Menopause

The word menopause literally means the permanent physiological, or natural, cessation of menstrual cycles, from the Greek roots 'meno' (month) and 'pausis' (a pause, a cessation). In other words, menopause means the natural and permanent stopping of the monthly female reproductive cycles, and in humans this is usually indicated by a permanent absence of monthly periods or menstruation.

The word is commonly used in regard to human females, where menopause happens more or less in midlife, signaling the end of the fertile phase of a woman's life. Menopause is perhaps most easily understood as the opposite process to menarche.

Menopause in women cannot however simply be defined as the permanent "stopping of the monthly periods", because in reality what is happening to the uterus is quite secondary to the process. For medical reasons, the uterus is sometimes surgically removed (hysterectomy) in a younger woman, and after this her periods will cease permanently and the woman will technically be infertile, but as long as at least one of her ovaries still functions, the woman will not have entered menopause. This is because even without the uterus, ovulation, and the release of the sequence of reproductive hormones that are an essential part of the reproductive cycles, will continue until the time of menopause is reached.

Menopause is triggered by the faltering, shutting down, or surgical removal of the ovaries, which are a part of the body's endocrine system of hormone production, in this case the hormones which make reproduction possible and influence sexual behavior.

The process of the ovaries shutting down is a phenomenon which involves the entire cascade of a woman's reproductive functioning, from brain to skin, and this major physiological event usually has some effect on almost every aspect of a woman's body and life.

Overview

Menopause starts as the ovaries begin to fail to be able to produce an egg or ovum every month. Since the process of producing and ripening the egg is also what creates several of the key hormones involved in the monthly cycle, this in turn interrupts the regular pattern of the hormone cycles, and gradually leads to the somewhat chaotic and long-drawn out shutting down of the whole reproductive system.

The break-up in the pattern of the menstrual cycles not only causes the levels of most of the reproductive hormones to drop over time, but also causes the reproductive hormones to fall out of phase with one another, which often leads to extreme and unpredictable fluctuations in the levels, which itself can cause numerous symptoms in most women, such as hot flashes.

After a number of years of erratic functioning, the ovaries almost completely stop producing the estrogen hormones, and progesterone. Decrease in testosterone levels begins gradually in young adulthood, but testosterone levels are thought not to drop significantly during the menopause transition, because the stroma of the postmenopausal ovary, and the adrenal gland, still continue to secrete small amounts of testosterone even during post-menopause.

Because of the various hormonal changes, the reproductive system ceases to function.

One of the first signs of menopause experienced by most women, is a menstrual cycle that changes in length, becoming either shorter or longer. This is caused by estrogen levels (estrogen maintains the regular length of your cycle), as menopause approaches and estrogen levels fall, the amount and length of bleeding in a period may become erratic.

Age of onset

The average age of menopause is 51 years. The normal age range for the occurrence of menopause is somewhere between the age of 45 and 55.

Last period ever occurring between the ages of 55 to 60 is known as a "late menopause". An "early menopause" on the other hand is defined as last period ever between the age of 40 to 45.

Rarely the ovaries stop working at a very early age, anywhere from the age of puberty to age 40, and this is known as premature ovarian failure (POF), also commonly referred to as "premature menopause" or "early menopause." 1% of women experience POF, and this is not considered to be due to the normal effects of aging. Some known causes of premature menopause include autoimmune disorders, thyroid disease, diabetes mellitus, chemotherapy, and radiotherapy, however, in the majority of spontaneous cases, the cause is unknown.

Premature menopause is diagnosed or confirmed by measuring the levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH); the levels of these hormones will be abnormally high if menopause has occurred. Rates of premature menopause have been found to be significantly higher in fraternal and identical twins; approximately 5% of twins reach menopause before the age of 40. The reasons for this are not completely understood. Transplants of ovarian tissue between identical twins have been successful in restoring fertility.

Menopause in other species

Menopause in the animal kingdom appears perhaps to be somewhat rare, although this has not been thoroughly researched. However, it is already quite apparent that humans are not the only species that experience it. Menopause has been observed in rhesus monkeys, some cetaceans, as well as in a variety of other species of vertebrates including the guppy, the platyfish, budgerigars or “parakeets”, laboratory rats and mice, the opossum, and all manner of primates

Menopause in human evolution

The Grandmother hypothesis suggests that menopause evolved in humans because it promotes the survival of grandchildren. According to this hypothesis, post reproductive women feed and care for children, adult nursing daughters, and grandchildren whose mothers have weaned them. Human babies require large and steady supplies of glucose to feed the growing brain. In infants in the first year of life, the brain consumes 60% of all calories, so both babies and their mothers require a dependable food supply. Some evidence suggests that hunters contribute less than half the total food budget of most hunter-gatherer societies, and often much less than half, so that foraging grandmothers can contribute substantially to the survival of grandchildren at times when mothers and fathers are unable to gather enough food for all the children. In general, selection operates most powerfully during times of famine or other privation. So although grandmothers might not be necessary during good times, many grandchildren cannot survive without them during times of famine.

