Our Research: Faculty/Research Laboratories

Stephanie Page, MD, PhD

Associate Professor, Department of Medicine, Division of Metabolism, Endocrinology and Nutrition

Section Head, Division of Metabolism, Endocrinology, and Nutrition, Harborview Medical Center

Email Address: page@u.washington.edu

Division of Metabolism, Endocrinology and Nutrition Website:  http://depts.washington.edu/metab/

Stephanie Page, MD, PhD

Background:

Dr. Page did her undergraduate work at Stanford University before moving to Seattle where she received her MD and PhD (in Immunology) from the University of Washington in 1999.  She completed her residency in Medicine at UW in 2002 and her fellowship training in Endocrinology and Metabolism at UW in 2006, under the mentorship of Dr. William J. Bremner.  Dr. Page serves as the  Section Head for the Division of Endocrinology and Metabolism at Harborview Medical Center in Seattle, where her clinical teaching and patient care responsibilities are centered. Dr. Page currently holds an R01 grant and is the Principal Investigator within the UW U54 Contraception Center as well as a lead investigator within the NIH-funded Contraception Clinical Trials Network. Dr. Page serves as Associate Director of the UW Endocrinology Fellowship and is a member of the American Society for Clinical Investigation.

Focus:

Dr. Page’s research focuses on male reproduction.  Current investigations are centered on understanding the impact of sex steroids on obesity, insulin resistance, diabetes and lipids in men.  In addition, Dr. Page’s research seeks to further our understanding of the influence of androgens on prostate health and the development of reversible male hormonal contraceptives.

Non-gonadal effects of Sex Steroids in Men: Impact on Adipose Tissue and Insulin Resistance
Dr. Page’s work is related to the effects of sex steroids on non-gonadal tissues, including adipose tissue, and metabolism.  Dr. Page performs her studies primarily in humans, examining directly how serum sex steroid manipulations impact the tissue microenvironment, including tissue hormone concentrations and cell-specific gene expression.  Androgens alter body composition, increasing lean body mass and decreasing fat mass, yet studies have not reproducibly shown expected improvements in insulin sensitivity with androgen supplementation.  Dr. Page’s recent work is exploring how androgen deprivation and replacement alter adipokine production and adipose tissue inflammation, major modulators of insulin sensitivity.  Complimentary studies in androgen receptor deficient mice are also underway to elucidate the mechanisms involved in androgen signaling and metabolic disease.

Androgens and HDL function
This research focus, developed collaboratively with Dr. Jay Heinecke, seeks to investigate the impact of sex steroids, and androgens in particular, on HDL biology. Exogenous androgens tend to decrease HDL-C (HDL concentration) yet low levels of circulating testosterone are associated with increased risk for cardiovascular disease in men.  A key hypothesis Dr. Page’s group is pursuing to explain this discrepancy is that changes in HDL-C mediated by androgens do not reflect changes in HDL function and that androgens have positive effects on HDL function and cardiovascular risk. Major goals of this project are to identify specific HDL-associated proteins that are modified by exogenous and endogenous sex steroids in men.

Representative Publications:

Page, ST, JK Amory, ED Bowman, BD Anawalt, AM Matsumoto, WJ Bremner and JL Tenover. Exogenous testosterone or testosterone plus finasteride improves physical performance and increases lean body mass in older men with low serum testosterone. 2005.  J. Clin. Endocrinol. Metab. 90:1502-10.

Rubinow KB, Snyder CN, Amory JK, Hoofnagle AN, Page ST. Acute testosterone deprivation reduces insulin sensitivity in men. 2012 Clin Endocrinol, 76:281-88.

Page, ST, Marck BT, Tolliver JM and AM Matsumoto. Tissue Selectivity of the Anabolic Steroid, 19-Nor-4-Androstenediol-3-diol in Male Sprague Dawley Rats: Selective Stimulation of Muscle Mass and Bone Mineral Density Relative to Prostate Mass. 2007.  Endocrinology 149:1987-93. PMCID: PMC2276724

Rubinow KB, Tang C, Hoofnagle AN, Snyder CN, Amory JK, Heinecke JW, and Page ST. Acute sex steroid withdrawal increases HDL cholesterol efflux capacity and HDL-Associated clusterin in young, healthy men.  2012 Steroids, 77:454-60.

