More Falsehoods About Bioidentical Hormones by Jeffrey Dach MD
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More Falsehoods About Bioidentical Hormones by Jeffrey Dach MD by Jeffrey Dach MD An article in an Australian Newspaper by Rachel Browne caught my attention because it was a hatchet job, using falsehoods to malign and discredit bioidentical hormones. (1-2) This Australian news article quotes John Eden, the infamous OB/Gyn found to be "In Bed " with the Synthetic Hormone Industry, and "author" of several ghost written medical journal articles. One of his ghostwritten articles tried to make doctors believe "that synthetic hormones are safe and do not cause cancer".(4-5) This is untrue. Numerous studies have shown without any doubt they do cause cancer. For example, The WHI (Womens Health Initiative was halted early because the synthetic hormone combination Prempro (containing a progestin) increased the risk of heart disease and breast cancer. The article informs us that twenty five percent of Australian women on bioidentical hormone programs. Dr Eden believes "these treatments are potentially dangerous and can lead to uterine cancer". Dr. Eden reported three cases of endometrial cancer while on bioidentical hormones.(3) What Dr. Eden doesn't tell you is that Bioidentical Hormones are FDA approved for preventing endometrial hyperplasia and reducing risk of endometrial cancer. The studies were done by Solvay for FDA approval of Prometrium (Progesterone, a bioidentical hormone) and this was published in the medical literature. What Dr Eden doesn't tell you is that neither bioidentical homrones nor synthetic hormones eliminate the risk of endometrial cancer. In fact in the WHI study, women who took with Prempro, (a synthetic hormone) suffered from 58 cases of endometrial cancer. They also reported 32 cases of invasive ovarian cancer, 13 cases of cervical cancer, and 7 cases of other gynecologic cancers. What Dr Eden doesn't tell you is that the medical system and drug industry caused more than 15,000 cases of endometrial cancer in the 1950's with Premarin, a pregnant horse estrogen pill. Finally, doctors figured out that estrogen caused endometrial cancer unless co-administered with progesterone which conteracts the endometial hyperplasia (stimulation) and reduces the risk of endometrial cancer to that of placebo. Progestins such as provera (MPA) were developed as synthetic chemically altered versions of progesterone for this purpose of preventing endometrial hyperplasia. These alteration were needed to obtain a patent on the chemical formula. What Dr Eden doesn't tell you is that four major studies have shown that Provera and all Progestins cause cancer and heart disease. Progesterone does not. Starting to make sense now? Links and References 1) Menopause experts warn against doctor pushing 'untested' HRT Rachel Browne August 14, 2011 Read more: www.theage.com.au/national/menopause-experts-warn-against-doctor-pushing-untested-hrt-20110813-1is6g.html#ixzz1WKABKhJZ Dr Eden said he watched the natural HRT industry first with interest and then with growing alarm as more and more women began using the untested products in an attempt to alleviate the symptoms of menopause. About a quarter of Australian women on HRT are now using the natural version, Dr Eden said. He believes the treatments are potentially dangerous and can lead to uterine cancer if prepared incorrectly and used over a long period. ''That's why we're now seeing a clutch of cases of cancer and that makes me very concerned,'' he said. He has published an article drawing the link between uterine cancer and bioidentical hormones in the Medical Journal of Australia and expressed his views to the TGA, to no avail. Read more: www.theage.com.au/national/menopause-experts-warn-against-doctor-pushing-untested-hrt-20110813-1is6g.html#ixzz1WKAVTZQq 2) www.bordermail.com.au/news/national/national/general/elixir-of-youth-or-cancer-risk/2257667.aspx Elixir of youth or cancer risk? RACHEL BROWNE 14 Aug, 2011 12:04 AM 3) www.mja.com.au/public/issues/187_04_200807/ede10581_fm.html Three cases of endometrial cancer associated with “bioidentical” hormone replacement therapy , John A Eden, Neville F Hacker and Michael Fortune The Medical Journal of Australia, MJA 2007; 187 (4): 244-245 4) www.theaustralian.com.au/news/features/ghost-stories/story-e6frg8h6-1225848936455 Ghost stories, Richard Guilliatt . The Australian April 03, 2010 12:01AM Dr John Eden came to Wyeth’s attention because his clinical studies of women being treated for breast cancer at the Royal Hospital for Women in Sydney suggested that high doses of progestin – the extra hormone in Wyeth’s new drug Prempro – could actually reduce recurrence of the disease. This appeared to contradict studies that showed progestin increased the breast cancer risk. In June 2000 Wyeth flew him to New York to present his research at a company-hosted symposium, and at dinner on the opening night he met the Wyeth marketing executive Mark Barbee. A month later, Barbee emailed Eden to say that the Australian’s research was “invaluable to us as we move our business forward”, offering the assistance of a writer to turn the ¬presentation into a published paper. Eden says today that he had no idea that Wyeth was in the process of financing more than 40 such papers. “If I had any idea, I would have said, ‘Forget it’,” he asserts. Like many researchers, he was used to getting editorial assistance from librarians and university staff, and he had accepted honoraria from drug companies for many years. He says Wyeth’s offer did not strike him as untoward. 5) www.crikey.com.au/2008/12/15/australian-doctor-discovered-in-bed-with-drug-company-and-hrt/ Monday, 15 December 2008 Australian doctor discovered in bed with drug company and HRT Health journalist Melissa Sweet writes: ---------------------------------------------------------- 6) www.ncbi.nlm.nih.gov/pubmed/12524095 Fertil Steril. 