WOMEN'S HEALTH
April 26, 2010

"That Time of the Month"

The hormonal changes surrounding ovulation are often intense.

If you’re a woman, the following portrait – or certain aspects of it – may ring a familiar bell:

Yesterday you were oddly, and perhaps irrationally, irritated by your coworker’s innocent mistake. Today you’re bloated and your face has broken out like it did when you were a teenager. Tonight you ate enough take-out to feed a family of three, your breasts hurt, and you started crying during a T.V. ad for toilet paper. If you’re a female, and some or all of these symptoms seem to occur on regular basis – say, every 28 days or so – you may be victim to a well-studied phenomenon called premenstrual syndrome (PMS).

Women may be understandably annoyed at such an assumption (particularly when it’s inaccurate), and while somewhat amusing, it may point to a larger lack of understanding of women’s cycles.

Though the above scenario may fall on the more extreme end of the spectrum, many women suffer from symptoms of PMS at some time or another during their lives. Though it’s a well-documented syndrome, many people are unfamiliar with the mechanisms behind it. Nowadays, a commonly used phrase to explain or dismiss a woman’s moodiness is: “she must have PMS.” Women may be understandably annoyed at such an assumption (particularly when it’s inaccurate), and while somewhat amusing, it may point to a larger lack of understanding of women’s cycles. Men in particular may also view PMS as an unsubstantiated scapegoat for female moodiness, and question whether it is real biological phenomenon at all.

There has always been some mystery and romance associated with the female cycle, perhaps stemming from its synchrony with the cycle of the moon. But aside from that, many people (women included) may not know exactly how the female reproductive cycle operates – specifically, what hormones are involved, how they are controlled, why PMS occurs (including both the physical and behavioral symptoms), and when exactly in the cycle fertility is possible and impossible. This article aims to clarify how the female cycle works overall, and just how the changes to the body and behavior occur throughout the course of a month.

The Menstrual Cycle

The menstrual cycle, by definition, begins on the first day of a woman’s period (the day that bloody discharge begins), and ends on the day before the following menstrual period. The discharge occurs because the body is ridding itself of the preparations that it had made during the previous cycle in the event that pregnancy might occur. In other words, it is getting rid of the thick uterine lining it had made (which would have been a cozy spot for a fertilized egg to implant itself), and it is getting rid of the egg that went unfertilized during the previous cycle. With the new cycle the body will now begin to set itself up for once again releasing an egg and preparing for pregnancy. The phases of the reproductive cycle are dependent upon the interaction of several key hormones (see below).

Hormones 101

Many people have heard of the two major hormones involved in the female reproductive cycle: estrogen and progesterone. Though these two hormones are indeed central players, there are also other hormones that are crucial to the cycle’s functioning – and all are ultimately under the control of two main brain regions. One area is the hypothalamus, which is important in basic bodily processes like hunger, sleep, and sexual arousal. The other is the pituitary gland, which is adjacent to the hypothalamus.

FSH is mainly responsible for signaling the ovaries to begin preparing mature eggs, or more precisely, mature follicles, which include several types of supporting cells that nourish and surround the egg.

The hypothalamus releases a hormone called gonadotropin-releasing hormone (GnRH), which is an important hormone in both women and men. This hormone signals the pituitary gland to make and release two additional hormones that actually signal the sex organs to start working: in women, these are follicle stimulating hormone (FSH) and luteinizing hormone (LH). These hormones begin to rise prior to ovulation (the release of the egg from an ovary), and signal the body to begin preparing for ovulation and potential pregnancy.

FSH is mainly responsible for signaling the ovaries to begin preparing mature eggs, or more precisely, mature follicles, which include several types of supporting cells that nourish and surround the egg. LH is responsible for the mature follicle to be released from the ovary during ovulation. In the male, FSH is important in signaling the supportive cells in the testes to begin producing sperm cells, and LH is necessary for testosterone to be synthesized.

Phases of the Female Reproductive Cycle

The reproductive cycle is divided into three phases: the follicular phase, the ovulatory phase, and the luteal phase.

