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Mini-Review

Sex-Steroid Imbalance in Females and Dry Eye

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Pages 162-175 | Received 21 Nov 2013, Accepted 07 Sep 2014, Published online: 07 Oct 2014

References

  • Stern ME, Gao J, Siemasko KF, Beuerman RW, Pflugfelder SC. The role of the lachrymal functional unit in the pathophysiology of dry eye. Exp Eye Res 2004;78:409–416
  • Gipson IK. The ocular surface: the challenge to enable and protect vision. The Friedenwald Lecture. Invest Ophthalmol Vis Sci 2007;48:4391–4398
  • Lemp MA. Advances in understanding and managing dry eye disease. Am J Ophthalmol 2008;146:350–356
  • The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop. Ocul Surf 2007;5:75–92
  • Nichols KK, Nichols JJ, Mitchell GL. The lack of association between signs and symptoms in patients with dry eye disease. Cornea 2004;23:762–770
  • Pult H, Purslow C, Murphy PJ. The relationship between clinical signs and dry eye symptoms. Eye 2011;25:502–510
  • Schein OD, Tielsch JM, Munoz B, Baqndeen-Roche K, West S. Relation between signs and symptoms of dry eye in the elderly. A population-based perspective. Ophthalmology 1997;104:1395–1401
  • Korb DR. Survey of preferred tests for diagnosis of the tear film and dry eye. Cornea 2000;19:483–486
  • Nichols KK, Nichols JJ, Zadnik K. Frequency of dry eye diagnostic test procedures used in various modes of ophthalmic practice. Cornea 2000;19:477–482
  • Methodologies to diagnose and monitor dry eye disease: report of the Diagnostic Methodology Subcommittee of the International Dry Eye WorkShop. Ocul Surf 2007;5:108–152
  • Report of the Research Subcommittee of the International Dry Eye Workshop. Ocul Surf 2007;5:179--195
  • Bron AJ, Yokoi N, Gafney E, Tiffany JM. Predicted phenotypes of dry eye: proposed consequences of its natural history. Ocul Surf 2009;7:78–92
  • The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye WorkShop. Ocul Surf 2007;5:93–107
  • Schaumberg DA, Sullivan DA, Buring JE, Dana MR. Prevalence of dry eye syndrome among US women. Am J Ophthalmol 2003;136:318–326
  • Krenzer KL, Dana MR, Ullman MD, Cermak JM, Tolls DB, Evans JE, et al. Effect of androgen deficiency on the human meibomian gland and ocular surface. J Clin Endocrinol Metab 2000;85:4874–4882
  • Schaumberg DA, Buring JE, Sullivan DA, Dana MR. Hormone replacement therapy and dry eye syndrome. JAMA 2001;286:2114–2119
  • Uncu G, Avci R, Uncu Y, Kaymaz C, Develioglu O. The effects of different hormone replacement therapy regimens on tear function, intraocular pressure and lens opacity. Gynecol Endocrinol 2006;22:501–550
  • Smith JA, Vitale S, Reed GF, Grieshaber SA, Goodman LA, Vanderhoof VH, et al. Dry eye signs and symptoms in women with premature ovarian failure. Arch Ophthalmol 2004;122:151–156
  • Davison SL, Bell R, Donath S, Montalto JG, Davis SR. Androgen levels in adult females: changes with age, menopause, and oophorectomy. J Clin Endocrinol Metab 2005;90:3847–3853
  • Strauss JF, Barbieri RL. Yen and Jaffe’s reproductive endocrinology. 5th ed. Philadelpha, PA: Elsevier; 2004. pp 633–668
  • Miller WL, Auchus RJ. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr Rev 2011;32:81–151
  • Stocco DM. StAR protein and the regulation of steroid hormone biosynthesis. Annu Rev Physiol 2001;63:193–213
  • Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004;89:2548–2556