Page ST, Krauss RM, Gross C, Ishida BY, Heinecke JW, Tang C, Amory JK, Schaefer PM, Cox CJ, Kane J, Purnell JQ, Weinstein R, and T Vaisar.  Impact of mifepristone, a glucocorticoid/progesterone antagonist, on HDL  cholesterol, HDL particle number, and HDL function.  2012 J Clin Endocrinol Metab, 97: 1598-605

Rubinow KB, Vaisar T, Tang C, Matsumoto AM, Heinecke JW, Page ST.  Testosterone replacement therapy in hypogonadal men alters the HDL proteome without impairing HDL-efflux capacity. 2012 J Lipid Research, 53: 1376-83.

  • Page, S, JB Miller, J. DiMario, EJ Hagar, A Moser and FE Stockdale.  Developmentally regulated expression of three slow isoforms of myosin heavy chain:  Diversity among the first fibers to form in avian muscle. 1992.  Developmental Biology.  154:118-28.

    Page, ST, WC Owen, K Price and PC Elwood.  Expression of the human placental folate receptor transcript is regulated in human tissues:  organization and full nucleotide sequence of the gene. 1993.  J. Mol. Biol.  229:1175-83.

    Saikawa, Y, CB Knight, T Saikawa, ST Page, BA Chabner and PC Elwood.  Decreased expression of the human folate receptor mediates transport-defective methotrexate resistance in KB cells. 1993.  J. Biol. Chem.  268:5293-301.

    Elwood, PC, K. Nachmanoff, Y Saikawa, ST Page, P Pacheco, S Roberts and KN Chung.  The divergent 5′ termini of the alpha human folate receptor (hFr) mRNAs originate from two tissue-specific promoters and alternative splicing: characterization of the alpha hFR gene structure. 1997.  Biochemistry  36:1467-78.

    Hamerman, JA, ST Page and AM Pullen.  Distinct methylation states of the CD8 gene in peripheral T cells and intraepithelial lymphocytes. 1997.  J. Immunol. 159:1240-6.

    Page, ST, NSC van Oers, RM Perlmutter, A Weiss and AM Pullen.  Differential contribution of Lck and Fyn protein tyrosine kinases to intraepithelial lymphocyte development. 1997.  Eur. J. Immunol.  27:554-62.

    Page, ST, LY Bogatzki, JA Hamerman, CH Sweenie, PJ Hogarth, M Malissen, RM Perlmutter and AM Pullen.  Intestinal intraepithelial lymphocytes include precursors committed to the T cell receptor ab lineage. 1998.  Proc. Natl. Acad. Sci. 95:9459-64.

    Page, ST, L. Bogatzki, JA Hamerman, M Malissen, R.M Perlmutter and AM Pullen. Differential effects of manipulating signaling in early T cell development in intestinal intraepithelial lymphocytes and thymocytes. 1999. Int. Immunol. 11:169-77.

    Herbst, KL, AD Coviello, S Page, JK Amory, BD Anawalt and W J Bremner. A single dose of the potent gonadotropin releasing-hormone antagonist acyline suppresses gonadotropins and testosterone for 2 weeks in healthy men. 2004.  J. Clin. Endocrinol. Metab. 89:5959-65.

    Page, ST, Herbst, KL, JK Amory, AD Coviello, AM Matsumoto and WJ Bremner. Testosterone suppresses adiponectin in normal men. 2005.  J. of Androl. 26:85-92.

    Page, ST, JK Amory, ED Bowman, BD Anawalt, AM Matsumoto, WJ Bremner and JL Tenover. Exogenous testosterone or testosterone plus finasteride improves physical performance and increases lean body mass in older men with low serum testosterone. 2005.  J. Clin. Endocrinol. Metab. 90:1502-10.