Follicular Phase
In the beginning of this phase, which begins on the first day of the menstrual period and usually lasts for about two weeks, estrogen and progesterone levels are low (assuming the egg from the last cycle was unfertilized). This dip in hormone levels signals the uterus to shed its lining, and a menstrual period begins. During this time, the pituitary gland is beginning to produce FSH. The FSH increase stimulates the ovaries to release estrogen and progesterone, and signals the main event of the follicular phase to begin: the preparation of mature eggs in the ovaries. Actually, somewhere between 3-30 follicles, each containing one egg, begin to grow, but ultimately, only one is “chosen” to become fully mature and released from the ovary. (The follicle itself also produces estrogen, which is highest right before the next phase – ovulation – occurs.) The follicular phase ends when LH levels spike, signaling ovulation to begin.

Ovulation Phase
The ovulation phase usually lasts for about 16-32 hours. When a mature follicle is ready to be released from the ovary, a large surge of LH results in the follicle being pushed out of the ovary. When this happens, the egg also bursts out of its protective follicle and finds its way to the fallopian tube and down into the uterus. The side of the body on which ovulation occurs doesn’t appear to follow any routine pattern (it doesn’t alternate from one side to other every month), and it’s unclear what determines which ovary releases an egg each month. There is a smaller surge in FSH, but the exact reason for this is still unknown.

It should also be mentioned that pregnancy is more likely to occur when sexual intercourse takes place prior to ovulation – specifically, in the six days preceding it…

By definition, the ovulation phase ends when the egg leaves the ovary. A woman can only become pregnant for about 12 hours after the egg has left the ovary. It should also be mentioned that pregnancy is more likely to occur when sexual intercourse takes place prior to ovulation – specifically, in the six days preceding it, as found in one study. In other words, fertilization is most likely to happen when sperm is already present in the reproductive tract of the female when she ovulates. Interestingly, some other studies have also found that women tend to be more sexually active in these six days preceding ovulation, which suggests that the body seems to “know” when its fertile time is.

Another phenomenon that can occur during ovulation is that a slight pain may be felt on one side of the body around this time. This pain is known as mittelschmerz (which translates into “middle pain”), and it seems to occur on the side of the body on which the egg is being released from the ovary. It can last anywhere from a few minutes to up to 48 hours. Though the phenomenon is not well-understood, it seems to occur prior to, during, or just after ovulation. Since ovulation involves the follicle literally bursting through the outer surface of the ovary (there is no opening from which it is released), the pain may originate from this action. Or alternatively, it may come from the rupture of the follicle, which releases some fluid into the abdominal cavity, and could potentially cause some degree of inflammation, leading to the discomfort.

Luteal Phase
This phase also lasts for about two weeks, and ends on the day before menstruation begins. In the luteal phase, progesterone levels are increasing markedly, mainly due to the action of the ruptured follicle: after it breaks open to release the egg, it recloses and is now called the corpus luteum. It releases increasing amounts of progesterone, which helps prepare the body for potential pregnancy by thickening the uterine lining (endometrium) so that it will be able to house and nourish a fertilized egg. If the egg goes unfertilized, however, the corpus luteum breaks down after about two weeks, and the cycle ends and the menstrual period begins.

It’s important, particularly for those having trouble getting pregnant, to note that fertilization will be less likely to occur after one’s body temperature has risen.

Progesterone is also responsible for increasing the body temperature. Many women may know that body temperature can be us as a marker to determine whether ovulation has occurred, and some women who are trying to become pregnant find that charting their basal body temperature for a few months may help predict when ovulation occurs. It’s important, particularly for those having trouble getting pregnant, to note that fertilization will be less likely to occur after one’s body temperature has risen because, as mentioned above, the days preceding ovulation are a woman’s most fertile days – and the temperature increase from progesterone indicates that ovulation has already occurred. But if a woman charts the rise and fall of body temperature over a few months, noting her specific pattern, she will be able to determine how many days there are, on average, between the start of her period and this rise in body temperature. Having sex in the days prior to her body temperature increase may be the best odds for becoming pregnant. (See NIH’s website for more information on predicting fertility: http://www.nlm.nih.gov/medlineplus/ency/article/007015.htm).