2003 Jan;79(1):221-2. Topical progesterone cream has an antiproliferative effect on estrogen-stimulated endometrium. Leonetti HB, Wilson KJ, Anasti JN. www.ncbi.nlm.nih.gov/pubmed/11910616 Climacteric. 2000 Sep;3(3):155-60. 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. Source Sydney Menopause Centre, Royal Hospital for Women, Barker Street, Randwick, New South Wales 2031, Australia. Abstract BACKGROUND: Transdermal progesterone is being used in some countries as a purported treatment for menopausal symptoms, either alone or prescribed in conjunction with estrogen, but little information exists regarding the biological activity and effectiveness of this method of delivery of progesterone in protecting the endometrium from excess proliferation. This study was designed to evaluate the use of sequential transdermal progesterone. End-points evaluated included endometrial cellular response and bleeding pattern as well as plasma hormone levels and salivary progesterone estimations. METHOD: Twenty-seven postmenopausal women were treated with continuous transdermal estrogen (28-day cycle) and a cream containing 16, 32 or 64 mg of progesterone in each 4-cm extrusion from a tube of Pro-Feme administered daily in a sequential (days 15-28 of cycle) regimen. Blood and endometrial samples were analyzed for progesterone response prior to therapy, after the first 14 days of unopposed transdermal estrogen and following 14 days of transdermal progesterone. Saliva samples were taken during the last 14 days of the 84-day study, when the final progesterone cream therapy was being applied. RESULTS: Hormone assay indicated that physiological levels of estradiol were achieved, but progesterone levels were insufficient to induce any detectable change in the endometrium. Only one patient experienced bleeding during the study period. Levels of salivary progesterone were so variable as to be considered completely unreliable in determining the potential influence on biological activity. 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. ------------------------------------------------------------------------------------------------ endometrrial cancer in WHI www.ncbi.nlm.nih.gov/pubmed/14519708?dopt=Abstract JAMA. 2003 Oct 1;290(13):1739-48. Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: the Women's Health Initiative randomized trial. Anderson GL, Judd HL, Kaunitz AM, Barad DH, Beresford SA, Pettinger M, Liu J, McNeeley SG, Lopez AM; Women's Health Initiative Investigators. Source Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Wash Abstract CONTEXT: The effects of continuous combined hormone therapy on gynecologic cancers have not been investigated previously in a randomized trial setting. OBJECTIVE: To determine the possible associations of estrogen plus progestin on gynecologic cancers and related diagnostic procedures. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled trial of 16 608 postmenopausal women, who had not had a hysterectomy at baseline and who had been recruited from 40 US clinical centers between September 1993 and October 1998 (average follow-up, 5.6 years). INTERVENTION: One tablet per day containing 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate (n = 8506) or placebo (n = 8102). MAIN OUTCOME MEASURE: Incident invasive cancer of the ovary and endometrium. RESULTS: In 5.6 years of follow-up, there were 32 cases of invasive ovarian cancer, 58 cases of endometrial cancer, 1 case of nonendometrial uterine cancer, 13 cases of cervical cancer, and 7 cases of other gynecologic cancers. The hazard ratio (HR) for invasive ovarian cancer in women assigned to estrogen plus progestin compared with placebo was 1.58 (95% confidence interval [CI], 0.77-3.24). The HR for endometrial cancer was 0.81 (95% CI, 0.48-1.36). No appreciable differences were found in the distributions of tumor histology, stage, or grade for either cancer site. The incidence of other gynecologic cancers was low and did not differ by randomization assignment. More women taking estrogen plus progestin required endometrial biopsies (33% vs 6%; P<.001). CONCLUSIONS: This randomized trial suggests that continuous combined estrogen plus progestin therapy may increase the risk of ovarian cancer while producing endometrial cancer rates similar to placebo. The increased burden of endometrial biopsies required to assess vaginal bleeding further limits the acceptability of this regimen. These data provide additional support for caution in the use of continuous combined hormones. rebuttal!!!!!! www.lolopk.org/WIB%20copy/pdf/AlternativeTherapies.pdf www.ncbi.nlm.nih.gov/pubmed/16320858 Altern Ther Health Med. 2005 Nov-Dec;11(6):36-8. Transdermal progesterone cream as an alternative progestin in hormone therapy. Leonetti HB, Landes J, Steinberg D, Anasti JN. Source Department of Obstetrics and Gynecology, St Luke's Hospital, Bethlehem, Pa, USA. Abstract OBJECTIVE: To evaluate the endometrial effects and determine patients' acceptance of transdermal progresterone cream compared to standard hormone therapy. METHODS: Healthy menopausal women were recruited and received a pretreatment endometrial biopsy (EM. They were randomized to 0.625 mg conjugated equine estrogen (CEE) daily and 2.5 mg medroxyprogesterone acetate (MPA) (Prempro, Wyeth USA) or daily 0.625 mg CEE and twice daily 20 mg transdermal PC (Pro-gest, Transitions for Health USA). At the end of 6 months, a repeat EMB was obtained, and the women were crossed over to other treatment. A final EMB was performed after the final 6 months. RESULTS: Twenty-six women completed both arms of the study. Seventy-seven percent of women preferred the CEE/PC to the CEE/MPA (P<.001). Of the 52 post-treatment endometrial biopsies: 40 revealed atrophic endometrium and 12 proliferative endometrium (7 in the oral progestin group and 5 in the PC group). There was no evidence of endometrial hyperplasia in any of the specimens. The incidence of vaginal spotting was similar in both groups. CONCLUSION: Patients preferred transdermal