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Open-Angle Glaucoma and the Risk of

Erectile Dysfunction
A Population-based Case-control Study
Shiu-Dong Chung, MD,1,2,3 Chao-Chien Hu, MD,4,5 Jau-Der Ho, MD,6,7 Joseph J. Keller, MPH,8
Tsung-Jen Wang, MD,4,5 Herng-Ching Lin, PhD3

Purpose: Open-angle glaucoma (OAG) is associated with systemic metabolic and cardiovascular disorders,
and both share common risk factors with erectile dysfunction (ED). However, few studies have investigated the
association of ED with OAG. This study aimed to estimate the association of ED with prior OAG by using a
nationwide, population-based data with a retrospective case-control cohort design in Taiwan.
Design: Age-matched case-control study.
Participants and Controls: We identified 4605 patients with ED as the cases and randomly selected 23 025
subjects as the controls (5 controls to 1 case).
Methods: We used conditional logistic regression analysis to estimate the odds ratio and 95% confidence
interval of having previously been diagnosed with OAG according to the presence/absence of ED after adjusting
for patient’s monthly income, geographical location, hypertension, diabetes, coronary heart disease, hyperlip-
idemia, obesity, and alcohol abuse.
Main Outcome Measures: We identified OAG cases not only based on an International Classification of
Diseases, Ninth Revision, Clinical Modification code, but also by the prescription of topical antiglaucoma medication.
Results: In total, prior OAG was found among 137 subjects (0.5 %); 53 individuals (1.1% of the ED patients)
from the cases and 84 individuals (0.4% of patients without ED) from the controls. Conditional logistic regression
analysis demonstrated that, after adjusting for potential confounders, patients with ED were more likely to have
prior OAG than controls (odds ratio, 2.85; 95% confidence interval, 2.10 – 4.07).
Conclusions: This study identifies a novel association between ED and prior OAG.
Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials
discussed in this article. Ophthalmology 2012;119:289 –293 © 2012 by the American Academy of Ophthalmol-

Glaucoma is among the leading causes of blindness world- no study has attempted to explore the association between
wide,1,2 and open-angle glaucoma (OAG) is among the ED and glaucoma. Using a population-based dataset, we
most prevalent forms.3 Risk factors for OAG include older examined the association of ED with prior OAG by com-
age, hypertension, diabetes, and a family history of glau- paring the risk of prior OAG between patients with ED and
coma. The prevalence of erectile dysfunction (ED) increases matched controls in Taiwan.
with age and ED shares several risk factors with OAG, such
as hypertension, diabetes mellitus, and cardiovascular
disorders.4 –7 Methods
Ocular hypertension is a major risk factor for both OAG
and the metabolic syndrome (MS), the characteristics of Database
which are themselves risk factors for ocular hypertension We used data from the Longitudinal Health Insurance Database
and include hypertension, diabetes, dyslipidemia, and obe- 2000 (LHID2000) to conduct this matched case-control study.
sity.8,9 One previous population-based study established an Taiwan began its National Health Insurance (NHI) program in
association of OAG with hyperlipidemia, diabetes mellitus, 1995. To help researchers perform studies of issues relevant to the
and hypertension.10 These comorbidities are also major risk NHI program, the Taiwan National Health Research Institute cre-
factors for both MS and ED.11 The higher prevalence of ated and released the LHID2000 to the public for research pur-
these metabolic and vascular disorders in patients with poses. The LHID2000 contains all the original claims data and
registration files of 1 000 000 individuals randomly sampled from
OAG suggests that insulin resistance might be at play in the the 2000 Registry for Beneficiaries (n ⫽ 23.72 million) of the
pathophysiology of glaucoma.9,10 Taken together, both Taiwan NHI program. The Taiwan National Health Research
OAG and ED are recognized to be associated with systemic Institute reported that there was no significant difference in the
diseases, which are associated with insulin resistance and gender distribution between the patients in the LHID2000 and all
metabolic disorders. However, to the best of our knowledge, the patients enrolled in the NHI program. The LHID2000 allows

