The menstrual cycle and stress response
With the onset of puberty women begin experiencing a monthly menstrual cycle. This is the monthly fluctuations in female sex hormones that commences with the onset of menses (the “period”) and continues until the onset of the next menses. The normal monthly menstrual cycle is characterized by specific patterns of estrogen and progesterone levels. These fluctuations are triggered by changes in two other hormones, luteinizing hormone and follicle stimulating hormone. Before understanding how stress changes across the menstrual cycle it is helpful to know a little more about the menstrual cycle, and why one might expect the stress response to differ throughout the cycle.
Day 1 of the menstrual cycle is the first day of menses. At this time of the cycle, estrogen and progesterone are at the lowest levels of the month. The low estrogen levels during this time tell the brain to release follicle stimulating hormone. Follicle stimulating hormone exerts its action on the ovaries. The ovaries contain eggs, each comfortably housed within a follicle. Once a follicle is mature, it will release the egg and ovulation will occur. As indicated by its name, follicle stimulating hormone, stimulates the follicle, or helps it mature.
The follicle is what produces and releases estrogen. Thus, while the low estrogen levels at the start of menses signal for release of follicle stimulating hormone, this release eventually leads to more and more estrogen production and release by the maturing follicles. As estrogen levels increase, follicle stimulating hormone release is inhibited, until estrogen levels meet a critical threshold, which is the highest level of estrogen all month. Reaching this critical threshold, causes the brain to release luteinizing hormone.
Luteinizing hormone is the hormone that will trigger ovulation. When it is released the most mature follicle will release its egg and ovulation takes place. After ovulation, estrogen levels plummet before slowly beginning to rise again. Estrogen will remain at moderate level the rest of the cycle until the next menses.
After ovulation is also when we finally see increases in progesterone. After the follicle releases the egg, the follicle remains behind and transforms into the corpus luteum. The corpus luteum releases both estrogen and progesterone, which is why progesterone levels only increase after ovulation. As the corpus luteum continues to transform further, progesterone and estrogen levels decrease, eventually hitting another critical threshold, and initiating the next menses. Please check out my favorite (and the funniest) depiction of the menstrual cycle by MedComic.
If you took the time to check out my page on Stress and Sex Hormones you might see why the stress response would change across the menstrual cycle. Since the stress hormone and sex hormone systems interact, the constant fluctuations of sex hormones across the menstrual cycle might also lead to fluctuations in the stress response across the menstrual cycle.
To test this, studies most often cut the menstrual cycle into 2 phases: the follicular phase, the time of the cycle before ovulation when follicle stimulating hormone is being released leading to follicular maturation; and the luteal phase, the time of the cycle after ovulation when the corpus luteum is releasing and raising estrogen and progesterone levels. The characteristics of these phases are often described as the low-hormone vs. high-hormone phases. As one might expect, given the large differences in hormone levels across these two phases, the stress response does differ between phases with larger cortisol responses during the high-hormone luteal phase than during the low-hormone follicular phase.
However, the high-hormone luteal phase has elevated levels of estrogen and progesterone, so how can we address my research interests and parse the effect of just estrogen levels? In order to study this, the follicular phase must be further broken down into two distinct phases: the “early follicular” phase, during menses when estrogen levels are low and follicle stimulating hormone is being released; and the “late follicular” phase, the end of the follicular phase, when estrogen levels are at their peak just before ovulation. Testing during the late follicular phase is very difficult, as the estrogen peak only lasts 1-2 days and there is no easy way to know or predict when it is occurring. Remember, the estrogen peak happens before ovulation and before the luteinizing hormone spike that triggers ovulation, so popular over-the-counter ovulations kits which test for luteinizing hormone levels are not useful for predicting the estrogen peak, but rather for letting us know the estrogen peak occurred about 3-4 days prior.
Despite the difficult nature of testing during this time, one line of my research does just that. For preliminary work related to the stress response across the follicular phase, please see our publication looking at the relationship between progesterone and cortisol levels in response to stress.