Terminology, definitions and commentary

Menopause

Clinically speaking, menopause is a date: for those women who still have a uterus, menopause is defined as the day after a woman's final period finishes.

In common everyday parlance however, the word "menopause" is usually not used to refer to one day, but to the whole of the menopause transition years. This span of time is also referred to as the change of life or the climacteric and more recently is known as "perimenopause", (literally meaning "around menopause").

Perimenopause

Perimenopause means the menopause transition years, the years both before and after the last period ever, when the majority of women find that they undergo at least some symptoms of hormonal change and fluctuation, such as hot flashes, mood changes, insomnia, fatigue, memory problems, etc.

During perimenopause, the production of most of the reproductive hormones, including the estrogens, progesterone and testosterone, diminishes and becomes more irregular, often with wide and unpredictable fluctuations in levels. During this period, fertility diminishes.

Symptoms of perimenopause can begin as early as age 35, although most women become aware of them about 10 years later than this. Perimenopause can last for a few years, or for ten years or even longer. In this respect it resembles puberty, a similar process which surrounds menarche. In fact menopause can usefully be compared to "puberty in reverse", and the psychological challenges and adjustments which take place over this time span can be compared to adolescence.

The actual duration and severity of perimenopause in any individual woman cannot be predicted in advance or during the process. Not every woman experiences symptoms during perimenopause. Approximately one third of all women get no noticeable symptoms other than that their periods become erratic and then stop. Another one third of women have moderate symptoms. The remaining one third of women have very strong symptoms which tend to have a longer duration. The tendency to have a very strong perimenopause may be inherited in some cases.

One piece of recent research appears to show that melatonin supplementation in perimenopausal women can produce a highly significant improvement in thyroid function and gonadotropin levels, as well as restoring fertility and menstruation and preventing the depression associated with the menopause.

Premenopause

Premenopause occurs before menopause and is the time during which ovarian hormones, estrogen and progesterone begin to decrease and brain hormones begin to increase. Menstrual periods may begin to become irregular. Most women become premenopausal after age forty.

Postmenopause

Postmenopause is all of the time in a woman's life that take place after her last period ever, or more accurately, all of the time that follows the point when her ovaries become inactive.

A woman who still has her uterus can be declared to be in post-menopause once she has gone 12 full months with no flow at all, not even any spotting. When she reaches that point, she is one year into post-menopause. The reason for this delay in declaring a woman post-menopausal is because periods become very erratic at this time of life, and therefore a reasonably long stretch of time is necessary to be sure that the cycling has actually ceased.

In women who have no uterus, and therefore have no periods, post-menopause can be determined by a blood test which can reveal the very high levels of Follicle Stimulating Hormone (FSH) that are typical of post-menopausal women.

A woman's reproductive hormone levels continue to drop and fluctuate for some time into post-menopause, so any hormone withdrawal symptoms that a woman may be experiencing do not necessarily stop right away, but may take quite some time, even several years, to disappear completely.

Any period-like flow that might occur during post-menopause, even just spotting, must be reported to a doctor. The cause may in fact be minor, but the possibility of endometrial cancer must be checked for and eliminated.

The causes of menopause

The causes of menopause can be considered from complementary proximate (mechanistic) and ultimate (adaptive evolutionary) perspectives.

From a proximate perspective: A natural or physiological menopause is that which occurs as a part of a woman's normal aging process. It is the result of the eventual atresia of almost all oocytes in the ovaries. This causes an increase in circulating follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels as there are a decreased number of oocytes responding to these hormones and producing estrogen. This decrease in the production of estrogen leads to the perimenopausal symptoms of hot flashes, insomnia and mood changes, as well as post-menopausal osteoporosis and vaginal atrophy.

However, menopause can be surgically induced by bilateral salpingo-oophorectomy (removal of both ovaries and both fallopian tubes), which is often, but not always, done in conjunction with hysterectomy. Cessation of menses as a result of removal of the ovaries is called "surgical menopause". The sudden and complete drop in reproductive hormone levels usually produces extreme hormone-withdrawal symptoms such as hot flashes, etc.

