The female reproductive hormone cycle is complex and comes with it's own set of challenges for many women. Many women are familiar with those sweet cravings or an increased appetite that seems to be associated with their menstrual cycle. Other women may experience menstrual dysfunction or irregularity without really understanding why. Interestingly, there is a relationship between the female reproductive hormones and dietary intake that is bidirectional, meaning that fluctuations in hormones can affect what you eat (and your appetite) AND conversely, what or how much you eat can affect your hormones.
First, let's break down the 'normal' menstrual cycle (as in 'textbook normal', not necessarily applicable to everyone):
In a 'normal' 28 day cycle, day 0 would be considered the beginning or onset of menstruation. On day 0 (also the end of the previous cycle), the egg that was released from the previous month's cycle has not been fertilized and thus hormone levels (that would have helped sustain the fertilized egg) have dropped.
This drop in circulating hormone concentrations signals the hypothalamus (in the brain) to begin menstruation (shedding of the uterine lining) and also signals the release of follicle stimulating hormone (FSH) from the pituitary gland (in the brain) in order to prep the next egg for release.
At this point: hormone levels were low, signaling menstrual bleeding and the release of FSH to prep another ovarian follicle.
The previous uterine lining is shed (menstrual bleeding) and the increase in FSH from the pituitary (in the brain) triggers the growth and maturation of a follicle on the ovary (prepping/maturing the egg) where this ovarian follicle secretes estrogen (namely estradiol, the major estrogen).
During the first half of the cycle (roughly days 0-14), this ovarian follicle is growing in response to FSH and is releasing estrogen in increasing amounts (thus the first half of the cycle is called the 'follicular phase').
FSH is continually released from the pituitary in the brain so that the ovarian follicle grows and the egg matures. This growing follicle releases estrogen in continually increasing amounts.
When estrogen levels peak (at the peak maturation of the follicle) around ~day 14, this peak of estrogen concentration signals the hypothalamus to release luteinizing hormone (LH) from the pituitary gland in a big surge.
With this surge of LH, the follicle bursts open to release the egg into the Fallopian tube while what remains of the follicle forms the corpus luteum which now secretes progesterone (in preparation to nourish a fertilized egg).
A peak in estrogen concentration signals that the egg is mature, so a surge of LH from the pituitary bursts open the follicle to release the egg. The remaining follicle forms the corpus luteum which secretes progesterone (to nourish/provide an environment for a fertilized egg).
As the egg travels down the Fallopian tube, the corpus luteum continues to build and secrete progesterone which builds and preps a uterine lining for implantation of a fertilized egg (thus the second half of the cycle is called the 'luteal phase' after that surge of luteinizing hormone).
If the egg reaches this lining without being fertilized, hormone levels drop, and this signals to the brain that the egg was not fertilized, and initiates menstrual bleeding again with another increase in FSH for a new follicle.
Progesterone is continually secreted from the corpus luteum until failed implantation (of an unfertilized egg). This signals a drop in progesterone secretion and the onset of menstrual bleeding.
This process repeats every ~28 days, but can have much variability for different individuals including the length of time for each cycle or each phase of the cycle, anatomical abnormalities, or issues with hormonal signaling where for example there could be decreased hormone production or hormonal feedback (at the hypothalamus, pituitary or ovaries), or impaired hormonal degradation and excretion (through the liver, gallbladder, and GI tract) that could impair feedback responses.
Here is a great video that walks through this process explained above:
So what does this have to do with nutrition?
Menstruation is therefore a hormonal process relying on the adequate functioning of the hypothalamus, pituitary, and ovaries in secreting hormones (in response to feedback) but ALSO on the liver, gallbladder, and digestive tract for effectively metabolizing and excreting circulating hormones. If circulating hormone concentrations do NOT decrease effectively, then hormone production in response to this decreased concentration ceases (and for those circulating hormones to decrease, they need to be metabolized and excreted from the body). To this extent, issues associated with the liver (for degrading the hormones), gallbladder (for producing bile that binds to the degraded hormones for excretion) or the intestinal tract (for excreting the degraded hormones via feces) could be associated with dysfunctions in reproductive hormone signaling.
[It may help to think of this system of feedback like the 'auto' function for your home's A/C temperature gauge. When the air temperature rises above the set temp, the A/C kicks on to cool the air down back to that set temperature. But if the air temp never goes above that set point, then the A/C will stay off. ]
When it comes to this hormonal feedback, a decrease in circulating hormones below a certain set point 'turns on' the production and release of new hormones, which continues to increase until the circulating hormone concentration hits the upper set limit. However, if the circulating hormones were not effectively cleared from circulation (like impaired liver, gallbladder, or GI function disabling hormonal degradation and excretion), then those hormonal concentrations continue to circulate as-is, which means that there is no signal to continue producing/releasing more hormones to initiate another cycle.