PC over oral MPA. This preliminary data indicate that CEE/PC has a similar effect on the endometrium as standard oral HT over a 6-month period. www.natural-progesterone-advisory-network.com/endometrial-uterine-hyperplasia-and-natural-progesterone/ Dr. Helene Leonetti’s study effectively proved that progesterone cream protects the uterine lining (the endometrium) as well as synthetic progestins do. Her study comparing PremPro with Premarin and progesterone cream was published in a major peer-reviewed medical journal (JAMA 2002; 287:216-220. Anasti JN, Leonetti HB, Wilson KJ. Topical progesterone cream has antiproliferative effect on estrogen-stimulated endometrium. Obstet Gynecol 2001; 97 (Suppl 4): S10). In Dr. Leonetti’s study, uterine tissue was examined before, during, and after using either PremPro (Premarin plus Provera) or a combination of Premarin and progesterone cream. The group using progesterone cream was found to be as well protected as the PremPro group. --------------- www.ncbi.nlm.nih.gov/pubmed/16428119 Climacteric. 2006 Feb;9(1):1-3. The 'bioidentical/bioequivalent' hormone scam. MacLennan AH, Sturdee DW. ------------------ www.islandnet.com/~wecomrx/pdf/Stanszyc-Transdermal%20Progesterone%20Review.pdf www.ncbi.nlm.nih.gov/pubmed/15772572 Menopause. 2005 Mar;12(2):232-7. Percutaneous administration of progesterone: blood levels and endometrial protection. Stanczyk FZ, Paulson RJ, Roy S. Source Department of Obstetrics and Gynecology, University of Southern California Keck School of Medicine, Los Angeles, ----------------------------------------- www.aafp.org/afp/991001ap/1371.html Abnormal Uterine Bleeding KATHLEEN A. ORIEL, M.D., and SARINA SCHRAGER, M.D. University of Wisconsin School of Medicine, Madison, Wisconsin -------------------------------- www.sciencedirect.com/science/article/pii/S0378512299000079 Endometrial cancer after combined hormone replacement therapy ... www.sciencedirect.com/science/article/pii/S0378512299000079 - Block all www.sciencedirect.com results by DM Gruber - 1999 - Cited by 11 - Related articles Methods: The cases of two postmenopausal women who developed endometrial cancer after taking continuous sequential HRT for 15 months are reported. ... jnci.oxfordjournals.org/content/89/15/1110.full.pdf of the National Cancer Institute, Vol. 89, No. 15, August 6, 1997 ARTICLES Estrogen–Progestin Replacement Therapy and Endometrial Cancer Malcolm C. Pike, Ruth K. Peters, Wendy Cozen, Nicole M. Probst-Hensch, Juan C. Felix, Peggy C. Wan, Thomas M. Mack* www.ncbi.nlm.nih.gov/pubmed/21682550 J Womens Health (Larchmt). 2011 Aug;20(8):1157-63. Epub 2011 Jun 17. Trends in endometrial cancer incidence rates in the United States, 1999-2006. Duong LM, Wilson RJ, Ajani UA, Singh SD, Eheman CR. Source Cancer Surveillance Branch, Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention , Atlanta, Georgia. Abstract Abstract Background: Risk factors for endometrial cancer, such as hormone replacement therapy (HRT) and obesity, have changed significantly in the last decade. We investigated trends in endometrial cancer histologic subtypes on a national level during 1999-2006. Methods: Data covering 88% of the U.S. population were from central cancer registries in the National Program of Cancer Registries (NPCR) and Surveillance, Epidemiology, and End Results (SEER) programs that met high-quality United States Cancer Statistics (USCS) criteria. Our analyses included females with microscopically confirmed invasive uterine cancer (n=257,039). Age-adjusted incidence rates and trends for all invasive uterine cancers and by endometrial cancer histologic subtypes (type I and II) were assessed. Results: There were 145,922 cases of type I endometrial cancers and 15,591 cases of type II for 1999-2006. We found that type I endometrial cancers have been increasing, whereas type II endometrial cancers and all invasive uterine cancers have been relatively stable throughout the 1999-2006 period. Conclusions: During the past decade, the overall burden of uterine cancer has been stable, although there have been changes in underlying histologies (e.g., endometrial). Changes in trends for underlying histologies may be masked when reviewing trends irrespective of histologic subtypes. Our findings suggest the need to examine trends of uterine cancer by histologic subtype in order to better understand the burden of endometrial cancer in relation to these subtypes to help women at increased risk for developing more aggressive types of endometrial cancer (e.g., type II). -------------- rebuttal www.ncbi.nlm.nih.gov/pubmed/10090424 Clin Ther. 1999 Jan;21(1):41-60; discussion 1-2. Oral micronized progesterone. de Lignières B. Source Department of Endocrinology and Reproductive Medicine, Hôpital Necker, Paris, France. Abstract This review sought to examine the rationale for selecting an oral micronized progesterone formulation rather than a synthetic progestin for some of the main indications for progestogens. Unopposed estrogen use is associated with a high risk (relative risk, 2.1 to 5.7) of endometrial hyperplasia and adenocarcinoma, and it has been understood for some time that a progestogen must be added for at least 10 to 14 days per month to prevent these effects. However, the most commonly used synthetic progestins, norethisterone and medroxyprogesterone acetate, have been associated with metabolic and vascular side effects (eg, suppression of the vasodilating effect of estrogens) in both experimental and human controlled studies. All comparative studies to date conclude that the side effects of synthetic progestins can be minimized or eliminated through the use of natural progesterone, which is identical to the steroid produced by the corpus luteum. The inconvenience associated with the use of injectable, rectal, or vaginal formulations of natural progesterone can be circumvented by using orally administered micronized progesterone. The bioavailability of micronized progesterone is similar to