We examined the effects of the menopause transition on plasma lipids, insulin-like growth factor I (IGF-I) and blood pressure. An initial cohort of 38, non-smoking, healthy premenopausal women (44-48 years) were examined at baseline and after a 6-year follow-up period. At follow-up, 18 women had spontaneously stopped menstruating, whereas 17 women remained premenopausal. Women who experienced natural menopause showed a greater decline in high-density lipoproteins (-5 +/- 4 mg dL-1 vs. -1 +/- 3 mg dL-1; P < 0.01) and a greater increase in low-density lipoproteins (13 +/- 12 vs. 5 +/- 10 mg dL-1; P < 0.05) and fasting triglycerides (14 +/- 15 vs. 5 +/- 11 mg dL-1; P < 0.05) than women who remained premenopausal. No menopause effect was noted for total cholesterol. We noted a greater decline in IGF-I levels in women who experienced a natural menopause (-21 +/- 11 ng mL-1) than women who remained postmenopausal (-4 +/- 10 ng mL-1). Systolic blood pressure increased in postmenopausal (13 +/- 10 mmHg) compared with premenopausal women (5 +/- 4 mmHg: P < 0.01), whereas no menopause effect was noted for diastolic blood pressure. The increase in the waist-to-hip ratio was related to a decrease in high-density lipoprotein (r = -0.49; P < 0.05) and increase in low-density lipoprotein (r = 0.48; P < 0.05). The decline in IGF-I was related to the decline in reported leisure time physical activity (0.44: P < 0.05). We conclude that the natural menopause transition is associated with a worsening of the lipid profile and decline in IGF-I, which might be mitigated by deleterious changes in body fat distribution and physical activity.