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Inventor of the 1st Heart Drug for women


PDF files of many of the reports below may be available in response to Email requests to Dimera.

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? Nature Clinical Practice Cardiovascular Medicine 5:387-395, 2008.

Hermsmeyer RK, Thompson TL. Progesterone Deficiency, in Chest Pain with Normal Coronary Arteries. Edited by Juan Carlos Kaski, Guy D. Eslick, and C. Noel Bairey-Merz. London: Springer-Verlag. 2013


WISE, WHI, WISDOM, HERS, and other reports that imply actions of ovarian steroid hormones on heart function and coronary disease constitute this section.

Roger VL et al. American Heart Association Heart Disease and Stroke Statistics-2012 Update. (Dallas, Texas: American Heart Association), Circulation 125:e209-e220, 2012. http://circ.ahajournals.org/content/125/1/e2 [The latest complete sets available are cited.]

Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, Vittinghoff E. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA. 280:605-613, 1998.

Shaw LJ, Bugiardini R, Merz CN. Women and ischemic heart disease: evolving knowledge. J Am Coll Cardiol. 54:1561-1575, 2009.

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.

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.

Johnson BD, Shaw LJ, Pepine CJ, Reis SE, Kelsey SF, Sopko G, Rogers WJ, Mankad S, Sharaf BL, Bittner V, Bairey Merz CN. Persistent chest pain predicts cardiovascular events in women without obstructive coronary artery disease: results from the NIH-NHLBI-sponsored Women's Ischaemia Syndrome Evaluation (WISE) study. Eur Heart J. 27(12):1408-1415, 2006.

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.

Merz CN, Olson MB, McClure C, Yang YC, Symons J, Sopko G, Kelsey SF, Handberg E, Johnson BD, Cooper-DeHoff RM, Sharaf B, Rogers WJ, Pepine CJ. A randomized controlled trial of low-dose hormone therapy on myocardial ischemia in postmenopausal women with no obstructive coronary artery disease: results from the National Institutes of Health/National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE). Am Heart J. 159(6):987.e1-7, 2010.

Mehta PK, Goykhman P, Thomson LE, Shufelt C, Wei J, Yang Y, Gill E, Minissian M, Shaw LJ, Slomka PJ, Slivka M, Berman DS, Bairey Merz CN. Ranolazine improves angina in women with evidence of myocardial ischemia but no obstructive coronary artery disease. J Am Col Cardiol Cardiovasc Imaging. 2011;4(5):514-522.

Smilowitz NR, Sampson BA, Abrecht CR, Siegfried JS, Hochman JS, Reynolds HR. Women have less severe and extensive coronary atherosclerosis in fatal cases of ischemic heart disease: an autopsy study. Am Heart J. 161:681-688, 2011.

Schoenenberger AW, Felber S, Gujer S, Moser A, Jamshidi P, Stuck AE, Erne P. Invasive findings in patients with angina equivalent symptoms but no coronary artery disease; Results from the heart quest cohort study. Int J Cardiol. 2012, Jan 10. [Epub ahead of print, PMID:22236508]


Independent evidence of progesterone virtues and MPA liabilities

Hermsmeyer RK, Thompson TL, Pohost GM, and Kaski JC. Cardiovascular effects of medroxyprogesterone acetate and progesterone: a case of mistaken identity? Nature Clinical Practice Cardiovascular Medicine 5:387-395, 2008.

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.

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.

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.


Evidence that progesterone, unlike estrogens or androgens, does not increase risk of breast cancer

This National Cancer Institute (of NIH) report presents the first scientific evaluation of progesterone in a controlled human study, and contains the noteworthy statement (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."

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 96:1856-1865, 2004.