Depression can occur in a subset of susceptible women

as a result of natural fluctuations in estrogen levels

associated with the developmental stages of a woman’s life.

Let’s break this sentence down into sections:

Depression can occur in a subset of susceptible women . . .

One of the things that we have tried to emphasize is that depression does not occur in all women. As we learned earlier, women are about twice as likely as men to experience depression at some point in their lives, but this does not mean that all women will experience the full symptoms of a major depressive disorder. However, there is a group of women who will develop depression, and this is likely due to a certain susceptibility, vulnerability, or predisposition. The factors that create this vulnerability are varied, including genetic and environmental factors. Women who have mothers or other relatives with depression are at a significantly higher risk for developing depression themselves. Similarly, women who have high levels of emotional stress, whether it be attachment difficulties with a child, the recent loss of a loved one, or difficult work environments, are also more likely to develop depression.

. . . as a result of natural fluctuations in estrogen levels . . .

For many women, however, this vulnerability or increased susceptibility to depression is created and/or enhanced by their response to a natural change in estrogen levels. These changes are ordinary and inherent to the menstrual cycle. In fact, there would be no menstrual cycle without these changes, so it is important to note that these changes are natural and expected for every woman.

This is important because many women feel alienated and estranged from their bodies during depression. They may be ashamed by what they perceive to be their imperfections, wishing they could change their weight or some facial feature, or they may feel somewhat victimized by their bodies, which seem to be merely carrying them along for the ride. But it is essential to recognize that estrogen fluctuations in themselves are not the culprit for depression. If this was true, then every woman, and perhaps every man for that matter, would develop depression because both women and men experience natural changes in estrogen levels throughout their life spans.

So if these estrogen changes themselves are not the culprit for depression, what is? Most likely it is a woman’s response or sensitivity to these changes. There does not appear to be any quantitative difference in the actual levels of estrogen in a woman’s body and brain between those who develop and do not develop depression. But some women have an unusual response to these natural changes such that it lowers their threshold for developing depression. These changes have a psychologically destabilizing action that renders the female brain more vulnerable to developing sadness, loss of pleasure, and reductions in the quality of appetite and sleep. In a sense, then, the depression that many women experience may be a distinct response to a natural hormonal change.

. . . associated with the developmental stages of a woman’s life.

And these hormonal changes appear to be related to reproductive transitions. It is at the significant stages of a woman’s reproductive life cycle that these hormonal changes occur, initiating a sequence of events that can result in depression for a subset of women. Although estrogen can fluctuate at various times, it is during puberty and premenstrual, postpartum, and menopausal phases that the most significant fluctuations occur. During the middle of puberty, adolescent girls are exposed to monthly surges of estrogen, disrupting normal hormonal balance and kindling larger changes in mood. This leaves adolescent girls particularly susceptible to feeling gloomy and self-critical, withdrawing from pleasurable activities, and experiencing observable changes in appetite, loss of energy, and disrupted sleep. For women with PMS, the drop in estrogen and rise in progesterone in the final (luteal) phase of the menstrual cycle can be associated with depression, irritability, anxiety, confusion, social withdrawal, and angry outbursts. When women give birth and the placenta is removed at delivery, the estrogen levels that have built up during pregnancy drop dramatically, typically lower than would be expected if the reproductive organs failed. It is this rise and fall of estrogen, this dramatic change in the hormonal environment, that can account for the mild and temporary sadness of the “baby blues,” the full symptoms of postpartum depression, and the more severe and serious symptoms of psychosis, mania, and disorganized behavior in postpartum psychosis. Furthermore, the fluctuation and decline in ovarian hormone production during perimenopause, as well as the cessation of menstruation in menopause and the absence of estrogen production in postmenopause, can trigger additional symptoms or episodes of depression. Hence, many episodes of depression in women seem to pivot around key moments of hormonal change.

The female brain appears to be biologically constructed toward greater sensitivity to these fluctuations in estrogen. Even prior to birth, there are organizational operations that modify the brain structure and neural circuitry in a way that differentiates the female body, brain, and neurodevelopment from those of the male. This includes the unique placement of a high density of receptors for estrogen in the brain structures that are responsible for emotional processing and mood, such as the limbic system. Estrogen exerts a second and activational operation on the female brain following birth, altering the availability of several biochemical messengers involved in the regulation of mood, including dopamine, norepinephrine, acetylcholine, glutamate, GABA, and serotonin. By controlling the creation, release, and breakdown of these neurotransmitters, estrogen acts in a way that is similar to antidepressants. In a sense, women’s brains are more vulnerable to developing depression in part because their brains are more sensitive than men’s brains to changes in estrogen levels.

The Estrogen-Depression Connection: The Hidden Link Between Hormones & Women’s Depression by Karen J. Miller, Ph.D. and Steven A. Rogers, Ph.D.