  • Luu-The V. Assessment of steroidogenesis and steroidogenic enzyme functions. J Steroid Biochem Mol Biol 2013;137:176–182
  • Pietras RJ, Szego CM. Specific binding sites for oestrogen at the outer surfaces of isolated endometrial cells. Nature 1977;265:69–72
  • Tuohimaa P, Bläuer M, Pasanen S, Passinen S, Pekki A, Punnonen R, et al. Mechanisms of action of sex steroid hormones: basic concepts and clinical correlations. Maturitas 1996;23:S3–S12
  • Deroo BJ, Korach KS. Estrogen receptors and human disease. J Clin Invest 2006;116:561–570
  • Prossnitz ER, Barton M. The G-protein-coupled estrogen receptor GPER in health and disease. Nat Rev Endocrinol 2011;7:715–726
  • Labrie F. Adrenal androgens and intracrinology. Semin Reprod Med 2004;22:299–309
  • Luu-The V, Labrie F. The intracrine sex steroid biosynthesis pathways. Prog Brain Res 2010;181:177–192
  • Koos RD. Minireview: putting physiology back into estrogens' mechanism of action. Endocrinology 2011;152:4481–4488
  • Kaore SN, Langade DK, Yadav VK, Sharma P, Thawani VR, Sharma R. Novel actions of progesterone: what we know today and what will be the scenario in the future? J Pharm Pharmacol 2012;64:1040–1062
  • Mani SK, Blaustein JD, O’Malley BW. Progesterone receptor function from a behavioral perspective. Horm Behav 1977;31:244–255
  • Simoncini T, Genazzani A. Non-genomic actions of sex steroid hormones. Eur J of Endocrinol 2003;148:281–292
  • Gruber DM, Huber JC. Gender-specific medicine: the new profile of gynecology. Gynecol Endocrinol 1999;13:1–6
  • Manolagas SC, Kousteni S, Jilka RL. Sex steroids and bone. Recent Prog Horm Res 2002;57:385–409
  • Vest RS, Pike CJ. Gender, sex steroid hormones, and Alzheimer's disease. Horm Behav 2013;63:301–307
  • Lovejoy JC. The influence of sex hormones on obesity across the female life span. J Womens Health 1998;7:1247–1256
  • Traish AM, Kypreos KE. Testosterone and cardiovascular disease: an old idea with modern clinical implications. Atherosclerosis 2011;214:244–248
  • Sullivan DA. Tearful relationships? Sex, hormones, the lachrymal gland, and aqueous-deficient dry eye. Ocul Surf 2004;2:92–123
  • Doughty MJ. Goblet cells of the normal human bulbar conjunctiva and their assessment by impression cytology sampling. Ocul Surf 2012;10:149–169
  • Versura P, Fresina M, Campos EC. Ocular surface changes over the menstrual cycle in women with and without dry eye. Gynecol Endocrinol 2007;23:385–390
  • Connor CG, Flockencier LL, Hall CW. The influence of gender on the ocular surface. J Am Optom Assoc 1999;70:182–186
  • Vavilis D, Maloutas S, Nasioutziki M, Boni E, Bontis J. Conjunctiva is an estrogen-sensitive epithelium. Acta Obstet Gynecol Scand 1995;74:799–802
  • Kramer P, Lubkin V, Potter W, Jacobs M, Labay G, Silverman P. Cyclic changes in conjunctival smears from menstruating females. Ophthalmology 1990;97:303–307
  • Cavdar E, Ozkaya A, Alkin Z, Ozkaya HM, Babayigit MA. Changes in tear film, corneal topography, and refractive status in premenopausal women during menstrual cycle. Cont Lens Anterior Eye 2014;37:209--212
  • Serrander AM, Peek KE. Changes in contact lens comfort related to the menstrual cycle and menopause. A review of articles. J Am Optom Assoc 1993;64:162–166
  • Tomlinson A, Pearce EI, Simmons PA, Blades K. Effect of oral contraceptives on tear physiology. Ophthalmic Physiol Opt 2001;21:9–16
  • Chen SP, Massaro-Giordano G, Pistilli M, Schreiber CA, Bunya VY. Tear osmolarity and dry eye symptoms in women using oral contraception and contact lenses. Cornea 2013;32:423–428