© 2012 by the American Academy of Ophthalmology ISSN 0161-6420/12/$–see front matter 289
Published by Elsevier Inc. doi:10.1016/j.ophtha.2011.08.015

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Ophthalmology Volume 119, Number 2, February 2012

researchers to follow-up on all the medical services utilized by diagnoses, we selected only those patients who had been pre-
these 1 000 000 individuals since the initiation of the NHI in 1995. scribed topical antiglaucoma medication. In addition, we only
Because the LHID2000 consists of deidentified secondary data included OAG diagnoses made before the index date.
released to the public for research purposes, this study was ex-
empted from full review by the director of the Taipei Medical
University Institutional Review Board.
Statistical Analysis
We used the SAS system (SAS System for Windows, Version 8.2,
SAS Inc., Cary, NC) to analyze data. We used the chi square test
Study Population for independence to compare the differences between cases and
A total of 4605 cases were considered eligible. The eligibility controls in terms of monthly income (NT$0 –15 840, NT$15 841–
selection criteria required all cases to be ⬎40 years of age and NT$25 000, ⱖNT$25 001), and the geographical location (North-
have been newly diagnosed with ED (impotence, organic, Inter- ern, Central, Eastern, and Southern Taiwan), and the urbanization
national Classification of Diseases, Ninth Revision, Clinical Mod- level of the patient’s residence (1 being the most urbanized and 5
ification [ICD-9-CM] code 607.84) between January 2002 and being the least). We used conditional logistic regression to calcu-
December 2009. Because the administrative database is criticized late the odds ratios (ORs) and 95% confidence intervals (CIs) to
for its diagnostic validity, we only included ED cases in this study examine associations between ED and exposure to OAG. All
if they received ⱖ2 ED diagnoses, with ⱖ1 being made by an analyses were conditioned on the study matching factors of age
urologist. In Taiwan, physicians will not make a diagnosis of ED (10-year strata) and index year. We considered the following
unless he or she has enough clinical or laboratory data to support variables as potential confounders on account of their possible
it on account of the culturally taboo nature of the diagnosis. We, association with ED: hypertension, diabetes, coronary heart dis-
therefore, believe that ED diagnosis made under the Taiwan NHI ease, hyperlipidemia, obesity, alcohol use, and alcohol abuse de-
demonstrates high validity. We assigned a subject’s first ED diag- pendence syndrome. These comorbidities were only included in
nosis between January 2002 and December 2009 as the index date. the model if they were diagnosed before the index date.
Controls with no diagnosis of psychogenic or organic ED were
selected from the remaining male subjects of the LHID2000, and
matched with a control-to-case ratio of 5 (n ⫽ 23 025) on the basis Results
of age (40 – 49, 50 –59, 60 – 69, and ⬎69 years) and index year. For
controls, the first use of ambulatory care occurring in the index Table 1 summarizes the demographic characteristics of cases and
year was designated as the index date. controls. Of the 27 630 sampled patients, the mean age was 57.3
We identified OAG cases based on a diagnosis of OAG (ICD- years (⫾11.3); 57.4 and 57.3 for cases and controls, respectively
9-CM codes 365.1 or 365.11). To increase the validity of OAG (P ⫽ 0.596). Cases were more likely to have comorbid hyperlip-

Table 1. Demographic Characteristics of Patients with Erectile Dysfunction (ED) and Controls in
Taiwan, 2002–2009 (n ⫽ 27 630)

