Estrogen-Based MHT Does Not Consistently Reduce Anxiety Symptoms in Midlife Women

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Estrogen-based menopausal hormone therapy (MHT) does not consistently reduce anxiety symptoms among midlife women, wrote study authors of research presented at The Menopause Society 2025 Annual Meeting. The authors emphasized that more targeted research is needed to understand which characteristics (eg, menopausal stage, symptom severity, treatment timing) may better predict which women are more likely to benefit from estrogen-based MHT for anxiety symptoms.¹

According to Cleveland Clinic, hormonal changes that occur during menopause can significantly impact mental health. Feelings of anxiety or depression can occur during menopause because of the fluctuation of estrogen and progesterone within the body. Additionally, these fluctuations can also cause daytime hot flashes, night sweats, and lack of sleep, which can further exacerbate anxiety and depressive symptoms.²

For some women, hormone therapy may relieve certain menopause symptoms, including anxiety and depression, by boosting the hormone levels in patients. Boosting these levels can help women better manage emotional symptoms; however, hormone therapy alone is not effective in treating severe mental health conditions.²

“Women are often asking if MHT will improve their anxiety symptoms, and we wanted to synthesize the information to counsel patients with evidence-based information,” lead author Carys Stefanie Sosea of McMaster University in Hamilton, Canada, said in a news release.³

For these reasons, the investigators aimed to assess the impacts of MHT on anxiety symptoms among perimenopausal and early postmenopausal women. They also evaluated whether treatment-related factors such as dosage, route of administration, and baseline symptom severity may influence therapeutic outcomes.

This systematic review was developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The review included research from relevant databases, including Ovid MEDLINE, PubMed, Ovid EMBASE, and Web of Science. The search strategy included a combination of controlled vocabularies and keywords that are related to hormone replacement therapies, menopause, and anxiety. Studies eligible for inclusion in the systematic review included randomized controlled trials (RCTs), cohort studies, and case-control studies that evaluated estrogen-based MHT administered to perimenopausal or early postmenopausal women either orally or transdermally. The authors reported that risk of bias was assessed independently using the Joanna Briggs Institute checklist, and that studies were rated as moderate to high quality.¹

A total of 7 studies were included in the review, of which 4 were RCTs and 3 population-based observational studies. Across the RCTs, over 12,000 peri- or early postmenopausal women were included, whereas the observational studies included about 175,000 women throughout their midlife years. Intervention arms tested conventional oral conjugated equine estrogens at 0.45 mg per day, oral 17β-estradiol ranging from 0.5 to 2 mg per day, or transdermal estradiol patches delivering 50 µg to 100 µg per day, with treatment duration varying from 6 weeks in the shortest study to 4 years in the longest. Anxiety outcomes were measured using validated self-report instruments, with the most common being the Profile of Mood States tension subscale, the Women’s Health Questionnaire anxiety/fear domain, and the General Anxiety Disorder-7. Others were identified through diagnostic coding in administrative datasets.¹

Across the studies, 2 trials demonstrated improvement in symptoms of anxiety. The 4-year KEEPs-Cog study detected a modest and statistically significant reduction in tension-anxiety scores among women receiving oral conjugated estrogens, which was not observed in those receiving an equivalent transdermal dose. In a 6-month Finnish trial, both oral and transdermal estradiol therapies were shown to reduce anxiety and fear scores; however, this was only observed in participants who also experienced moderate to severe vasomotor symptoms. In addition, 4 studies found no meaningful change in anxiety using MHT following appropriate adjustment for confounding variables. One study, which was a cross-sectional survey, suggested that current MHT users reported a higher prevalence of clinical anxiety, although its design precluded causal inference.¹

The investigators concluded that, collectively, estrogen-based MHT does not appear to consistently reduce anxiety symptoms among midlife women. They emphasized that modest benefits may be seen in perimenopausal or early postmenopausal women, particularly among those who are symptomatic and within a few years of their final menstrual period. The route, dose, and baseline severity of symptoms also appeared to impact treatment response, with oral estrogen demonstrating the most promise. Despite these data, the authors urged that more targeted research is needed to clarify which characteristics may better predict who are most likely to benefit from estrogen-based MHT to address anxiety.¹

“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,” Stephanie Faubion, MD, MBA, FACP, medical director for The Menopause Society, said in the news release.³

REFERENCES

1. Sosea CS, Mejia-Gomez JC, Wolfman W, Leslie B, Shea AK. P-162 – The Effects of Estrogen-Based Menopause Hormone Therapy on Anxiety Symptoms in Perimenopausal and Early Postmenopausal Women: A Systematic Review. Presented at: The Menopause Society Annual Meeting; Orlando, Florida. October 21–25, 2025.

2. Cleveland Clinic. Can Menopause Cause Anxiety?. Accessed October 23, 2025. https://health.clevelandclinic.org/is-menopause-causing-your-mood-swings-depression-or-anxiety

3. The Menopause Society. Feeling Anxious During Menopause? Hormone Therapy May or May Not Help. News release. October 20, 2025. Accessed October 23, 2025. https://menopause.org/press-releases/feeling-anxious-during-menopause-hormone-therapy-may-or-may-not-help