  • Tatlipinar S, Gedik S, Irkeç M, Orhan M, Erdener U. Ocular ferning during the menstrual cycle in healthy women. Eur J Ophthalmol 2001;11:15–18
  • Nelson LM, Covington SN, Rebar RW. An update: spontaneous premature ovarian failure is not an early menopause. Fertil Steril 2005;83:1327–1332
  • Schechter JE, Pidgeon M, Chang D, Fong YC, Trousdale MD, Chang N. Potential role of disrupted lachrymal acinar cells in dry eye during pregnancy. Adv Exp Med Biol 2002;506:153–157
  • Huang J, Lu M, Ding C. Na(+)/K(+)-ATPase expression changes in the rabbit lachrymal glands during pregnancy. Curr Eye Res 2013;38:18–26
  • Ding C, Lu M, Huang J. Changes of the ocular surface and aquaporins in the lachrymal glands of rabbits during pregnancy. Mol Vis 2011;17:2847–2855
  • Sullivan DA. Hormonal influence on the secretory immune system of the eye. In: Freir S, editor. The neuroendocrine-immune network. Boca Raton, FL: CCR Press; 1990. pp 199–237
  • Sullivan DA, Jensen RV, Suzuki T, Richards SM. Do sex steroids exert sex-specific and/or opposite effects on gene expression in lachrymal and meibomian glands? Mol Vis 2009;10:1553–1572
  • Fuchsjager-Mayrl G, Nepp J, Schneeberger C, Sator M, Dietrich W, Wedrich A, et al. Identification of oestrogen and progesterone receptor mRNA expression in the conjunctiva of premenopausal women. Invest Ophthalmol Vis Sci 2002;43:2841–2844
  • Vecsei PV, Kircher K, Kaminski S, Nagel G, Breitenecker G, Kohlberger PD. Immunohistochemical detection of oestrogen and progesterone receptor in human cornea. Maturitas 2000;31:169–172
  • Esmaeli B, Harvey JT, Hewlett B. Immunohistochemical evidence for oestrogen receptors in meibomian glands. Ophthalmology 2000;107:180–184
  • Auw-Haedrich C, Feltgen N. Estrogen receptor expression in meibomian glands and its correlation with age and dry-eye parameters. Graefes Arch Clin Exp Ophthalmol 2003;241:705–709
  • Gans LA, Lee SF, Lemp MA, Pepose JS. Oestrogen and progesterone receptors and human conjunctiva. Am J Ophthalmol 1990;15:474–477
  • Suzuki T, Kinoshita Y, Tachibana M, Matsushima Y, Kobayashi Y, Adachi W, et al. Expression of sex steroid hormone receptors in human cornea. Curr Eye Res 2001;22:28–33
  • Wied GL, Bibbo M. Hormonal cytology. In: Bibbo M, editor. Comprehensive cytopathology. Philadelphia, PA: WB Saunders Co; 1991. pp 85–114
  • Rocha EM, Wickham LA, da Silveira LA, Krenzer KL, Yu FS, Toda I, et al. Identification of androgen receptor protein and 5 alpha-reductase mRNA in human ocular tissues. Br J Ophthalmol 2000; 84:76–84
  • Gao J, Lambert RW, Wickham LA, Sullivan DA. Androgen regulation of secretory component mRNA levels in the rat lachrymal gland. Lachrymal gland, tear film, and dry eye syndromes. Adv Exp Med Biol 1994;350:219–224
  • Sullivan DA, Sullivan BD, Evans JE, Schirra F, Yamagami H, Liu M, et al. Androgen deficiency, Meibomian gland dysfunction, and evaporative dry eye. Ann N Y Acad Sci 2002;966:211–222
  • Sullivan DA, Allansmith MR. Hormonal modulation of tear volume in the rat. Exp Eye Res 1986;42:131–139
  • Beauregard C, Brandt P. Down regulation of interleukin-1 beta-induced nitric oxide production in lachrymal gland acinar cells by sex steroids. Curr Eye Res 2004;29:59–66
  • Wickham LA, Gao J, Toda I, Rocha EM, Ono M, Sullivan DA. Identification of androgen, estrogen and progesterone receptor mRNAs in the eye. Acta Ophthalmol Scand 2000;78:146–153