that of other natural steroids, and interindividual and intraindividual variability of area under the curve is similar to that seen with synthetic progestins. A clear dose-ranging effect has been demonstrated, and long-term protection of the endometrium has been established. Micronized progesterone has been used widely in Europe since 1980 at dosages ranging from 300 mg/d (taken at bedtime) 10 days a month for women wishing regular monthly bleeding to 200 mg 14 days a month or 100 mg 25 days a month for women willing to remain amenorrheic. This therapy is well tolerated, with the only specific side effect being mild and transient drowsiness, an effect minimized by taking the drug at bedtime. The prospective, comparative Postmenopausal Estrogens/Progestin Intervention trial has recommended oral micronized progesterone as the first choice for opposing estrogen therapy in nonhysterectomized postmenopausal women. ---------------------------------- www.jabfm.org/cgi/reprint/24/2/202.pdf JABFM March–April 2011 Vol. 24 No. 2 CLINICAL REVIEW Counseling Postmenopausal Women about Bioidentical Hormones: Ten Discussion Points for Practicing Physicians Richa Sood, MD, Lynne Shuster, MD, Robin Smith, MD, Ann Vincent, MD, and Aminah Jatoi, MD Progestogens (bioidentical progesterone and synthetic progestins) have been used to balance the effects of unopposed estrogen on uterine endometrium and prevent uterine cancer. All progestogens currently available for menopausal HT are approved for this purpose by the FDA.2 -------------------------------------------- www.drugs.com/pro/prometrium.html Accurate, FDA approved Prometrium information Prometrium® (progesterone, USP) Capsules 100 mg Capsules 200 mg CLINICAL STUDIES - Effects on the endometrium In a randomized, double-blind clinical trial, 358 postmenopausal women, each with an intact uterus, received treatment for up to 36 months. The treatment groups were: Prometrium Capsules at the dose of 200 mg/day for 12 days per 28-day cycle in combination with conjugated estrogens 0.625 mg/day (n=120); conjugated estrogens 0.625 mg/day only (n=119); or placebo (n=119). The subjects in all three treatment groups were primarily Caucasian women (87 percent or more of each group). The results for the incidence of endometrial hyperplasia in women receiving up to 3 years of treatment are shown in Table 3. A comparison of the Prometrium Capsules plus conjugated estrogens treatment group to the conjugated estrogens only group showed a significantly lower rate of hyperplasia (6 percent combination product versus 64 percent estrogen alone) in the Prometrium Capsules plus conjugated estrogens treatment group throughout 36 months of treatment. INDICATIONS AND USAGE - Prometrium Capsules are indicated for use in the prevention of endometrial hyperplasia in nonhysterectomized postmenopausal women who are receiving conjugated estrogens tablets. They are also indicated for use in secondary amenorrhea. -------------------------- www.ncbi.nlm.nih.gov/pubmed/15901742 J Clin Pharmacol. 2005 Jun;45(6):614-9. Over-the-counter progesterone cream produces significant drug exposure compared to a food and drug administration-approved oral progesterone product. Hermann AC, Nafziger AN, Victory J, Kulawy R, Rocci ML Jr, Bertino JS Jr. Source Department of Medicine, Bassett Healthcare, Cooperstown, New York, USA. Abstract Progesterone products are available in prescription form as well as over-the-counter (OTC) topical preparations sold for "cosmetic" uses. In a randomized study design, the authors compared the drug exposure from an OTC progesterone cream to a Food and Drug Administration-approved oral preparation at the labeled daily doses recommended for each product. Twelve healthy postmenopausal women received 200-mg oral progesterone capsules once daily for 12 days or progesterone cream 40 mg twice daily for 12 days. At steady state (day 12 of each phase), whole-blood samples were collected over 24 hours (oral progesterone) or 12 hours (topical progesterone) and assayed for total progesterone concentration. No significant differences were found in dose-normalized 24-hour progesterone exposure comparing the cream to oral capsules (median AUC(0-24) 12.5 ng x h/mL vs 10.5 ng x h/mL, respectively; P = .81). In light of the potential risks associated with long-term progesterone use, the authors question whether topical progesterone products should be available OTC. Estrogens and progestins: background and history, trends in use, and guidelines and regimens approved by the US Food and Drug Administration Marcia L. Stefanick, PhD www.ncbi.nlm.nih.gov/pmc/articles/PMC2219716/ J Gen Intern Med. 2007 July; 22(7): 1030–1034. Bioidentical Hormones for Menopausal Hormone Therapy: Variation on a Theme Adriane Fugh-Berman, MD corresponding author and Jenna Bythrow, MS candidate J. Bythrow is currently employed as a pharmaceutical sales representative with Eli Lilly. BACKGROUND Progesterone creams and natural or bioidentical compounded estrogen preparations are being promoted to consumers as safe alternatives to conventional menopausal hormone therapy and as health-promoting tonics. No reliable data support these claims. SAFETY Natural hormones, including estradiol, estriol, estrone, and progesterone, can be expected to have the same adverse event profile as conventional menopausal hormone regimens. SALIVARY HORMONE TESTS Salivary tests may be used to persuade asymptomatic consumers to use hormones (or symptomatic patients to use higher doses than those needed to mitigate symptoms), a practice that can be expected to result in adverse events. ------------------------ zzzzzzzzzzzzzzzzzzzzzzzzzz Menopause experts warn against doctor pushing 'untested' HRT Rachel Browne August 14, 2011 Read more: www.theage.com.au/national/menopause-experts-warn-against-doctor-pushing-untested-hrt-20110813-1is6g.html#ixzz1WKABKhJZ Dr Eden said he watched the natural HRT industry first with interest and then with growing alarm as more