Does hormone replacement therapy (HRT) improve mood swings?

Hormone Replacement Therapy for Mood Swings

Hormone replacement therapy (HRT) can be effective in improving mood swings in perimenopausal women, but its benefits for this purpose must be weighed against potential risks including breast cancer, cardiovascular disease, and thromboembolism.

Efficacy of HRT for Mood Symptoms

HRT has demonstrated effectiveness in improving mood symptoms, particularly during the perimenopausal transition:

• Meta-analysis data shows HRT has a significant effect on reducing depressed mood with an overall effect size of 0.68, indicating that women receiving treatment had lower levels of depressed mood than 76% of control patients 1
• Estrogen therapy specifically has been shown to be effective in improving mood in perimenopausal women (effect size = 0.69) 1
• Evidence is more convincing for HRT's positive effect on mood in younger perimenopausal women than in older postmenopausal women 2

Timing Considerations

The timing of HRT initiation appears critical for mood benefits:

• HRT is most effective for mood symptoms when administered during perimenopause or early postmenopause 2
• Women with previous affective disorders that are cyclic or associated with reproductive events may be at increased risk for depression at menopause and may particularly benefit from HRT 3

Treatment Approach for Mood Symptoms

When considering HRT for mood swings:

1. For mild mood symptoms with vasomotor symptoms: Trial of HRT is appropriate before considering psychotropic medications 3
2. For severe mood symptoms or those without vasomotor symptoms: Antidepressants should be considered first or in addition to HRT 3
3. For treatment-resistant cases: A combination of HRT and antidepressants has shown effectiveness in depressed perimenopausal and postmenopausal women 4

Hormone Formulation Considerations

The specific hormone formulation affects mood outcomes:

• Estrogen alone appears most beneficial for mood (effect size = 0.69) 1
• Progesterone alone or combined with estrogen shows smaller mood benefits (effect size = 0.39 and 0.45, respectively) 1
• The progestogenic component in combined HRT may potentially counteract the beneficial effects of estrogen on mood and even induce negative mood symptoms 4
• Androgen alone or combined with estrogen shows larger mood benefits (effect size = 1.37 and 0.90, respectively) 1

Risk Considerations

HRT carries significant risks that must be weighed against potential mood benefits:

• Increased breast cancer incidence with estrogen plus progestin (RH, 1.26 [95% CI, 1.00 to 1.59]) 5
• Increased risk for coronary heart disease (RH, 1.29 [95% CI, 1.02 to 1.63]) 5
• Increased risk for venous thromboembolism 5
• Increased risk for stroke 5
• Increased risk for cholecystitis 5

Clinical Recommendations

For managing mood swings in menopausal women:

1. For women with mild-to-moderate mood symptoms accompanied by vasomotor symptoms, consider HRT using the lowest effective dose for the shortest duration possible
2. Use transdermal routes of administration when possible to minimize coagulation impact 6
3. Consider natural progesterone when combined therapy is needed, as it has fewer antiapoptotic properties on breast cells 6
4. For severe mood symptoms or those without vasomotor symptoms, consider antidepressants as first-line treatment
5. Regular reassessment of the woman's health status is mandatory to evaluate ongoing benefit-risk ratio 6

Important Caveats

• The USPSTF did not evaluate HRT for treating menopausal symptoms such as mood swings in their recommendations against routine use for chronic disease prevention 5
• Benefits of HRT for mood may be most pronounced in women with significant menopausal symptoms rather than in asymptomatic women 5
• Individual risk factors for breast cancer, cardiovascular disease, and thromboembolism should be carefully assessed before initiating HRT for mood symptoms