  • Knop E, Knop N, Millar T, Obata H, Sullivan DA. The international workshop on meibomian gland dysfunction: report of the subcommittee on anatomy, physiology, and pathophysiology of the meibomian gland. Invest Ophthalmol Vis Sci 2011;52:1938–1978
  • Suzuki T, Sullivan DA. Estrogen stimulation of proinflammatory cytokine and matrix metalloproteinase gene expression in human corneal epithelial cells. Cornea 2005;24:1004–1009
  • Suzuki T, Sullivan DA. Comparative effects of estrogen on matrix metalloproteinases and cytokines in immortalized and primary human corneal epithelial cell cultures. Cornea 2006;25:454–459
  • Zylberberg C, Seamon V, Ponomareva O, Vellala K, Deighan M, Azzarolo AM. Estrogen up-regulation of metalloproteinase-2 and -9 expression in rabbit lachrymal glands. Exp Eye Res 2007;84:960–972
  • Wang C, Shi X, Chen X, Wu H, Zhang H, Xie J, et al. 17-β-estradiol inhibits hyperosmolarity-induced proinflammatory cytokine elevation via the p38 MAPK pathway in human corneal epithelial cells. Mol Vis 2012;18:1115–1122
  • Arakaki R, Ishimaru N, Hayashi Y. Immunotherapeutic targets in estrogen deficiency-dependent Sjögren's syndrome-related manifestations. Immunotherapy 2010;2:339–346
  • Cripps MM, Bromberg BB, Welch MH. Gender-dependent lachrymal protein secretion (ARVO abstract). Invest Ophthalmol Vis Sci 1986;27:25
  • Sullivan DA, Kelleher RS, Vaerman JP, Hann LE. Androgen regulation of secretory component synthesis by lachrymal gland acinar cells in vitro. J Immunol 1990;145:4238–4244
  • Sullivan DA, Krenzer KL, Sullivan BD, Tolls DB, Toda I, Dana MR. Does androgen insufficiency cause lachrymal gland inflammation and aqueous tear deficiency? Invest Ophthalmol Vis Sci 1999;40:1261–1265
  • Cermak JM, Krenzer KL, Sullivan RM, Dana MR, Sullivan DA. Is incomplete androgen insensitivity syndrome associated with alterations in the meibomian gland and ocular surface? Cornea 2003;22:516–521
  • Mantelli F, Moretti C, Micera A, Bonini S. Conjunctival mucin deficiency in complete androgen insensitivity syndrome (CAIS). Graefes Arch Clin Exp Ophthalmol 2007;245:899–902
  • Khandelwal P, Liu S, Sullivan DA. Androgen regulation of gene expression in human meibomian gland and conjunctival epithelial cells. Mol Vis 2012;18:1055–1067
  • Crow JM, Nelson JD, Remington SG. Human lipocalin-1 association with 3H-testosterone and 3H-estradiol. Curr Eye Res 2009;34:1042–1049
  • Labrie F. Extragonadal synthesis of sex steroids: intracrinology. Ann Endocrinol (Paris) 2003;64:95–107
  • Labrie F, Bélanger A, Luu-The V, Labrie C, Simard J, Cusan L, et al. DHEA and the intracrine formation of androgens and estrogens in peripheral target tissues: its role during aging. Steroids 1998;63:322–328
  • Labrie F, Labrie C. DHEA and intracrinology at menopause, a positive choice for evolution of the human species. Climateric 2013;16:205–213
  • Schirra F, Suzuki T, Dickinson DP, Townsend DJ, Gipson IK, Sullivan DA. Identification of steroidogenic enzyme mRNAs in the human lachrymal gland, meibomian gland, cornea, and conjunctiva. Cornea 2006;25:438–442
  • Sullivan DA, Wickham LA, Rocha EM, Kelleher RS, da Silveira L, Toda I. Influence of gender, sex steroid hormones and the hypothalamic-pituitary axis on the structure and function of the lachrymal gland. Adv Exp Med Biol 1998;438:11–42
  • Waterhouse JP. Focal adenitis in salivary and lachrymal glands. Proc R Soc Med 1963;56:911–918
