Can Hormone Replacement Therapy (HRT) improve mood in menopausal women?

Hormone Replacement Therapy for Mood Improvement in Menopausal Women

Oral conjugated equine estrogens (o-CEE) can significantly improve depression and anxiety symptoms in recently postmenopausal women, while transdermal estradiol does not show the same mood benefits. 1

Effectiveness of HRT for Mood Symptoms

Hormone replacement therapy (HRT) shows varying effectiveness for mood symptoms depending on the timing and formulation:

• The Kronos Early Estrogen Prevention Study (KEEPS) demonstrated that oral conjugated equine estrogens (0.45 mg/day) plus micronized progesterone (200 mg/day for 12 days monthly) improved depression and anxiety symptoms over 48 months of treatment compared to placebo 1
• The effect size for depression symptom improvement was medium (ES=0.49) and for anxiety was small to medium (ES=0.26) 1
• Transdermal estradiol (50 μg/day) plus micronized progesterone did not show significant mood benefits compared to placebo 1
• Estrogen therapy appears most effective for mood symptoms when initiated during perimenopause rather than after menopause is complete 2

Treatment Recommendations

For menopausal women with mood symptoms:

1. First-line approach for mild mood symptoms with vasomotor symptoms:

   • Consider oral conjugated equine estrogens (0.625 mg/day) with appropriate progestogen if the woman has a uterus 3
   • Use the lowest effective dose for the shortest time needed 3

2. For more severe mood symptoms:

   • Consider antidepressant medication either as first-line or in addition to HRT 4
   • SSRIs/SNRIs are effective non-hormonal alternatives for managing mood symptoms 5

Important Considerations and Risks

When considering HRT for mood symptoms:

• HRT should not be used solely for the primary prevention of chronic conditions 6
• Combined estrogen/progestogen therapy increases breast cancer risk when used for more than 3-5 years 5
• The progestogenic component in combined HRT may counteract the beneficial effects of estrogen on mood 2
• Benefits for mood are most pronounced in perimenopausal women rather than those who are postmenopausal 2

Monitoring and Follow-up

For women on HRT for mood symptoms:

• Regular monitoring should include:
  • Blood pressure, lipid profile, and weight 3
  • Assessment of mood symptoms and response to therapy
  • Breast cancer screening as recommended 3

Non-Hormonal Alternatives

If HRT is contraindicated or declined:

• Low-dose paroxetine, venlafaxine, and gabapentin are effective non-hormonal alternatives for vasomotor symptoms that may also help with mood 5
• Clinical hypnosis has shown some benefit for hot flashes 5
• Soy products may provide modest improvement in hot flashes and vaginal dryness 5

Pitfalls to Avoid

• Avoid prescribing HRT solely for mood symptoms in women more than 10 years post-menopause, as benefits are less clear and risks increase 3, 2
• Don't assume all mood symptoms in menopausal women require HRT; approximately 15-30% of perimenopausal women experience clinically significant depression that may require specific antidepressant treatment 2
• Be cautious about the progestogen component in combined HRT, as it may negatively impact mood 2

HRT remains a reasonable option for improving mood symptoms in menopausal women, particularly when initiated during perimenopause, but should be prescribed at the lowest effective dose for the shortest duration needed while carefully weighing individual benefits and risks.