As mentioned above, removal of the uterus, hysterectomy, does not itself cause menopause, although pelvic surgery can sometimes precipitate a somewhat earlier menopause, perhaps because of a compromised blood supply to the ovaries. Removing the ovaries however, causes an immediate and powerful "surgical menopause", even if the uterus is left intact.

Cigarette smoking has been found to decrease the age at menopause by as much as one year, and women who have undergone hysterectomy with ovary conservation go through menopause 3.7 years earlier than average. However, premature menopause (before the age of 40) is generally idiopathic.

An ultimate perspective on menopause is given above in the "Menopause in human evolution" section.

Symptoms of perimenopause, the menopause transition time

As the body struggles to adapt to the rapidly changing levels of natural hormones, a number of symptoms appear. Both users and non-users of hormone replacement therapy identify lack of energy as the most frequent and distressing symptom.

Other symptoms include vasomotor symptoms such as hot flashes and palpitations, psychological symptoms such as depression, anxiety, irritability, mood swings and lack of concentration, and atrophic symptoms such as vaginal dryness and urgency of urination. Together with these symptoms, the average woman also has increasingly erratic menstrual periods.

These perimenopause symptoms are caused by an overall drop, as well as dramatic but erratic fluctuations, in the levels of estrogens, progestin, and testosterone. Some of these symptoms, such as formication, may be associated directly with hormone withdrawal.

The symptoms that are due to low estrogen levels (for example vaginal atrophy and skin drying) remain present even after the menopause transition years are over. However, many symptoms that are caused by the extreme fluctuations in hormone levels (hot flashes, mood changes) commonly disappear or improve significantly once perimenopause has been completed.

Vasomotor instability

• hot flashes or hot flushes, including night sweats and, in a few people, cold flashes
• sleep disturbances, poor quality sleep, light sleep, insomnia

Urogenital atrophy, also known as vaginal atrophy, (main article: Atrophic vaginitis)

• thinning of the membranes of the vulva and the outer urinary tract, along with considerable shrinking and loss in elasticity of all of the outer and inner genital areas
• itching
• dryness
• bleeding
• watery discharge
• urinary frequency
• urinary urgency
• urinary incontinence
• increased susceptibility to urinary tract infections

Skeletal

• osteopenia and the risk of osteoporosis gradually developing over time
• joint pain, muscle pain
• back pain

Skin, soft tissue

• breast atrophy
• skin thinning and becoming drier
• decreased elasticity of the skin
• formication, a sensation of pins and needles, or ants crawling on or under the skin

Psychological

• mood disturbance
• irritability
• fatigue
• memory loss, and problems with concentration
• depression and/or anxiety

Changing hormones during menopause changes your mood, a drop in estrogen is associated with depression and restoring levels to normal frequently lifts depression.

Sexual

• decreased libido
• vaginal dryness and vaginal atrophy
• problems reaching orgasm
• dyspareunia or painful intercourse

One cohort study found that menopause was associated with hot flashes; joint pain and muscle pain; and depressed mood. In the same study, it appeared that menopause was not associated with poor sleep, decreased libido, and vaginal dryness.

Need for more education about menopause

Many women arrive at their menopause years without knowing anything about what they might expect, or when or how the process might happen, and how long it might take. Very often a woman has not been informed in any way about this stage of life by her physician or by her social group. Research has found that only about one-third of women in menopause receive any education about it from their doctors. Many women feel hesitant about talking to their doctors on this subject, and many have difficulty finding a doctor who will listen to their concerns. Not all doctors think that menopause should be treated, since it is a natural process.

In the USA at least, there appears to be a lingering taboo which hangs over this subject. As a result, a woman who happens to undergo a strong perimenopause with a large number of different symptoms, may become confused and anxious, fearing that something abnormal is happening to her. There is a strong need for more information and more education on this subject.

Treatment of symptoms

Perimenopause is a natural stage of life, but when the symptoms are severe, they may be alleviated through medical treatments. Hormone replacement therapy (US abbr.) (HT is the preferred British abbr.) and SSRIs provide the best relief, but equine estrogens and synthetic progestin forms of HRT appear to increase health risks, especially in women who start this treatment after menopause.

A six month placebo-controlled Italian clinical trial of nocturnal administration of three mg. of synthetic melatonin found a remarkable and highly significant improvement in perimenopausal and menopausal women of thyroid function, positive changes of gonadotropins towards more juvenile levels, and abrogation of menopause-related depression in women receiving melatonin versus a placebo.

