How the menstrual cycle is regulated: science points to an internal clock of the body and mitigates the influence of the lunar phases

The first day of menstruation is the starting point of a very complex vital process that science still does not fully understand: the ovarian cycle. The first phase of this phenomenon begins with the period, which usually lasts about 28 days, and which also involves, apart from menstrual bleeding, the growth of the ovarian follicles until a mature egg is found that is released into the fallopian tubes and the degradation of the endometrium before the start of a new menstruation. All of this happens periodically during a woman's fertile life at a more or less constant rate, but scientists still do not know what determines the timing of these cycles and why each phase lasts as long as it does. Due to the temporal similarities, some experts have found a link between this phenomenon and the lunar cycle, but this theory, with limited and contradictory results, has always generated great controversy among the scientific community. New research, published this Wednesday in the journal

Science Advances,

furthers the understanding of this process and suggests that, more than the lunar phases or any other external variable, it is probably an internal clock of the body, like the circadian timer that marks the rhythm of life, which regulates the ovarian cycle.

According to Claude Gronfier, a scientist at the Neuroscience Research Center in Lyon (France) and author of the study, the traditional explanation for why the menstrual cycle has a period of 28 days "is that it results from a fine balance between endocrine processes" that lead to the different phases of this phenomenon. His colleague and first author of the research, René Ecochard, from the University Hospital of Lyon, illustrates the stages of this cycle, starting with a first phase of latency, which lasts about a week and begins with the first day of bleeding: “The The main process that takes place during this period is the selection of a follicle that will then lead to ovulation. Then, there is another stage, which is “the fertile window,” which also lasts about a week in which “the growth of the follicle takes place until ovulation, as well as the secretion of liquid mucus in the cervix to receive the sperm.” . The third part of the cycle, known as the “postovulatory phase,” notes Ecochard, extends over about two weeks, from the day after ovulation to the day before the start of the next menstrual period. “Interestingly, and surprisingly, there has never been a consensus explanation as to why these different phases, added together, last approximately 28 days, in addition to the fact that each of them also has a certain duration,” Gronfier explains in an email response.

After analyzing nearly 27,000 menstrual cycles from 2,300 European women and another 4,800 from 721 North Americans, the authors of the study found evidence that “it is more than likely” that the rhythmic characteristics of the menstrual cycle are explained by an internal mechanism of the body similar to the clock. circadian, which is that central timekeeper, located in the hypothalamus, that tells the time to the rest of the body. This molecular device, which is synchronized with the light and darkness of the day, is responsible, together with the small independent timers of the tissues, of anticipating and preparing the cells for what is to come, such as eating at midday or leaving. to sleep at night.

“What our article shows is that these processes do not simply follow one another, in such a way that each one begins when the previous one ends. “Our results strongly suggest that a clock-like mechanism drives the rhythmicity of the menstrual cycle, such that its periodicity remains within a certain range and oscillates around the intrinsic rhythmicity of the cycle (which varies between women),” explains Gronfier. Thus, this synchronizing mechanism can even correct the fluctuations that occur in a specific cycle, in the same way that it takes a few days to fix the circadian imbalance that occurs after an intercontinental trip, for example. “If the [ovarian] cycle lengthens, for whatever reason, this clock-based process adapts to quickly shorten it, and if it shortens, this clock-based process adapts to lengthen it as well,” the author adds.

Gronfier and his team's hypothesis does not come out of nowhere. In the article they say that there is already "some evidence" that the phases of menstrual cycles can also be under the influence of circadian rhythms and that an alteration of this vital rhythm is also associated with dysfunctions in menstrual function. Juan Antonio Madrid, professor of Physiology and director of the Chronobiology and Sleep Laboratory at the University of Murcia, points out that there is a connection between the circadian clock and menstrual cycles, but with nuances: “Women with irregular cycles tend to have worse rhythms. daily circadian rhythms and poorer sleep quality. Sleep and good circadian rhythms regulate the menstrual cycle and, in turn, the menstrual cycle influences sleep. If we divide the ovarian cycle in half and place ovulation in the middle, we see that the hormones change in each phase and there are also temperature changes.” But that does not mean, the chronobiologist points out, that it is the circadian clock that modulates the menstrual cycle. “In the article, they believe that there is an internal clock similar to the circadian clock that we have in the brain, but they do not identify what it is or where it is. We cannot say that the circadian clock is controlling the menstrual cycle,” says Madrid, who did not participate in this study.

