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Comparative Medicine
Dr. Thomas Clarkson

Thomas B. Clarkson, DVM

Professor of Comparative Medicine
Tel: (336) 716-4570
Fax: (336) 716-1601
tclarkso@wfubmc.edu

  • Board Certification: Diplomate, ACLAM, Laboratory Animal Medicine
Education:
  • Postgraduate: University of Georgia, DVM, 1954
Interests:
  • Teaching: Postmenopausal Health; Estrogen Replacement Therapy; Alternative Estrogens; Animal Models of Women's Health
  • Research: Coronary Artery Atherosclerosis and Coronary Heart Disease of Females; New Directions in Hormone Replacement Therapy; Behavioral and Psychosocial Influences on Chronic Diseases; Animal Models
  • Clinical: Nonhuman Primate Medicine 
In the News:
  • Dr. Clarkson talked briefly about the last 50 years in Comparative Medicine in the first issue of the Pathology Department's alumni newsletter "Pathology inSight."
  • In his introduction to the 2004 issue of the Institute for Laboratory Animal Research Journal, Dr. Jay Kaplan wrote that "the application of animal models to women's health originates in large part with the ideas and investigations of [Dr. Thomas] Clarkson." The Section on Comparative Medicine, led by Dr. Clarkson from 1974 to 1997, has long been a leader in efforts to learn more about women's health issues -- including depression, hot flashes, reproductive cancers, cardiovascular disease, and osteoporosis -- using animal studies.
Current Projects: Postmenopausal Coronary Artery Atherosclerosis, Estrogens, Phytoestrogens, Diet 

Our objective is to better understand the pathogenesis of atherosclerosis by observing the similarities and dissimilarities in lesion development between human beings and various animal species, especially nonhuman primates. A particular focus of our research is women's health, particularly illnesses like osteoporosis and cardiovascular diseases that are exacerbated because of the natural loss of estrogen when women go through menopause.

Although we know traditional hormone replacement therapy confers benefits, very few women are compliant when prescribed treatment. Our group has focused intensely over the past several years on phytoestrogens, the naturally occurring plant estrogens found in many foods. Using our postmenopausal cynomolgus macaque model, we have obtained experimental evidence that soy phytoestrogens may be a useful alternative to traditional hormone replacement therapy in the prevention of cardiovascular disease. The soy phytoestrogens improve plasma lipoprotein profiles, inhibit atherogenesis, upregulate brain molecular markers important for cognition and, importantly, are estrogen antagonist for breast and endometrium. Currently, we are seeking to understand the relationships between dose and outcomes important to both males and females, the mechanisms by which the phytoestrogens so markedly increase Apo A1 and decrease LDL cholesterol, the importance of soy protein per se to its phytoestrogen effects, and to elucidate the relative potency of the two major phytoestrogens (genistein and daidzein) in cardioprotection. 

A woman's cardiovascular risk increases over her lifetime.

FIGURE LEGEND: Schematic design of a woman's risk of cardiovascular disease over the life span. A focus of investigations throughout the Center is the assessment of factors that create the high-risk trajectory, and which interventions can alter that trajectory to a low-risk one.
Recent Publications:

Törmälä R, Appt SE, Clarkson TB, Tikkanen MJ, Ylikorkala O, Mikkola TS. Individual differences in equol production capability modulate blood pressure in tibolone-treated postmenopausal women. Climacteric 2007;10:471–479.

Törmälä R, Appt S, Clarkson TB, Groop PH, Rönnback M, Ylikorkala O, Mikkola TS. Equol production capability is associated with favorable vascular function in postmenopausal women using tibolone; no effect with soy supplementation. Atherosclerosis. 2007 Oct 23 [Epub ahead of print]

Clarkson TB, Karas RH.  Do the cardiovascular disease risks and benefits of oral versus transdermal estrogen therapy differ between perimenopausal and postmenopausal women? Menopause. 2007 Sep 28; [Epub ahead of print]

Jones JC, Appt SE, Bourland JD, Hoyer PB, Clarkson TB, Kaplan JR. Multidetector computed tomographic morphology of ovaries in cynomolgus macaques (Macaca fascicularis). J Am Assoc Lab Anim Sci. 2007 Sep;46(5):54-63.

Clarkson TB. Estrogen effects on arteries vary with stage of reproductive life and extent of subclinical atherosclerosis progression. Menopause. 2007 May-Jun;14(3 Pt 1):373-84.

