Hormone Therapy and Mood Regulation

Introduction to Progesterone Therapy

Progesterone has been thought to have anxiolytic and anesthetic properties that could potentially help with mood regulation, modulating serotonergic receptors, which theoretically could provide mood benefits, however, the clinical evidence for these proposed benefits is inconsistent and often contradictory 1
Progesterone undergoes a 10-fold increase during pregnancy and rapidly returns to baseline within 1-2 weeks postpartum, and sudden withdrawal of progesterone has been hypothesized to contribute to postpartum mood disorders 1
Progesterone can affect serotonergic receptor function, which is involved in mood regulation 1

The American College of Obstetricians and Gynecologists recommends using cyclical rather than continuous progesterone when possible (200mg for 12-14 days every 28 days) to minimize negative mood effects 2
Natural micronized progesterone may have fewer side effects than synthetic progestins like medroxyprogesterone acetate (MPA), and shows a better safety profile for cardiovascular risk and blood pressure 3

The Endocrine Society suggests assessing mood symptoms after 4-6 weeks of hormone therapy adjustments, and being alert for symptoms of depression that may emerge during progesterone administration 2
If mood symptoms are a primary concern, consider estrogen therapy alone for women who have had a hysterectomy, and focus on optimizing estrogen therapy, as low estrogen levels are associated with increased risk of depression 2

The American College of Physicians recommends considering transdermal estrogen administration as first-line approach for mood symptoms, and the Endocrine Society does not recommend progestins for transgender women due to risk factors 2, 6
There is no clear evidence of mood benefits of progesterone in transgender women, with some patients discontinuing use due to poor mood effects 6