Periwell
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Category: MoodClinical Profile

Low Mood & Depression

A profound sense of sadness, tearfulness, or emotional flatness that differs from situational blues.

Biological Mechanism

Estrogen increases serotonin synthesis and decreases its degradation. As estrogen plummets, so does serotonin availability. Additionally, the lack of progesterone's neurosteroid metabolites destabilizes GABA, leading to a pervasive, treatment-resistant biological depression.

Common Misdiagnoses

Major Depressive Disorder (MDD), Bipolar Type II (due to mood swings), Situational depression

Evidence-Based Treatments

  • 01Transdermal estradiol

    Demonstrated to improve perimenopausal depression, often faster than antidepressants.

  • 02Antidepressants (SSRIs/SNRIs)

    Applicable if HRT is contraindicated or as an adjunct, but shouldn't be the default first line if symptoms are clearly cycle-related.