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Perimenopause

Perimenopause—the transition from reproductive adulthood to menopause (1 year after the last menstruation) is called perimenopause. Perimenopause may begin as early as age 35 and end as late as 59. Even when cycles remain regular, experiences change.

1. The jobs of perimenopause are to adjust to the idea of becoming older and no longer able to bear a child and to get rid of all our remaining ovarian eggs so that we don’t end up with periods in a nursing home! It is important during perimenopause to learn to both “take care of” ourselves and feel good about it (perhaps after years of feeling we must care for others). Finally, perimenopause requires us to be learn to cope with unpredictable flow, changing experiences, night sweats/hot flushes or flashes (for many) and sleep disruption (for most).

2. It is normal in very early perimenopause to experience changes in flow, fertility, sleep, cramps, night sweats and headaches while still having regular menstruation. Because more eggs are “recruited” and stimulated each cycle, estrogen levels become higher and unpredictable and ovulation, if it does occur, has lower-than-normal progesterone levels. It is also normal to gain weight (approximately 5 kg over the entire 5-10+ year span). From irregular cycles until a year beyond the last flow is approximately four years. It is normal for a quarter of women to experience heavy flow and many women to have an inexplicable decreased interest in sex.

3. Perimenopausal women need accurate information about the time course and expected changes of perimenopause, courage to face the future as no longer young or fertile women, flexible work and home responsibilities and effective and contraception and treatments for heavy flow, hot flushes/flashes and night sweats.

4. Many things can go wrong in perimenopause including combined physical and emotional disorientation, heavy or flooding menstruation (in 25%), hot flushes/flashes and night sweats for almost 80% (but frequent/intense in only 9%), sleep disturbances, sore breasts or lumps, unwanted pregnancy, development of high blood pressure, arrhythmias, chest pains and obesity (for some), increased falls and fractures and disruption of work, home and family lives (for a few). It is extremely valuable to know what may be ahead and to appreciate why it is happening, to have someone trusted to talk with and to make a commitment to regular exercise and a healthy diet. Heavy flow is helped by ibuprofen (http://www.cemcor.ca/resources/very-heavy-menstrual-flow) and by taking progesterone for 14-21 days each cycle as described here. Cyclic progesterone also helps with very early perimenopausal premenstrual breast, fluid, mood and night sweat symptoms as well as improving sleep. In summary, perimenopause is a potentially long (10+ years), variable, unpredictable and poorly understood time of women’s lives—it is as different from menopause as chalk from cheese. With information, basic good health and some skilled support we can all survive “estrogen’s storm season”.

Relevant Topics

Fertility

Fertility—in its broadest sense—for women means being able to become pregnant and to deliver a baby.Too often in thinking of fertility we ignore men's important part in this process; problems with a man, although less well documented, likely account for half of all infertility.

Fertility in women requires a lot of things to be optimal—we require normal anatomy (ovaries, open and working fallopian tubes, uterus, cervix and vagina), regular menstrual cycles (having enough estrogen) and ovulation (egg release) providing an egg that can be fertilized. In addition, the corpus luteum from which the egg is released needs to provide enough progesterone and keep providing it for at least 12 days (so that the endometrium will be prepared for the fertilized egg to implant). Obviously we have to be interested in and have sex at the right time in the cycle. We are usually most fertile from the start to the end of stretchy midcycle mucus. It is essential also to have normal immune function that is compatible with the sperm so that the egg doesn't block sperm fertilization and so that the fertilized egg is not blocked from implanting into the uterus. After all that, the corpus luteum needs to continue to make enough progesterone to support the implanted egg until about 12 weeks into the pregnancy at which time the placenta takes over making progesterone.

Thus fertility is a multi-organ, multi-system complex process that usually works quite normally.

