Estrogens have neuroprotective and antidepressant effects. During the perimenopause, when estrogen levels fluctuate and then fall significantly, women may experience a broad spectrum of symptoms: vasomotor symptoms, such as night sweats and hot flashes, sleep disturbance, changes in weight and appetite, problems with cognitive functioning. In addition, we have data to indicate that women are more vulnerable to depression.
Longitudinal studies in the general population consistently demonstrated that depressive symptoms are more common during the menopausal transition than premenopause. Observed rates of depression during the perimenopausal depression vary, typically ranging from 20% to 40%.
Our research indicates that women are vulnerable for new onset of depression during the menopausal transition. In the Harvard Study of Moods and Cycles, a population-based prospective study of premenopausal women, Cohen and colleagues examined the association between the menopausal transition and first onset of major depression. A cohort of premenopausal women (36-45 years of age) with no lifetime diagnosis of major depression (n = 460) was followed prospectively.. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to screen for depressive symptoms over a period of up to 6 years.
Premenopausal women with no history of depression who entered the perimenopause were twice as likely to develop significant depressive symptoms when compared with women who remained premenopausal during the period of observation. The risk for depression was somewhat greater in women who reported vasomotor symptoms and was also increased among women who experienced negative life events proximate to this transition.
Premenopausal History of Depression
Women with a history of depression prior to menopause are more vulnerable to depression during the menopausal transition. The Study of Women’s Health Across the Nation (SWAN) followed a cohort of 443 perimenopausal women (ages 42 – 52 years) as they transitioned into the menopause (Bromberger et al, 2015). During the 13 years of prospective follow-up, 39% of the women experienced an episode of major depression. Women without a lifetime history of MDD at baseline had a lower risk of developing MDD during the menopausal transition than those with a prior MDD history (28% v. 59%).
While some women may experience their first episode of depression during the perimenopause, most women with perimenopausal depression have a history of depression.
Age at Onset of Menopause
According to a recent study investigating the association between age at menopause and risk for depression, early onset of menopause may increase risk for depression. In this meta-analysis, data was obtained from 14 studies, representing a total of 67,714 women. Researchers observed that women who experienced natural menopause at a later age were less likely to experience postmenopausal depression than women who entered into menopause at an earlier age. For every two year increase in age at menopause, rates of depression decreased by 5%. Women who experienced menopause at age 40 years or later were about half as likely to experience depression as women who experienced premature menopause. The findings were similar whether or not the woman had a history of depression prior to menopause.
The authors concluded that longer exposure to endogenous estrogens, expressed as older age at menopause and longer reproductive period, is associated with a lower risk of depression in later life.
Vasomotor Symptoms
Vasomotor symptoms (VMS) or hot flashes and night sweats, are common during the menopausal transition and can significantly affect quality of life. Up to 80% of women experience VMS during the menopausal transition, with the majority of women describing moderate-to-severe VMS.
In a cohort of 2,020 perimenopausal Australian women, 267reported having moderate-to-severe vasomotor symptoms. When compared to women with no or mild VMS, women with moderate–severe VMS were nearly three times more likely to have moderate–severe depressive symptoms (odds ratio [OR] 2.80, 95% CI 2.01–3.88, p?<?0.001).
Surgical Menopause
Each year about 600,000 women in the United States undergo a hysterectomy. Somewhere between 55% and 80% also have an oophorectomy. After the removal of the ovaries, menopause follows immediately and is associated with a constellation of symptoms including hot flashes and insomnia. Some, but not all studies, suggest that women who have undergone bilateral oophorectomy are more likely to experience depression (Rocca et al 2018, Mantani et al 2010).
Other Risk Factors
Other risk factors for depression during the perimenopause include being Black, having financial difficulties, history of childhood adversity, recent adverse life events, and low social supports Poor physical health and comorbid medical conditions have been associated with increased risk for depression; in addition, perimenopausal depression is more common in women with higher BMI.
Current Research Highlights Screening for Menopausal Depression
Patients and clinicians may not be fully aware that women are at increased risk for depression during the menopausal transition. The U.S. Preventive Services Task Force (USPSTF) recommends that clinicians screen all adults for depression, highlighting the importance of screening in populations at particularly high risk for depression. While these recommendations have prompted increased awareness of psychiatric illness in pregnant and postpartum women; this level of vigilance does not exist for perimenopausal women who are also vulnerable to depressive illness.
Primary care providers and OB-GYNs play a pivotal role in the detection of and management of perimenopausal depression. However, we need to provide better information regarding perimenopausal depression and tools for depression screening, so that this population of vulnerable women do not slip through the cracks. Many perimenopausal women experience disabling symptoms for long periods of time; yet the misconceptions regarding menopause prevent women from getting the help they need.
Ruta Nonacs, MD PhD
REFERENCES
Bromberger JT, Schott L, Kravitz HM, Joffe H. Risk factors for major depression during midlife among a community sample of women with and without prior major depression: are they the same or different? Psychol Med. 2015 Jun;45(8):1653-64.
Bromberger JT, Epperson CN. Depression During and After the Perimenopause: Impact of Hormones, Genetics, and Environmental Determinants of Disease. Obstet Gynecol Clin North Am. 2018;45(4):663-678. doi:10.1016/j.ogc.2018.07.007
Georgakis MK, Thomopoulos TP, Diamantaras AA, Kalogirou EI, et al. Association of Age at Menopause and Duration of Reproductive Period With Depression After Menopause: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2016 Jan 6:1-12.
Maki PM, Kornstein SG, Joffe H, et al. Guidelines for the evaluation and treatment of perimenopausal depression: summary and recommendations. Menopause. 2018;25(10):1069-1085. doi:10.1097/GME.0000000000001174
Mantani A, Yamashita H, Fujikawa T, Yamawaki S. Higher incidence of hysterectomy and oophorectomy in women suffering from clinical depression: retrospective chart review. Psychiatry Clin Neurosci. 2010;64(1):95-98. doi:10.1111/j.1440-1819.2009.02044.x
Rocca WA, Grossardt BR, Geda YE, et al. Long-term risk of depressive and anxiety symptoms after early bilateral oophorectomy. Menopause. 2018;25(11):1275-1285. doi:10.1097/GME.0000000000001229
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;26(7):712-718. doi:10.1089/jwh.2016.6142
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