References
Last Updated June 2008
Relevant Dimera publications
Miyagawa K, Rösch J, Stanczyk F, Hermsmeyer K. Medroxyprogesterone interferes with ovarian steroid protection against coronary vasospasm. Nature Medicine 3:324-327, 1997a.
Hermsmeyer K, Miyagawa K, Kelley ST, Rösch J, Hall AS, Axthelm MK, and Greenberg B. Reactivity based coronary vasospasm independent of atherosclerosis in rhesus monkeys. J Am Col Cardiol 29:671-680, 1997.
Miyagawa K, Vidgoff J, Hermsmeyer K. Calcium release mechanism of primate reactivity based coronary vasospasm. Am J Physiol 272:H2645-H2654, 1997b.
Minshall RD, Stanczyk FZ, Miyagawa K, Uchida B, Axthelm MK, Novy M, Hermsmeyer K. Ovarian steroid protection against coronary artery hyperreactivity in rhesus monkeys. J Clin Endoc Metabol 83:649-659, 1998a.
Minshall RD, Miyagawa K, Chadwick CC, Novy MJ, Hermsmeyer K. In Vitro modulation of primate coronary vascular muscle cell reactivity by ovarian steroid hormones. FASEB J 12:1419-1429, 1998b.
Hermsmeyer K, Minshall R, Miyagawa K, Vidgoff J. Estrogen and progesterone protective actions on coronary arteries in rhesus monkeys. Estrogen and the Vessel Wall, Rubanyi GM and Kauffman R, ed., Harwood Academic Publishers, Switzerland, Endothelial Cell Res, series 3, 237-250, 1998.
Burry KA, Patton PE, Hermsmeyer K. Percutaneous absorption of progesterone in postmenopausal women treated with transdermal estrogen. Am J Obstet Gynecol 180:1504-1511, 1999.
Paris JM, Williams KJ, Hermsmeyer RK, Delansorne R. Nomegestrol acetate and vascular reactivity: nonhuman primate experiments. Steroids 65:621-627, 2000.
Minshall, RD, Pavcnik D, Halushka PV, Hermsmeyer K. Progesterone regulation of vascular thromboxane A2 receptors in rhesus monkeys. Am J Physiol 281:H1498-1507, 2001.
Minshall RD, Pavcnik D, Browne DL, Hermsmeyer K. Nongenomic vasodilator action of progesterone on primate coronary arteries. J Appl Physiol 92:701-708, 2002.
Hermsmeyer RK, Mishra RG, Pavcnik D, Uchida B, Axthelm MK, Stanczyk FZ, Burry KA, Illingworth DR, Kaski JC, Nordt FJ. Prevention of coronary hyperreactivity in pre-atherogenic menopausal rhesus monkeys by transdermal progesterone, Arteriosclerosis, Thrombosis, and Vascular Biology 24:955-961, 2004.
Mishra RG, Hermsmeyer RK, Miyagawa K, Sarrel P, Uchida B, Stanczyk FZ, Burry KA, Illingworth DR, and Nordt FJ. Medroxyprogesterone acetate and dihydrotestosterone induce coronary hyperreactivity in intact male rhesus monkeys. Journal of Clinical Endocrinology & Metabolism 90(6):3706-3714, 2005.
Mishra RG, Stanczyk FZ, Burry KA, Oparil S, Katzenellenbogen BS, Nealen ML, Katzenellenbogen JL, and Hermsmeyer RK. Metabolite ligands of estrogen receptor beta reduce primate coronary hyperreactivity. Am J Physiol Heart Circ Physiol 290:H295-H303, 2006.
Hermsmeyer RK, Thompson TL, Pohost GM, and Kaski JC. Cardiovascular effects of medroxyprogesterone acetate and progesterone: a case of mistaken identity?--A comparison of medically distinct progestins in Nature Clinical Practice Cardiovascular Medicine July 2008 issue that will be of significance for all women. [The full abstract can now be accessed on the National Library of Medicine website--PubMed--with keywords, "cardiovascular and progesterone".]
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Reports from the Women's Health Initiative (WHI), Women's International Study of long Duration Oestrogen after Menopause (WISDOM), and important related references
American Heart Association Statistical Fact Sheets 2007 Update. Dallas, Texas. American Heart Association; ©2006, American Heart Association (AHA), 2006. [Data analyses are presented as of 2004, which are the latest complete set available.]