Gronfier also admits that they do not know how circadian rhythms determine the length of menstrual cycles. "We don't know yet, but we believe that the circadian synchronization system—well known for its regulatory role in a large number of physiological rhythmicities, such as the sleep-wake cycle, cognition, memory, metabolism, temperature and cell cycle, just to name a few—is involved, as it is involved in another well-known rhythmic process that we call seasonality or annual rhythmicity (which exists not only in animal species that reproduce seasonally, but also in humans). Therefore, the almost monthly rhythm could also originate from the circadian oscillation.”

Controversial moon effect

The authors also analyze the potential effect of the lunar cycle (it lasts 29.5 days) and do not rule out this theory, but specify that the links found are “weak.” In a context of contradictory scientific literature - there are studies that show a more frequent appearance of menstruation after the new moon and others, on the contrary, point out data in favor of the appearance of the period when the moon is brighter or just before and after the full moon—the authors of this research see that the menstrual cycle began more frequently on a crescent moon in Europe, while in North America it occurred on a full moon. “We do not have an explanation for this difference between the continents, but we believe that a more in-depth study of this issue is justified,” they point out in the article, although some hypotheses are proposed.

One of them, Gronfier recalls, looks towards a potential evolutionary footprint. “There is the possibility that our ancestors, animal species,

Homo sapiens

and others, have developed a synchronization with the lunar cycle, which, especially during the full moon, provides a lot of light at night. Our monkey cousins ​​and felines also have nocturnal behaviors that follow the lunar cycle and we see these behaviors that have been maintained through evolution as examples of other behaviors and physiological processes that have been maintained because those lunar rhythmicities used to have a purpose. Our species, as well as most others now, has lost access to the lunar cycle (in terms of night light) with the invention of artificial light, not long ago in terms of evolution. Of course, all of this is hypothetical and needs to be supported by scientific studies and results before we can present them as real,” the scientist points out.

Madrid, on the other hand, is more reticent about proposals about the influence of the lunar cycle: “It was a very nice hypothesis, but if it were truly a synchronizer and not a mere coincidence, it is difficult to understand biologically that a different synchronization mechanism exists. among women in North America and Europe. There is a slight increase in menstruation, but it does not coincide in different places and the statistical evidence is very weak.”

The authors admit that more work and studies in larger populations are needed to test their hypotheses “and unravel the mechanisms” behind this potential internal clock, but their findings open the door to studying chronobiological approaches to address, for example, dysfunctions. in the ovarian cycle. “We are trying to determine the precise mechanisms involved in the rhythmicity of the menstrual cycle, so that we can manipulate them when they are dysfunctional. For example, if the circadian clock is indeed involved, then we can investigate whether improving circadian timing or advancing or delaying the circadian phase (with phototherapy, for example, or other chronobiological approaches) could improve fertility. There is a lot of work ahead,” Gronfier assumes.

An atlas of the ovary

There are still many unknowns surrounding the most basic reproductive physiology of half the planet and the ovaries continue to be, to a large extent, an enigma for the scientific community. In this context, other research from the University of Michigan has now taken a leap in knowledge of the female sexual organs by publishing last week in the journal

Science Advances

, a cellular atlas of the ovary. The detailed analysis of the population of cells that populate these organs illuminates the way to expand, in the future, the margins of fertility.

The atlas has revealed, for example, what factors make a follicle (where eggs are gestated) mature correctly, since most of them wither before releasing hormones or eggs. “Now that we know which genes are expressed in oocytes, we can test whether affecting these genes could result in the creation of a functional follicle. This can be used to create an artificial ovary that could eventually be transplanted back into the body,” Ariella Shikanov, professor of biomedical engineering at the University of Michigan and author of the study, said in a statement.