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Macular degeneration and early menopause: a case-control study

BMJ 1995; 310 doi: (Published 17 June 1995) Cite this as: BMJ 1995;310:1570
  1. Johannes R Vingerling, resident in ophthalmologya,
  2. Ida Dielemans, resident in ophthalmologya,
  3. Jacqueline C M Witteman, senior lecturer in epidemiologyb,
  4. Albert Hofman, professor of epidemiologyb,
  5. Diederick E Grobbee, professor of clinical epidemiologyb,
  6. Paulus T V M de Jong, professor of ophthalmologya
  1. a Department of Ophthalmology, Erasmus University Medical School, Rotterdam, Netherlands
  2. b Department of Epidemiology and Biostatistics, Erasmus University Medical School, Rotterdam, Netherlands
  1. Correspondence to: Dr P T V M de Jong, Netherlands Ophthalmic Research Institute, Postbox 12141, 1100AC Amsterdam, Netherlands.
  • Accepted 21 March 1995

Age related macular degeneration is a main cause of blindness in elderly people. The disease affects the macula lutea and results in a central scotoma in the visual field. The cause of the disease is poorly understood, and treatment is only successful in a few cases. Recent findings of an association between use of postmenopausal exogenous oestrogens and a lower risk of macular degeneration suggest a role for oestrogens in the pathogenesis of the disease.1 We hypothesised that a higher risk of macular degeneration occurs in women with an early menopause.

Subjects, methods, and results

Data were obtained from the Rotterdam study.2 All women aged 55 years and over who were resident in the suburb of Ommoord in Rotterdam were invited for the study. The response rate was 78% (4616/5918). Macular degeneration was considered to be present if either atrophic or neovascular age related macular degeneration was visible on colour pictures of the fundus. Age at and type of menopause were self reported and checked by a study physician. The cause of menopause was classified as natural hysterectomy, removal of one or both ovaries with or without hysterectomy, radiotherapy, or drug treatment. Overall, 3680 women (80%) had gradable fundus photographs of at least one eye and complete data on the menopause. Macular degeneration was present in 59 women (1.6%). We matched each case with five controls born in the same year who did not have macular degeneration, resulting in 295 controls. We calculated relative risks with 95% confidence intervals using conditional logistic regression analysis.

The table shows the relative risk of macular degeneration according to age and type of menopause. No significant excess risk was found for early spontaneous menopause and early hysterectomy. Women with early menopause after removal of one or both ovaries had a significantly increased risk of macular degeneration compared with women who had their menopause at 45 years or later (relative risk 3.8; 95% confidence interval 1.1 to 12.6). Of 16 women whose menopause was the result of oophorectomy at 45 years or later, none had macular degeneration. This indicates a significant excess risk of early compared with late menopause by oophorectomy (exact lower 95% confidence limit 1.7).

Relative risk of macular degeneration by type of menopause. Values are numbers of women.

View this table:


Our findings suggest that early artificial menopause increases the risk of macular degeneration and are compatible with the view that oestrogens have a role in the pathogenesis of the disease.1 The association between early artificial menopause and macular degeneration may be related to an early decline of oestrogen production or, alternatively, to factors related to operation or irradiation. The absence of an increased risk of macular degeneration associated with oophorectomy at 45 or over favours an association with the arrest of oestrogen production. Combining unilateral and bilateral oophorectomy may have resulted in an underestimation of this association. We found no association with early spontaneous menopause. The mean age of women with early spontaneous menopause was similar to that of women with early medically induced menopause. The results may be affected by misclassification since women tend to underestimate the age of spontaneous cessation of menses.

The mechanism of the association is unknown. Previous studies suggested that surgical menopause with removal of both ovaries increases the risk of cardiovascular disease and atherosclerosis.3 4 5 Possibly, similar factors underlie the development of macular degeneration.

We thank the participants of the Rotterdam study and the field workers of the research centre. This study was supported by grants from the NESTOR programme for geriatric research (supported by the Netherlands Ministries of Health and Education); Topcon Europe; Stichting Haagsch Oogheelkundig Fonds; Stichting Blindenhulp; Merck Sharp and Dohme—Chibret; Rotterdamse Vereniging Blindenbelangen; Netherlands Society for the Prevention of Blindness; Stichting Bevordering Van Volkskracht; Stichting voor Ooglijders; Stichting Fondsenwervingsacties Volksgezondheid; and the GPh Verhagen-Stichting.


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