Patients With ED Controls

(n ⴝ 4605) (n ⴝ 23 025)
Variable Total No. % Total No. % P
Age (yrs) 1.000
40-49 1239 26.9 6195 26.9
50-59 1593 34.6 7965 34.6
60-69 1021 22.2 5105 22.2
⬎69 753 16.3 3765 16.3
Age, mean (standard deviation) 57.4 (11.4) 57.3 (11.2) 0.596
Monthly income (NT$) ⬍0.001
No income 283 6.2 1992 8.7
1–15,840 839 18.2 3468 15.1
15 841–25 000 1591 34.5 9779 42.4
ⱖ25 001 1892 41.1 7786 33.8
Hyperlipidemia 1323 28.7 4576 19.9 ⬍0.001
Diabetes 1154 25.1 4145 18.0 ⬍0.001
Hypertension 1834 39.8 8511 37.0 ⬍0.001
Coronary heart disease 1001 21.7 3945 17.1 ⬍0.001
Obesity 43 0.9 74 0.3 ⬍0.001
Alcohol abuse/alcohol dependence syndrome 26 0.6 128 0.6 0.943
Geographic region ⬍0.001
Northern 2393 52.0 10 777 46.8
Central 993 21.6 5502 23.9
Eastern 1107 24.0 6137 26.7
Southern 112 2.4 609 2.6
Urbanization level ⬍0.001
1 (most urbanized) 1625 35.3 6646 28.9
2 1395 30.3 6598 28.7
3 749 16.3 3811 16.6
4 485 10.5 3362 14.6
5 (least urbanized) 351 7.6 2608 11.3


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Chung et al 䡠 Increased Risk of ED in Patients with OAG

Table 2. Prevalence and Crude Odds Ratios (ORs) for Open-Angle Glaucoma (OAG) among the
Sampled Patients

Patients with
Total Erectile Dysfunction Controls
(n ⴝ 27 630) (n ⴝ 4605) (n ⴝ 23 025)
Presence of OAG n % n % n %
Yes 137 0.5 53 1.1 84 0.4
No 27 493 99.5 4552 98.9 22 941 99.6
OR (95% CI) — 3.18* (2.25–4.49) 1.00

CI ⫽ confidence interval.
The OR was calculated by conditional logistic regressions, which was conditioned on age group and the year of index

idemia (28.7% vs 19.9%; P⬍0.001), diabetes (25.1% vs 18.0%; OAG cases that existed before the index date were found among
P⬍0.001), hypertension (39.8% vs 37.0%; P⬍0.001), coronary ED patients (OR, 3.18; 95% CI, 2.25– 4.49; P⬍0.001).
heart disease (21.7% vs 17.1%; P⬍0.001), and obesity (0.9% vs; After adjusting for patient age, monthly income, geograph-
0.3%; P⬍0.001) than controls. The prevalence of alcohol abuse/ ical location, urbanization level, hypertension, diabetes, coro-
alcohol dependence syndrome was similar for cases and control. In nary heart disease, and hyperlipidemia, the conditional logistic
addition, cases had a greater tendency to have monthly incomes of regression analysis conditioned on age group and index year
ⱖNT$25 001 (P⬍0.001), and to reside in the northern part of Taiwan revealed that, compared with controls, ED patients were more
(P⬍0.001), and in more urbanized communities (P⬍0.001) when likely to have OAG before the index date (OR, 2.85; 95% CI,
compared with controls. 2.10 – 4.07; P⬍0.001; Table 3). Obesity and alcohol abuse/
Table 2 shows the association between ED and OAG. Among alcohol dependence syndrome were not adjusted for in the
all the subjects in the city, 137 (0.5%) suffered from OAG. Fifty- regression modeling because of the small number of cases in
three ED subjects (1.1%) and 84 of the non-ED controls (0.4%) some cells. In addition, the regression showed that hyperten-
had OAG before the index date. Conditional logistic regression sion, diabetes, coronary heart disease, and hyperlipidemia were
analysis demonstrated that a significantly higher proportion of the all associated with ED.

Table 3. Univariate and Covariate-Adjusted Odds Ratios (ORs) for Erectile Dysfunction (ED)
among the Sampled Patients (n ⫽ 27 630)