What does this mean nutritionally?
High oxidative demands like smoking (impacting the liver)
High detoxification demands like alcohol, drug, or medication/supplement use (impacting the liver)
High metabolic demands like impaired glucose metabolism/diabetes (impacting the liver)
Gallbladder removal or complications that slow bile production and release (gall stones, inflammation, etc)
Gut microbiota dysbiosis from antibiotic use/exposure (reducing excretion via intestinal tract)
Constipation from medications or low fiber diet (reducing excretion via intestinal tract)
...can ultimately limit the necessary fluctuations in hormonal concentrations needed for the menstrual cycle.
And what about dietary intake?
These processes that ensue regarding hormonal production, secretion, and the building up of the uterine lining are anabolic processes that require adequate energy availability. There are several study findings to suggest that it is inadequate energy intake that is associated with amenorrhea (absence of menstrual bleeding) observed in athletic populations, and not necessarily the training intensity or duration (stress) impacting the hormones. (Howe, et al. 2014) When energy availability is low (like in an athlete that is under-eating), then energy is conserved for body maintenance and the large demands in energy expenditure for exercise, to where reproductive energy requirements are therefore suppressed. (Howe, et al. 2014) This low energy intake may be intentional like in sports that emphasize weight, leanness, or aesthetics, or can be unintentional like an athlete simply not knowing how much they should be eating for their activity level. Low energy intake (whether intentional or unintentional) and amenorrhea make up two arms of the female athlete triad. The third arm of the triad is osteoporosis (or low bone mineral density) which occurs due to the combined low energy intake coupled with low estrogen production (which is associated with low energy intake and amenorrhea) where estrogen plays a vital role in maintaining and protecting bone health. [This is why postmenopausal women are at a heightened risk for osteoporosis and bone fractures as there is an estrogen deficiency that would otherwise help to protect and maintain bone health.] *More on this in a bit...
**As a side note: Estrogen may influence/ decrease appetite through CCK and indirectly decrease meal size. (Howe, et al. 2014) It is theorized that the appetite-supressing effect of estrogen may be a reason for weight gain in postmenopausal women, where estrogen production ceases after menopause. (Howe, et al. 2014)
Additionally, it should be worth noting that hormones themselves are proteins and where the pituitary hormones specifically (FSH and LH) are glycoproteins (carbohydrate attached to a protein) to where adequate protein and carbohydrate consumption may also play a vital role in appropriating adequate menstrual function. There are several animal studies that have observed this relationship:
[Take note: due to the complexity of the female hormone cycle, and potential ethical compromise, there is little established research of this topic in humans. Much of the available evidence is based on animal studies.]
So how does dietary intake affect hormonal production?
Animal studies have alluded to an important link between energy intake and hormonal production and signaling where prolonged dietary energy restriction impaired reproductive activity through a diminished release of LH from the pituitary in response to decreased signaling from the hypothalamus. (Schillo 1992) In essence, low energy intake decreased the actions of the hypothalamus releasing a hormonal factor that signals LH release from the pituitary. (Schillo 1992)
Taking this one step further...
Evidence suggests that a large energy deprivation can decrease production of the hypothalamic hormone GnRH (that hormone releasing factor that is sent from the hypothalamus to the pituitary) which would subsequently be associated with decreased estrogen exposure (from less pituitary hormone FSH signaling a follicle to release estrogen), and thus decreased effects of estrogen including not only menstruation and reproduction, but bone mineralization, impaired endothelial functioning, and dyslipidemia. (Williams, et al. 2015) This is also known as functional hypothalamic amenorrhea where the large energy deficiency is associated with decreased hypothalamic hormone release and subsequently impaired or ceased menstruation. Some of these menstrual irregularities can range from defects in the luteal phase (short or inadequate phase), anovulation (not releasing an egg), oligomenorrhea (menstrual cycle lasting 36-90 days), and amenorrhea (absence of menses for >90 days). (Williams, et al. 2015) Studies of short term (5 days) of a large caloric deficit (500-700 calories below normal maintenance amount) are associated with decreased LH pulses, among other metabolic consequences like decreased IGF-1, leptin, and insulin. (Williams, et al. 2015) **Meaning even short-term caloric deficit is associated with menstrual dysfunction.
