Objective: Prevalence of depression is suggested to be substantially higher in women around menopause. Declining estrogen levels might be an explanation. This study attempts to determine whether depressive symptomatology in healthy women is independently related to menopausal transition. Method: All caucasian women born between 1941 and 1947, living in the city of Eindhoven the Netherlands were invited to take part in a screening program (n=8098) of whom 78% participated (n=6648). About 92% returned the questionnaires of which 81% (n=4975) was fully completed. Women using estrogens and/or having undergone hysterectomy and/or ovariectomy were excluded (43.6%). Of the remaining 2820 women, after 3.5 years, 2748 returned another postal questionnaire, of which 76% was fully completed (n=2103). Depressive symptomatology was assessed using the Edinburgh Depression Scale (EDS). Independent relationship between an intra-individual change in EDS score during the follow-up period and menopausal transition was analysed by multiple logistic regression (enter as well as stepwise method). Results: Beside the classical determinants of depression (unemployment OR 3.1, CI 1.6–5.8, inability to work OR 1.7, CI 1.0–2.8, financial problems OR 2.9, CI 1.1–7.3 death of a partner OR 2.6, CI 1.1–6.1, death of a child OR 5.9, CI 1.1–32.1 and a previous episode of depression OR 2.0, CI 1.5–2.7) transition from pre to perimenopause and peri to postmenopause was significantly related to a high increase (>5.4) of the EDS score (OR 1.8, CI 1.1–3.3 and OR 1.8, CI 1.5–2.7, respectively). Conclusion: The transition from pre to perimenopause as well as from peri to postmenopause seems to be independently related to a high increase of depressive symptomatology. This suggests that the decrease of ovarian estrogen production is a risk factor for depressive symptomatology.