The higher levels of progesterone and estrogen during the luteal phase not only prepare the uterus for potential pregnancy, but the breasts undergo changes as well, which many women notice as menstruation approaches. Most notably, the breasts may enlarge slightly, due to the hormones’ effects on the milk ducts, which are dilating in preparation for pregnancy. And this swelling may cause the breasts to feel sensitive or downright painful during PMS.

Premenstrual Syndrome

The cycle of hormones and the body changes they signal set the stage for premenstrual syndrome. As described in the opening of this article, many women experience at least some symptoms of PMS at some point in their lives. Symptoms include bloating, breast tenderness, food cravings, weight gain, skin problems, irritability or aggressiveness, difficulty concentrating, changes in libido (sex drive), depression, and feeling tired or lethargic. The severity of symptoms can range from mildly annoying to seriously incapacitating. Some women have to miss days or work or school because their symptoms prevent them from functioning normally at these times. The more severe form of PMS is known as premenstrual dysphoric disorder (PMDD), and women who are diagnosed with it must suffer have at least five different symptoms, with at least one being significantly related to mood (i.e., depression, anxiety, irritability, etc.). (See discussion of PMDD below for more information on symptoms and treatment.)

It is estimated that 5-8% of women suffer from moderate to severe PMS, but some studies have found the overall number to be higher, possibly as many as 28%. But because so many women suffer from at least mild symptoms of PMS, some researchers believe that some level of “discomfort” in the days preceding menstruation can be considered “physiological not pathological” – in other words, it’s just a normal part of the cycle, rather than something to be considered an illness.

It is estimated that 5-8% of women suffer from moderate to severe PMS, but some studies have found the overall number to be higher, possibly as many as 28%.

So what causes PMS symptoms? The symptoms appear to be related to fluctuating hormone levels in the body. But this has also been confirmed through several kinds of studies, including those in which women suffering from severe PMS symptoms have undergone complete ovariectomies (removal of the ovaries) to stop them from cycling, and have reported that after the surgery, their symptoms stop completely. But believe it or not, the exact reasons behind the changes in hormones leading to both the physical and psychological symptoms have not been fully mapped out. It has been shown that while both physical and psychological symptoms are stable from month to month, it is the psychological symptoms – anxiety, depression, mood swings – instead of the physical ones that lead to the women encountering problems functioning normally in their daily lives.

Mood-Related Symptoms

It’s believed that rising levels of estrogen right before ovulation and progesterone right after ovulation may be responsible for at least the psychological symptoms that many women feel. And of these two hormones, some have suggested that the monthly rises in progesterone may be more responsible than estrogen for the undesirable mood changes felt during PMS, but some of the supporting research comes from menopausal women taking estrogen-replacement therapy (and these women report decreases in depression). But other studies have suggested that estrogen and progesterone may have equal effects in causing moodiness. A nice study looked at women who suffered from PMS, and whose symptoms were stopped when the researchers administered a specific compound to prevent them from ovulating. Then, when the researchers gave them either progesterone or estrogen, their symptoms started up again. This suggests that the two hormones may both play roles in bringing about the mood changes in PMS.

They say that mood-related PMS symptoms reflect an “abnormal response to normal hormonal changes” that all women experience.

Why do some women suffer from PMS-related mood problems and some women don’t? It could be that the hormone levels in PMS-sufferers are different – but there hasn’t been any research to suggest that this is the case. In fact, in the study mentioned above, the researchers also looked at this very question. They found that when women who never suffered from PMS were given either estrogen or progesterone, they did not feel any changes in mood, whereas the other group of women – the PMS-sufferers – did feel mood changes when either hormone was given. The researchers feel that this suggests that the difference is not in circulating hormone levels, but rather it is in the way the body responds to the hormones that are present. In fact they say that mood-related PMS symptoms reflect an “abnormal response to normal hormonal changes” that all women experience.

So where might the differences lie? Many studies have suggested that differences in the brain chemical serotonin may be at work. For example, one study found that administering a chemical that mimics the effects of serotonin significantly improved symptoms in PMS sufferers. The fact that serotonin is involved in PMS-related mood problems is not surprising, since the compound is a major player in depression, and is very often the target of a class of anti-depression drugs known as selective serotonin reuptake inhibitors (SSRIs). So again, it may be that women prone to PMS differ not in the hormones themselves, but in the way that the brain and the brain chemicals involved in regulating mood respond to normal hormonal fluctuations.

