It has previously been reported that women seeking treatment at menopause clinics are more likely to report significant physical symptoms (e.g., vasomotor complaints), as well as depressive symptoms and anxiety. On the other hand, most women in the community do not experience significant depression while transitioning into the menopause. Thus, it is important to understand why some (but not all) women develop depressive symptoms during the menopausal transition.  In other words, are we able to identify significant risk factors for the development of a menopause-related mood disturbance?

In a nationally representative, cross-sectional survey of 2,020 Australian women between the ages of 40 and 65, symptoms were assessed using the Menopause-Specific Quality of Life Questionnaire, the Beck Depression Inventory-II, with score of ? 20 defined as moderate-severe depressive symptoms.

Moderate to severe vasomotor symptoms (VMS) were reported by 267 of the 2,020 women (13.3%). As assessed using the BDI-II, 14.1% of the women were classified as having at least mild depressive symptoms and 6.3% had moderate to severe depressive symptoms.  After adjusting for multiple factors, the researchers observed that women with moderate-severe VMS were more likely to have moderate-severe depressive symptoms (odds ratio [OR] 2.80).

Women with moderate-severe depressive symptoms, as compared to women with mild VMS, were also more likely to report the use of psychotropic medications (48.9% vs. 20.1%), to report smoking (25.9% vs. 12.2%), and to engage in binge drinking at least weekly (15.1% vs. 10.3%). Based on the cross-sectional design of this study, it is difficult to determine if these factors increase the risk of depressive symptoms or are merely patterns of behavior that are associated with moderate to severe depressive symptoms.  

While this study, and several others, have identified vasomotor symptoms as a risk factor for depressive symptoms in perimenopausal women, it is likely that the relationship between menopausal symptoms and depression is bidirectional.  In other words, having depression may modulate a woman’s transition into the menopause or her experience of this event.

While most studies exploring the relationship between mood and the menopausal transition have been cross-sectional, the Harvard Study of Moods and Cycles prospectively followed 332 women with and 644 women without a history of major depression who were enrolled between 36 and 45 years of age. Menopausal symptoms and depressive symptoms were assessed over a follow-up period of three years.

Over the course of the study, women with a history of depression were 1.2 times as likely to transition into the perimenopause than women with no history.  In addition, women with more severe depression at enrollment into the study, compared to nondepressed women, had twice the risk of an earlier perimenopausal transition. Women with a lifetime history of depression also had higher levels of follicle-stimulating hormone and luteinizing hormone and lower estradiol levels at study enrollment and across the three years of follow up.  This study indicates that depression may contribute to ovarian decline.

While these studies indicate that we need to clinically consider the comorbidity of menopausal  symptoms and depression in perimenopausal women, other interesting questions emerge. Can we reduce the risk of depression by treating menopausal symptoms?  Are women on hormone replacement therapy at reduced risk for menopause-related mood changes? Next week, we will cover a recent study which suggests that hormone replacement therapy (transdermal estradiol and oral progesterone) may reduce the risk of  clinically significant depressive symptoms among nondepressed perimenopausal women.  

Ruta Nonacs, MD PhD


Harlow BL, Wise LA, Otto MW, Soares CN, Cohen LS.  Depression and its influence on reproductive endocrine and menstrual cycle markers associated with perimenopause: the Harvard Study of Moods and Cycles.  Arch Gen Psychiatry. 2003 Jan;60(1):29-36.

Worsley R, Bell RJ, Gartoulla P, Robinson PJ, Davis SR.  Moderate-Severe Vasomotor Symptoms Are Associated with Moderate-Severe Depressive Symptoms.  J Womens Health (Larchmt). 2017 Mar 6.