  • Sullivan DA, Allansmith MR. The effect of aging on the secretory immune system of the eye. Immunology 1988;63:403–410
  • Craig JP, Tomlinson A. Age and gender effects on the normal tear film. Adv Exp Med Biol 1998;438:411–415
  • Nava A, Barton K, Monroy DC, Pflugfelder SC. The effects of age, gender, and fluid dynamics on the concentration of tear film epidermal growth factor. Cornea 1997;16:430–438
  • Tamboli DA, Harris MA, Hogg JP, Realini T, Sivak-Callcott JA. Computed tomography dimensions of the lachrymal gland in normal Caucasian orbits. Ophthal Plast Reconstr Surg 2011;27:453–456
  • Sullivan DA. Sex hormones and Sjögren's syndrome. J Rheumatol Suppl 1997;50:17–32
  • Brennan MT, Sankar V, Leakan RA, Grisius MM, Collins MT, Fox PC, et al. Sex steroid hormones in primary Sjögren's syndrome. J Rheumatol 2003;30:1267–1271
  • Porola P, Laine M, Virkki L, Poduval P, Konttinen YT. The influence of sex steroids on Sjögren's syndrome. Ann N Y Acad Sci 2007;1108:426–432
  • Konttinen YT, Fuellen G, Bing Y, Porola P, Stegaev V, Trokovic N, et al. Sex steroids in Sjögren's syndrome. J Autoimmun 2012;39:49–56
  • Mavragani CP, Fragoulis GE, Moutsopoulos HM. Endocrine alterations in primary Sjogren's syndrome: an overview. J Autoimmun 2012;39:354–358
  • Mostafa S, Seamon V, Azzarolo AM. Influence of sex hormones and genetic predisposition in Sjögren's syndrome: a new clue to the immunopathogenesis of dry eye disease. Exp Eye Res 2012;96:88–97
  • Valtysdóttir ST, Wide L, Hällgren R. Low serum dehydroepiandrosterone sulfate in women with primary Sjogren’s syndrome as an isolated sign of impaired HPA axis function. J Rheumatol 2001;28:1259–1265
  • Sullivan DA, Bélanger A, Cermak JM, Bérubé R, Papas AS, Sullivan RM, et al. Are women with Sjogren’s syndrome androgen-deficient? J Rheumatol 2003;30:2413–2419
  • Laine M, Porola P, Udby L, Kjeldsen L, Cowland JB, Borregaard N. Low salivary dehydroepiandrosterone and androgen-regulated cysteine-rich secretory protein 3 levels in Sjogren’s syndrome. Arthritis Rheum 2007;56:2575–2584
  • Labrie F, Belanger A, Cusan L, Gomez JL, Candas B. Marked decline in serum concentrations of adrenal C19 sex steroid precursors and conjugated androgen metabolites during aging. J Clin Endocrinol Metab 1997;82:2396–2402
  • Dessein PH, Joffe BI, Stanwix AE, Moomal Z. Hyposecretion of the adrenal androgen dehydroepiandrosterone sulfate and its relation to clinical variables in inflammatory arthritis. Arthritis Res 2001;3:183–188
  • Labrie F, Bélanger A, Bélanger P, Bérubé R, Martel C, Cusan L, et al. Metabolism of DHEA in postmenopausal women following percutaneous administration. J Steroid Biochem Mol Biol 2007;103:178–188
  • Capellino S, Straub RH, Cutolo M. Aromatase and regulation of the estrogen-to-androgen ratio in synovial tissue inflammation: common pathway in both sexes. Ann N Y Acad Sci 2014;1317:24--31
  • Valtysdottir ST, Wide L, Hallgren R. Mental wellbeing and quality of sexual life in women with primary Sjögren's syndrome are related to circulating dehydroepiandrosterone sulphate. Ann Rheum Dis 2003;62:875–879
  • Hartkamp A, Geenen R, Kruize AA, Bossema ER, Godaert GL, Bootsma H, et al. Serum dehydroepiandrosterone sulphate levels and laboratory and clinical parameters indicating expression of disease are not associated with fatigue, well-being and functioning in patients with primary Sjögren's syndrome. Clin Exp Rheumatol 2011;29:318–321