Presence of ED
Variables Univariate OR (95% CI) Adjusted OR (95% CI)
Patients with open-angle glaucoma
Yes 3.18† (2.25–4.49) 2.85† (2.10–4.07)
No 1.00 1.00
Age 1.00 (0.99–1.01) 1.01 (0.99–1.01)
Monthly income (NT$)
No income (reference group) 1.00 1.00
1–15 840 1.70† (1.47–1.97) 1.79† (1.54–2.07)
15 841–25 000 1.15* (1.00–1.31) 1.32† (1.15–1.52)
ⱖ25 001 1.71† (1.50–1.96) 1.81† (1.57–2.09)
Hyperlipidemia 1.62† (1.51–1.74) 1.43† (1.32–1.55)
Diabetes 1.52† (1.41–1.64) 1.33† (1.23–1.45)
Hypertension 1.91† (1.78–2.05) 1.70† (1.58–1.83)
Coronary heart disease 1.34† (1.24–1.45) 1.23† (1.13–1.34)
Geographic region
Northern (reference group) 1.00 1.00
Central 0.81† (0.75–0.88) 1.02 (0.93–1.11)
Eastern 0.81† (0.75–0.88) 0.92 (0.85–1.01)
Southern 0.83 (0.67–1.02) 1.12 (0.90–1.39)
Urbanization level
1 (most urbanized, reference group) 1.00 1.00
2 0.87† (0.80–0.94) 0.89* (0.82–0.97)
3 0.80† (0.73–0.88) 0.82† (0.74–0.90)
4 0.59† (0.53–0.66) 0.62† (0.55–0.70)
5 (least urbanized) 0.55† (0.49–0.62) 0.60† (0.52–0.68)

CI ⫽ confidence interval.
*P⬍0.01; †P⬍0.001.


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Ophthalmology Volume 119, Number 2, February 2012

Discussion are supported by Fadini et al,22 whose study also demonstrated

that OAG and ocular hypertension patients presented with low
In this study, after adjusting for confounding factors, we flow-mediated dilatation. They additionally demonstrated that
found that ED patients had a 2.85-fold greater risk of prior there was a marked reduction in circulating endothelial pro-
OAG diagnosis than controls. To our knowledge, this is the genitor cells, which are significant indicators of systemic vas-
first study to document the association between ED and cular endothelial dysfunction.
OAG based on a population-based dataset. This finding This study identified the link between ED and OAG.
suggests that there may be a common mechanism of disease Increasing evidence has elucidated the common risk factors
for ED and OAG, which is not entirely explained by the shared by ED and OAG. The pathomechanisms that exist in
variables included in the multiple logistic model. According subjects with the MS and contribute to the development of
to the definition of the National Cholesterol Education Pro- endocrine and vasogenic disarrangements are speculated to
gram Adult Treatment Panel III, the MS is composed of be involved in the pathology of ED and OAG. After adjust-
criteria relating to obesity, hyperglycemia, dyslipidemia, ing for the medical comorbidities related to the MS, ED
and hypertension.12 In addition to its relationship to dia- remained an independent risk factor for prior OAG.
betes and cardiovascular risks, the MS recently has been The present study provided the framework for a concep-
associated with glaucoma.8,11 The association between the tual relationship between ED and OAG, but future investi-
MS and ED is strongly suggested by epidemiologic and gations are required to elucidate what was begun here. The
basic studies.13–16 The main features of the MS, including results of this study suffer from a few limitations that should
hyperglycemia and insulin resistance, may result in sys- be addressed. The first limitation of this study is the use of
temic chronic inflammation and lead to endothelial damage ICD coding to diagnose ED. Discussing sexuality is rela-
and atherosclerosis.12 Recently, chronic inflammatory status tively culturally taboo in Taiwan and may contribute to the
has been identified to be associated glaucoma.17 Jiang et al18 seemingly low frequency of ED when compared with stud-
evaluated retinal RNA obtained from canine eyes with ies from Western countries. Furthermore, because this study
advanced glaucoma, and found that the genes with elevated utilized ICD-9 data for the analyses, we had no way to
expression were largely associated with inflammation, and discern the severity of ED.
had roles in antigen presentation, protein degradation, and Nevertheless, in our nationwide, population-based anal-
innate immunity. They speculated that pronounced retinal ysis, we collected baseline conventional risk factors and
neuroinflammation might develop during the final stages of
comorbidities, and despite their inclusion in our models, ED
glaucoma in canines.
remained a significant risk factor. Second, individual infor-
Nevertheless, the detailed mechanisms underlying im-
mation, such as a family history of OAG, migraines, steroid
mune disarrangements and chronic inflammation remain
use, and obesity, was not available through the administra-
putative. While endothelial dysfunction progressed, vascu-
tive dataset. All of these factors may contribute to OAG.
lar nitric oxide (NO) will be markedly reduced. There are
multiple crucial functions for NO in maintaining vascular Third, the OAG diagnoses are sourced from an administra-
efficiency such as inhibiting adhesion of platelets and leu- tive database and therefore may be less accurate than diag-
kocytes to the vascular wall and decreasing proliferation of noses collected individually through a standardized proce-
vascular smooth muscle to avoid the initiation of athero- dure. However, we only included the OAG diagnoses that
sclerosis.19 In addition, hyperglycemia would stimulate in- included a prescription for a topical antiglaucoma medica-
creased production of free radicals, such as superoxide tion. Fourth, antiglaucoma medications may be more asso-
anion, which inactivate NO normal functioning.19 Based on ciated with ED than OAG itself. In addition, some systemic
these concepts, it is suggested that the strong relationship medications can result in ED.23 However, the present study
between MS and endothelial dysfunction, vascular insuffi- cannot rule out the confounding effects of medications on
ciency and NO dysfunction, which both also have been ED. Finally, although we have adjusted for hypertension,
identified to be involved in the pathophysiology of ED. diabetes, coronary heart disease, and hyperlipidemia in the
Similarly, several previous studies have shown strong regression model, the study’s design cannot preclude the
associations between OAG and endothelial dysfunction or possibility of suffering from an ascertainment bias—that is,
NO dysfunction. It is agreed that vascular dysregulation, patients with systemic conditions may be more likely to
which may be a consequence of endothelial dysfunction undergo examinations, thus making it more likely that such
because the endothelium is involved in the control of vas- a patient’s OAG or ED status would be picked up on account
cular tone and blood flow, may play an important role in the of greater exposure. Thus, it follows that patients with OAG,
pathophysiology of glaucoma.20 Su et al21 recently conducted by virtue of their greater exposure, are more likely to report ED
a case-control study comparing endothelium-dependent, than those who have less contact with physicians. Therefore,
flow-mediated dilatation and endothelium-independent, further studies are suggested to evaluate ED before medica-
nitroglycerin-mediated vasodilation in patients with normal- tions are started and systemic conditions ascertained by exam-
tension glaucoma, OAG, and healthy aged- and sex- ination in cases and controls before concluding a direct asso-
matched controls.21 Based on their findings, patients with ciation between OAG and ED.
both types of glaucoma have impaired flow-mediated dila- This study leveraged the data from the Taiwan
tation. Furthermore, they demonstrated that both normal- LHID2000 to succeed in identifying a novel association
tension glaucoma and primary OAG are associated with between ED and prior OAG. Our findings suggest that
peripheral vascular endothelial dysfunction.21 These findings prospective studies should be undertaken to develop the


