BACKGROUND The purpose of this study was to examine and compare menstrual-cycle-dependent topographic changes in the optic nerve head of normally menstruating women with different grades of type 2 diabetes mellitus. METHODS We studied the right eyes of 123 normally menstruating women (36 with severe nonproliferative diabetic retinopathy [NPDR], 42 with mild NPDR and 45 healthy subjects). All subjects underwent a complete ocular examination at baseline. At 4 hormonally distinct phases of the menstrual cycle (early follicular, late follicular, mid-luteal and late luteal), we analysed the topography of the optic nerve head, using a confocal scanning laser ophthalmoscope, and measured the serum levels of estradiol, progesterone and luteinizing hormone. RESULTS We excluded from analysis the data for 8 patients with severe NPDR, 10 patients with mild NPDR and 15 control subjects who were lost to follow-up examinations during the menstrual cycle. The mean age and optic disc area did not differ significantly among the 3 groups. The duration of diabetes was significantly longer in the patients with severe NPDR than in those with mild NPDR (p < 0.05). The women with severe NPDR had a significantly increased neuroretinal rim area and a significantly decreased cup-shape measure, linear cup/disc ratio, cup/disc area ratio and cup area in the late luteal phase compared with the other phases of the menstrual cycle (p < 0.05). Those with mild NPDR or a normal retina had no significant topographic changes in the optic nerve head during the menstrual cycle. CONCLUSIONS Severe NPDR is associated with significant topographic changes in the rim and cup of the optic nerve head during the menstrual cycle. This must be considered in the evaluation of women with both diabetes and glaucoma. The normal fluctuations in serum sex hormone levels during the menstrual cycle of diabetic women seem to affect the optic nerve head more when the disease is advanced.