  • Forsblad-d'Elia H, Carlsten H, Labrie F, Konttinen YT, Ohlsson C. Low serum levels of sex steroids are associated with disease characteristics in primary Sjogren's syndrome: supplementation with dehydroepiandrosterone restores the concentrations. J Clin Endocrinol Metab 2009;94:2044–2051
  • Genazzani AR, Stomati M, Valentino V, Pluchino N, Pot E, Casarosa E, et al. Effect of 1-year, low-dose DHEA therapy on climacteric symptoms and female sexuality. Climacteric 2011;14:661–668
  • Porola P, Straub RH, Virkki LM, Konttinen YT, Nordström DC. Failure of oral DHEA treatment to increase local salivary androgen outputs of female patients with Sjögren's syndrome. Scand J Rheumatol 2011;40:387–390
  • Pillemer SR, Brennan MT, Sankar V, Leakan RA, Smith JA, Grisius M, et al. Pilot clinical trial of dehydroepiandrosterone (DHEA) versus placebo for Sjögren's syndrome. Arthritis Rheum 2004;51:601–604
  • Hartkamp A, Geenen R, Godaert GL, Bootsma H, Kruize AA, Bijlsma JW, et al. Effect of dehydroepiandrosterone administration on fatigue, well-being, and functioning in women with primary Sjögren syndrome: a randomised controlled trial. Ann Rheum Dis 2008;67:91–97
  • Sullivan DA. Possible mechanisms involved in the reduced tear secretion in Sjögren’s syndrome. In: Homma M, Sugai S, Tojo T, Miyasaka N, Akizuki M, editors. Sjögren's syndrome. State of the Art. Amsterdam: Kugler Press; 1994. pp 13–19
  • Zoukhri D. Effect of inflammation on lachrymal gland function. Exp Eye Res 2006;82:885–898
  • Dawson L, Tobin A, Smith P, Gordon T. Antimuscarinic antibodies in Sjogren’s syndrome: where are we, and where are we going? Arthritis Rheum 2005;52:2984–2995
  • Dawson LJ, Stanbury J, Venn N, Hasdimir B, Rogers SN, Smith PM. Antimuscarinic antibodies in primary Sjogren’s syndrome reversibly inhibit the mechanism of fluid secretion by human submandibular salivary acinar cells. Arthritis Rheum 2006;54:1165–1173
  • Shimazaky J, Goto E, Masafumi O, Shimmura S, Tsubota K. Meibomian gland dysfunction in patients with Sjögren syndrome. Ophthalmology 1998;105:1485–1488
  • Goto E, Matsumoto Y, Kamoi M, Endo K, Ishida R, Dogru M, et al. Tear evaporation rates in Sjögren syndrome and non-Sjögren dry eye patients. Am J Ophthalmol 2007;144:81–85
  • Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, et al. Classification criteria for Sjogren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 2002;61:554–558
  • Vitali C, Bootsma H, Bowman SJ, Dorner T, Gottenberg JE, Mariette X, et al. Classification criteria for Sjogren's syndrome: we actually need to definitively resolve the long debate on the issue. Ann Rheum Dis 2013;72:476–478
  • Versura P, Frigato M, Mulé R, Malavolta N, Campos EC. A proposal of new ocular items in Sjögren's syndrome classification criteria. Clin Exp Rheumatol 2006;24:567–572
  • Versura P, Frigato M, Cellini M, Mulè R, Malavolta N, Campos EC. Diagnostic performance of tear function tests in Sjogren's syndrome patients. Eye (Lond) 2007;21:229–237
  • Baldini C, Talarico R, Tzioufas AG, Bombardieri S. Classification criteria for Sjogren's syndrome: a critical review. J Autoimmun 2012;39:9–14
  • Schaumberg DA, Nichols JJ, Papas EB, Tong L, Uchino M, Nichols KK. The international workshop on meibomian gland dysfunction: report of the subcommittee on the epidemiology of, and associated risk factors for, MGD. Invest Ophthalmol Vis Sci 2011;52:1994–2005
  • Schirra F, Richards SM, Liu M, Suzuki T, Yamagami H, Sullivan DA. Androgen regulation of lipogenic pathways in the mouse meibomian gland. Exp Eye Res 2006;83:291–296
