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Progesterone??
- Dolev Gilmore (2 May 2005)
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Progesterone and synthetics acting like progesterone
- Ellen CG Grant (3 May 2005)
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Re: Progesterone and synthetics acting like progesterone
- Dolev Gilmore (4 May 2005)
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Re: Progesterone and synthetics acting like progesterone
- Dolev Gilmore (5 May 2005)
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Re: Re: Progesterone and synthetics acting like progesterone
- Ellen C G Grant (5 May 2005)
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Re: Re: Re: Progesterone and synthetics acting like progesterone
- Dolev Gilmore (6 May 2005)
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Nutritionists , progesterone and synthetics acting like progesterone
- Ellen C G Grant (6 May 2005)
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Dolev Gilmore, Naturopath Modiim, Israel 73122
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The statement, "replacement with progesterone caused four times more breast cancer than with oestrogen only" is extremely misleading. The research reference (note 4) specifically uses in its title the word "progestin", a synthetic molecule, not "progesterone", which is the molecule made naturally in every human body. The difference is not merely semantic. All of the steroid molecules are very similar, but each change causes widely different effects. For example, the difference between testosterone and estradiol, in other words the difference between male and female attributes, is merely one tiny hydrogen atom and a couple of double bonds. The molecular structural difference between progesterone and progestin is greater than this. Natural progesterone is strongly anti-cancer. Competing interests: None declared |
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Ellen CG Grant, physician and medical gynaecologist Kingston. KT2 7JU, UK
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There is no evidence that I have seen that progesterone is strongly anti-carcinogenic. On the contrary progesterone is immunosuppressive and prevents foetal rejection in pregnancy. Endogenous progesterone stimulates growth in breast glands during the secretory phase of an untreated cycle and in pregnancy, just as exogenous progestogens do. Progesterone and progestagens increase mitosis and proliferation in breast tissue.1 For nearly 200 years endogenous progesterone production has been stopped in premenopausal women by bilateral oophorectomies for the treatment of breast cancer. The first patient I saw who had rubbed progesterone cream on her breast, developed breast cancer in that breast. Progestogen, progestagen or progestin means acting like progesterone. Unlike natural and synthetic oestrogens, different names were given to synthetic progesterones because they often have extra actions, such as more oestrogenic or androgenic effects. In 1975 megestrol acetate was withdrawn from the market because of causing mammary carcinomas in beagles, as did high or low doses of the similar pregnane progestagen medroxyprogesterone acetate (MPA). Progesterone in the form of medroxyprogesterone acetate increases survival of breast cancer cells with non-repaired DNA breaks and chromosomal abnormalities and increases the rate of abnormal metaphases. 1 Anderson T J. Battersby S, King R J B, McPherson K. Breast epithelial responses and steroid receptors during oral contraception use. Hum Pathol 1989; 12; 1137-43. 2 Ory K, Lebeau J, Levalois C, Bishay K et al. Apoptosis inhibition mediated by medroxyprogesterone treatment of breast cancer cell lines. Breast Cancer Res Treat 2001:68:187-98. Competing interests: None declared |
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Dolev Gilmore, Naturopath Modiim, Israel 73122
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There is no such thing as "Progesterone in the form of medroxyprogesterone acetate". They are two different molecules. The latter may have some progesterone-like effects, but there are many effects which are different or opposite. This is obvious, since medroxyprogesterone acetate is not pro-gestation, and cannot be given to pregnant women, as far as I know. The following are some statements about progesterone's anti-cancer effects: 1. "These results clearly demonstrated that progesterone administration suppressed the cell proliferation and induced apoptosis in malignant mesothelioma cells." (Horita K et.al Progesterone induces apoptosis in malignant mesothelioma cells.) 2."Topical and vaginal application of progesterone cream appears to have an antiproliferative effect on the endometrium." (Anasti JN, Leonetti HB, Wilson KJ. Topical progesterone cream has antiproliferative effect on estrogen- stimulated endometrium.) 3. "Progesterone inhibits the proliferation of normal breast epithelial cells in vivo, as well as breast cancer cells in vitro." (Formby B, Wiley TS. Progesterone inhibits growth and induces apoptosis in breast cancer cells: inverse effects on Bcl-2 and p53.) 4. "Exposure to progesterone for 10 to 13 days reduces E2-induced proliferation of normal breast epithelial cells in vivo." (Chang KJ et.al. Influences of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo.) 5. "Progesterone (PROG) has been shown to reduce the risk of developing ovarian carcinoma in postmenopausal women who have undergone estrogen and progestogen replacement therapy, and it has been clinically used to treat some types of ovarian tumors.... PROG treatment markedly up- regulated p53 expression in these cells. (Bu SZ et.al. Progesterone induces apoptosis and up-regulation of p53 expression in human ovarian carcinoma cell lines.) All these studies used progesterone, not a synthetic molecule. It is unfortunate that the improper use of these words in scientific research has clouded proper understanding of the subject. The work of Dr. John Lee on the subject of natural progesterone is extremely important. Competing interests: None declared |
