Estrogen and mood

Antidepressants are still first-line treatments for major depressive
disorder across the female life cycle, but when they fail, novel
approaches that integrate the use of estrogen are now being
investigated, including the use of estrogen by itself or in combination
with antidepressants.
--Dr. Stephen Stahl, UC San Diego

Investigators such as Dr. Stahl have an increasing appreciation of the many actions of estrogen on the brain. The same types of cellular receptors for estrogen that abound in reproductive tissues are also found throughout the brain, notably in many areas involved in mood and memory functions. Does your mind mind a lack of estrogen?

Dr. Stahl notes that phases of a woman's life associated with large hormonal fluctuations --think postpartum and perimenopausal-- are times in which a woman is at highest risk for the onset of major depression. Women with a history of a depressive episode following any estrogen shift are even more vulnerable to a recurrence following other 'reproductive events' later in life. In other words, if you think premenstrual was difficult, look out for perimenopause.

Stahl calls this phenomenon 'kindling,' and theorizes that each mood crash associated with estrogen withdrawal may actually damage the brain. He dubs this process excitotoxicity in which the neurons are literally excited to death, and these episodes increase the future risk of treatment-resistant depression under similar hormonal circumstances.

A study supporting the use of estrogen in the treatment of depression was conducted at Massachusetts General Hospital. Fifty perimenopausal women --defined here as the transitional state from cycling hormones to no hormones at all marked by irregular periods and elevated FSH levels-- were diagnosed with varying degrees of depression. Half were randomized by investigators to receive estradiol (known to some as 'bio-identical' estrogen) via a skin patch such as Vivelle Dot or Estraderm. The control subjects got sticky, hormone-free blanks.

Two-thirds of the estradiol treatment group were depression free after three months of patchwork compared to only one-fifth of those without hormones.