  • Schirra F, Richards SM, Sullivan DA. Androgen influence on cholesterogenic enzyme mRNA levels in the mouse meibomian gland. Curr Eye Res 2007;32:393–398
  • Steagall RJ, Yamagami H, Wickham LA, Sullivan DA. Androgen control of gene expression in the rabbit meibomian gland. Adv Exp Med Biol 2002;506:465–476
  • Richards SM, Yamagami H, Schirra F, Suzuki T, Jensen RV, Sullivan DA. Sex-related effect on gene expression in the mouse meibomian gland. Curr Eye Res 2006;31:119–128
  • Schirra F, Suzuki T, Richards SM, Jensen RV, Liu M, Lombardi MJ, et al. Androgen control of gene expression in the mouse meibomian gland. Invest Ophthalmol Vis Sci 2005;46:3666–3675
  • Sullivan DA, Yamagami H, Liu M, Steagali RJ, Schirra F, Suzuki T, et al. Sex steroids, the meibomian gland and evaporative dry eye. Adv Exp Med Biol 2002;506:389–399
  • Sullivan BD, Evans JE, Dana MR, Sullivan DA. Influence of aging on the polar and neutral lipid profiles in human meibomian gland secretions. Arch Ophthalmol 2006;124:1286–1292
  • Sullivan BD, Evans JE, Cermak JM, Krenzer KL, Dana MR, Sullivan DA. Complete androgen insensitivity syndrome: effect on human meibomian gland secretions. Arch Ophthalmol 2002;120:1689–1699
  • Sullivan BD, Evans JE, Krenzer KL, Dana MR, Sullivan DA. Impact of antiandrogen treatment on the fatty acid profile of neutral lipids in human meibomian gland secretions. J Clin Endocrinol Metab 2000;85:4866–4873
  • Suzuki T, Schirra F, Richards SM, Jensen RV, Sullivan DA. Estrogen and progesterone control of gene expression in the mouse meibomian gland. Invest Ophthalmol Vis Sci 2008;49:1797–1808
  • Butler L, Santoro N. The reproductive endocrinology of the menopausal transition. Steroids 2011;76:627–635
  • Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. J Clin Endocrinol Metab 2002;87:589–598
  • Santoro N, Randolph JF Jr. Reproductive hormones and the menopause transition. Obstet Gynecol Clin North Am 2011;38:455–466
  • Hale GE, Robertson DM, Burger HG. The perimenopausal woman: endocrinology and management. Steroid Biochem Mol Biol 2014;142:121–131
  • Labrie F, Martel C, Balser J. Wide distribution of the serum dehydroepiandrosterone and sex steroid levels in postmenopausal women: role of the ovary? Menopause 2011;18:30–43
  • Rannevik G, Jeppsson S, Johnell O, Bjerre B, Laurell-Borulf Y, Svanberg L. A longitudinal study of the perimenopausal transition: altered profiles of steroid and pituitary hormones, SHBG and bone mineral density. Maturitas 1995;21:103–113
  • Yasui T, Matsui S, Tani A, Kunimi K, Yamamoto S, Irahara M. Androgen in postmenopausal women. J Med Invest 2012;59:12–27
  • Burger HG, Dudley EC, Cui J, Dennerstein L, Hopper JC. A prospective longitudinal study of serum testosterone dehydroepiandrosterone sulfate and sex hormone binding globulin levels through the menopause transition. J Clin Endocrin Metab 2000;85:2832–2838
  • Marjoribanks J, Farquhar C, Roberts H, Lethaby A. Long term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev 2012;7:CD004143
  • Hodis HN, Mack WJ. Hormone replacement therapy and the association with coronary heart disease and overall mortality: clinical application of the timing hypothesis. J Steroid Biochem Mol Biol 2014;142:68--75
  • Clarkson TB, Meléndez GC, Appt SE. Timing hypothesis for postmenopausal hormone therapy: its origin, current status, and future. Menopause 2013;20:342–353