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Dolev Gilmore, Naturopath Modiim, israel 73122
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In addition to my previous comments, I would like to point out the following: 1. The abstract of the study by Anderson (note 1 of the author's response to my first response) specifically states that progestin was used, not progesterone. 2. Bilateral oophorectomies also stop estrogen production, and perhaps this is what treats breast cancer, not the elimination of progesterone production. 3. The experience of John Lee and other clinicians who prescribe natural progesterone is that precancerous conditions in the breast often clear up. Competing interests: None declared |
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Ellen C G Grant, physician and medical gynaecologist Kingston-upon-Thames, KT2 7JU, UK
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Medroxy progesterone acetate (Provera in the UK) is indeed given to pregnant or potentially pregnant women as part of assisted infertility programmes, without first testing the all-important zinc, copper and magnesium status. This is inspite of warning of teratogenicity, increases in infections, fibroids and bone loss. Some form of progesterone is usually given to “aid” implantation and to “prevent” early miscarriages. Naturopaths perhaps believe that progesterone cream is a kind of universal panacea, as do many other alternative medicine practitioners. While the medical establishment dismisses this hormone-containing cream as being “virtually homeopathic” because so little is absorbed into the blood stream, progesterone has achieved a cult status among nutritionists which seems to be entirely unjustifiable. What is the evidence from the work of the late Dr. John Lee, or of his predecessor the late Dr Katharina Dalton, on the subject of natural progesterone which is extremely important? 1,2 Lonetti and colleagues were unable to confirm that applying a quarter teaspoon of cream containing 20 mg progesterone to the skin daily had any protective effect on bone mineral density but did confirm a reduction in vasomotor symptoms.3 This is alarming evidence that enough progesterone is being absorbed to have the usual steroid-immunosuppressive effect on menopausal symptoms in some women. At the 2004 Annual Meeting of the American Society for Clinical Pharmacology, Hermann and colleagues presented evidence that progesterone cream (Pro-gest) at a dose of 40 mg twice daily gives equal exposure to oral progesterone at a dose of 200 mg daily. This raised concern that progesterone cream needs to be regulated in the US since it may provide significant exposure compared to FDA approved products. Menopausal symptoms warn of nutritional deficiencies and allergic reactions and any exogenous hormone use should be contra-indicated. Chasing the holy grail of suppressing warning symptoms with HRT has cost the lives numerous women. The Million Women Study found increases in breast cancer and mortality with hormone use, irrespective of which type of progesterone was used. Progesterones and oestrogens have long been used in high doses for treatment of recurrent or metastatic endometrial or breast cancer cancers but with numerous adverse effects. Any type of progesterone can induce endometrial gland atrophy. Endometrial glands are lined by small low cells which have high monoamine oxidase activities in the late post secretory phase of a normal luteal cycle and for most of the time when progesterone- dominant contraceptive or menopausal formulations are being used. The fact that progesterone and progestins induce the same changes in endometrial glandular enzymes and blood vessels was ignored by Dalton and Lee, as were my efforts to enlighten them, that acting-like-progesterone means precisely that as far as important cell enzymes are concerned. Bu and colleagues used progesterone at a concentration similar to that seen during the third trimester of pregnancy.4 Surely not even the followers of Dalton and Lee can believe that progesterone cream raises progesterone levels to those seen during the third trimester of pregnancy. In pregnancy and in a normal cycle the immunosuppressive effects of progesterone are balanced by high levels of oestrogens. Recent studies are investigating why taking progesterone caused increases in breast cancer within the first 12 months of combined HRT use in large prematurely terminated international trials. Progesterone- dependent up- regulation of tissue factor, the initiator of the extrinsic coagulation pathway, is associated with an enhanced risk of metastasis.5 Increases breast angiogenesis makes some rapidly growing breast cancers resistant to treatment with hormone blocking drugs.6 Anderson and his colleagues found progesterone induced similar changes in the breast in normal and in progestin-treated cycles. They assessed the events of cell proliferation by thymidine labeling index (TLI) in morphologically normal breast lobules from women of reproductive age. TLI was higher during the second half of the menstrual cycle both in women with natural menstrual cycles and in those with artificial cycles due to oral contraceptive use.7 It is the same old hormone story - each disciple believes in special magic formulae for treating a physiological condition and chooses to disregard the evidence of much greater harms from using exogenous hormones. 