Anxiety and depression in midlife transition and beyond: The role of estrogens

Depression and anxiety are amongst the most prevalent and disabling conditions worldwide, imposing significant burden to individuals, families, and their communities. It is now known that both conditions affect females more often than males, and that some can be particularly more vulnerable to symptoms (new, recurrent) during reproductive-related windows of vulnerability, including the menopause transition and early postmenopausal years.

As estrogen exerts neuro-modulatory effects on mood, cognition, and behaviour through monoaminergic systems (e.g., 5-HT, NE), rapid fluctuations of estradiol (E2) levels seem to be associated with heightened risk for/emergency of anxiety and depression during midlife years, along with other menopause-associated complaints such as vasomotor symptoms and sleep disturbances.

Psychopharmacologic and behavioural interventions remain the first-line treatment for depression and anxiety across the life span; however, estrogen-based therapies, particularly transdermal estradiol, should be considered as part of the treatment armamentarium for symptomatic, midlife women.