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Chung et al 䡠 Increased Risk of ED in Patients with OAG

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Footnotes and Financial Disclosures

Originally received: May 17, 2011. Department of Ophthalmology, Taipei Medical University Hospital, Tai-
Final revision: August 5, 2011. pei, Taiwan.
Accepted: August 5, 2011. 7
Department of Ophthalmology, Taipei Medical University, Taipei, Tai-
Available online: October 29, 2011. Manuscript no. 2011-743. wan.
Division of Urology, Department of Surgery, Far Eastern Memorial 8
School of Medical Laboratory Sciences and Biotechnology, Taipei Med-
Hospital, Ban Ciao, Taipei, Taiwan.
ical University, Taipei, Taiwan.
Graduate Institute of Clinical Medicine, College of Medicine, National
Financial Disclosure(s):
Taiwan University, Taipei, Taiwan.
The authors have no proprietary or commercial interest in any of the
School of Health Care Administration, Taipei Medical University, Taipei, materials discussed in this article.
Department of Ophthalmology, Shin Kong Wu-Ho-Su Memorial Hospi- Herng-Ching Lin, PhD, School of Health Care Administration, Taipei
tal, Taipei, Taiwan. Medical University, 250 Wu-Hsing St., Taipei 110, Taiwan. E-mail:
School of Medicine, Fu-Jen Catholic University, Hsingchuang, Taiwan.


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