Adams MR, Anthony MS, Chen H, Clarkson TB. Replacement of dietary soy protein isolate with concentrates of soy 7S or 11S globulin has minimal or no effects on plasma lipoprotein profiles and biomarkers of coronary risk in monkeys. Atherosclerosis. 2007 Mar 8; [Epub ahead of print]

Wood CE, Clarkson TB, Appt SE, Franke AA, Boue SM, Burow ME, McCoy T, Cline JM. Effects of soybean glyceollins and estradiol in postmenopausal female monkeys. Nutr Cancer. 2006;56(1):74-81.

Appt SE, Kaplan JR, Clarkson TB, Cline JM, Christian PJ, Hoyer PB. Destruction of primordial ovarian follicles in adult cynomolgus macaques after exposure to 4-vinylcyclohexene diepoxide: a nonhuman primate model of the menopausal transition. Fertil Steril. 2006 Oct;86 Suppl 4:1210-6.

Wood CE, Appt SE, Clarkson TB, Franke AA, Lees CJ, Doerge DR, Cline JM. Effects of high-dose soy isoflavones and equol on reproductive tissues in female cynomolgus monkeys. Biol Reprod. 2006 Sep;75(3):477-86.

Gu L, House SE, Prior RL, Fang N, Ronis MJ, Clarkson TB, Wilson ME, Badger TM. Metabolic phenotype of isoflavones differ among female rats, pigs, monkeys, and women. J Nutr. 2006 May;136(5):1215-21.

Appt SE, Clarkson TB, Lees CJ, Anthony MS. Low dose estrogens inhibit coronary artery atherosclerosis in postmenopausal monkeys. Maturitas. 2006 Sep 20;55(2):187-94.

Mikkola TS, Clarkson TB. Coronary heart disease and postmenopausal hormone therapy: conundrum explained by timing? J Womens Health (Larchmt). 2006 Jan-Feb;15(1):51-3.

Clarkson TB. Does tibolone exacerbate atherosclerosis? Eur Heart J. 2006 JMar;27(6):635-7.

Badeau M, Tikkanen MJ, Appt SE, Adlercreutz H, Clarkson TB, Hoikkala A, Wahala K, Mikkola TS. Determination of plasma genistein fatty acid esters following administration of genistein or genistein 4'7-O-dioleate in monkeys. Biochim Biophys Acta. 2005 Dec 30;1738(1-3):115-20.

Lees CJ, Ederveen AG, Spanjers CP, Clarkson TB. Effects of tibolone on bone quality in ovariectomized monkeys. Menopause. 2005 Sep-Oct;12(5):613-8.

Miller VM, Clarkson TB, Harman SM, Brinton EA, Cedars M, Lobo R, Manson JE, Merriam GR, Naftolin F, Santoro N. Women, hormones, and clinical trials: a beginning, not an end. J Appl Physiol. 2005 Aug;99(2):381-3.

Clarkson TB, Appt SE. Controversies about HRT-lessons from monkey models. Maturitas. 2005 May 16;51(1):64-74.

Wagner JD, Clarkson TB. The applicability of hormonal effects on atherosclerosis in animals to heart disease in postmenopausal women. Semin Reprod Med. 2005 May;23(2):149-56. Review.

Register TC, Cann JA, Kaplan JR, Williams JK, Adams MR, Morgan TM, Anthony MS, Blair RM, Wagner JD, Clarkson TB. Effects of Soy Isoflavones and Conjugated Equine Estrogens on Inflammatory Markers in Atherosclerotic, Ovariectomized Monkeys. J Clin Endocrinol Metab. 2005 Mar;90(3):1734-40.

Mikkola TS, Clarkson TB, Notelovitz M. Postmenopausal hormone therapy before and after the women's health initiative study: what consequences? Ann Med. 2004;36(6):402-13.

Clarkson TB, Appt SE, Wood CE, Cline JM. Lessons to be learned from animal studies on hormones and the breast. Maturitas. 2004 Sep 24;49(1):79-89.

Clarkson TB, Anthony MS, Cline JM, Lees CJ, Ederveen AG. Multisystem evaluations of the long-term effects of tibolone on postmenopausal monkeys. Maturitas. 2004 Aug 30;48 Suppl 1:24-9.

Naftolin F, Taylor HS, Karas R, Brinton E, Newman I, Clarkson TB, Mendelsohn M, Lobo RA, Judelson DR, Nachtigall LE, Heward CB, Hecht H, Jaff MR, Harman SM; Women's Health Initiative. The Women's Health Initiative could not have detected cardioprotective effects of starting hormone therapy during the menopausal transition. Fertil Steril. 2004 Jun;81(6):1498-501.

Clarkson TB, Appt SE. MPA and postmenopausal coronary artery atherosclerosis revisited. Steroids. 2003 Nov; 68(10-13): 941-51.