and more women began using the untested products in an attempt to alleviate the symptoms of menopause. About a quarter of Australian women on HRT are now using the natural version, Dr Eden said. He believes the treatments are potentially dangerous and can lead to uterine cancer if prepared incorrectly and used over a long period. ''That's why we're now seeing a clutch of cases of cancer and that makes me very concerned,'' he said. He has published an article drawing the link between uterine cancer and bioidentical hormones in the Medical Journal of Australia and expressed his views to the TGA, to no avail. Read more: www.theage.com.au/national/menopause-experts-warn-against-doctor-pushing-untested-hrt-20110813-1is6g.html#ixzz1WKAVTZQq www.bordermail.com.au/news/national/national/general/elixir-of-youth-or-cancer-risk/2257667.aspx Elixir of youth or cancer risk? RACHEL BROWNE 14 Aug, 2011 12:04 AM www.mja.com.au/public/issues/187_04_200807/ede10581_fm.html Three cases of endometrial cancer associated with “bioidentical” hormone replacement therapy John A Eden, Neville F Hacker and Michael Fortune The Medical Journal of Australia, MJA 2007; 187 (4): 244-245 www.theaustralian.com.au/news/features/ghost-stories/story-e6frg8h6-1225848936455 Ghost stories, Richard Guilliatt From: The Australian April 03, 2010 12:01AM Dr John Eden came to Wyeth’s attention because his clinical studies of women being treated for breast cancer at the Royal Hospital for Women in Sydney suggested that high doses of progestin – the extra hormone in Wyeth’s new drug Prempro – could actually reduce recurrence of the disease. This appeared to contradict studies that showed progestin increased the breast cancer risk. In June 2000 Wyeth flew him to New York to present his research at a company-hosted symposium, and at dinner on the opening night he met the Wyeth marketing executive Mark Barbee. A month later, Barbee emailed Eden to say that the Australian’s research was “invaluable to us as we move our business forward”, offering the assistance of a writer to turn the ¬presentation into a published paper. Eden says today that he had no idea that Wyeth was in the process of financing more than 40 such papers. “If I had any idea, I would have said, ‘Forget it’,” he asserts. Like many researchers, he was used to getting editorial assistance from librarians and university staff, and he had accepted honoraria from drug companies for many years. He says Wyeth’s offer did not strike him as untoward. www.crikey.com.au/2008/12/15/australian-doctor-discovered-in-bed-with-drug-company-and-hrt/ Monday, 15 December 2008 Australian doctor discovered in bed with drug company and HRT Health journalist Melissa Sweet writes: ---------------------------------------------------------- www.ncbi.nlm.nih.gov/pubmed/12524095 Fertil Steril. 2003 Jan;79(1):221-2. Topical progesterone cream has an antiproliferative effect on estrogen-stimulated endometrium. Leonetti HB, Wilson KJ, Anasti JN. www.ncbi.nlm.nih.gov/pubmed/11910616 Climacteric. 2000 Sep;3(3):155-60. 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. Source Sydney Menopause Centre, Royal Hospital for Women, Barker Street, Randwick, New South Wales 2031, Australia. Abstract BACKGROUND: Transdermal progesterone is being used in some countries as a purported treatment for menopausal symptoms, either alone or prescribed in conjunction with estrogen, but little information exists regarding the biological activity and effectiveness of this method of delivery of progesterone in protecting the endometrium from excess proliferation. This study was designed to evaluate the use of sequential transdermal progesterone. End-points evaluated included endometrial cellular response and bleeding pattern as well as plasma hormone levels and salivary progesterone estimations. METHOD: Twenty-seven postmenopausal women were treated with continuous transdermal estrogen (28-day cycle) and a cream containing 16, 32 or 64 mg of progesterone in each 4-cm extrusion from a tube of Pro-Feme administered daily in a sequential (days 15-28 of cycle) regimen. Blood and endometrial samples were analyzed for progesterone response prior to therapy, after the first 14 days of unopposed transdermal estrogen and following 14 days of transdermal progesterone. Saliva samples were taken during the last 14 days of the 84-day study, when the final progesterone cream therapy was being applied. RESULTS: Hormone assay indicated that physiological levels of estradiol were achieved, but progesterone levels were insufficient to induce any detectable change in the endometrium. Only one patient experienced bleeding during the study period. Levels of salivary progesterone were so variable as to be considered completely unreliable in determining the potential influence on biological activity. 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. ------------------------------------------------------------------------------------------------ rebuttal!!!!!! www.lolopk.org/WIB%20copy/pdf/AlternativeTherapies.pdf www.ncbi.nlm.nih.gov/pubmed/16320858 Altern Ther Health Med. 2005 Nov-Dec;11(6):36-8. Transdermal progesterone cream as an alternative progestin in hormone therapy. Leonetti HB, Landes J, Steinberg D, Anasti JN. Source Department of Obstetrics and Gynecology, St Luke's Hospital, Bethlehem, Pa, USA. Abstract OBJECTIVE: To evaluate the endometrial effects and determine patients' acceptance of transdermal progresterone cream compared to standard hormone therapy. METHODS: Healthy menopausal women were recruited and received a pretreatment endometrial biopsy (EM  . They were randomized to 0.625 mg conjugated equine estrogen (CEE) daily and 2.5 mg medroxyprogesterone acetate (MPA) (Prempro, Wyeth USA) or daily 0.625 mg CEE and twice daily 20 mg transdermal PC (Pro-gest, Transitions for Health USA). At the end of 6 months, a repeat EMB was obtained, and the women were crossed over to other treatment. A final EMB was performed after the final 6 months.