Some other drugs afford limited relief from hot flashes. A woman and her doctor should carefully review her symptoms and relative risk before determining whether the benefits of HT/HRT or other therapies outweigh the risks. Until more becomes understood about the possible risk, women who elect to use hormone replacement therapy are generally well advised to take the lowest effective dose of hormones for the shortest period possible, and to question their doctors as to whether certain forms might pose fewer dangers of clots or cancer than others.

Hormone therapy, also known as hormone replacement therapy

See also Hormone replacement therapy (menopause).

In addition to relief from hot flashes, hormone therapy remains an effective treatment for osteoporosis.

In HT or HRT, one or more estrogens, usually in combination with progesterone, (and sometimes testosterone) are administered, not only to partially compensate for the body's loss of these hormones, but also in an attempt to keep the levels of these hormones in the body much more consistent than they are naturally in perimenopause.

In those women who have no uterus (usually due to a previous hysterectomy) estrogen alone is a suitable hormone therapy. Women who still have a uterus need to take progesterone in addition to estrogen, in order to ensure that the endometrium, the lining of the uterus, does not build up too much, which would be a risk for cancer of the endometrium.

There are several types of hormone therapies, with various possible side effects.

Conjugated equine estrogens

See also Types of Hormone Replacement Therapy

Conjugated equine estrogens contain estrogen molecules conjugated to hydrophilic side groups (e.g. sulfate) and are produced from the urine of pregnant Equidae (horses) mares. Premarin is the prime example of this, either alone or in Prempro, where it is combined with a synthetic progestin, medroxyprogesterone acetate. However Premarin, and especially Prempro, are associated with serious health risks.

In January 2003, the FDA required Wyeth to affix a "black box" warning to PremPro, stating

"WARNING

Estrogens and progestins should not be used for the prevention of cardiovascular disease. The Women’s Health Initiative (WHI) reported increased risks of myocardial infarction, stroke,

invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women during 5 years of treatment with conjugated equine estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) relative to placebo (see CLINICAL PHARMACOLOGY, Clinical Studies). Other doses of conjugated estrogens and medroxyprogesterone acetate, and other combinations of estrogens and progestins were not

studied in the WHI ... "

Adverse effects of conjugated equine estrogens

See also Types of Hormone Replacement Therapy

Women had been advised for many years by numerous doctors and drug company marketing efforts (at least in the USA) that hormone therapy with conjugated equine estrogens after menopause might reduce their risk of heart disease and prevent various aspects of aging. However, a large, randomized, controlled trial (the Women's Health Initiative) found that women undergoing HT or HRT with conjugated equine estrogens (Premarin), whether or not used in combination with a synthetic progestin (Premarin plus Provera, known as Prempro), had an increased risk of breast cancer, heart disease, stroke, and Alzheimer's disease. Although this increase in risk was small, but it passed the thresholds that had been established by the researchers in advance as sufficient to ethically require stopping the study.

When these results were reported in 2002, the popular media recognized it as a significant news story, while the manufacturer continued to minimize the degree of risk involved. However most news stories failed to mention that the average age of the women in WHI was 62 years old, significantly older than the time when most doctors start patients, and well into postmenopause. In order to be in the study patients had to be asymptomatic of hot flashes, so they would not know if they received the placebo. For these reasons WHI was not representative of generally accepted clinical practice.

Many women discontinued equine estrogens altogether, with or without their doctor's approval. The number of prescriptions written for Premarin and PremPro in the United States dropped within a year almost to half of their previous level. This sharp drop in prescriptions for Premarin and Prempro was followed by large and successively larger drops in new breast cancer diagnoses, at six months, one year, and 18 months after the drop in Premarin and Prempro prescriptions, for a cumulative 15% drop by the end of 2003. Prescriptions of Prempro and Premarin fell dramatically in Canada as well, but no similarly dramatic drop in Canada's breast cancer rates was observed during the same time period. Studies designed to track the further progression of this trend after 2003 are under way, as well as studies designed to quantify how much of the drop was related to the reduced use of HT/HRT.

Other forms of hormone therapy

See also Types of Hormone Replacement Therapy

The adverse biological effects of xenoestrogens and progestins revealed by studies of Premarin and PremPro do not necessarily generalize to supplementation with human forms of estrogen and progesterone. For example, a pilot study reported in JAMA by Smith, Heckbert, et al. found clinical evidence that oral conjugated equine estrogens caused clotting, but the other estrogen compound tested in the same study, bioidentical esterified estrogens, does not. conjugated equine estrogens were found to be associated with increased venous thrombotic risk. In sharp contrast, the study found that users of esterified estrogen had no increase in venous thrombotic risk.

