A systematic review found estrogen-based hormone therapy did not consistently reduce anxiety or depression in midlife women.
Anxiety and depression are among the most common psychological symptoms reported during the menopause transition. Both conditions are influenced by hormonal fluctuations, but the degree to which estrogen-based hormone therapy alleviates these symptoms remains unclear. Findings from two systematic reviews, presented at The Menopause Society’s 2025 Annual Meeting in Orlando, Florida, highlight inconsistent effects of estrogen-based therapy on anxiety and depression among perimenopausal and early postmenopausal women.1,2
Researchers from McMaster University and the University of Toronto conducted two separate systematic reviews and meta-analyses to examine the influence of estrogen-based hormone therapy on mental health symptoms during midlife. One review focused on anxiety, while the second investigated depression.
For the anxiety analysis, seven studies were identified, including randomized controlled trials, cohort studies, and case-control studies evaluating estrogen-based therapy via oral or transdermal routes. Collectively, these studies enrolled more than 1,200 perimenopausal or postmenopausal women, with additional observational studies encompassing roughly 175,000 midlife participants.
For the depression analysis, 23 studies published between 2001 and 2024 were reviewed, spanning a range of designs and sample sizes—from small clinical trials of 30 to 50 participants to population-based studies involving more than 800,000 women. Most intervention studies followed participants for 8 to 24 weeks, though some extended up to 4 years.
In both reviews, researchers found that estrogen-based therapy produced variable outcomes depending on factors such as menopause stage, route of administration, and baseline symptom severity.
In the anxiety review, estrogen therapy did not consistently reduce anxiety symptoms in midlife women. Modest benefits were observed among perimenopausal or early postmenopausal participants, especially those within a few years of their final menstrual period and with prominent anxiety symptoms at baseline. Oral estrogen appeared to show the most favorable, though limited, effects.
The depression review revealed similarly mixed findings. Fourteen studies reported improvements in depressive symptoms—particularly among perimenopausal women or those with a history of depression—while six studies showed no benefit or negative associations. Three large observational analyses even suggested a possible increased risk of depression with systemic therapy in some populations.
The presence of vasomotor symptoms influenced outcomes in several studies, though some evidence indicated mood benefits independent of vasomotor symptom reduction. Results also varied by formulation, with both transdermal and oral regimens demonstrating benefits in certain groups.
Carys Stefanie Sosea, lead author of the anxiety review from McMaster University, explained the rationale for synthesizing existing evidence: “Women are often asking if menopause hormone therapy will improve their anxiety symptoms, and we wanted to synthesize the information to counsel patients with evidence-based information.”
Stephanie Faubion, MD, MBA, medical director for The Menopause Society, emphasized the importance of individualized care. “Anxiety symptoms are common in the menopause transition. Identifying the potential impact of estrogen-based therapy on these symptoms and whether there are differences in terms of formulation, route of administration, and dose is important so that clinicians can better individualize treatment,” she said.
The depression review reached a similar conclusion, noting that treatment response may depend on individual characteristics such as menopausal stage, prior mood disorder history, and specific symptom profile. Estrogen withdrawal was also found to trigger recurrence of depressive symptoms in some women, underscoring the biological sensitivity of mood to hormonal fluctuations.
According to investigators, the available evidence does not support a uniform recommendation for the use of estrogen-based hormone therapy to treat anxiety or depression in menopausal women. The findings suggest a need for targeted research to clarify which patients may benefit most and under what treatment conditions.
As the authors concluded, “Estrogen therapy for menopausal depression should be approached with careful consideration of individual patient factors … rather than as a one-size-fits-all treatment.”
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