sc.gc.ca/english/protection/warnings/2002/2002_01e.htm
http://www.reuters.com/news_article.jhtml?type=healthnews&StoryID=1281830
http://www.healthwatcher.net/Quackerywatch/Alternative-medicine/ltr990417chatela
ine.html
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