Fibroids

Fibroids are non-cancerous little balls of muscle that start in the uterus's muscle wall and grow in response higher levels of estrogen. Most women after about age 30 are growing fibroids; however, most of us will never have any problems related to them. Very rarely fibroids can interfere with pregnancy, or grow so big that they cause urine or bowel blockage, bladder symptoms or pain. Fibroids shrink when women become menopausal.

Most women first learn that they have fibroids when they develop heavy flow (often in perimenopause). Because there is the wrong understanding that fibroids cause heavy flow, many family doctors will then order a uterine ultrasound. Very commonly this ultrasound shows fibroids. However that doesn't mean that the fibroids are causing the heavy flow. Higher estrogen levels cause both heavy flow and fibroid growth.

Fibroids tend to grow in three directions—within the muscle (the most common situation), pushing outside of the uterus (called subserosal or, if on a stalk, pedunculated) and into the endometrium (called submucosal). Submucosal fibroids are the only one of these three kinds of fibroids that could potentially cause abnormal vaginal bleeding—they make up less than 1 of every 10 fibroids. Instead, heavy bleeding is caused by the higher estrogen and lower progesterone levels of perimenopause and these hormonal changes make fibroids grow. Remember that fibroids are common and usually cause no problems.

Cramps and painful periods

"Cramps" is the common name for painful periods or what doctors call dysmenorrhea. Cramps typically start just before and are most severe during the first days of menstrual flow. Younger women and those who have never been pregnant or delivered a baby are more likely to have and to have worse cramps. Interestingly, cramps also seem to increase in perimenopause (the transition to menopause). The pain of cramps is due to increased release by the lining and muscle walls of the uterus of a fatty hormone called a prostaglandin. More prostaglandins are made when the opening of the uterus is very tight (and therefore pressure inside it builds to high levels) and also when estrogen levels are higher. It is likely (but not yet adequately studied) that higher progesterone levels counterbalance estrogen's effects and decrease cramps. Painful periods can be effectively treated with ibuprofen, an over-the-counter pain pill that is from the "anti-prostaglandin family". Ibuprofen (400 mg or two 200-mg tablets) must be taken at the first hint of cramps and a further 200 mg tablet taken as soon as the pain begins to return (even if that is only an hour later). If you wait, ibuprofen won't help because ibuprofen works to prevent the formation of the prostaglandins that the cause the pain.

Hot flushes

Hot flushes (flashes in the USA) and night sweats are a common and mysterious experience of midlife and menopausal women. They are episodic, start suddenly, last a few minutes and make us feel too hot with/without sweating. Night sweats are hot flushes occurring during sleep—they may or may not cause wakening. Although previously hot flushes were thought to be caused by low estrogen levels, in their brain actions, hormonal associations and experiences, they closely resemble an addict's drug withdrawal. CeMCOR attributes hot flushes to "estrogen withdrawal." The key trigger appears to be a dropping estrogen level (from high to normal or normal to low). Stopping estrogen hot flush treatment can make hot flushes worse than before estrogen was started.

How do dropping estrogen levels cause hot flushes? They trigger the release of norepinephrine, a brain stress hormone, as well as a "dog's breakfast" of other brain and stress hormones. Norepinephrine narrows the range of body temperatures in which we feel comfortable (thermoneutral zone); we both get too hot when it is only a little warm and too cold when it is only a little cool.

Hot flushes are worse when we are under stress (not just emotional stress but also being in pain or depressed), when we are overweight (especially in perimenopause), if we have irregular times for eating and sleeping and if we smoke. Hot flush strategies and treatments are effective when they decrease our responses to stressful situations. These successful strategies include regularly exercising, learning and practicing relaxation/meditation/slow, deep yoga-type breathing, eating and (as much as possible) sleeping regularly. Many herbal and alternative therapies improve hot flushes somewhat; the "placebo-response" to anything we believe will help us reduces hot flushes by 20 to 50 percent.

