THE MYSTERY. Changes in sex hormonal function during the menstrual cycle, whether the cycle is regular or irregular, can have profound effects on a woman’s sleep. Pregnancy can impact sleep. A common disease of the ovaries can cause sleep apnea.
The Case of the Sleepy Woman with Irregular Periods
After almost five years of suffering from severe daytime sleepiness that made her unable to hold a job because she could not stay awake, a twenty-nine-year-old woman had reached the end of her rope. For months she had been awakening every morning with a headache. Her family doctor noted that these headaches, combined with the daytime sleepiness, were becoming progressively more serious and having a negative effect on the quality of her life. Her doctor also noted that she had been snoring loudly since she was a teenager. She was referred to the sleep disorders center where I work for both her snoring and her sleepiness problem.
Her examination at the sleep center revealed she was overweight: at five foot five she was 160 pounds. What was more unusual about her was that she had more facial hair than is normal for a woman and very hairy arms and legs as well as hair on her chest between her breasts. The medical term for this pattern of excess hair is hirsutism. When I asked about her menstrual cycle she told me that her periods were very irregular; for many months she had not had a period at all. But what, she asked, could her menstrual cycle have to do with her sleep patterns? In her case, everything.
The Menstrual Cycle
In most females, starting about age twelve the menstrual cycle is monotonously regular, lasting about twenty-eight days, the same duration as the lunar cycle. Genes were identified in 2009 that play a role in controlling the age that menstruation begins. Certain genes control the body’s circadian rhythm (see Chapter 8), and some of these genes are affected by the menstrual cycle, perhaps because of the accompanying profound changes in hormone levels. What starts each cycle remains a mystery. Research reported in 2015 showed that variations in the genes that control the circadian system can lead to irregular menstrual cycles.
According to the 2007 National Sleep Foundation poll of over a thousand women, 60 percent of American women get a good night’s sleep only a few nights each week or less and 67 percent frequently experience a sleep problem. Additionally, 43 percent say that daytime sleepiness interferes with their daily activities. The sleep problems affect almost every aspect of their lives. They might leave home late or perform poorly at work, be too stressed or fatigued for sexual activity, or have little inclination to socialize. Sleep problems are experienced by women of all ages and increase in severity as they move through the different biological stages of their lives, which involve dramatic changes in the levels of reproductive hormones. The menstrual cycle is the most basic rhythm of a woman’s life, yet millions of women have disturbed sleep because of menstrual symptoms.
Reproductive or sex hormones affect many organs of the body, including the brain: an abnormal amount and type of sex hormones can be the cause of serious medical and sleep problems. For example, women are more likely to develop symptoms related to depression at times when the levels of these hormones are increasing or decreasing—during puberty, in the days before menstruation, after giving birth to a baby, or before and after the onset of menopause. Not coincidentally, depression is also associated with sleep problems. People with sleep problems are much more likely to be depressed.
As complex as an orchestral piece, the menstrual cycle requires the proper sequencing of hormones and activities in at least four different tissues of the body: the hypothalamus and pituitary gland, which are in the central nervous system; the ovaries; and the uterus. The cycle is made up of three distinct phases:
1. Follicular phase. One of the dormant eggs in the follicle in the ovary develops, and at the same time the lining of the uterus begins to prepare itself to nourish a fertilized egg.
2. Ovulation. On day fourteen (in most women), midway through the monthly cycle, the egg is released and makes its way into the fallopian tube.
3. Luteal phase. The uterine lining thickens in preparation for possible fertilization. If fertilization does not occur, the lining of the uterus is shed. This causes the menstrual bleeding. The cycle then repeats.
Every woman is intimately familiar with the rhythms of her menstrual cycle, but not every woman realizes how the three phases can affect the quality and quantity of her sleep. Simply put, the level of hormones fluctuates intensely, swinging between low and high levels each month in women of childbearing age, and affecting many tissues of the body, including the nervous system, which controls sleep. Disruptions in sleep can occur during the regular menstrual cycles, and more serious sleep problems can occur in three conditions linked to hormonal changes: premenstrual syndrome (PMS), premenstrual dysphoric disorder (PMDD), and polycystic ovarian syndrome (PCOS).