Interestingly, metabolic status (like a negative or positive energy balance) seems to be closely linked to this hormonal regulation, but NOT body fat concentrations. (Schillo 1992) For example, adequate glucose and free fatty acids in the blood (like after digesting a meal) may likely drive this mechanism for hormonal release (signaling to the brain that the body is well nourished and able to handle the demands for a fertilized egg) whereas body fat content alone may NOT promote this signaling of nourishment. (Schillo 1992) **It was previously thought that amenorrhea seen in athletes was due to low body fat percentages, but where body fat percentage is actually LESS of a factor in determining reproductive hormonal function, whereas adequate energy intake is...
Could this explain why there may be women who exercise and diet regularly (as a part of a 'healthy lifestyle'), are of a normal body weight, and normal body fat percentage, but still experiencing menstrual irregularities?
How sensitive is the female body to 'too much' of diet and activity compared to the 'right amount'?
There are study findings to suggest that the degree of energy deprivation (as in exercising extensively in addition to a severe caloric deficit) is associated with the frequency of menstrual disturbances. (Williams, et al. 2015) In this study, a sample of sedentary women with normal menstrual cycle functioning (at baseline) were randomized to either:
A true control "CON" (no exercise, no caloric deficit)
Exercise control "EXCON"(exercise but eating to remain in energy balance= NO caloric deficit at all)
OR one of four different exercise/diet groups where they exercised with increasing magnitude and followed a diet of varying/increasing calorie deficit
Group 1: 15% caloric deficit through exercise alone
Group 2: 30% caloric deficit through exercise alone
Group 3: 30% caloric deficit through =15% caloric deficit from diet +15% caloric deficit through exercise
Group 4: 60% caloric deficit through =30% caloric deficit from diet+ 30% caloric deficit through exercise
According to this study, the conditions with a larger caloric deficit (Groups 2, 3, and 4) exhibited more frequent menstrual disturbances than the exercise-control group or group 1. (Williams, et al. 2015) This could imply that there is a dose-response relationship between the magnitude of a caloric deficit (a large caloric deficit produced from dietary restriction AND increased energy expenditure) that is largely associated with disturbances in menstruation. **Take note: it was the magnitude of a caloric deficit that was associated with more frequent menstrual irregularities.
And what about specific nutrient intake?
Recall from above that FSH and LH, released from the pituitary, are glycoproteins meaning these hormones are composed of both a protein and a carbohydrate moiety. Protein status is pretty closely regulated as long as intake is adequate enough to meet needs (protein/nitrogen balance). If protein needs are increased (like with resistance training, periods of growth, sickness, etc) then intake should be increased to accommodate. There are animal study findings to suggest that if dietary protein is restricted (or intake is not meeting needs) then LH is decreased as well. (Polkowska, et al. 2003) This should make sense as a negative protein balance would indicate a reduced ability to handle nourishing a fertilized egg.
The carbohydrate component to these hormones is notably associated with biological activity where study findings suggest that removal of this carbohydrate moiety decreased hormonal bioactivity, specifically for FSH. (Bishop et al. 1994) Interestingly, study findings show low FSH concentrations in women with prediabetes and diabetes. (Wang, et al. 2016) This is due to decreased insulin signaling/actions (in prediabetes/diabetes) which then decreases glucose (carbohydrate) uptake into the cell, meaning there is LESS ability to actually USE glucose, and therefore impairs the ability to utilize glucose for carbohydrate-specific work, like producing glycoprotein hormones in this case. (Wang, et al. 2016)
Now let's look at the reverse of this relationship between hormones and dietary intake...
How do hormones impact how we eat?
It may come as no surprise to many women to hear that appetite and food cravings can increase throughout the menstrual cycle, and where these deviations from a normal metabolic state (increased appetite) can be due to those fluctuations in hormones. When estrogen is high and progesterone is low (during the follicular phase, or the first half of the cycle), resting metabolic rate (RMR) is also low, as well as energy intake. (Howe, et al. 2014) During the luteal phase (second half of the cycle) when estrogen is low and progesterone is high, RMR increases as does energy intake (by roughly +300 additional calories/day). (Howe, et al. 2014)
There is evidence to support this notion of a positive energy balance (taking in more calories than expending) and increased cravings, specifically for carbohydrate and fat-rich foods, during the luteal phase (the second part of the cycle) compared to a negative energy balance in the follicular phase. (Krishnan, et al. 2016) This could make sense if we consider the anabolic processes occurring during the luteal phase (building up of a uterine lining) as therefore indicating a need to INCREASE calorie intake (in order to provide additional energy nutrients for this demanding work) and thus the cravings may come as a biological tool for increasing calorie intake.