Although estrogen is the classical hot flush therapy, estrogen with progestin is more effective than estrogen alone; progestins alone are as effective as estrogen. Recently CeMCOR proved that natural progesterone is both effective and safe for menopausal hot flushes; there was no rebound increase in hot flushes when progesterone was stopped. CeMCOR is currently doing a Canada-wide study of progesterone for perimenopausal hot flushes (/studies/perimenopausal-hot-flush-study).

Night sweats (/resources/topics/night-sweats) mean hot flushes (or hot flashes) that occur during sleep. Night sweats appear to be many women's first experience of hot flushes. CeMCOR scientists found that night sweats that occurred only intermittently across the cycle were more likely to occur around menstruation for women in very early perimenopause. At the time, these early perimenopausal women had regular cycles and few daytime hot flushes.

Insulin resistance

To understand Insulin Resistance we must start with insulin. Insulin is a hormone made in the pancreas whose job is to bring fuel, which is sugar, into the cells that need it. Insulin levels are normal low overnight when we're not eating and increase very quickly after food, especially sweets. If we are totally without insulin (called Type 1 Diabetes Mellitus) we will die as our cells starve. However, today, at least in the developed world, sugary and highly processed foods are in abundance, obesity and inactivity are common and the result is increased insulin resistance.

Insulin Resistance means that we can make insulin but that insulin can't do its job of getting sugar into cells. Therefore our body must make more insulin. Insulin is a growth stimulator, especially of fat around the organs in our bellies and fat within the liver. Also, although it is complex, higher insulin levels make us hungrier! This vicious cycle leads to Type 2 Diabetes in which we have enough insulin, but not enough insulin action. Insulin resistance is also related to higher risks for heart disease, stroke and some cancers.

Insulin resistance used to begin in older aged men and women but now it is occurring in younger and younger people, even in children. Insulin resistance tends to run in families that had elders or anyone diagnosed with Type 2 Diabetes. However, we are all at risk. The best sign of insulin resistance is a big belly—a waist circumference (at the level of the waist or half way between the top of our hip bone and our lowest rib) of more than 88 cm in white women or more than ___ in Asian women; in white men the insulin resistance means a waist circumference of more than 102 cm or more than ____ in Asian men. An even better measure is waist circumference divided by height which should be no greater than half (0.5%).

The best ways to prevent insulin resistance are to be physically active (at least a half an hour of moderate exercise a day) and to avoid simple sugars (candy, sugary drinks, deserts). An inexpensive medicine called "Metformin" can be prescribed to help our insulin work better and to decrease inappropriate hunger.

Night sweats

Night sweats mean hot flushes (or hot flashes) that occur during sleep. Night sweats appear to be many women's first experience of hot flushes. CeMCOR scientists found that night sweats that occurred only intermittently across the cycle were more likely to occur around menstruation for women in very early perimenopause. At the time, these early perimenopausal women had regular cycles and few daytime hot flushes.

We know less about night sweats than we do about hot flushes since many studies do not track them separately from daytime ones. When night sweats become more intense and sweaty they are more likely to us wake up. Even if we aren't startled awake feeling too hot and sweating, night sweat occurrence during the night may make us feel we've had a less-than-restful sleep.

Like hot flushes, night sweats are more common when we are stressed, overweight or obese, physically inactive or smokers. Improving our responses to stress (relaxation/meditation/yoga breathing), losing weight so we have a normal weight, exercising regularly and stopping smoking will all improve night sweats. Anything we believe will help (like a placebo in a controlled trial) will improve night sweats about 20-50 percent. Night sweats are classically treated with estrogen and even more effectively with estrogen and a synthetic form of progesterone (progestin). CeMCOR scientists recent showed in a randomized controlled trial that natural progesterone was effective for treating night sweats and hot flushes in healthy women within 10 years of starting menopause. Although progesterone is effective in improving sleep, it similarly improved daytime hot flushes and night sweats.