RESULTS:
Twenty-six women completed both arms of the study. Seventy-seven percent of women preferred the CEE/PC to the CEE/MPA (P<.001). Of the 52 post-treatment endometrial biopsies: 40 revealed atrophic endometrium and 12 proliferative endometrium (7 in the oral progestin group and 5 in the PC group). There was no evidence of endometrial hyperplasia in any of the specimens. The incidence of vaginal spotting was similar in both groups.
CONCLUSION:
Patients preferred transdermal PC over oral MPA. This preliminary data indicate that CEE/PC has a similar effect on the endometrium as standard oral HT over a 6-month period.
www.natural-progesterone-advisory-network.com/endometrial-uterine-hyperplasia-and-natural-progesterone/
Dr. Helene Leonetti’s study effectively proved that progesterone cream protects the uterine lining (the endometrium) as well as synthetic progestins do. Her study comparing PremPro with Premarin and progesterone cream was published in a major peer-reviewed medical journal (JAMA 2002; 287:216-220. Anasti JN, Leonetti HB, Wilson KJ. Topical progesterone cream has antiproliferative effect on estrogen-stimulated endometrium. Obstet Gynecol 2001; 97 (Suppl 4): S10).
In Dr. Leonetti’s study, uterine tissue was examined before, during, and after using either PremPro (Premarin plus Provera) or a combination of Premarin and progesterone cream. The group using progesterone cream was found to be as well protected as the PremPro group.
---------------
www.ncbi.nlm.nih.gov/pubmed/16428119
Climacteric. 2006 Feb;9(1):1-3.
The 'bioidentical/bioequivalent' hormone scam.
MacLennan AH, Sturdee DW.
------------------
www.islandnet.com/~wecomrx/pdf/Stanszyc-Transdermal%20Progesterone%20Review.pdf
www.ncbi.nlm.nih.gov/pubmed/15772572
Menopause. 2005 Mar;12(2):232-7.
Percutaneous administration of progesterone: blood levels and endometrial protection.
Stanczyk FZ, Paulson RJ, Roy S.
Source
Department of Obstetrics and Gynecology, University of Southern California Keck School of Medicine, Los Angeles, CA, USA. fstanczyk@socal.rr.com
-----------------------------------------
www.aafp.org/afp/991001ap/1371.html
Abnormal Uterine Bleeding
KATHLEEN A. ORIEL, M.D., and
SARINA SCHRAGER, M.D.
University of Wisconsin School of Medicine, Madison, Wisconsin
--------------------------------
endometrrial cancer in WHI
www.ncbi.nlm.nih.gov/pubmed/14519708?dopt=Abstract
JAMA. 2003 Oct 1;290(13):1739-48.
Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: the Women's Health Initiative randomized trial.
Anderson GL, Judd HL, Kaunitz AM, Barad DH, Beresford SA, Pettinger M, Liu J, McNeeley SG, Lopez AM; Women's Health Initiative Investigators.
Source
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Wash 98109, USA. garnet@whi.org
Abstract
CONTEXT:
The effects of continuous combined hormone therapy on gynecologic cancers have not been investigated previously in a randomized trial setting.
OBJECTIVE:
To determine the possible associations of estrogen plus progestin on gynecologic cancers and related diagnostic procedures.
DESIGN, SETTING, AND PARTICIPANTS:
Randomized, double-blind, placebo-controlled trial of 16 608 postmenopausal women, who had not had a hysterectomy at baseline and who had been recruited from 40 US clinical centers between September 1993 and October 1998 (average follow-up, 5.6 years).
INTERVENTION:
One tablet per day containing 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate (n = 8506) or placebo (n = 8102).
MAIN OUTCOME MEASURE:
Incident invasive cancer of the ovary and endometrium.
