Study suggests hormone replacement therapy associated with dry eye syndrome

Duration of therapy also influences risk of dry eye.

Issue: March 1, 2001

ByBob Kronemyer

BOSTON — Women who use postmenopausal hormone replacement therapy have a significantly higher prevalence of dry eye syndrome compared to women who have never used such therapy, according to data from a large cohort. The study found that women who currently use or previously used hormone replacement therapy (HRT) were about 70% more likely (odds ratio: 1.69) to have dry eye compared to women who never took HRT.

“I wouldn’t say we were very surprised by the results of our study,” said first author Debra A. Schaumberg, ScD, OD, MPH, an associate epidemiologist at Brigham and Women’s Hospital and an instructor in medicine at Harvard Medical School. One of the co-authors, David A. Sullivan, PhD, a scientist at Schepens Eye Research Institute here, had already conducted extensive basic science research on the relationship of sex steroid hormones and dry eye syndrome (DES). Another co-author, Dr. Dana, had collaborated with Dr. Sullivan, showing the detrimental effects of anti-androgens on dry eye.

“Based on some of these findings, as well as those of other researchers, we thought there might be an adverse effect from estrogens in particular,” Dr. Schaumberg said.

Participants in the observational epidemiologic study were from the Women’s Health Study, which began enrollment in 1992, includes 39,876 women. Information on HRT use was obtained by mailed questionnaires at baseline, 12 months and 36 months. Data regarding a history of clinically diagnosed DES, as well as symptoms of dryness and irritation, were obtained on the 48-month follow-up questionnaire. A total of 36,995 female health professionals answered all questions concerning DES.

“About 7% of the study population had a household income of less than $20,000 a year,” Dr. Schaumberg said. Overall, study participants “are knowledgeable women who are excellent reporters of their health. We also maintained a very high participation rate.”

Combination therapy

The study found that women who used a combination therapy (estrogen plus either progesterone or progestin) had a 27% higher chance (odds ratio: 1.27) of having dry eye. “About half the women who took any HRT used estrogen alone, while the other half took this combination,” Dr. Schaumberg said.

“It is interesting to note, though, that this 27% higher risk in women who took the combination therapy is significantly lower than the 70% increase risk in women who took estrogen alone. It appears that combination therapy modifies in some way the adverse effect of estrogen alone,” she said.

The investigators also performed a separate analysis to determine whether the duration of HRT use had any influence on the prevalence of DES. “Duration of HRT use was significantly associated with the risk of DES,” Dr. Schaumberg said. There was an estimated 16% higher risk of clinically diagnosed DES or severe symptoms for each increase of 3 years in the total duration of HRT use. For instance, “women who took HRT for 6 years had a 35% higher risk of having DES compared to those women who never took HRT,” she said.

Adjustment for race, geographic region, education level, household income, and frequency of eye examinations had little impact on the overall findings of the study. “There are some fairly large differences in the use of hormones according to these variables, but these factors cannot explain the relationship that we found,” Dr. Schaumberg said.

Still, among reasons whether or not to prescribe HRT, “dry eye is probably relatively less important than consideration of risk of breast cancer or preventing osteoporosis or cardiovascular disease, for example, since dry eye rarely leads to permanent vision impairment or blindness,” she said.

Study limitations

The study, which was presented at the American Academy of Ophthalmology meeting, also has some limitations. “We can’t tell which came first — the dry eye or the use of HRT,” said Dr. Schaumberg. “There is a chance that women with symptoms or clinical signs of dry eye were more likely to be prescribed HRT. But we don’t think this is very likely, particularly given the fact that we find significant differences in the magnitude of the relationship when we look at estrogen alone versus combination therapy.” The relationship found in the duration of use also discounts this explanation.

A more plausible explanation is that “there is a true association between dry eye and HRT,” Dr. Schaumberg said. “We know from basic research that androgens have a beneficial effect on the tear film of the eye. We know that estrogens have inhibitory effects on sebaceous glands in the body. In fact, one of the major tear-producing glands is a large sebaceous gland,” she said.

Additional evidence from some small studies indicates adverse effects from estrogen in Sjögren’s syndrome, a disease characterized by severe dry eye.

Particularly for ophthalmologists, “patients who are on HRT should be asked about symptoms of dry eye,” Schaumberg said. Practitioners should also carefully assess the ocular surface. “Dry eye is a condition that can be sometimes overlooked in a routine exam. Sometimes people don’t volunteer the symptoms, even though they may have frequent suffering. You really do have to ask patients about it.”

For Your Information:

Debra A. Schaumberg, ScD, OD, MPH, can be reached at Brigham and Women’s Hospital, 900 Commonweath Ave. East, Boston, MA 02215-1204; (617) 278-0849; fax: (617) 731-3843; e-mail: dschaumberg@rics.bwh.harvard.edu. Dr. Schaumberg has no direct financial interest in the products mentioned in this article, nor is she a paid consultant for any companies mentioned.