Progesterone therapy

Progesterone is women's second important and essential hormone and a partner of estrogen. Wherever estradiol is acting in women's bodies (bone, brain, breasts, uterus, skin and everywhere), progesterone is also acting. Women have two reproductive hormonesestrogen and progesterone. Men only have one (testosterone).

Progesterone therapy means taking natural progesterone (oral micronized progesterone) that is bio-identical. If, for cost reasons, a progestin must be substituted, medroxyprogesterone is the closest in action to progesterone (and, like progesterone, also improves hot flushes and increases bone density). Progesterone must be given at bedtime since its major "side effect" (smile) is to improve sleep; it is effective in a dose of 300 mg at bedtime daily which keeps the serum progesterone at or above the luteal phase level for a full 24-hour day.

Cyclic progesterone, for menstruating women of any age, means progesterone for the last two weeks of a menstrual cycle or of a month. Based on a randomized controlled trial, this treatment with cyclic progesterone increases spinal bone density and provides regular flow for women who have reversible (usually stress-related) reasons their periods have stopped or are far apart. Cyclic progesterone is also an essential therapy for premenopausal women with anovulatory androgen excess (AAE)(also called polycystic ovary syndrome [PCOS]) because it prevents endometrial cancer, slows the pulse frequency of luteinizing hormone (LH) thus decreasing testosterone production, provides regular menstrual-type flow and blocks the formation of the skin hormone that causes pimples and unwanted face hair. Cyclic progesterone is also a safe and effective treatment of perimenopausal cyclic night sweats (that occur around the time of flow for women whose cycles are still regular). In perimenopause, cyclic progesterone may also (especially if ibuprofen is also taken) help decrease heavy flow. Cyclic progesterone also helps with the sleep and premenstrual symptoms in perimenopause.

Early menopause (before age 40) can be treated with estradiol and cyclic or daily progesterone. This treatment is continued until a woman becomes age 50-52. With cyclic progesterone those women young enough to want regular flow will achieve it when estrogen is given in a long cycle (from the first to the 25th of the month) and progesterone from the 14 to the 27th. (Note—this is the only time ovarian hormone therapy is truly "replacement.")

Progesterone (taken daily) is effective treatment of menopausal hot flushes as shown by a CeMCOR randomized trial. Daily progesterone also significantly improves sleep in menopausal women (based on three controlled trials). In short, progesterone is effective therapy for women's menstrual cycle disturbances or perimenopause and menopause-related problems.

Sleep disturbances

Restful sleep is essential for health and well-being. Sleep disturbances may arise from many situational stresses, feeling anxious or sad, from illness or pain, related to night sweats or due to the environment (a nursing baby, a snoring partner or unpredictable noises in the neighborhood). Sleep plays an essential role in our circadian rhythm—around-the-clock timing related to eating, temperature, reproduction and all fundamental processes necessary for the health of all of our tissues.

Natural progesterone helps sleep when given in therapy doses (300 mg at bedtime) by mouth as oral micronized progesterone (but not as progesterone cream or even vaginal progesterone). This sleep-inducing effect of progesterone has been proven in controlled trials in men as well as in menopausal women.

Progesterone shortens the time to fall asleep, lessens night time awakening and increases total sleep time while not being addicting or causing morning "hangover" effects. After three months of taking progesterone women's morning responses on a whole battery of memory and other brain tests were unchanged or improved compared to themselves when not on progesterone. In the first nights of taking progesterone, you can feel dizziness or "drunk" if you are awakened within an hour or two of taking it. And, if you are really behind on rapid-eye-movement sleep, you might feel like sleeping in to catch up when you first take progesterone. Finally, progesterone is safe from overdosing since it is the only sleep-promoting medicine that speeds rather than slowing or stopping breathing.

Join a Study:

Hot and Bothered? Perimenopausal Women Needed for Hot Flush Study

CeMCOR is now recruiting Canadian women for this CIHR-funded randomized controlled trial to test whether oral micronized progesterone is more effective than placebo as therapy for hot flushes and night sweats in perimenopausal women.

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