    Anawalt, BD, Amory JK, Herbst KL, Coviello AD, Page ST, Bremner WJ and AM Matsumoto. Very low-dosage oral levonorgestrel plus intramuscular testosterone enanthate suppresses spermatogenesis without causing weight gain in normal young men:  a randomized clinical trial. 2005.  J. of Androl. 26:405-13.

    Amory, JK, Page ST and Bremner WJ. Oral testosterone in oil: pharmacokinetic effects of 5a reduction by finasteride or dutasteride and food intake in men. 2006.  J. Androl.  27:72-8.

    Amory, JK, Page ST and Bremner WJ.  Recent advances in male hormonal contraception. 2006.  Nature Clin. Endocrinol. Metab. 2:32-41.

    Brockenbrough, AT, Dittrich MO, Page ST, Smith T, Stivelman J and WJ Bremner.  Transdermal androgen therapy to augment erythropoietin in the treatment of anemia of chronic renal disease. 2006.  Am. J. Kidney Dis. 47:251-62.

    Kupelian V, Page ST, Araujo AB, Travison TG, Bremner WJ and JB McKinlay.  Low SHBG, total Testosterone, and symptomatic androgen deficiency are associated with development of the Metabolic Syndrome in non-obese men: results from the Massachusetts Male Aging Study (MMAS). 2006.  J. Clin Endocrinol Metab. 91:843-50.

    Page, ST, Plymate SR, Bremner, WJ, Hess, DL, Matsumoto, AM, Lin, DW, Nelson, PS and JD Wu. Effects of medical castration and testosterone replacement on CD4+CD25+ Regulatory T Cells, CD8+ T-cell IFNg expression and NK cells: evidence for a physiological role for testosterone and/or its metabolites in cellular immune function. 2006.  Amer. J. Phys. Endo. Metab. 290:E856-63.

    Kupelian,V, Shabsigh, R, TravisonTG, Page ST, AraujoAB and JB McKinlay. Is There A Relationship Between Sex-Hormones And Erectile Dysfunction? Results From The Massachusetts Male Aging Study (MMAS). 2006 J. Urol. 176:2584-8.

    Page, ST, KupelianV, BremnerWJ and JB McKinlay. The Androgen Receptor Gene CAG Repeat Polymorphism Does not Predict Increased Risk of Heart Disease: Longitudinal Results from the Massachusetts Male Aging Study (MMAS). 2006.  Clin. Endocrinol. 66:333-9.

    Page, ST, Lin DW, Mostaghel EA, Hess, DL, True LD, Amory JK, Nelson PS, Matsumoto A and WJ Bremner. Persistent intraprostatic androgen concentrations after medical castration in healthy men. 2006.  J. Clin. Endocrinol. Metab. 91:3850-6.

    Page, ST, Amory, JK, Anawalt, BD, Irwig, MS, Brockenbrough, A, Matsumoto, AM and WJ Bremner.  Testosterone gel combined with depomedroxyprogesterone acetate is a novel and effective male hormonal contraceptive regimen: suppression of spermatogenesis is not enhanced by the addition of the GnRh antagonist, acyline. 2006.  J. Clin. Endocrinol. Metab. 91:4374-80.

    Amory, JK, Muller CH, Page ST, Pagel ER, Bhandari A, Leifke E, Subramanyam B, Bone W, Radlmier A and WJ Bremner.  Miglustat has no apparent effect on spermatogenesis in normal men. 2006.  Hum. Reprod. 22:702-7.

    Amory, JK, Page ST, Anawalt, BD, Matsumoto, AM and WJ Bremner. Acceptability of a combination testosterone gel and depomedroxyprogesterone acetate male contraceptive regimen. 2007.  Contraception 75:218-23.

    Amory, JK, Page ST, Anawalt, BD, Coviello AD, Matsumoto, AM and WJ Bremner. Elevated serum INSL3 is associated with failure to completely suppress spermatogenesis in men receiving male hormonal contraception. 2007.  J. Androl. 28:548-54.

    Araujo, A, Kupelian V, Page ST, Handelsman DJ, Bremner WJ and JB McKinlay.  Sex steroids and all-cause and cause-specific mortality in men. 2007.  Arch. Intern. Med. 167:1252-60.

