Over their lifetimes, women are twice as likely to suffer clinical depression than men. Low or imbalanced hormone levels can prompt depression in either sex, and insufficient estrogen in women has long been suspected. Now a comprehensive review of 30 years of research indicates that the trouble may not be low estrogen levels per se but sharp variations in those levels.

Estrogen balances often change significantly during puberty and menopause, as well as during a woman’s monthly reproductive cycle. In each circumstance, when the level shifts, a woman may experience a greater chance of depression, says Stephanie L. Douma, a researcher with Natural Resources Canada in Ottawa, who conducted the work independently. Details will be published in the February 2006 issue of Advances in Nursing Science.

Douma says women who are experiencing mood problems and the doctors who may treat them may not be thinking about the fluctuation scenarios and therefore may not be stabilizing estrogen at optimum levels.

The study also has implications for hormone replacement therapy, which many women undergo during or after menopause. For example, women may take hormone pills only every third day to counter a higher potential risk for breast cancer that might be linked to too much medication. But that protocol means the hormone level never stabilizes, Douma says.

Douma hopes that the findings will prompt more investigations into best practices for regulating estrogen and that doctors will more routinely monitor their patients’ levels. These measures, she says, will help keep estrogen-associated depression at bay.