1 Grant ECG. Medical treatment for menorrhagia and the cult of progesterone http://bmj.com/cgi/eletters/328/7442/730-d#54980, 29 Mar 2004 2 Grant ECG. Katharina Dalton and progesterone dangers http://bmj.com/cgi/eletters/329/7473/1048-b/DC1#83129, 31 Oct 2004 3 Leonetti HB, Wilson KJ, Anasti JN. Transdermal progesterone cream for vasomotor symptoms and postmenopausal bone loss. Obstet Gynecol. 1999; 94: 225-8. 4 Bu SZ, Yin DL, Ren XH, et al. Progesterone induces apoptosis and up-regulation of p53 expression in human ovarian carcinoma cell lines. Cancer 1997; 79: 1944-50. 5 Kato S, Pinto M, Carvajal A, et al. Progesterone increases tissue factor gene expression, procoagulant activity, and invasion in the breast cancer cell line ZR-75-1.J Clin Endocrinol Metab. 2005;90:1181-8. 6 Wu J, Richer J, Horwitz KB, Hyder SM. Progestin-dependent induction of vascular endothelial growth factor in human breast cancer cells: preferential regulation by progesterone receptor B. Cancer Res. 2004;64:2238-44 7 Going JJ, Anderson TJ, Battersby S, MacIntyre CC. Proliferative and secretory activity in human breast during natural and artificial menstrual cycles. Am J Pathol 1988 ;130: 193-204. Competing interests: None declared |
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Dolev Gilmore, Naturopath Modiim, Israel 73122
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1. The research of Lonetti is indeed evidence against the use of progesterone for building bone. However, innumerable members of our cult have seen panacea-type results. In my tiny practice, I have seen bone density improve as much as 15% in one year (as measured by DEXA), accompanied by the dissapearance of chronic bone pain and marked improvement of other hormone-related symptoms. These results are consistant with those reported by Dr. Lee and many others. What can I do? Thorough reading of Dr. Lee's books and articles, along with thousands of "anecdotal" reports, have convinced me. 2. I searched the Million Women Study's web site and could not find reference to use of progesterone, only synthetics. 3. "Bu and colleagues used progesterone at a concentration similar to that seen during the third trimester of pregnancy". It is hard for me to understand that if progesterone is anti-cancerous at a high dose it will be cancerogenic at a lower dose. 4. The study by Kato and colleagues says progesterone in the title, but their statement, "Progesterone in hormonal preparations increases the incidence of breast cancer" leads me to believe that they are referring to a progestin, since hormonal preparations contain progestins, not progesterone, although I do not have access to their full article. As we have stated, the terms are mistakenly interchanged in scientific publication. 5. The "large prematurely terminated international trials" all used synthetic progestins. 6. The increased breast angiogenesis was reported by Wu and colleagues who used progestin. If one begins with the assumption that progesterone and progestins are the same, he will just not "get it". They are not the same. The misuse of these terms clouds the issues. If a researcher or doctor wishes to educate members of our cult, this obstacle must be overcome. If we are mistaken, we are willing to be shown this, but it can not be done by bringing progestin studies. If anyone has anything to say to me on this subject, I will be happy to hear from you at rgilmore@bezeqint.net Competing interests: None declared |
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Ellen C G Grant, physican and medical gynaecologist Kingston-upon-Thames, KT2 7JU, UK
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It is nutritionists who believe that exogenous progesterone is safe and nutritionists usually also give nutritional supplementation. As osteoporosis is mostly due to deficiencies of zinc and magnesium, these supplements can improve the levels of bone specific alkaline phosphatase and prevent urinary losses of zinc and calcium. However, users of exogenous hormones are more likely to have essential nutrient deficiencies and therefore more likely to develop osteoporosis. Exogenous hormones also increase bone vascularity and can give an erroneous impression of increased bone density on scans. I don’t know why Lee and Dalton’s disciples never see women with adverse reactions to exogenous “natural” progesterone because I have seen many since I was a Clinical Assistant to the late endocrinologist Dr Gerald Swyer, at University College Hospital in 1960. He made a point of mentioning that many women had consulted him because they had had gained weight, developed migraine, depression or irregular bleeding when taking “natural” progesterone. Naturopaths may not know that carcinogens can be used to treat cancer. The example of radiotherapy is obvious and the use of large doses of hormones in cancer therapy has long been established. Alternative medicine practitioners seem happy to ignore the basic scientific facts that synthetic progesterones act predominantly like progesterone, even if they may also have extra oestrogenic or androgenic actions. Why they feel compelled to dice with women’s lives in this way is a complete mystery to me. Nutritional Medicine is a powerful tool which makes hormone use unnecessary in my experience. There is nothing natural about exogenous hormones. Competing interests: None declared |
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