Depression’s Disproportionate Impact on Women

Depression is a common disorder, and the lifetime prevalence of depression is twice as great in women than men. As one of the greatest causes of disability for women worldwide, the symptoms of depression can include prolonged feelings of sadness, hopelessness, and loss of interest in activities that were once engaging and enjoyable.

In March, Hadine Joffe, MD, MSc, delivered a Grand Rounds presentation hosted by Yale’s Department of Psychiatry’s Division of Women’s Behavioral Health directed by Carolyn M. Mazure, PhD.

Joffe is the Executive Director of Mary Horrigan Connors Center for Women's Health Research at Brigham and Women's Hospital and Paula Johnson Professor of Psychiatry in the Field of Women’s Health at Harvard Medical School.

In her presentation titled “Interrogating Female-Specific Contributions and Translating Therapeutic Strategies,” she discussed the progression of depressive disorders in women across the lifespan, characterized female-specific contributors to depression risk in midlife, and identified clinical strategies for treating depressive and sleep disorders during menopause.

“My patients are the reason I’m drawn to this research,” said Joffe. “For too long, we haven’t been able to give them answers to their questions: ‘Why did this depression happen after giving birth?’ ‘Why do I feel more depressed after my hysterectomy?’ Women are more than half our population, and they deserve the precision of information to guide better care.”

Depressive Disorders in Women Over the Lifespan

Joffe has made significant contributions to an increased understanding of women’s health, particularly related to mental health, the impact of hormones on health outcomes, and reproductive health. An accomplished academic leader, clinician, and clinical reproductive neuroscientist, Joffe’s major research focus is on brain health in midlife women across the menopause transition, while also having studied premenstrual dysphoric disorder and depression related to pregnancy and perimenopause.

Among the brain-based biological differences that may account for higher rates of depression in women than men are the structural and functional variances in brain regions. Changes in hormone levels during puberty, menstruation, pregnancy, postpartum, and menopause also can contribute to an increase in depression risk. Moreover, a higher rate of stress and societal pressures can contribute to increased emotional burden, resulting in depressive episodes over a woman’s life.

In her presentation, Joffe also underscored that depression recurrence is the norm for women, meaning that not only are women more likely to experience depression than men, but are also more likely to experience repeated episodes of depression.

Understanding Depression Risk in Midlife Women

Menopause marks the end of reproductive potential for women and typically occurs around the age of 52. It is defined as having begun 12 consecutive months after a woman no longer menstruates. An important and understudied precursor to menopause is perimenopause, which occurs as women begin to experience irregular, unpredictable, and infrequent menstrual cycles. The average age for women to begin perimenopause is 48, lasting an average four years, yet women can begin perimenopause as early as their late 30s.

With the significant hormone shifts and changes during both perimenopause and menopause, the risk of depression must be considered. During perimenopause, estrogen and progesterone levels can fluctuate unpredictably, and both hormones play important roles in regulating mood-related brain chemicals such as serotonin and dopamine.

In a 2024 discovery, Joffe and her team explored the long-held belief that menopause causes depression. This was largely due to reports in widely cited papers as a “double to quadrupled risk of depression or depressive disorders over the menopause transition.” By studying groups of women over time, Joffe and her team revealed “the increased risk of major depressive disorders over the menopause transition appears predominately in individuals with previous major depressive disorder.”

Although women may have increased risk of mood changes during the menopause transition, “We wanted to make sure that menopause itself isn’t associated – in a universal way – with this adverse problem, because it isn’t,” Joffe said during an interview with The Washington Post.

This paradigm shift improves patient care and a woman’s experience because clinicians now know they must consider the relevance of prior depressive episodes when evaluating a patient’s risk profile during menopause.

Treating Depression and Sleep Disorders During Menopause

Treatment evaluation includes determining where a woman is in the menopausal transition, presence of hot flashes, sleep disturbances, and other mental health history.

Since the publication in 2019 of “Guidelines for the Evaluation and Treatment of Perimenopausal Depression: Summary and Recommendations,” authored by Joffe, she and her team have initiated new research studies to better understand the relationship between sleep, menopause, and mood. They are also exploring how menopause affects metabolic and brain health.

Approximately 80% of women in America will experience VMS – vasomotor symptoms – colloquially referred to as hot flashes and night sweats as they transition through menopause. VMS describes the sudden feeling of “heat,” often accompanied by a flushed appearance and sweating caused by fluctuating hormones. Severity and prevalence can be influenced by a variety of factors including age, ethnicity, and lifestyle.

When VMS occurs at night, it significantly disrupts sleep. Night sweats contribute to increased WASO (Wake After Sleep Onset), and the more time spent awake during the night, the greater the decline in sleep quality. Joffe and her colleagues have shown women who perceived frequent nighttime hot flashes were more likely to experience mild symptoms of depression than those who reported fewer or no nighttime hot flashes.

“The results of our research suggest menopausal women who report experiencing nighttime hot flashes and sleep disruption should be screened for mood disturbances. Any treatment of mood symptoms in this population also should incorporate efforts to address sleep and nighttime hot flashes,” said Joffe.

Different treatment strategies exist to aid women suffering from both VMS and depression or depressive symptoms. For women suffering major depression, the depression must be addressed first. Antidepressant treatment is often paired with interventional approaches, such as behavioral therapies. For women experiencing depressive symptoms, such as loss of interest in a once pleasurable activity or difficulty concentrating, an antidepressant paired with hormone therapy to address VMS plus a behavioral therapy could prove beneficial, according to Joffe.

To improve sleep, which in turn improves mood, “sleep hygiene” is key. This includes an appropriate bedroom environment and avoiding screens, caffeine, digital stimulants, looking at the clock, and staying in bed when tossing and turning for an extended time. There also are powerful behavioral tools that can be learned through cognitive behavioral therapy for insomnia (CBT-i). These are designed to aid in sleep hygiene and include stimulus control, sleep restriction, relaxation, restructuring undesired thinking patterns, and reflecting.

“Dr. Joffe is a leader in our shared field – women’s health research – and it was a true pleasure to host her here at Yale,” said Mazure, Director of Women’s Health Research at Yale, Norma Weinberg Spungen and Joan Lebson Bildner Professor of Women’s Health Research, and professor of psychiatry and psychology. “Most notably to me, beyond her many achievements and contributions, is the quality of her work, as well as the strength of her commitment in informing our view on women’s health and translating science into clinical benefit.”