Rise in erectile dysfunction association with glaucoma

Vancouver, British Columbia-A recent study found an association between erectile dysfunction (ED) and glaucoma that is not attributed to the use of beta-blocker therapy.  

History of beta-blockers and ED

Several studies in the 1980s found that ED was a side effect of systemic and topical beta-blocker therapy.^1-4

“It has been postulated that the sexual dysfunction accompanying β-blockade may be due to a number of mechanisms including: increased α-sympathetic tone causing shunting of blood away from the penis, depression and sedation mediated by the central nervous system, and overall decreased activity of the central nervous sympathetic system,” the study’s authors write.

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But more recent studies have concluded that there is only a minimal increase in the incidence of sexual dysfunction in patients on beta-blocker therapy-if at all-and that this increase may actually be related to patient knowledge and expectation of this side effect rather than an organic cause, also known as nocebo effect.^5-8

Researchers also say open-angle glaucoma is associated with a higher incidence of ED because of their common risk factors, such as dyslipidemia, systemic hypertension, diabetes, etc.⁹

Next: The study

The study

Researchers used a comprehensive, province-wide database of physician visits and diagnoses and prescription drug dispensing to identify 1,380 cases of ED and found 13,800 corresponding controls. Researchers then used a conditional logistic regression model to estimate rate ratios for the diagnosis of glaucoma defined as at least two physician visits for glaucoma in the year before the index date and use of a prescription of a topical beta-blocker in the 30 days before the index date. A variety of risk factors were adjusted for.

The study found that the crude rate ratio of the current diagnosis of ED in a population with at least two separate diagnoses of glaucoma was 1.34, and when adjusted for variables in (including oral beta-blockers use, other antihypertensives, and various comorbidities), this ratio was 1.37.

Use of topical beta-blockers in the 30 days before the diagnosis of ED did not have a significant association with a diagnosis of ED, with a crude rate ratio of 1.05. The study found that topical ocular prostaglandin use was also not associated with ED with a crude rate ratio of 0.96.

“The association between glaucoma and ED, therefore, cannot be attributed to topical beta-blocker use,” the study’s authors write.

Related: High IOP, corneal edema with unknown etiology

Researchers say that some studies have suggested that glaucoma and ED have a commonality of risk factors, but their adjustment for the most prevalent risk factors should have corrected for them. But they say it is possible that either the effect of these risk factors was not entirely eliminated despite the correction or that there are other risk factors, not accounted for, that led to the association.

 “The correlation established after the comorbid variables have been neutralized is very interesting and, as stated by the authors, requires further investigation to determine cause,” says Optometry Times Editorial Advisory Board member J. James Thimons, OD, FAAO. “It would be remarkable if chronic open-angle glaucoma (COAG) was an independent variable in the development of ED. That could lead to a major rethinking of the role of the disease and its impact on other systemic functions such as memory, depression, cognitive function etc.”

Optometry Times Editorial Advisory Board Ben Casella, OD, says the results of this large-scale case study point to hemodynamic dysfunction as a likely contributing cause in many glaucoma cases

“Extrapolating a bit, this is especially evidenced by the fact that patients with normal tension glaucoma and/or erectile dysfunction tend to be older,” he says.

Next: Checking with urology colleagues

Checking with urology colleagues

William O. Brant, MD, assistant professor of surgery (urology) at the Center for Reconstructive Urology and Men’s Health, University of Utah, Salt Lake City, says this study highlights that ED is generally a manifestation of systemic vascular disease.

“As researchers note, risk factors for chronic glaucoma are similar to risk factors for ED, even if the patient has not (yet) manifest other issues such as coronary artery disease,” he says. “One surprising finding is the low number of ED patients within the large cohort, making me suspicious that ED may be underdiagnosed.”

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Dr. Brant says urologists assessing ED should always consider both the presenting problem as well as the underlying causes. It is important to assess cardiovascular risk factors during a thorough history, he says.  

“In our clinic, we commonly refer our new ED patients to cardiologists, dieticians, and exercise physiologists as well as treating the ED,” says Dr. Brant. “As part of a thorough history, we should ask about glaucoma, and patients with glaucoma should be asked about ED by their other providers.”

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References:

1. Kandeel FR. Male Sexual Dysfunction: Pathophysiology and Treatment. London: Informa Healthcare; 2007.

2. Shore JH, Fraunfelder FT, Meyer SM. Psychiatric side effects from topical ocular timolol, a beta-adrenergic blocker. J Clin Psychopharmacol. 1987;7:264–7.

3. Fraunfelder FT, Meyer SM. Sexual dysfunction secondary to topical ophthalmic timolol. JAMA. 1985;253:3092–3.

4. Lynch MG, Whitson JT, Brown RH, et al. Topical beta-blocker therapy and central nervous system side effects. A preliminary study comparing betaxolol and timolol. Arch Ophthalmol. 1988;106:908–11.

5. Silvestri A, Galetta P, Cerquetani E, et al. Report of erectile dysfunction after therapy with beta-blockers is related to patient knowledge of side effects and is reversed by placebo. Eur Heart J. 2003;24:1928–32.

6. Ko DT, Hebert PR, Coffey CS, et al. Beta-blocker therapy and symptoms of depression, fatigue, and sexual dysfunction. JAMA. 2002;288:351–7.

7. Lama PJ. Systemic adverse effects of beta-adrenergic blockers: an evidence-based assessment. Am J Ophthalmol. 2002;134:749–60.

8. Bhatt R, Whittaker KW, Appaswamy S, et al. Prospective survey of adverse reactions to topical antiglaucoma medications in a hospital population. Eye (Lond). 2005;19:392–5.

9. Chung SD, Hu CC, Ho JD, et al. Open-angle glaucoma and the risk of erectile dysfunction: a population-based case-control study. Ophthalmology. 2012;119:289–93.