Sleep Patterns of Women with Normal Menstrual Cycles
For most women who have regular periods, the menstrual cycle is not associated with sleep complaints, although research studies have found that there are subtle changes in the amount of sleep women get and in the levels of daytime sleepiness they experience. Research published in 2016 reported that the most frequent sleep disruption occurs when hormone levels change the most quickly: during ovulation and immediately before menstruation. At these times women may experience a few nights of sleeplessness. Some women, however, do not notice a change in their sleeping patterns, or might feel only slightly sleepier. Women with irregular cycles experience greater sleep disruption.
Women typically sleep the most during the early follicular phase. In the days before ovulation, the estrogen levels increase and the amount of rapid eye movement sleep also increases slightly. Women sleep the least during ovulation. This is probably because of the effect on the brain of high levels of hormones that cause ovulation.
In the third phase of the cycle, there is an increase in progesterone, which causes the body temperature to rise. The number of brief awakenings is highest in the few nights right before bleeding starts, when levels of progesterone and estrogen are both dropping. Women might find themselves sleeping fitfully. In the late luteal phase, many women report that it takes them longer to fall asleep, they sleep less, and the quality of the sleep is poor compared with that at the beginning of the cycle.
Some otherwise normal women may develop very severe incapacitating sleepiness during menstruation. Birth control pills can be effective in preventing the sleepiness.
Some women have painful cramps before and during menstruation, which can cause wakefulness. Many women find it hard to get to sleep during this stage, and after they fall asleep they tend to have less REM sleep and a slightly elevated body temperature. Such women are likely to be sleepier than normal.
Women who take birth control pills, which control the menstrual cycle, may have different sleep patterns from those who use other types of contraception. The main effect of the pills is to prevent ovulation, so women who use birth control pills may not experience the mild effects on sleep related to ovulation. These women may still have symptoms related to menstruation, but some women who have severe sleep difficulties during menstruation might find that the symptoms were less severe than they were before they began using the pill.
Sleep and Other Problems Related to PMS or PMDD
Women with PMS exhibit a variety of symptoms (trouble sleeping, irritability, mood changes, bloating) before menstruation. According to a 2012 study, about 76 percent of women with PMS experience sleep difficulties.
Most women who have PMS experience the symptoms a few days before the start of menstrual bleeding (the late luteal phase). Usually the symptoms end when the bleeding starts or within two to three days afterward.
Scientists have been unable to pinpoint a single mechanism that causes PMS because many hormonal and chemical changes occur before menstruation, and each woman with PMS probably has a more or less unique combination of symptoms caused by a unique combination of chemical changes. Because the symptoms vary so greatly, doctors should consider other potential disorders that have similar symptoms when diagnosing PMS. Symptoms such as sleeplessness, hot flashes, and a rapid heart rate might be found in hyperthyroidism (excess thyroid production) or menopausal transition. Tiredness could be caused by hypothyroidism (inadequate thyroid production). Some experts believe that in a small number of women, abnormal thyroid function may lead to symptoms of PMS. And in some women, the sleep problems and mood swings associated with PMS might actually be symptoms of depression.
We can divide the symptoms of PMS into two general categories: those that affect the nervous system and those that affect other parts of the body. The nervous system symptoms include problems sleeping (which can be severe), mood swings, irritability, anger, headaches, memory loss, and tremors. The symptoms involving other parts of the body include breast swelling, fluid retention, muscle aches, nausea, and vomiting. Most women with PMS have only a few of the symptoms, however, though many have trouble sleeping and may experience daytime sleepiness.
For a diagnosis of PMS, the symptoms should be present over several consecutive menstrual cycles and be severe enough to interfere with the woman’s mental state and activities of daily living. Because the range of symptoms affecting almost all the organ systems of the body is staggering, a diagnosis of PMS is still a difficult one to make. As yet we have no standard test that can confirm such a diagnosis. Women may go to various doctors, sometimes for years, before their PMS is diagnosed.
Because women with PMS exhibit so many differing symptoms, the treatment is not specific to the syndrome (whose cause is still unknown) but is based on the symptoms themselves, with the expectation that the symptoms will disappear after menstruation begins.
Three approaches to the type of medication to help PMS and its effect on sleep are common:
· Relief of specific symptoms such as pain
· Change of hormone levels
· Prevention of the mood disorders before they occur
If a woman has been experiencing pain (tender breasts, severe cramps), the doctor might suggest an over-the-counter pain medication that has anti-prostaglandin properties (also called nonsteroidal anti-inflammatory medications or NSAIDs). In the United States, examples of NSAIDS available over the counter include those containing ibuprofen (Advil, Motrin, Nuprin, and Midol 200) and those containing naproxen (Aleve). Generic versions of these medications are also available. Check with a pharmacist before choosing a medication. For bloating and water retention, a doctor may prescribe a mild diuretic. These medications are not taken daily, only when symptoms are severe.