    Amory, JK, Coviello AD, Page ST, Anawalt, BD, Matsumoto, AM and WJ Bremner. Serum 17-hydroxyprogesterone strongly correlates with intratesticular testosterone in normal men receiving human chorionic gonadotropin. 2008.  Fertil. Steril. 89:380-6. PMCID: PMC2674872

    Mostaghel EA* and Page, ST*,  LinDW, FazliL, ColemanIM, True  LD, KnudsenB, HessDL, Nelson CC, MatsumotoAM, BremnerWJ, GleaveME and PS Nelson. Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer. 2007.  Cancer Res. 67:5033-41. *co-first authors

    Aaltonen P, Amory JK, Anderson RA, Behre HM, Bialy G, Blithe D, Bone W, Bremner WJ, Colvard D, Cooper TG, Elliesen J, Gabelnick HL, Gu YQ, Handelsman DJ, Johansson EA, Kersemaekers W, Liu P, Mackay T, Matlin S, Mbizvo M, McLachlan RI, Meriggiola MC, Mletzko S, Mommers E, Muermans H, Nieschlag E, Odlind V, Page ST, Radlmaier A, Sitruk-Ware R, Swerdloff R, Wang C, Wu F, Zitzmann M.   Tenth summit meeting consensus: recommendations for regulatory approval for hormonal male contraception. 2007  J. Androl. 28:362-3.

    Montgomery, RB, Goldman B, Tangen CM, Hussain M, Petrylak DP, Page S, Klein EA and ED Crawford. Association of body mass index with response and survival in men with metastatic prostate cancer: Southwest Oncology Group trials 8894 and 9916. 2007.  J. Urol. 178:1946-51.

    Hall, SA, Page ST, Travison TG, Montgomery RB, Link CL and JB McKinlay. Do statins affect androgen levels in men? Results from the Boston Area Community Health  (BACH) Survey. 2007.  Cancer Epi Biomark Prev. 16:1587-94. 

    Page, ST, Kalhorn TK, Bremner WJ, Anawalt BD, Matsumoto AM and JK Amory. Intratesticular androgens and spermatogenesis during severe gonadotropin suppression induced by male hormonal contraceptive treatment. 2007.  J. Androl. 28:734-41.

    Page, ST, Mohr BA, Link CL, O’Donnell AB, Bremner WJ and JB McKinlay. Higher Testosterone Levels are Associated with Increased HDL-C in Men with Cardiovascular Disease: Results from the Massachusetts Male Aging Study. 2007. Asian J. Androl. 10:193-200. PMCID: PMC2666971

    Kalhorn, TF, PageST, HowaldWN, Mostaghel EA and PS Nelson. Analysis of Testosterone and DHT from Biological Fluids as the Oxime Derivatives using HPLC/MS/MS. 2007.  Rapid Commun. Mass Spectrom. 21:3200-6.

    Amory, JK, Kalhorn TF and ST Page. Pharmacokinetics and Pharmacodynamics of Oral Testosterone Enanthate Plus Dutasteride for Four Weeks in Normal Men: Implications for Male Hormonal Contraception. 2008.  J. Androl. 29:260-71. PMCID: PMC2664381

    Amory, JK, Anawalt BD, Matsumoto AM, Page ST, Bremner WJ, Wang C, Swerdloff R and RV Clark. The effect of 5-reductase inhibition with dutasteride and finasteride on bone mineral density, serum lipoproteins, hemoglobin, PSA and sexual function in healthy young men. 2008. J. Urol. 179:2333-8. PMCID: PMC2684818

    Page, ST, Marck BT, Tolliver JM and AM Matsumoto. Tissue Selectivity of the Anabolic Steroid, 19-Nor-4-Androstenediol-3b,17b-diol in Male Sprague Dawley Rats: Selective Stimulation of Muscle Mass and Bone Mineral Density Relative to Prostate Mass. 2007.  Endocrinology 149:1987-93. PMCID: PMC2276724

    Page, ST, Bremner WJ, Clark RV, Bush MA, Zhi H, Caricofe RB, Smith PM and JK Amory. Oral Nanomilled Testosterone Plus Dutasteride Effectively Normalizes Serum Testosterone in Normal Men with Induced Hypogonadism. 2008.  J. Androl. 29:222-7.

