The idiopathic full-thickness macular hole (IFTMH) is an important cause of poor vision in the elderly affecting predominantly women over the age of 60 years. While it is accepted that vitreoretinal traction is an important local factor in the development of IFTMH, the underlying cause is not known. The aim of this study was to identify possible systemic risk factors for the development of IFTMH. Two hundred and thirty-seven patients with IFTMH (cases) attending the Macular Hole Clinic at Moorfields Eye Hospital were identified. These were compared with 172 patients without macular holes (controls) attending other clinics in the same hospital. Cases and controls were frequency-matched by sex. The prevalence of the following factors in both groups was ascertained by interview: ethnic origin, place of birth, housing tenure, any systemic diseases, current and lifetime consumption of medication, severe dehydrational episodes, menstrual and obstetric history, onset and severity of menopause and use of exogenous oestrogens (in women only), osteoporosis, vegetarianism, use of vitamin supplementation, and smoking and alcohol consumption. Height and weight were measured for all participants. Cases of IFTMH macular holes were predominantly women (67%) and aged 65 years and older (74%). We found very few systemic risk factors that were significantly associated with IFTMH. There was a higher prevalence of diabetes in controls (12% vs 5%). There was no association between the majority of indicators of oestrogen exposure in women and macular holes, but cases had a more difficult menopause as judged by the severity of hot flushes at menopause: odds ratio 2.6 (1.4-4.6). In common with other studies, we found only a few systemic factors associated with IFTMH. The study did confirm, however, that IFTMH is a strongly gender-related disease. There is some evidence for the role of sudden changes in hormonal balance, as seen by the increased reporting of severity of symptoms around the menopause along with (statistically non-significant) increased risks associated with hysterectomy and oophorectomy. The particular aetiological factor which puts women at increased risk of macular holes requires further studies.