Copper deposition may be caused by oral contraceptives

Researchers documented two cases in which oral contraceptives were found to cause elevated serum copper levels and a granular-like dusting on the corneal endothelium, according to a report published in Optometry and Vision Science. Their elevated serum copper levels returned to normal after the women stopped taking the pills.

Gustavo Garmizo, OD, FAAO, told Primary Care Optometry News in an interview that he and Barry J. Frauens, OD, FAAO, published their case reports to bring attention to this little-known side effect and save patients from the expense and morbidity risk of extensive, unnecessary testing. As optometrists become more aware of these deposits, Dr. Garmizo hopes more information about their nature and clinical implications can be ascertained.

Case studies

In the first case, a 26-year-old woman had been on the oral contraceptive Yasmin (drospirenone/ethinyl estradiol, Bayer) for 2 years before the deposits were noted and remained on the contraceptive another 4 years. During this time, the pigment deposition had become much more extensive and dense, forming a complete ring.

When the patient discontinued her oral contraceptive, her serum copper level dropped to normal after 3 weeks, and after 8 weeks the corneal deposits had greatly diminished.

The second case documented a 43-year-old myopic woman taking Triphasil (levonorgestrel/ethinyl estradiol, Wyeth) for 15 years to regulate her menopausal symptoms. According to the report, a slit-lamp evaluation revealed trace to 1+ bluish-green deposits inferiorly at the level of Descemet’s membrane, similar to those seen in case 1, but to a much lesser extent.

After discontinuing oral contraception, serum copper and ceruloplasmin levels were back to normal, but the patient did not feel well physically or psychologically due to her menopausal symptoms. She began taking Yasmin, and after 4 weeks serum copper and ceruloplasmin levels were again elevated.

Although corneal deposits continue to be present, they are minimal and — at the time of the study — did not seem to be increasing after 2 years of Yasmin, according to the authors.

Differentiating corneal copper

Deposits may occur on the cornea for a number of reasons, the first and most common of which is due to Wilson’s disease. According to Dr. Garmizo, corneal deposits are often subtle and may be overlooked; high magnification is required to see them clearly. The deposits seen in a typical Kayser-Fleischer ring differ from the deposits in the case report in several ways.

“The copper deposition that we’re seeing here is more central on the endothelium, while the Kayser-Fleischer ring is more in the periphery,” he said. “It’s also bluish-green, while the Kayser-Fleischer ring is reddish-brown.”

Another difference between the rings is how they begin to appear. The copper deposits reported in the case study were greater inferiorly with a clear space to the limbus, while Kayser-Fleischer rings first deposit superiorly with no clear space to the limbus and then regress in reverse order upon treatment, the report states.

Causes of deposition

Several conditions have been documented to deposit copper in the cornea, among them Wilson’s disease, leukemia and cancers such as multiple myeloma and pulmonary carcinoma.

“In Wilson’s disease the copper is actually low in the blood and is not carried through the way it’s supposed to,” Dr. Garmizo said. “It accumulates in the tissues — the cornea, brain and the liver.”

Potential side effects

Although no symptoms have been reported in the two cases studied, research suggests that elevated copper might be associated with the increased risk of cardiovascular complications that occur in conjunction with the use of birth control pills.

A study conducted by the National Center for Chronic Disease Prevention and Health Promotion examined the relationship between serum copper and coronary heart disease. This study, along with several other prospective studies, found elevated serum copper concentrations to be associated with cardiovascular disease, but more research is necessary to determine whether copper is a marker for disease or if there is a causal relationship, the researchers said.

For more information:

• Gustavo Garmizo, OD, FAAO, can be reached at West Broward Eye Care Associates, 7822 N. University Drive, Tamarac, FL 33321; (954) 726-0204, fax: (954) 721-1578; e-mail: gusgarmizo@aol.com.

References:

• Ford ES. Serum copper concentration and coronary heart disease among U.S. adults. Am J Epidemiol. 151(12):1182-1188. http://aje.oxfordjournals.org/cgi/content/abstract/151/12/1182

• Garmizo G, Frauens BJ. Corneal copper deposition secondary to oral contraceptives. Optom Vis Sci. 2008;85(9):E802-807.