    Page, ST, Amory JK and WJ Bremner.  Advances in Male Contraception. 2008.  Endocrine Reviews 29:465-93.   PMCID: PMC2528850

    Page ST, Amory JK and AM Matsumoto. Does testosterone supplementation improve health and function in older men? A call for long-term, randomized trials. 2008. Nat Clin Pract Endocrinol Metab. 4:374-5. PMCID: PMC2657091

    Roth, MY, Amory JK and ST Page. Treatment of male infertility secondary to morbid obesity. 2008. Nat Clin Pract Endocrinol Metab. 4:415-9. PMCID: PMC2664380

    Wu, JD, Lin DW, Page ST, Lungren AD, True LD, and SR Plymate.  Oxidative DNA damage in the prostate may predispose men to a higher risk of prostate cancer. 2009 Transl Oncol.  2:39-45. PMCID: PMC2647701

    Mahabadi, V, Amory JK, Swerdloff RS, Bremner WJ, Page ST, Sitruk-Ware R, Christensen PD, Kumar N, Tsong Y, Blithe D, and C Wang. Daily Application of Transdermal Nestorone® and Testosterone Gels Suppresses Serum Gonadotropins in Healthy Men.  2009.  J. Clin. Endocrinol. Metab. 94:2313-20. PMCID: PMC2708961

    Amory, JK, Leonard T, Page ST,  O’Toole E, McKenna M and WJ Bremner.  Oral Administration of the GnRH Antagonist Acyline, in a GIPET®-Enhanced Tablet Form, Acutely Suppresses Serum Testosterone in Normal Men: Single-Dose Pharmacokinetics and Pharmacodynamics. 2009  Cancer Chemother Pharmacol. 64:641-5. PMCID: PMC2721900

    Roth, MY, Lin K, Amory JK, Matsumoto AM, Anawalt BD, Snyder CN, Kalhorn TF, Bremner WJ, and ST Page. Serum LH correlates highly with intra-testicular steroid levels in normal men. 2010 J. Androl. 31:138-45. PMCID: PMC2866133

    Attardi, BJ,  Page ST, Hild SA, Coss CC, and AM Matsumoto. Mechanism of action of bolandiol (19-Nortestosterone-3β,17β-Diol), a unique anabolic steroid with androgenic, estrogenic, and progestational activities. 2010 J Steroid Biochem Mol Biol. 118:151-61. PMCID: PMC2276724

    Wright, JL, Page, ST, Lin DW and JL Stanford. Early onset male pattern   baldness and prostate cancer risk in a population based case-control study. 2010 Cancer Epidemiology  34:131-5.

    Snyder, CN, Clark RV, Caricofe RB, Bush MA, Roth MY, Page ST, Bremner WJ, and JK Amory. Pharmacokinetics of two novel formulations of modified release oral testosterone alone and with finasteride in normal men with experimental hypogonadism. 2010 J Androl 31:527-35. PMCID: PMC3047498

    Sun, S, Sprenger, CCT, Vessella, RL, Haugk K, Soriano K, Mostaghel EA, Page ST, Coleman IM, Nelson PS, Nguyen HM, and SR Plymate. A novel, frequently occurring androgen receptor splice variant confers castration resistance in prostate cancer. 2010 J Clin Invest 120:2715-30. PMCID: PMC2912187

    Roth, MY, Page ST, Lin K, Anawalt BD, Matsumoto AM, Snyder CN, Marck BT, Bremner WJ, and Amory, JK. Dose-dependent increase in intratesticular testosterone by very

    Page, ST.  Late-onset hypogonadism in older men: new diagnostic criteria.   2010 Nat Rev Endocrinol 6:602-3.

    Page, ST, DW Lin, E Mostaghel, J Wright, BT Marck, JK Amory and AM Matsumoto. Dihydrotestosterone administration does not increase intraprostatic androgen concentrations or alter prostate androgen action in healthy men: a randomized-controlled trial.  2011 J Clin Endocrinol Metab.