Grady D et al. Postmenopausal hormone therapy increases risk for venous thromboembolic disease:the Heart and Estrogen/progestin Replacement Study. Ann Intern Med 132:689-696, 2000.
Grady D et al. Cardiovascular Disease Outcomes During 6.8 Years of Hormone Therapy. JAMA 288:49-57, 2002.
Hulley S et al. Noncardiovascular Disease Outcomes During 6.8 Years of Hormone Therapy. JAMA 288:58-66, 2002.
Rossouw JE et al. Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women - Principal Results from the Women's Health Initiative Randomized Controlled Trial. JAMA 288:321-333, 2002
Manson JE et al. Estrogen plus progestin and the risk of coronary heart disease. NEJM 349:523-534, 2003.
Barrett-Connor E, Grady D, Stefanick ML. The rise and fall of menopausal hormone therapy. Annu Rev Public Health 26:115-140, 2005.
Hsia J, Langer RD, Manson JE, Kuller S, Johnson K, Hendrix S, Pettinger M, et al. Conjugated equine estrogens and heart disease: the Women's Health Initiative. Arch Int Med 166:357-365, 2006.
Grodstein F, Manson JE, Stampfer MJ. Hormone therapy and coronary heart disease: the role of time since menopause and age at hormone initiation. J Womens Health (Larchmt). 15:35-44, 2006.
Rossouw JE, Prentice RL, Manson JE, Wu L, Barad D, Barnabei VM, Ko M, LaCroix AZ, Margolis KL, Stefanick ML. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA 297:1465-1477, 2007.
Vickers MR, MacLennan AH, Lawton B, Ford D, Martin J, Meredith SK, DeStavola BL, Rose S, Dowell A, Wilkes HC, Darbyshire JH, Meade TW; WISDOM group. Main morbidities recorded in the women's international study of long duration oestrogen after menopause (WISDOM): a randomised controlled trial of hormone replacement therapy in postmenopausal women. British Med J 235:339-351, 2007.
Heiss G, Wallace R, Anderson GL, Aragaki A, Beresford SA, Brzyski R, Chlebowski RT, Gass M, LaCroix A, Manson JE, Prentice RL, Rossouw J, Stefanick ML; WHI Investigators. Health risks and benefits 3 years after stopping randomized treatment with estrogen and progestin. JAMA 299:1036-1045, 2008.
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Independent evidence of progesterone virtues and MPA liabilities
Nilsen J and Brinton RD. Divergent impact of progesterone and medroxyprogesterone acetate (Provera) on nuclear mitogen-activated protein kinase signaling. PNAS 100:10506-10511, 2003.
Rosano GM, Webb CM, Chierchia S, Morgani GL, Babraele M, Sarrel PM, de Ziegler D, Collins P. Natural progesterone, but not medroxyprogesterone acetate, enhances the beneficial effect of estrogen on exercise-induced myocardial ischemia in postmenopausal women. J Am Coll Cardiol 36:2154-2159, 2000.
Stanczyk F. All progestins are not created equal. Steroids 68: 879-890, 2003.
Turgeon JL, McDonnell DP, Martin KA, Wise PM. Hormone Therapy: Physiological Complexity Belies Therapeutic Simplicity. Science 304: 1269-1273, 2004.
Wright DW, Kellermann AL, Hertzberg VS, Clark PL, Frankel M, Goldstein FC, Salomone JP, Dent LL, Harris OA, Ander DS, Lowery DW, Patel MM, Denson DD, Gordon AB, Wald MM, Gupta S, Hoffman SW, Stein DG. ProTECT: A randomized clinical trial of progesterone for acute traumatic brain injury. Ann Emerg Med 49:391-402, 2007.
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Evidence that progesterone, unlike estrogens or androgens, does not increase risk of breast cancer
This paper presents the first scientific evaluation of progesterone in a controlled human study, and contains the noteworthy statement (on p. 1863),
"To our knowledge, our study was the first to investigate whether progesterone levels are associated with breast cancer risk in postmenopausal women, and we observed no statistically significant association." [bold emphasis added on this page]
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 96:1856–65, 2004.
Evidence that elective ovariectomy at the time of hysterectomy possibly removes ovarian benefits
Parker WH, Broder MS, Liu Z, Shoupe D, Farquhar C, Berek JS. Ovarian conservation at the time of hysterectomy for benign disease. Obstet Gynecol. 106:219-226, 2005.
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