Shadoan MK, Anthony MS, Rankin SE, Clarkson TB, Wagner JD. Effects of tibolone and conjugated equine estrogens with or without medroxyprogesterone acetate on body composition and fasting carbohydrate measures in surgically postmenopausal monkeys. Metabolism. 2003 Sep;52(9):1085-91.

Mikkola TS, Anthony MS, Clarkson TB, St Clair RW. Serum cholesterol efflux potential is an independent predictor of coronary artery atherosclerosis. Atherosclerosis. 2003 Sep;170(1):31-8.

Blair RM, Appt SE, Franke AA, Clarkson TB. Treatment with antibiotics reduces plasma equol concentration in cynomolgus monkeys (Macaca fascicularis). J Nutr. 2003 Jul;133(7):2262-7.

Goodrich JA, Clarkson TB, Cline JM, Jenkins AJ, Del Signore MJ. Value of the micropig model of menopause in the assessment of benefits and risks of postmenopausal therapies for cardiovascular and reproductive tissues. Fertil Steril. 2003 Mar;79(3 Suppl 1):779-88.

Grodstein F, Clarkson TB, Manson JE. Understanding the divergent data on postmenopausal hormone therapy. N Engl J Med. 2003 Feb 13;348(7):645-50.

Blair RM, Appt SE, Bennetau-Pelissero C, Clarkson TB, Anthony MS, Lamothe V, Potter SM. Dietary soy and soy isoflavones have gender-specific effects on plasma lipids and isoflavones in golden Syrian f(1)b hybrid hamsters. J Nutr. 2002 Dec;132(12):3585-91.

Cline JM, Register TC, Clarkson TB. Effects of tibolone and hormone replacement therapy on the breast of cynomolgus monkeys. Menopause. 2002 Nov-Dec;9(6):422-9.

Register TC, Wagner JD, Zhang L, Hall J, Clarkson TB. Effects of tibolone and conventional hormone replacement therapies on arterial and hepatic cholesterol accumulation and on circulating endothelin-1, vascular cell adhesion molecule-1, and E-selectin in surgically menopausal monkeys. Menopause. 2002 Nov-Dec;9(6):411-21.

Clarkson TB, Anthony MS, Mikkola TS, St Clair RW. Comparison of tibolone and conjugated equine estrogens effects on carotid artery atherosclerosis of postmenopausal monkeys. Stroke. 2002 Nov;33(11):2700-3.

Gibbs RB, Nelson D, Anthony MS, Clarkson TB. Effects of long-term hormone replacement and of tibolone on choline acetyltransferase and acetylcholinesterase activities in the brains of ovariectomized, cynomologus monkeys. Neuroscience. 2002;113(4):907-14.

Cline JM, Register TC, Clarkson TB. Comparative effects of tibolone and conjugated equine estrogens with and without medroxyprogesterone acetate on the reproductive tract of female cynomolgus monkeys. Menopause. 2002 Jul-Aug;9(4):242-52.

Clarkson TB. The new conundrum: do estrogens have any cardiovascular benefits? Int J Fertil Womens Med. 2002 Mar-Apr;47(2):61-8.

Mikkola TS, Anthony MS, Clarkson TB, St Clair RW. Serum cholesterol efflux potential in postmenopausal monkeys treated with tibolone or conjugated estrogens. Metabolism. 2002 Apr;51(4):523-30.

Clarkson TB. Soy, soy phytoestrogens and cardiovascular disease. J Nutr. 2002 Mar;132(3):566S-569S. Review.

Clarkson TB. Raloxifene revisited. Fertil Steril. 2002 Mar;77(3):445-7. Review.

Kaplan JR, Manuck SB, Anthony MS, Clarkson TB. Premenopausal social status and hormone exposure predict postmenopausal atherosclerosis in female monkeys. Obstet Gynecol. 2002 Mar;99(3):381-8.

Mikkola TS, Clarkson TB. Estrogen replacement therapy, atherosclerosis, and vascular function. Cardiovasc Res. 2002 Feb 15;53(3):605-19. Review.

Blair RM, Cline JM, Anthony MS, Clarkson TB. Use of the progestin challenge test in nonhuman primates (Macaca fascicularis). Fertil Steril. 2002 Feb;77(2):387-91.

Williams JK, Hall J, Anthony MS, Register TC, Reis SE, Clarkson TB. A comparison of tibolone and hormone replacement therapy on coronary artery and myocardial function in ovariectomized atherosclerotic monkeys. Menopause. 2002 Jan-Feb;9(1):41-51.