REVIEW ARTICLE| Volume 55, ISSUE 1, P3-11, February 2020

Hormone replacement therapy for dry eye disease patients: systematic review and meta-analysis


      Hormone replacement therapy (HRT) is used by women to get relief from menopausal symptoms, including dry eyes. However, it is not entirely certain that HRT helps relieve dry eye disease (DED). The focus of this study is to systematically review the literature of the relevant studies to understand and determine the correlation between HRT and DED. Literature was systematically reviewed using Distiller SR. Meta-analysis was conducted using STATA 15.0. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated, and heterogeneity was assessed using statistics. Fixed-effect and random-effects models were computed based on heterogeneity. Subgroups analysis was done by follow-up. Our meta-analysis results indicated significant reduction in dry eye with HRT treatment at 1-month follow-up (SMD = −1.97; CI: −3.83, −0.11), a nonsignificant increase in tear breakup time at 3-month (SMD = −0.91; CI: −3.26, 1.44) and 6-month (SMD = −1.05; CI: −3.91, 1.82) follow-ups. Our meta-analysis results indicated a nonsignificant improvement in DED with HRT treatment at 1-month (SMD = −0.97; CI: −2.35, 0.4), 3-month (SMD = 0.19; CI: −0.91, 1.29), and 6-month (SMD = −0.48; CI: −1.39, 0.43) follow-ups.Overall, nonsignificant improvement in postoperative tear production, as well as tear breakup time, was seen after HRT treatment at follow-ups in dry eye patients. More good-quality randomized control trials are needed to make accurate conclusions.


