Can low estrogen levels in menopausal women cause anxiety?

Low Estrogen in Menopausal Women and Anxiety

Yes, low estrogen levels in menopausal women can cause anxiety symptoms, as there is a significant correlation between declining estrogen and psychological symptoms including anxiety during menopause. 1

Relationship Between Estrogen and Anxiety

Evidence for the Connection

• A 2022 study found that psychological symptoms (including anxiety and mood changes) showed the strongest correlation with low serum estradiol levels compared to other menopausal symptoms 1
• Research has demonstrated an inverse correlation between serum estradiol values and menopausal symptoms, with psychological symptoms showing the highest correlation 1
• The Study of Women's Health Across the Nation found that women with low anxiety at baseline were more likely to report high anxiety symptoms during perimenopause and postmenopause compared to premenopause (odds ratio 1.56-1.61) 2

Biological Mechanisms

• A review of 30 years of literature indicates that mood disturbances are associated with:
  • Sudden withdrawal of estrogen
  • Estrogen fluctuations
  • Sustained estrogen deficiencies 3
• Estrogen receptors play a key role in anxiety regulation, with specific genetic variants in estrogen receptors (ESR1 and ESR2) being associated with anxiety disorders in postmenopausal women 4

Clinical Implications

Assessment of Menopausal Anxiety

When evaluating anxiety in menopausal women, consider:

• Timing of symptom onset in relation to menopause transition
• Severity of symptoms using validated tools like the Menopause Rating Scale (MRS)
• Presence of other menopausal symptoms (hot flashes, night sweats, vaginal dryness)
• Previous history of anxiety or mood disorders
• Potential contributing factors (life stressors, health concerns)

Treatment Considerations

For menopausal women experiencing anxiety related to low estrogen:

1. Hormone Replacement Therapy (HRT):

   • HRT with 17β-estradiol or tibolone has been shown to improve symptoms of anxiety in menopausal women 5
   • However, another study found that estrogen replacement therapy was not associated with improvements in anxiety symptoms in non-depressive hysterectomized postmenopausal women 6
   • HRT should be prescribed at the lowest effective dose for the shortest duration consistent with treatment goals 3

2. Important Cautions with HRT:

   • HRT is associated with increased risks of venous thromboembolism, stroke, and possible increased risk of breast cancer with long-term use 7
   • The USPSTF recommends against the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal women 3
   • HRT should not be used routinely for the specific purpose of preventing chronic disease 3

3. Non-Hormonal Alternatives:

   • Low-dose paroxetine, venlafaxine, and gabapentin are effective non-hormonal alternatives for vasomotor symptoms that may also help with mood 7
   • Clinical hypnosis has shown some benefit for hot flashes 7
   • Soy products may provide modest improvement in hot flashes 7

Special Considerations

Vulnerability Factors

• Women with low anxiety at premenopause may be more susceptible to developing high anxiety during and after the menopausal transition 2
• Genetic variants in estrogen receptors (ESR1 and ESR2) may influence vulnerability to anxiety disorders in postmenopausal women 4
• There is evidence of a significant gene-environment interaction, where women currently using HRT had a reduced risk of phobia with certain ESR1 gene variants 4

Timing of Intervention

• The timing of HRT initiation relative to menopause onset may affect associated benefits and harms, though randomized trials have not prospectively evaluated this 3
• Post hoc analyses suggest increased probability of harm with increasing age at initiation and longer duration of HRT use 3

In conclusion, the evidence supports that low estrogen levels during menopause contribute to anxiety symptoms in many women. Treatment decisions should weigh the potential benefits of symptom relief against the established risks of hormone therapy, with consideration of individual risk factors and preferences.