Physical Symptoms of PMS
As mentioned earlier, some of the classic physical symptoms of PMS include bloating, weight gain, breast tenderness, acne, and food (or fluid) cravings, but they may also headache, muscle aches and joint pain, fatigue, and constipation or diarrhea. Believe it or not, it’s still unclear what causes these symptoms, and it appears that considerably more research has been devoted to understanding the psychological symptoms over the physical ones. Some studies have failed to find any measurable changes in a woman’s body weight during PMS. But what’s interesting is that despite the fact that there were no changes in body weight in these women, they did show significant abdominal bloating, and they perceived that their body weight had increased. Based on this type of finding, some researchers doubt that water weight gain is the culprit, as has sometimes been suggested.

A woman’s body is going through a lot over the course of a month: the body “prepares” for pregnancy and then scraps that idea if the egg goes unfertilized – and then it does it all over again next month!

Some other studies have suggested that certain compounds that increase the effects of the neurotransmitter dopamine help explain breast tenderness and possibly other physical PMS symptoms, including weight gain. These chemicals also seem to work by decreasing blood levels of the hormone prolactin, which is responsible for milk production during pregnancy. Though some of these compounds are prescription drugs, one is a natural remedy called chasteberry, which can be found at many health food stores. According to the NIH, chasteberry has been used for millennia to reduce PMS symptoms; but since it may affect dopamine levels in the brain – and potentially hormone levels in the body – you should check with your doctor before using the supplement.

Some experts still question whether the physical symptoms of PMS are indeed due to hormone fluctuations in the body or whether they may be the result of women simply being less tolerant of bodily discomfort while they are experiencing mood-related symptoms. For example, if a woman is irritated, moody, and a bit depressed during PMS, it is possible that she would be more sensitive to her body, and perceive physical symptoms as more severe than they actually are. Support for this idea may come from studies like the one mentioned above, in which women felt that they had gained weight, even though they had not.

However, any woman who has experienced PMS will probably agree that there are some very real physical symptoms involved. While the mood symptoms may heighten the physical ones – making a woman more likely to pick up on discomfort and less able to bounce back from it – it seems likely that the complex, and well-documented, hormone changes throughout the month may be also responsible for physical changes to the body. A woman’s body is going through a lot over the course of a month: the body “prepares” for pregnancy and then scraps that idea if the egg goes unfertilized – and then it does it all over again next month! Clearly more research is needed to sort out the underlying causes of the physical PMS symptoms that so many women experience from month to month.

Premenstrual Dysphoric Disorder (PMDD)

Sometimes a woman's premenstrual mental and physical symptoms become severe. Of the ten major symptoms associated with PMS, women who are diagnosed with PMDD must experience at least five of these symptoms regularly, and at least one must be of the first four symptoms (see list below). The American Psychiatric Association (APA) recognizes the following symptoms as part of PMS and/or PMDD:

  • Depression
  • Anxiety
  • Highly changeable moods
  • Anger or Irritability;
  • Problems Concentrating
  • Fatigue
  • Changes in Appetite
  • Sleep Problems
  • Feeling Out-of-Control or Overwhelmed
  • Physical Symptoms (bloating, food craving, breast tenderness, headache, etc., all of which fall into this one category)

Interestingly, the mood-related symptom that is most often reported by women is not depression, but rather irritability.

Women who experience PMDD may have significant problems functioning normally in work, school, and even in social activities and personal relationships during this time. They may often miss days of work or school as a result. In fact, one study found that the degree to which a woman’s life is disrupted as a result of PMDD is on the same level of some of the major mood disorders. As you might guess, because PMDD is largely behavioral in nature, it may coexist with or be intensified by the presence of other mood disorders, such as depression, anxiety, panic disorder, and dysthymia (which is less severe than major depression, but can still be long-term), as well as other personality disorders. While it is separate from these disorders, it is not uncommon for there to be some overlap between them. Interestingly, the mood-related symptom that is most often reported by women is not depression, but rather irritability.