The medications that change mood and hormone levels are powerful and have potentially severe side effects, and women should take them only in consultation with their doctor. Antidepressants approved by the U.S. Food and Drug Administration (FDA) for the treatment of severe PMS and PMDD include Prozac (fluoxetine), Zoloft (sertraline), and Celexa (citalopram). The FDA has approved a contraceptive medication called Yaz as well to treat the symptoms of PMS. I don’t recommend any of these drugs if the main or only symptom being treated is sleeplessness. If the sleeplessness is caused by PMS, it will improve in a few days after bleeding begins.
The effect of long-term use of these drugs on PMS is not known, so the patient should discuss the pros and cons of the drugs with her doctor. Remember, the symptoms generally disappear once menstruation begins, so the best approach might be to take nothing. This is especially true if the woman is planning on getting pregnant in the near future. If the woman becomes pregnant while taking these medications, she should contact her doctor at once.
Medications are not the only way to counteract sleeplessness caused by PMS. Women who notice that it is taking them much longer than usual to fall asleep or who are waking up frequently at night should reduce caffeine intake as a first step. (At the very least, they should stop drinking coffee or tea after lunch.) Similarly, although many people believe that alcohol will help them fall asleep, it can also cause them to wake up later on in the night, disrupting their sleep. Women with PMS should therefore avoid alcohol at night. Women who have repeatedly experienced disrupted sleep during their menstrual cycle often expect to have a bad night’s sleep before menstruation. The expectation of a bad night causes stress and can itself lead to a bad night. Women may benefit from learning relaxation methods that reduce the stress caused by the expectation of a bad night. If the sleep problem is very severe and does not respond to the treatments for PMS, the sleep problem may not be related to PMS. In that case, other types of problems should be considered. If the sleep difficulty remains severe, the woman should seek help from a gynecologist.
If mood and nervous system premenstrual symptoms are very severe, they might indicate a more serious problem, premenstrual dysphoric disorder (PMDD). If, along with the symptoms of PMS, a woman experiences symptoms of depression (hopelessness, severe sadness, or thoughts of suicide; see Chapter 16) or anxiety, wide mood swings, severe uncontrollable anger or irritability, and marked problems with sleeping, she may be suffering from PMDD. A woman with PMDD might experience severe insomnia and have extreme difficulty falling asleep and staying asleep. She might awaken very early in the morning and not be able to fall asleep again. Some patients with bipolar disease are misdiagnosed as having PMDD. Doctors whose patients experience severe problems that worsen before menstruation should evaluate these symptoms carefully when making their diagnoses. Up to 75 percent of women with PMDD notice an improvement in their symptoms with antidepressant treatments. Research from Japan reported in 2016 showed that increasing fish consumption improves performances in athletes with PMDD!
Sleep and Other Problems Related to PCOS
Most tissues that produce one hormone are capable of producing other chemically related hormones. In most women with polycystic ovarian syndrome (PCOS), the ovaries produce too much of the male sexual hormones (androgens). Research reported in 2015 suggests that women can have one of four variations of PCOS. In one type, there is excess male hormone production with abnormal ovulation and ovarian cysts. In the second type, excess male hormone production also occurs, accompanied by abnormal ovulation but without ovarian cysts. In the third type, excess male hormone production is accompanied by ovarian cysts but normal ovulation. In the fourth type, ovarian cysts and abnormal ovulation occur but without increased male hormone production. It is likely that in women with the second type (without ovarian cysts) fat cells might be producing the excess male hormone.
When there are high levels of male hormones in women, this may lead to low levels of follicle-stimulating hormone. As a result, the eggs in the follicles might not develop. The follicles swell and form collections of fluid called cysts, and many follicles with undeveloped eggs can form these cysts, hence the name “polycystic.” The ovaries sometimes increase in size dramatically, becoming as large as a baseball, or even larger. These abnormal hormone levels cause two sets of problems: as shown in the twenty-nine-year-old patient, women may develop excess hair and other features normally found in males, or they might experience problems with their reproductive system. Such severe symptoms might seem unusual, but PCOS is in fact a common disorder, found in about 5 to 20 percent of premenopausal women. In about a quarter of teenage girls who don’t menstruate, PCOS is the probable cause.