Due to the controversy about Premarin-based hormone therapy, a number of doctors are now moving patients who request hormone therapy to help them through perimenopause, to bioidentical hormone products.

Estrace is a form of the precursor to estrogen in the human body known as estradiol, which products have produced fewer side effects than conjugated equine estrogens. Prometrium is a bioidentical progesterone which can be used in conjunction with Estrace.

However, all hormone replacement therapies probably do carry some health risks, including high blood pressure, blood clots, and increased risks of breast and uterine cancers. Women who have had a hysterectomy seem to tolerate estrogen-only therapy better than mixed-hormone therapy.

The anti-seizure medication gabapentin (Neurontin) seems to be second only to HRT in relieving hot flashes.

Antidepressants

Antidepressants such as paroxetine (Paxil), Fluoxetine hydrochloride (Prozac), and Venlafaxine hydrochloride (Effexor) have been used with some success in the treatment of hot flashes, improving sleep, mood, and quality of life. Of these, Paxil has been the most studied and may provide the most consistent relief . There is a theoretical reason why SSRI antidepressants might help with memory problems-- they increase circulating levels of the neurotransmitter serotonin in the brain and restore hippocampal function. Prozac has been repackaged as Sarafem and is approved and prescribed for premenstrual dysphoric disorder (PMDD), a mood disorder often exacerbated during perimenopause and early menopause. PMDD has been found by PET scans to be accompanied by a sharp drop in serotonin in the brain and to respond quickly and powerfully to SSRIs.

Blood pressure medicines

About as effective as antidepressants for hot flashes, but without the other mind and mood benefits of antidepressants, are blood pressure medicines including clonidine (Catapres). These drugs may merit special consideration by women suffering both from high blood pressure and hot flashes.

Complementary and alternative therapies

Medical non-hormone treatments provide less than complete relief, and each has side effects.

In the area of complementary and alternative therapies, acupuncture treatment is promising. There are some studies indicating positive effects, especially on hot flashes but also others showing no positive effects of acupuncture regarding menopause.

There are claims that soy isoflavones are beneficial concerning menopause. However, one study indicated that soy isoflavones did not improve or appreciably affect cognitive functioning in postmenopausal women.

Other remedies that have proven no better than a placebo at treating hot flashes and other menopause symptoms include red clover isoflavone extracts and black cohosh. Black cohosh has potentially serious side-effects such as the stimulation of pre-existing breast cancer, therefore prolonged administration is not recommended in any case.

Other therapies

Individual counseling or support groups may be helpful to handle sad, depressed, or confusing feelings women may be having as they pass through what can be a very challenging transition time.

Vaginal moisturizers such as Replens can help women with thinning vaginal tissue or dryness, and lubricants such as K-Y Jelly or Astroglide, can help with lubrication difficulties that may be present during intercourse. It is worth pointing out that moisturizers and lubricants are different products for different issues: some women feel unpleasantly dry all of the time apart from during sex, and they may do better with moisturizers all of the time. Those who need only lubricants are fine just using the lubrication products during intercourse.

Low-dose prescription vaginal estrogen products such as Estrace cream or the Estring are generally a safe way to use estrogen topically, in order to help vaginal thinning and dryness problems (see vaginal atrophy) while only minimally increasing the levels of estrogen in the bloodstream.

In terms of managing hot flashes, lifestyle measures, such as drinking cold liquids, staying in cool rooms, using fans, removing excess clothing layers when a hot flash strikes, and avoiding hot flash triggers such as hot drinks, spicy foods, etc, may partially supplement (or even obviate) the use of medications for some women.

See also

• Premature menopause, also known as Premature ovarian failure
• Menstruation
• Menstrual cycle
• Menarche
• Estrogen
• Progesterone
• Post-Menopausal Bleeding
• Testosterone
• Follicle-stimulating hormone
• Hormone replacement therapy
• Atrophic vaginitis
• Louann Brizendine MD (an expert on hormones and human behaviour, author of The Female Brain)
• Jerilynn Prior MD (researcher, president of Society for Menstrual Cycle Research)
• Menopause the Musical (a theatrical production)
• Andropause (sometimes called male menopause)

External links

• Menopause Section of The Hormone Foundation
• Power Surge Menopause Community at power-surge.com
• Council on Hormone Education at hormonecme.org
• Menopause in the UK
• North American Menopause Society at menopause.org
• Menopause at Curlie