The FDA has approved the three following SSRIs to treat PMDD in addition to depression: sertraline (Zoloft®), fluoxetine (Prozac® and Sarafem®), and paroxetine HCI (Paxil CR®). If you feel that you might suffer from PMDD, it is important to talk to your doctor about what steps to take to treat it effectively.

Treatments for PMS/PMDD

Depending on the severity of PMS, treatments can range from natural remedies to prescription antidepressants. And there are other steps you can take to manage symptoms at home before considering other options.

The U.S. Department of Health and Human Services recommends several treatment methods to try at home. These include:
  • taking multivitamins with folic acid and calcium/vitamin D supplements
  • exercising regularly
  • eating a healthy diet (rich in whole grains, fruits, vegetables, and low in fat and "junk” food)
  • reducing salt intake, which may reduce the tendency to retain water
  • reducing caffeine
  • reducing alcohol intake, especially when PMS symptoms occur
  • not smoking
  • finding effective ways to manage and reduce stress

Eating several small portions of complex carbohydrates throughout the day has also been shown to reduce symptoms, probably due to the amino acid tryptophan that is present in complex carbs. Tryptophan is a precursor of serotonin, which is the target of SSRIs (see below), so it may act by helping the brain produce more serotonin. For physical symptoms like cramping, headaches, and muscle aches, you may try over-the-counter medications like ibuprofen or acetaminophen for temporary relief. Medications that are designed specifically for PMS symptoms like Midol® may also be of help. Exercise helps too. Women who exercise regularly or who were sedentary and begin add exercise to their routine report fewer physical and psychological symptoms than women who don’t exercise.

As mentioned earlier, chasteberry has shown to be somewhat effective at reducing some of the physical symptoms associated with PMS. Another study found that it was also effective at reducing PMDD symptoms – in fact, it was just as effective as the SSRI fluoxetine (Prozac® or Sarafem®) in terms of the number of women who responded to it. Fluoxetine was more effective at reducing the psychological symptoms, however, while chasteberry was better at attacking the physical symptoms of PMDD. There may be other natural remedies that could be effective at reducing PMS/PMDD symptoms, but it’s important to research these products thoroughly and talk to your doctor before putting anything new in your body. “Natural” compounds are still chemical compounds, just like prescription drugs, and can affect the body in significant ways.

SSRIs like sertraline (Zoloft®), fluoxetine (Prozac® or Sarafem®), and paroxetine HCI (Paxil CR®) have been shown to work for PMS/PMDD in many cases, and are more effective than other kinds of antidepressants in treating symptoms, and are much more effective than placebo. As researchers have pointed out, this finding, along with the fact that SSRIs work much more quickly on PMS symptoms than they do on depression symptoms, implies that their effects are larger than simply acting as antidepressants. This idea is also supported by the fact that SSRIs help alleviate physical as well as psychological symptoms of PMS.

While adjusting the hormone levels in the body may seem intuitive at first glance, as mentioned earlier, since it is unlikely that women who experience PMS actually have a hormone imbalance, this method has not produced any notable effects. What’s been more effective is to give women a compound that increases the effects of the hormone GnRH,(gonadotropic releasing hormone) discussed earlier. This treatment, while somewhat extreme, has been more successful than giving either estrogen or progesterone. However, because this treatment does stop a women from cycling, women receiving GnRH experience some of the unwanted symptoms of menopause. Adding estrogen or progesterone along with the treatment has been effective at alleviating some of the menopause-like side effects.

Final Thoughts

If you feel that you are suffering from PMS or PMDD, it’s important to talk to your doctor about the best ways to manage it. These disorders are real phenomena; they have biological underpinnings that have been well-studied over the years and are, for the most part, well-understood by the medical community. In other words, PMS is not something made up by women to excuse their own moodiness or one made up by men to blame it on. Both the psychological and physical components of PMS should be taken seriously, and there are effective ways to manage both. The female body does a phenomenal amount of work over the course of a month, and while the symptoms of PMS are not always fun, the female reproductive system is remarkable and complex (if a bit mysterious!), and something to be celebrated.

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