The most common symptoms of PCOS are male hair distribution, over-weight, and problems with the menstrual cycle or difficulty in becoming pregnant. The problem may first become apparent when a woman is being investigated for infertility. Women with PCOS, for example, may have facial hair or develop acne well past the teenage years, in their twenties and thirties, and might even develop baldness. Infrequent menstrual cycles and even complete cessation of menstruation are common in PCOS patients. Women with PCOS also develop a resistance to the effect of the hormone insulin, which usually lowers blood sugar. This can lead to diabetes in about 10 percent of women with this condition and an increased risk of cardiovascular disease. These women also have abnormal blood lipids, which increases their risk for heart disease; because of their excess weight and the male distribution of the extra weight, they are much more likely to develop obstructive sleep apnea. (It is not just the weight that leads to the apnea, but the location of the fat tissue. Women with PCOS have a male fat distribution—that is, the waist increases more than the hip size. PCOS women have a larger waist-hip ratio than the other women and much higher levels of testosterone.)
If a woman is obese and has acne and facial and body hair in a distribution normally found in men, PCOS should always be suspected. Abnormal or absent periods and infertility are common. Diabetes, hypertension, and sleep apnea may also be present. In one study reported in 2014, 66 percent of women with PCOS were shown to have a sleep-breathing disorder. These patients snore, stop breathing during sleep, and experience daytime sleepiness. Women with PCOS who suffer from sleep apnea are also much more likely to have metabolic problems and nonalcoholic fatty liver disease.
Women who suspect they have this condition should see a doctor, especially if they want to become pregnant. Losing weight can be very effective in helping to manage the hormonal changes, and may also help alleviate the sleep-breathing problem. Metformin, a medication often prescribed for diabetics, increases the response to the insulin produced by the body; this can improve the symptoms of PCOS and may normalize the menstrual cycle. For some women, metformin can also lead to weight loss, which leads to a decrease in male hormone production and an improvement in the body’s ability to respond to insulin, important in controlling diabetes. Sometimes even a relatively small weight loss can lead to dramatic improvement in the chance for a successful pregnancy or normal menstruation; it may also help relieve sleep apnea. If the patient is unable to lose weight, an effective treatment to relieve sleep apnea is continuous positive airway pressure (CPAP) treatment, which I discuss in Chapter 12. Patients wear a mask attached by a hose to a device that generates pressure and keeps the breathing passage open. Recent research suggests that the apnea may itself reduce the effectiveness of the hormone insulin. Reduced insulin levels or decreased insulin effects play an important role in diabetes, and treatment of the apnea in PCOS may improve diabetes in these patients.
Back to the the Sleepy Woman with Irregular Periods
My twenty-nine-year-old patient’s irregular periods were caused by a disease that made her ovaries produce too much male hormone (hence the irregular periods) and resulted in a disorder that is more common in men than women: sleep apnea. An overnight sleep test showed that she stopped breathing repeatedly, about once a minute, while she slept. When she was asleep the muscles in her throat relaxed and the upper breathing passage became blocked, which caused her breathing to stop. Each time this happened, the level of her blood oxygen dropped to a dangerously low level, and her brain would wake her up in order to open up the breathing passage and start her breathing again. This happened hundreds of times during the night, and was the cause of her snoring, her severe sleepiness, and her headaches.
Cysts in the patient’s ovaries had produced too much male hormone. She had the symptoms of PCOS. The male hormone also caused her to have abnormal periods, to be overweight, and to have a male distribution of body hair. To relieve the immediate problem of daytime sleepiness and headaches and improve her quality of life, she was started on CPAP, and as a result her morning headaches stopped within days. She is now seeing a gynecologist to manage her menstrual problems and trying to lose weight, and she feels great. The sex hormones affect women’s bodies in profound ways, and for this patient, abnormal sex hormones had caused a sleep disorder that had jeopardized her life.
Most women (about two-thirds) experience some form of sleep disturbance linked to menstruation. Although medical science has learned to better understand and help women with these problems, women should be aware that menstruation causes sleep problems and that PMS can make sleep problems worse. Nowadays, however, these sleep problems can be treated once they have been identified.