RESULTS:
In 5.6 years of follow-up, there were 32 cases of invasive ovarian cancer, 58 cases of endometrial cancer, 1 case of nonendometrial uterine cancer, 13 cases of cervical cancer, and 7 cases of other gynecologic cancers. The hazard ratio (HR) for invasive ovarian cancer in women assigned to estrogen plus progestin compared with placebo was 1.58 (95% confidence interval [CI], 0.77-3.24). The HR for endometrial cancer was 0.81 (95% CI, 0.48-1.36). No appreciable differences were found in the distributions of tumor histology, stage, or grade for either cancer site. The incidence of other gynecologic cancers was low and did not differ by randomization assignment. More women taking estrogen plus progestin required endometrial biopsies (33% vs 6%; P<.001).
CONCLUSIONS:
This randomized trial suggests that continuous combined estrogen plus progestin therapy may increase the risk of ovarian cancer while producing endometrial cancer rates similar to placebo. The increased burden of endometrial biopsies required to assess vaginal bleeding further limits the acceptability of this regimen. These data provide additional support for caution in the use of continuous combined hormones.
www.sciencedirect.com/science/article/pii/S0378512299000079
Endometrial cancer after combined hormone replacement therapy ...
www.sciencedirect.com/science/article/pii/S0378512299000079 - Block all www.sciencedirect.com results
by DM Gruber - 1999 - Cited by 11 - Related articles
Methods: The cases of two postmenopausal women who developed endometrial cancer after taking continuous sequential HRT for 15 months are reported. ...
jnci.oxfordjournals.org/content/89/15/1110.full.pdf
of the National Cancer Institute, Vol. 89, No. 15, August 6, 1997
ARTICLES
Estrogen–Progestin Replacement Therapy and
Endometrial Cancer
Malcolm C. Pike, Ruth K. Peters, Wendy Cozen, Nicole M. Probst-Hensch,
Juan C. Felix, Peggy C. Wan, Thomas M. Mack*
www.ncbi.nlm.nih.gov/pubmed/21682550
J Womens Health (Larchmt). 2011 Aug;20(8):1157-63. Epub 2011 Jun 17.
Trends in endometrial cancer incidence rates in the United States, 1999-2006.
Duong LM, Wilson RJ, Ajani UA, Singh SD, Eheman CR.
Source
Cancer Surveillance Branch, Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention , Atlanta, Georgia.
Abstract
Abstract Background: Risk factors for endometrial cancer, such as hormone replacement therapy (HRT) and obesity, have changed significantly in the last decade. We investigated trends in endometrial cancer histologic subtypes on a national level during 1999-2006. Methods: Data covering 88% of the U.S. population were from central cancer registries in the National Program of Cancer Registries (NPCR) and Surveillance, Epidemiology, and End Results (SEER) programs that met high-quality United States Cancer Statistics (USCS) criteria. Our analyses included females with microscopically confirmed invasive uterine cancer (n=257,039). Age-adjusted incidence rates and trends for all invasive uterine cancers and by endometrial cancer histologic subtypes (type I and II) were assessed. Results: There were 145,922 cases of type I endometrial cancers and 15,591 cases of type II for 1999-2006. We found that type I endometrial cancers have been increasing, whereas type II endometrial cancers and all invasive uterine cancers have been relatively stable throughout the 1999-2006 period. Conclusions: During the past decade, the overall burden of uterine cancer has been stable, although there have been changes in underlying histologies (e.g., endometrial). Changes in trends for underlying histologies may be masked when reviewing trends irrespective of histologic subtypes. Our findings suggest the need to examine trends of uterine cancer by histologic subtype in order to better understand the burden of endometrial cancer in relation to these subtypes to help women at increased risk for developing more aggressive types of endometrial cancer (e.g., type II).
--------------
rebuttal
www.ncbi.nlm.nih.gov/pubmed/10090424
Clin Ther. 1999 Jan;21(1):41-60; discussion 1-2.
Oral micronized progesterone.
de Lignières B.
Source
Department of Endocrinology and Reproductive Medicine, Hôpital Necker, Paris, France.
Abstract
This review sought to examine the rationale for selecting an oral micronized progesterone formulation rather than a synthetic progestin for some of the main indications for progestogens. Unopposed estrogen use is associated with a high risk (relative risk, 2.1 to 5.7) of endometrial hyperplasia and adenocarcinoma, and it has been understood for some time that a progestogen must be added for at least 10 to 14 days per month to prevent these effects. However, the most commonly used synthetic progestins, norethisterone and medroxyprogesterone acetate, have been associated with metabolic and vascular side effects (eg, suppression of the vasodilating effect of estrogens) in both experimental and human controlled studies. All comparative studies to date conclude that the side effects of synthetic progestins can be minimized or eliminated through the use of natural progesterone, which is identical to the steroid produced by the corpus luteum. The inconvenience associated with the use of injectable, rectal, or vaginal formulations of natural progesterone can be circumvented by using orally administered micronized progesterone. The bioavailability of micronized progesterone is similar to that of other natural steroids, and interindividual and intraindividual variability of area under the curve is similar to that seen with synthetic progestins. A clear dose-ranging effect has been demonstrated, and long-term protection of the endometrium has been established. Micronized progesterone has been used widely in Europe since 1980 at dosages ranging from 300 mg/d (taken at bedtime) 10 days a month for women wishing regular monthly bleeding to 200 mg 14 days a month or 100 mg 25 days a month for women willing to remain amenorrheic. This therapy is well tolerated, with the only specific side effect being mild and transient drowsiness, an effect minimized by taking the drug at bedtime. The prospective, comparative Postmenopausal Estrogens/Progestin Intervention trial has recommended oral micronized progesterone as the first choice for opposing estrogen therapy in nonhysterectomized postmenopausal women.
