Hormone Therapy for Menopause May Also Help Depressive Symptoms

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A new study found menopausal hormone therapy was associated with a significant reduction in depressive symptoms over time with a greater reduction combined with antidepressants.

Hormone therapy not only treats physiologic menopause symptoms such as hot flashes but also depressive symptoms, a new study found.1

“Our findings provide further evidence that [menopausal hormone therapy] can improve not only the vasomotor symptoms of menopause but also the depressive symptoms experienced among women and that a synergistic approach using both [menopausal hormone therapy] and antidepressant medications may be of benefit for some women with bothersome symptoms affecting quality of life,” investigators wrote, led by Rahavi Gnanasegar, BHSc, from the Research Institute of St. Joseph’s Healthcare Hamilton in Canada.

Not only does hormone’s influence on neurotransmitter receptor pathways regulate mood during menopause but hot flashes and genitourinary issues could contribute to bad moods—all of which could play a role in depressive symptoms. Women with menopause tend to have a high rate of depression, and depressive symptoms are most likely to occur during and immediately following the menopause transition.

Since the effect of menopausal hormone therapy on mood-related symptoms is unestablished, investigators conducted a study to assess changes in depressive symptoms after the therapy. Specifically, they examined changes on the Center for Epidemiological Studies Depression scale based on the kind of treatment used and menopausal hormone therapy dose. The team also controlled for relevant demographic variables, including smoking, education level, and age.

The sample included 170 women, aged 21 – 72 years, receiving care at St. Joseph’s Healthcare Menopause Clinic in Hamilton, Ontario who completed a self-report questionnaire with questions regarding their medical history and validated tools for depressive symptoms. Participants completed a shortened questionnaire version at the follow-up visit 3 – 12 months later.

More than half (62%) of the women at the specialized menopause clinic had a high rate of depressive symptoms. When investigators assessed whether the stage of menopause contributed to the increased depression risk, they did not find an association but did observe a direct correlation for lower education level (high school or less) (odds ratio [OR], 4.8; 95% CI, confidence interval [CI], 1.4 – 16.2) and younger age (OR = 0.96; CI, 0.92 – 0.99).

The team discovered menopausal hormone therapy was associated with a significant reduction in CESD-10 scores over time (paired t-test, t = 6.4; P < .01). They observed meaningful improvements in depressive symptoms alone (mean change, 2.3 points) and along with antidepressant medication (mean change, 3.9 points) (P < .001).

Investigators found a significant positive interaction between menopausal hormone therapy and antidepressant use (F [1,161] = 5.20; P = .024). Additionally, ANOVA analyses showed, after controlling for age, menopausal hormone therapy was a significant factor in the change over time of the CESD-10 scores.

“Of note, our clinic sees a high proportion of women referred from the gynecology oncology and endometriosis teams, with a high rate of iatrogenic menopause,” investigators wrote. “In fact, 39% of the population underwent iatrogenic menopause, and these patients showed much less improvement in mood at the follow-up visit when using MHT alone. We saw greater improvement when paired with an antidepressant therapy.”

Although menopausal hormone therapy showed significant improvements in depressive symptoms, even after the treatment, women who were younger, smoked, and had a lower education level were linked with greater depression scores. However, more research is needed as a limitation the investigators pointed out was the lack of diversity since participants only came from a single menopause clinic.

“This study showed a beneficial effect of hormone therapy on mood symptoms during menopause when used alone and a synergistic effect when used in combination with antidepressants,” said Stephanie Faubion, MD, MBA, medical director for The Menopause Society, in a press release.2 “It also highlights the high prevalence of mood symptoms during this transition and the need to address women’s symptoms holistically rather than having a singular focus on hot flash management.”


  1. Gnanasegar, R, Wolfman, W, Galan, L. Does Menopause Hormone Therapy Improve Symptoms of Depression? Findings From a Specialized Menopause Clinic. Menopause: The Journal of The Menopause Society. Vol. 31, No. 4, pp. 00-00 DOI: 10.1097/GME.0000000000002325
  2. Feeling Depressed as A Result Of Menopause? Hormone Therapy May Help. EurekAlert! February 22, 2024. Accessed February 29, 2024.