There is however an interesting interplay between hormones (specifically estradiol/estrogen, progesterone, and leptin) to help explain this change in appetite and eating behavior...
Leptin is a noted hormone secreted from adipose tissue that influences satiety (keeps you feeling LESS hungry, more satiated=keeps you from eating), and it is positively associated with adipose tissue meaning MORE adipose tissue is associated with MORE leptin and thus more signaling for satiety (reduces appetite). This is like the body telling the brain that it has enough stored fuel already, and so increased cravings/appetite are not needed. Leptin is also increased (so it is decreasing appetite) when in a positive energy balance or overfeeding, again signaling that there is enough energy for the body and therefore no need for an increased appetite or cravings. Fasting (or a negative energy balance like a caloric deficit) and LOSS of adipose tissue decreases leptin, which STIMULATES appetite/cravings in the brain (the body telling the brain that it is losing energy/stored fuel, and therefore needs to increase appetite in order to increase intake of energy).
Now how does leptin play a role in reproductive hormones...
There are study findings to suggest that leptin increases at the peaks of the follicular and luteal phases (when estradiol and progresterone are highest, respectively, in young women (aged 18-30yr). (Krishnan, et al 2016) This increase in leptin would indicate reduced appetite at the peaks of these two phases of the cycle. It is suggested that leptin and estradiol/estrogen are both anorexigenic hormones (they both decrease appetite/food intake) like seen in the follicular phase (where elevated estrogen is associated with reduced appetite/energy intake during the first half of the cycle), but where progesterone is likely not anorexigenic due to the reported increase in sweet and fat cravings with increased energy intake during the luteal phase. (Krishnan, et al. 2016) **In women, there is a reported association between estradiol concentrations and binge eating where low estradiol levels are found in women with binge eating disorders compared to higher estradiol concentrations in non-bingeing women. (Krishnan, et al. 2016) In contrast to the healthy (non-bingeing) women included in this study, the binge-eating women showed an observed higher rate of carbohydrate and sweet cravings with higher estradiol (the opposite of what is normally found in non-bingeing women).
In this study, a sample of healthy young women were recruited who were considered to have normal menstrual cycles, not taking oral contraceptives, and no recent significant weight change or history of health complications. (Krishnan, et al. 2016) Their hormones were tracked as well as body composition, food intake, and food cravings for one full menstrual cycle. There was a reported significant increase in carbohydrate cravings during the luteal phase associated with progesterone levels, while fat cravings were inversely associated with leptin during the luteal phase. (Krishnan, et al. 2016) This implies that the menstrual hormone response to the luteal phase (second half of the cycle) involved increasing cravings for carbohydrates, BUT where body fat content (amount of adipose tissue) or energy intake (like being in a caloric deficit) impacting leptin concentrations dictated fat cravings. **Less adipose tissue/loss of adipose tissue/negative energy balance=less leptin=MORE cravings for fat-rich foods. This implies that being on a restrictive diet may increase your cravings for fat during the second half of your cycle.
It gets even more complex...
It was also suggested that there was an inverse association between leptin and estradiol in the late follicular phase. (Krishnan, et al. 2016) With increasing/near peak concentrations of estradiol, leptin was decreased which could indicate LESS satiety and thus MORE feelings of hunger to support adequate energy intake. (Krishnan, et al. 2016) [Remember both leptin and estradiol/estrogen are considered anorexigenic hormones that decrease appetite. Increases in either hormone would decrease appetite, but in this case, as estrogen increases near it's peak, leptin decreases which could indicate an increase in appetite.] Additionally, intake of sweets (carbohydrates) was inversely associated with leptin, regardless of the menstrual phase (meaning the MORE leptin being released from more adipose tissue, or overfeeding, or positive energy balance= the LESS intake of sweets). Notably, it was the ratio of estradiol to leptin in the luteal phase that was associated with increased habitual intake of sweets. (Krishnan, et al. 2016)
Major take-home point: A balance in energy intake with energy expenditure is most likely to balance out reproductive hormonal signaling and cravings.
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Krishnan S, Tryon R, Horn W, et al. Estradiol, SHBG, and leptin interplay with food craving and intake across the menstrual cycle. Physiology and Behavior. 2016; 165(15):304-312. http://www.sciencedirect.com.proxy.lib.fsu.edu/science/article/pii/S0031938416304346?via%3Dihub
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Wang N, Kuang L, Han B, et al. Follice stimulating hormone associates with prediabetes and diabetes in postmenopausal women. Acta Diabetologica. 2016; 53: 227-236. https://www-ncbi-nlm-nih-gov.proxy.lib.fsu.edu/pmc/articles/PMC4826410/
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