----------------------------------
www.jabfm.org/cgi/reprint/24/2/202.pdf
JABFM March–April 2011 Vol. 24 No. 2
CLINICAL REVIEW
Counseling Postmenopausal Women about
Bioidentical Hormones: Ten Discussion Points for
Practicing Physicians
Richa Sood, MD, Lynne Shuster, MD, Robin Smith, MD, Ann Vincent, MD,
and Aminah Jatoi, MD
Progestogens (bioidentical progesterone and synthetic progestins) have been used to balance the effects of unopposed estrogen on uterine endometrium and prevent
uterine cancer. All progestogens currently available for menopausal HT are approved for this purpose by the FDA.2
--------------------------------------------
www.drugs.com/pro/prometrium.html
Accurate, FDA approved Prometrium information
Prometrium®
(progesterone, USP)
Capsules 100 mg
Capsules 200 mg
CLINICAL STUDIES - Effects on the endometrium
In a randomized, double-blind clinical trial, 358 postmenopausal women, each with an intact uterus, received treatment for up to 36 months. The treatment groups were: Prometrium Capsules at the dose of 200 mg/day for 12 days per 28-day cycle in combination with conjugated estrogens 0.625 mg/day (n=120); conjugated estrogens 0.625 mg/day only (n=119); or placebo (n=119). The subjects in all three treatment groups were primarily Caucasian women (87 percent or more of each group). The results for the incidence of endometrial hyperplasia in women receiving up to 3 years of treatment are shown in Table 3. A comparison of the Prometrium Capsules plus conjugated estrogens treatment group to the conjugated estrogens only group showed a significantly lower rate of hyperplasia (6 percent combination product versus 64 percent estrogen alone) in the Prometrium Capsules plus conjugated estrogens treatment group throughout 36 months of treatment.
INDICATIONS AND USAGE - Prometrium Capsules are indicated for use in the prevention of endometrial hyperplasia in nonhysterectomized postmenopausal women who are receiving conjugated estrogens tablets. They are also indicated for use in secondary amenorrhea.
--------------------------
www.ncbi.nlm.nih.gov/pubmed/15901742
J Clin Pharmacol. 2005 Jun;45(6):614-9.
Over-the-counter progesterone cream produces significant drug exposure compared to a food and drug administration-approved oral progesterone product.
Hermann AC, Nafziger AN, Victory J, Kulawy R, Rocci ML Jr, Bertino JS Jr.
Source
Department of Medicine, Bassett Healthcare, Cooperstown, New York, USA.
Abstract
Progesterone products are available in prescription form as well as over-the-counter (OTC) topical preparations sold for "cosmetic" uses. In a randomized study design, the authors compared the drug exposure from an OTC progesterone cream to a Food and Drug Administration-approved oral preparation at the labeled daily doses recommended for each product. Twelve healthy postmenopausal women received 200-mg oral progesterone capsules once daily for 12 days or progesterone cream 40 mg twice daily for 12 days. At steady state (day 12 of each phase), whole-blood samples were collected over 24 hours (oral progesterone) or 12 hours (topical progesterone) and assayed for total progesterone concentration. No significant differences were found in dose-normalized 24-hour progesterone exposure comparing the cream to oral capsules (median AUC(0-24) 12.5 ng x h/mL vs 10.5 ng x h/mL, respectively; P = .81). In light of the potential risks associated with long-term progesterone use, the authors question whether topical progesterone products should be available OTC.
Estrogens and progestins: background and history, trends
in use, and guidelines and regimens approved by the US
Food and Drug Administration
Marcia L. Stefanick, PhD
www.ncbi.nlm.nih.gov/pmc/articles/PMC2219716/
J Gen Intern Med. 2007 July; 22(7): 1030–1034.
Bioidentical Hormones for Menopausal Hormone Therapy: Variation on a Theme
Adriane Fugh-Berman, MDcorresponding author and Jenna Bythrow, MS candidate
J. Bythrow is currently employed as a pharmaceutical sales representative with Eli Lilly.
BACKGROUND
Progesterone creams and natural or bioidentical compounded estrogen preparations are being promoted to consumers as safe alternatives to conventional menopausal hormone therapy and as health-promoting tonics. No reliable data support these claims.
SAFETY
Natural hormones, including estradiol, estriol, estrone, and progesterone, can be expected to have the same adverse event profile as conventional menopausal hormone regimens.
SALIVARY HORMONE TESTS
Salivary tests may be used to persuade asymptomatic consumers to use hormones (or symptomatic patients to use higher doses than those needed to mitigate symptoms), a practice that can be expected to result in adverse events.
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Posted by Jeffrey Dach MD at 08-29-2011 
Categories: Falsehoods Raise Doubts About Bioidentical Hormones With Falsehoods by Jeffrey Dach MD, endometrial cancer, More Falsehoods About Bioidentical Hormones by Jeffrey Dach MD
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Categories: Falsehoods Raise Doubts About Bioidentical Hormones With Falsehoods by Jeffrey Dach MD, endometrial cancer, More Falsehoods About Bioidentical Hormones by Jeffrey Dach MD
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