The risk of depression in women increase 2-4 times in the years leading up to the last menstrual period, known as the menopause transition (i.e., ‘perimenopause’). Excessive perimenopausal estrogen fluctuation has been hypothesized to play a role, though the factors predicting sensitivity to perimenopausal hormone flux are not well known. Research from animal models suggests that past exposure to pregnancy and childbirth and the immense hormonal flux that accompanies it can lessen mood sensitivity to hormonal fluctuations. The current study aimed to examine whether the number and recency of a woman’s past pregnancies would be associated with altered sensitivity to estrogen fluctuation in the context of the menopause transition. To test this, 100 perimenopausal women were recruited for a 12-week study: once a week, participants answered a mood survey and collected their first-morning urine sample to allow for the measurement of urinary metabolites of estrogen and progesterone. Details about their reproductive history, including the number and timing of any previous pregnancies, were assessed. Results revealed a significant interaction between number of pregnancies and weekly estrogen fluctuation on mood, such that women with a greater number of pregnancies were less sensitive to increases in estrogen. Length of time since last pregnancy did not significantly predict sensitivity to hormonal fluctuations. These findings suggest that women with few or no previous pregnancies may be at greater risk for developing depressive mood in the menopause transition.