      L'hormonothérapie substitutive (HTS) est utilisée pour soulager les symptômes de la ménopause, notamment la sécheresse oculaire. Or, on ne sait pas avec certitude si l'HTS soulage véritablement la sécheresse oculaire. On a donc procédé à une revue systématique de la littérature médicale, à l'aide du logiciel Distiller SR, pour extraire les études pertinentes qui permettraient de comprendre et de déterminer le lien qui unit l'HTS et la sécheresse oculaire. Une méta-analyse a ainsi été réalisée au moyen du logiciel STATA 15.0. On a calculé la différence moyenne standardisée (DMS) et l'intervalle de confiance (IC) à 95 %. L'hétérogénéité a été mesurée au moyen de paramètres statistiques et a servi à générer des modèles à effets fixes et à effets aléatoires. L'analyse des sous-groupes a été réalisée en fonction de la durée du suivi. Selon notre méta-analyse, on note une diminution significative de la sécheresse oculaire grâce à l'HTS après un suivi de 1 mois (DMS = −1,97; IC de −3,83 à −0,11) de même qu'une augmentation non significative du temps de rupture du film lacrymal à 3 mois (DMS = −0,91; IC de −3,26 à 1,44) et à 6 mois (DMS = −1,05; IC de −3,91 à 1,82). Si l'on en croit les résultats de notre méta-analyse, la sécheresse oculaire bénéficie d'un soulagement non significatif sous l'effet de l'HTS à 1 mois (DMS = −0,97; IC de −2,35 à 0,4), à 3 mois (DMS = 0,19; IC de −0,91 à 1,29) et à 6 mois (DMS = −0,48; IC de −1,39 à 0,43). Dans l'ensemble, on a enregistré une amélioration non significative de la production lacrymale et du temps de rupture du film lacrymal après la mise en route d'une HTS lors de suivis de patientes présentant une sécheresse oculaire. La tenue d'autres études comparatives randomisées de grande qualité permettra de tirer des conclusions plus précises.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Canadian Journal of Ophthalmology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Brewitt H
        • Sistani F
        Dry eye disease: the scale of the problem.
        Surv Ophthalmol. 2001; 45: S199-S202
        • Holland EJ
        • Luchs J
        • Karpecki PM
        • et al.
        Lifitegrast for the treatment of dry eye disease.
        Ophthalmology. 2017; 124: 53-60
        • Miljanović B
        • Dana R
        • Sullivan DA
        • Schaumberg DA
        Impact of dry eye syndrome on vision-related quality of life.
        Am J Ophthalmol. 2007; 143 (e2): 409-415
        • Labbé A
        • Wang YX
        • Jie Y
        • Baudouin C
        • Jonas JB
        • Xu L
        Dry eye disease, dry eye symptoms and depression: the Beijing Eye Study.
        Br J Ophthalmol. 2013; 97: 1399-1403
        • Versura P
        • Campos EC
        Menopause and dry eye: a possible relationship.
        Gynecol Endocrinol. 2005; 20: 289-298
        • Nelson HD
        • Humphrey LL
        • Nygren P
        • Teutsch SM
        • Allan JD
        Postmenopausal hormone replacement therapy.
        JAMA. 2002; 288: 872
        • Liberati A
        • Altman DG
        • Tetzlaff J
        • et al.
        The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.
        PLoS Med. 2009; 6e1000100
        • Downs SH
        • Black N.
        The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions.
        J Epidemiol Commun Health. 1998; 52: 377-384
        • Affinito P
        • Di A
        • Sardo S
        • et al.
        Effects of hormone replacement therapy on ocular function in postmenopause.
        Menopause. 2003; 10: 482-487
        • Alawlaqi A
        • Hammadeh M.
        Examining the relationship between hormone therapy and dry-eye syndrome in postmenopausal women: a cross-sectional comparison study.
        Menopause. 2016; 23: 550-555
        • Altintaş O
        • Caglar Y
        • Yüksel N
        • Demirci A
        • Karabaş L
        The effects of menopause and hormone replacement therapy on quality and quantity of tear, intraocular pressure and ocular blood flow.
        Ophthalmologica. 2004; 218: 120-129
        • Chaikittisilpa S
        • Tulvatana W
        • Taechakraichana N
        • Panyakhamlerd K
        • Limpaphayom K
        Hormone replacement therapy and tear volume in postmenopausal women with dry eye.
        J Obstet Gynaecol. 2000; 12: 135-139
        • Erdem U
        • Ozdegirmenci O
        • Sobaci E
        • Sobaci G
        • Göktolga U
        • Dagli S
        Dry eye in post-menopausal women using hormone replacement therapy.
        Maturitas. 2007; 56: 257-262
        • Evans V
        • Millar TJ
        • Eden JA
        • Willcox MDP
        Menopause, hormone replacement therapy and tear function.
        in: Sullivan DA Stern ME Tsubota K Dartt DA Sullivan RM Bromberg BB Lacrimal Gland, Tear Film, and Dry Eye Syndromes 3. Springer, Boston, MA2002: 1029-1033 (Advances in Experimental Medicine and Biology, vol 506)
        • Feng Y
        • Feng G
        • Peng S
        • Li H
        The effects of hormone replacement therapy on dry eye syndromes evaluated by Schirmer test depend on patient age.
        Cont Lens Anterior Eye. 2016; 39: 124-127
        • Golebiowski B
        • Badarudin N
        • Eden J
        • et al.
        The effects of transdermal testosterone and oestrogen therapy on dry eye in postmenopausal women: a randomised, placebo-controlled, pilot study.
        Br J Ophthalmol. 2016; 101: 926-932
        • Jensen AA
        • Higginbotham EJ
        • Guzinski GM
        • Davis IL
        • Ellish NJ
        A survey of ocular complaints in postmenopausal women.
        J Assoc Acad Minority Phys. 2000; 11: 44-49
        • Jin X
        • Lin Z
        • Liu Y
        • Lin L
        • Zhu B
        Hormone replacement therapy benefits meibomian gland dysfunction in perimenopausal women.
        Medicine (Baltimore). 2016; 95: e4268
        • Pelit A
        • Bagis T
        • Kayaselcuk D
        • Akova Y
        • Aydin P
        Tear function tests and conjunctival impression cytology before and after hormone replacement therapy in postmenopausal women.
        Eur J Ophthalmol. 2003; 13: 337-342
        • Piwkumsribonruang N
        • Somboonporn W
        • Luanratanakorn P
        • Kaewrudee S
        • Tharnprisan P
        • Soontrapa S
        Effectiveness of hormone therapy for treating dry eye syndrome in postmenopausal women: a randomized trial.
        J Med Assoc Thai. 2010; 93: 647-652
        • Schaumberg DA
        • Buring JE
        • Sullivan DA
        • Dana MR
        Hormone replacement therapy and dry eye syndrome.
        JAMA. 2001; 286: 2114-2119
        • Scuderi G
        • Contestabile MT
        • Gagliano C
        • Iacovello D
        • Scuderi L
        • Avitabile T
        Effects of phytoestrogen supplementation in postmenopausal women with dry eye syndrome: a randomized clinical trial.
        Can J Ophthalmol. 2012; 47: 489
        • Shaharuddin B
        • Ismail-Mokhtar SF
        • Hussein E
        Dry eye in post-menopausal Asian women on hormone replacement therapy.
        Int J Ophthalmol. 2008; 1: 158-160
        • Taner P
        • Akarsu C
        • Atasoy P
        • Bayram M
        • Ergin A
        The effects of hormone replacement therapy on ocular surface and tear function tests in postmenopausal women.
        Ophthalmologica. 2004; 218: 257-259
        • Unlü C
        • Güney E
        • BİS Akçay
        • Akçalı G
        • Erdoğan G
        • Bayramlar H
        Comparison of ocular-surface disease index questionnaire, tearfilm break-up time, and Schirmer tests for the evaluation of the tearfilm in computer users with and without dry-eye symptomatology.
        Clin Ophthalmol. 2012; 6: 1303-1306
        • Uncu G
        • Avci R
        • Uncu Y
        • Kaymaz C
        • Develioğlu O
        The effects of different hormone replacement therapy regimens on tear function, intraocular pressure and lens opacity.
        Gynecol Endocrinol. 2006; 22: 501-505