  • Nagler RM, Pollack S. Sjogren’s syndrome induced by estrogen therapy. Semin Arthritis Rheum 2000;30:209–214
  • Erdem U, Ozdegirmenci O, Sobaci E, Goktolga U, Dagli S. Dry eye in postmenopausal women using hormone replacement therapy. Maturitas 2007;56:257–262
  • Uncu G, Avici R, Uncu Y, Kaymaz C, Develioglu O. The effects of different hormone replacement therapy regiments on tear function, intraocular pressure and lens opacity. Gynecol Endocrinol 2006;22:501–505
  • Jensen AA, Higginbotham EJ, Guzinski GM, Davis IL, Ellish NJ. A survey of ocular complaints in postmenopausal women. J Assoc Acad Minor Phys 2000;11:44–49
  • Okon A, Jurowski P, Gos R. The influence of the hormonal replacement therapy on conjunctival epithelium morphology among peri- and postmenopausal women. Klinika Oczna 2001;103:183–186
  • Rocha EM, Mantelli F, Nominato LF, Bonini S. Hormones and dry eye syndrome: an update on what we do and don’t know. Curr Opin Ophthalmol 2013;24:348–355
  • Davis SR, Worsley R. Androgen treatment of postmenopausal women. J Steroid Biochem Mol Biol 2014;142:107--114
  • Labrie F. DHEA, important source of sex steroids in men and even more in women. Prog Brain Res 2010;182:97–148
  • Davis SR, Panjari M, Stanczyk FZ. Clinical review: DHEA replacement for postmenopausal women. J Clin Endocrinol Metab 2011;96:1642–1653
  • Versura P, Campos EC. Menopause and dry eye. A possible relationship. Gynecol Endocrinol 2005;20:289–298
  • Sator MO, Joura EA, Golaszewski T, Gruber D, Frigo P, Metka M, et al. Treatment of menopausal keratoconjunctivitis sicca with topical oestradiol. Br J Obstetr Gynaecol 1998;105:100–102
  • Lubkin V. An evaluation of the safety and efficacy of 0.1% & 0.25% 17β-estradiol in postmenopausal women with dry eye syndrome. USPN 6,096,733, Issued Aug. 2000
  • Nathanson JA, McKee M. Identification of an extensive system of nitric oxide-producing cells in the ciliary muscle and outflow pathway of the human eye. Invest Ophthalmol Vis Sci 1995;36:1765–1772
  • Worda C, Nepp J, Huber JC, Sator MO. Treatment of keratoconjunctivitis sicca with topical androgen. Maturitas 2001;37:209–212
  • Safety and Efficacy of testosterone 0.03% Ophthalmic Solution Compared to Vehicle for the Treatment of MGD (ClinicalTrials.gov ID NCT00755183)
  • Nanavaty MA, Long M, Malhotra R. Transdermal androgen patches in evaporative dry eye syndrome with androgen deficiency: a pilot study. Br J Ophthalmol 2014;98:567–569
  • Schiffman RM, Bradford R, Bunnell B, Lai F, Bernstein P, Whitcup SW. A multi–center, double–masked, randomized, vehicle–controlled, parallel group study to evaluate the safety and efficacy of testosterone ophthalmic solution in patients with meibomian gland dysfunction. Invest Ophthalmol Vis Sci 2006;47:E-Abstract 5608
  • Schechter JE, Warren DW, Mircheff AK. A lachrymal gland is a lachrymal gland, but rodent's and rabbit's are not human. Ocul Surf 2010;8:111–134
  • Mehta R, Jain RK, Badve S. Personalized medicine: the road ahead. Clin Breast Cancer 2011;11:20–26
  • Manson JE. The role of personalized medicine in identifying appropriate candidates for menopausal estrogen therapy. Metabolism 2013;62:S15–S19
  • Novack GD. Personalized medicine and the ocular surface. Ocular Surf 2010;8:157–159
  • Aragona P, Rolando M. Towards a dynamic customised therapy for ocular surface dysfunctions. Br J Ophthalmol 2013;97:955–960

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