Is hormone replacement therapy (HRT) recommended for patients experiencing mood symptoms during perimenopause, despite having normal hormone levels?

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From the Guidelines

Hormone replacement therapy (HRT) is not recommended for patients experiencing mood symptoms during perimenopause with normal hormone levels, due to the potential risks outweighing the benefits, as indicated by the US Preventive Services Task Force recommendations 1. When considering treatment for perimenopausal women with mood symptoms, it is essential to weigh the potential benefits against the risks. The most recent and highest quality study, published in 2017, suggests that menopausal hormone therapy (MHT) can be used in female cancer survivors, but alternatives should be tried first, and patients should be referred to a specialist for dosing and management 1. Some key points to consider when evaluating the use of HRT for mood symptoms in perimenopausal women include:

  • The therapeutic effect of estrogen on mood regulation, as it modulates serotonin, dopamine, and norepinephrine systems in the brain
  • The potential risks associated with HRT, including increased risk of stroke, pulmonary embolism, and invasive breast cancer
  • The importance of individualizing treatment duration and using the lowest dose possible to control symptoms
  • The need to evaluate contraindications, such as history of breast cancer, coronary heart disease, or previous venous thromboembolism, before initiating HRT
  • The consideration of alternative treatments, such as lifestyle modifications, stress management, and selective serotonin reuptake inhibitors (SSRIs) for more severe symptoms. In general, the decision to use HRT for mood symptoms in perimenopausal women should be made on a case-by-case basis, taking into account the individual patient's risks and benefits, and using the most recent and highest quality evidence available 1.

From the Research

Hormone Replacement Therapy for Perimenopausal Mood Symptoms

  • Hormone replacement therapy (HRT) may be effective in alleviating menopause-related depressive symptoms, particularly in perimenopausal women 2.
  • Estrogen therapy has been consistently reported to improve mood in perimenopausal women, although its efficacy for overt depression or during postmenopause is more questionable 2.
  • The progestogenic component in combined hormone therapy may counteract the beneficial influence of estrogens on mood and even induce negative mood symptoms 2.

Considerations for HRT in Perimenopausal Women

  • HRT may be considered for perimenopausal women experiencing mood symptoms, despite having normal hormone levels, as it may contribute to alleviating menopause-related depressive symptoms 2, 3.
  • The administration of HRT should be individualized and followed across time, taking into account the woman's medical history and risk-benefit balance 4.
  • In cases of more severe depressive conditions, a combination of antidepressant and hormone therapy may be effective 2, 5.

Alternative Treatment Options

  • Progestin-only therapy has been shown to improve vasomotor symptoms in some studies, but its effect on mood symptoms is unclear 6.
  • Non-hormonal management options, such as lifestyle modifications and alternative therapies, may also be considered for perimenopausal women experiencing mood symptoms 3.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

The Menopause Transition: Signs, Symptoms, and Management Options.

The Journal of clinical endocrinology and metabolism, 2021

Research

Menopausal hormone therapy in women with medical conditions.

Best practice & research. Clinical endocrinology & metabolism, 2021

Research

Menopause: neuroendocrine changes and hormone replacement therapy.

Journal of the American Medical Women's Association (1972), 2004

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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