    Roth, MY and Page, ST.  A role for dihydrotestosterone treatment in older men?  2011 Asian J Androl. 13:19-200.

    Roth, MY, Page ST, Lin K, Anawalt BD, Matsumoto AM, Marck B, Bremner WJ, and JK Amory.  The effect of gonadotropin withdrawal and stimulation with human chorionic gonadotropin on intratesticular androstenedione and DHEA in normal men.  2011 J Clin Endocinrol Metab. 96:1175-81.

    Page, ST, Hirano L, Gilchriest J, DigheM, MarckBT, and AM Matsumoto. Dutasteride reduces prostate size and prostate-specific antigen in older hypogonadal men with benign prostatic hyperplasia undergoing testosterone replacement therapy.  2011 J Urol.  186:191-7.

    Page ST. Physiologic role and regulation of intratesticular sex steroids. 2011 Curr Opin Endocrinol Diabetes Obes 18:217-23.

    Rubinow KB, Amory JK, Page ST. Androgens exert sexually dimorphic effects on angiogenesis: novel insight into the relationship between androgens and cardiovascular disease. 2011 Asian J. Androl  13:626-7.

    Rubinow KB, Snyder CN, Amory JK, Hoofnagle AN, Page ST. Acute testosterone deprivation reduces insulin sensitivity in men. 2012 Clin Endocrinol, 76:281-88.

    Lee, A, Rubinow KB, Clark RV, Caricofe RB, Bush MA, Zhi H, Roth MY, Page ST, Bremner WJ, Amory JK.  Pharmacokinetics of modified slow-release oral testosterone over nine days in normal men with experimental hypogonadism.  In press, J Androl 7/18/2011.

    Rubinow KB, Tang C, Hoofnagle AN, Snyder CN, Amory JK, Heinecke JW, and Page ST. Acute sex steroid withdrawal increases HDL cholesterol efflux capacity and HDL-Associated clusterin in young, healthy men.  2012 Steroids, 77:454-60.

    Page ST, Krauss RM, Gross C, Ishida BY, Heinecke JW, Tang C, Amory JK, Schaefer PM, Cox CJ, Kane J, Purnell JQ, Weinstein R, and T Vaisar. Impact of mifepristone, a glucocorticoid/progesterone antagonist, on HDL  cholesterol, HDL particle number, and HDL function.  2012 J Clin Endocrinol Metab, 97: 1598-605

    Roth MY, Bay K, Amory JK, Anawalt BD, Matsumoto AM, Marck BT, Bremner WJ, and Page ST.  Serum INSL3 is highly correlated with intratesticular testosterone in normal men with acute, experimental gonadotropin deficiency stimulated with low-dose hCG.  2012 Fertil Steril, Epub 10/3/2012.

    Mostaghel, EA, Lin DW, Amory JK, Wright JL, Marck BT, Nelson PS, Matusmoto AM and ST Page.  Impact of male hormonal contraception on prostate androgens and androgen action in healthy men: a randomized-controlled trial. 2012 J Clin Endrinol Metab, 97:2809-17.

    Rubinow KB, Vaisar T, Tang C, Matsumoto AM, Heinecke JW, Page ST.  Testosterone replacement therapy in hypogonadal men alters the HDL proteome without impairing HDL-efflux capacity. 2012 J Lipid Research, 53: 1376-83.

    Ilani, N, Roth MY, Amory JK, Swerdloff RS, Page ST, Bremner WJ, Sitruk-Ware R, Kumar N, Blithe D and C Wang.  A new combination of testosterone and nestorone transdermal gels for male hormonal contraception. 2012 J Clin Endocrinol Metab, Epub July 12, 2012.

Current Collaborations:

Within the Diabetes and Obesity Center of Excellence and its Affiliated Members
Jay Heinecke, MD
Greg Morton, PhD

Lab Members:

Katya Rubinow, MD
Lori Cooper, MD
Kathryn Torres-Duncan, BS