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Macular degeneration and early menopause: a case-control study

^a Department of Ophthalmology, Erasmus University Medical School, Rotterdam, Netherlands, ^b Department of Epidemiology and Biostatistics, Erasmus University Medical School, Rotterdam, Netherlands

Correspondence to: Dr P T V M de Jong, Netherlands Ophthalmic Research Institute, Postbox 12141, 1100AC Amsterdam, Netherlands.

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.
-----------------------------------------------------------------------
                            Macular degeneration     Relative risk
--------------------------------------------------- (95% confidence
                             Absent        Present     interval)*
-----------------------------------------------------------------------
Age at menopause (years):
  >/=45                       253            45              1.0
  <45                          42            14       1.9 (1.0 to 3.8)
Cause of early menopause:
  Spontaneous                  30             6       1.2 (0.5 to 3.3)
  Surgical:
    Hysterectomy only          4              1       2.1 (0.2 to 24.9)
    Oophorectomy+              6              5       3.8 (1.1 to 12.6)
  Irradiation                  1              2       4.2 (0.6 to 30.2)
  Drug use                     1              0              --
-----------------------------------------------------------------------
*Adjusted for age.
+Unilateral or bilateral oophorectomy with or without hysterectomy.

Comment

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.

1. Eye Disease Case-Control Study Group. Risk factors for neovascular age-related macular degeneration. Arch Ophthalmol 1992;110:1701-8. [Abstract]
2. Hofman A, Grobbee DE, de Jong PTVM, van den Ouweland FA. Determinants of disease and disability in the elderly: The Rotterdam elderly study. Eur J Epidemiol 1991;7:403-22. [Medline]
3. Colditz GA, Willett WC, Stampfer MJ, Rosner B, Speizer FE, Hennekens CH. Menopause and the risk of coronary heart disease in women. N Engl J Med 1987;316:1105-10. [Abstract]
4. Witteman JCM, Grobbee DE, Kok FJ, Hofman A, Valkenburg HA. Increased risk of atherosclerosis in women after the menopause. BMJ 1989;298:642-4.
5. Palmer JR, Rosenberg L, Shapiro S. Reproductive factors and risk of myocardial infarction. Am J Epidemiol 1992;136:408-16. [Abstract/Free Full Text]

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