出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2015/07/25 06:34:43」(JST)
Menopause | |
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Classification and external resources | |
Specialty | Gynecology |
ICD-10 | N95.0 |
ICD-9-CM | 627.2 |
DiseasesDB | 8034 |
MedlinePlus | 000894 |
eMedicine | article/264088 |
MeSH | D008593 |
Menopause, also known as the climacteric, is the time in most women's lives when menstrual periods stop permanently, and she is no longer able to have children.[1][2] Menopause typically occurs between 45 and 55 years of age.[1] Medical professionals often define menopause as having occurred when a woman has not had any vaginal bleeding for a year.[3] It may also be defined by a decrease in hormone production by the ovaries.[4] In those who have had surgery to remove the uterus but still have ovaries, menopause may be viewed to have occurred at the time of the surgery or when hormone levels fall.[4] Following the removal of the uterus, symptoms typically occur earlier at the average of 45 years of age.[5]
Before menopause, a woman's periods typically become irregular, which means that periods may be longer or shorter in duration, or be lighter or heavier in terms of the amount of flow. During this time, women often experience hot flashes; these typically last from 30 seconds to ten minutes, and may be associated with shivering, sweating and reddening of the skin.[6] Hot flashes often stop occurring after a year or two.[2] Other symptoms may include vaginal dryness, trouble sleeping, and mood changes.[6] The severity of symptoms varies between women.[2] While menopause is often thought to be linked to an increase in heart disease, this primarily occurs due to increasing age and does not have a direct relationship with menopause. In some women, problems that were previously present like endometriosis or painful periods will improve after menopause.[2]
Menopause is usually a natural change.[7] It can occur earlier in those who smoke tobacco.[3][8] Other causes include surgery that removes both ovaries or some types of chemotherapy.[3] At the physiological level, menopause happens because of a decrease in the ovaries' production of the hormones estrogen and progesterone.[1] While typically not needed, a diagnosis of menopause can be confirmed by measuring hormone levels in either the blood or urine.[9] Menopause is the opposite of menarche, the time at which a girl's periods start.[10]
Specific treatment is not usually needed. Some symptoms, however, may be improved with treatment. With respect to hot flashes, avoiding smoking, caffeine, and alcohol is often recommended. Sleeping in a cool room and using a fan may also help.[11] The following medications may help: menopausal hormone therapy (MHT), clonidine, gabapentin, or selective serotonin reuptake inhibitors.[11][12] Exercise may help with sleeping problems. While MHT was once routinely prescribed, it is now only recommended in those with significant symptoms, as there are concerns about side effects.[11] High-quality evidence for the effectiveness of alternative medicine has not been found.[2]
During early menopause transition, the menstrual cycles remain regular but the interval between cycles begins to lengthen. Hormone levels begin to fluctuate. Ovulation may not occur with each cycle.[13]
The date of the final menstrual period is usually taken as the point in time when menopause has occurred.[13] During menopausal transition and after menopause, women can experience a wide range of symptoms.
During the transition to menopause, menstrual patterns can show shorter cycling (by 2–7 days);[13] longer cycles remain possible;[13] There may also be irregular bleeding (lighter, heavier, spotting).[13] Dysfunctional uterine bleeding is often experienced by women approaching menopause due to the hormonal changes that accompany the menopause transition. In post-menopausal women however, any genital bleeding is an alarming symptom that requires an appropriate study to rule out the possibility of malignant diseases. However, spotting or bleeding may simply be related to vaginal atrophy, a benign sore (polyp or lesion) or may be a functional endometrial response. The European Menopause and Andropause Society has released guidelines for assessment of the endometrium, which is usually the main source of spotting or bleeding.[14]
Symptoms that may appear during menopause and continue through postmenopause include:
Other physical symptoms of menopause include: lack of energy, joint soreness, stiffness,[13] back pain,[13] breast enlargement,[13] breast pain,[13] heart palpitations,[13] headache,[13] dizziness,[13] dry, itchy skin,[13] thinning, tingling skin, weight gain,[13] urinary incontinence,[13][15] urinary urgency,[13] interrupted sleeping patterns,[13][16][17][18] heavy night sweats,[13] hot flashes.[13]
Psychological symptoms include: anxiety,[19] poor memory,[13] inability to concentrate,[13] depressive mood,[13][19] irritability,[13] mood swings,[13] less interest in sexual activity.[13]
In the Western world, the typical age of menopause (last period from natural causes) is between 40 and 61[20] and the average age for last period is 51 years.[21] The average age of natural menopause in Australia is 51.7 years.[22] In India and the Philippines, the median age of natural menopause is considerably earlier, at 44 years.[23]
In rare cases, a woman's ovaries stop working at a very early age, ranging anywhere from the age of puberty to age 40, and this is known as premature ovarian failure (POF). Spontaneous premature ovarian failure affects 1% of women by age 40, and 0.1% of women by age 30.
Women who have undergone hysterectomy with ovary conservation go through menopause on average 3.7 years earlier than the expected age. Other factors which can promote an earlier onset of menopause (usually 1 to 3 years early) are: smoking cigarettes, or being extremely thin.[24]
Premature ovarian failure (POF) is diagnosed or confirmed by high blood levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) on at least 3 occasions at least 4 weeks apart.[25]
Known causes of premature ovarian failure include autoimmune disorders, thyroid disease, diabetes mellitus, chemotherapy, being a carrier of the fragile X syndrome gene, and radiotherapy. However, in the majority of spontaneous cases of premature ovarian failure, the cause is unknown, i.e. it is generally idiopathic.[25]
Women who have some sort of functional disorder affecting the reproductive system (e.g., endometriosis, polycystic ovary syndrome, cancer of the reproductive organs) can go into menopause at a younger age than the normal timeframe. The functional disorders often significantly speed up the menopausal process.
An early menopause can be related to cigarette smoking, higher body mass index, racial and ethnic factors, illnesses, and the surgical removal of the ovaries, with or without the removal of the uterus.[26]
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 can be surgically induced by bilateral oophorectomy (removal of ovaries), which is often, but not always, done in conjunction with removal of the Fallopian tubes (salpingo-oophorectomy) and uterus (hysterectomy).[27] Cessation of menses as a result of removal of the ovaries is called "surgical menopause". The sudden and complete drop in hormone levels usually produces extreme withdrawal symptoms such as hot flashes, etc.
Removal of the uterus without removal of the ovaries does not directly cause menopause, although pelvic surgery of this type can often precipitate a somewhat earlier menopause, perhaps because of a compromised blood supply to the ovaries.[citation needed]
The menopause transition, and postmenopause itself, is a natural life change, not usually a disease state or a disorder. The transition itself has a variable degree of effects.[28]
The stages of the menopause transition have been classified according to a woman's reported bleeding pattern, supported by changes in the pituitary follicle-stimulating hormone (FSH) levels.[29]
In younger women, during a normal menstrual cycle the ovaries produce estradiol, testosterone and progesterone in a cyclical pattern under the control of FSH and luteinising hormone (LH) which are both produced by the pituitary gland. Blood estradiol levels remain relatively unchanged, or may increase approaching the menopause, but are usually well preserved until the late perimenopause. This is presumed to be in response to elevated FSH levels.[30] However, the menopause transition is characterized by marked, and often dramatic, variations in FSH and estradiol levels, and because of this, measurements of these hormones are not considered to be reliable guides to a woman's exact menopausal status.[31]
Menopause occurs because of the natural or surgical cessation of estradiol and progesterone production by 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. After menopause, estrogen continues to be produced in other tissues, notably the ovaries, but also in bone, blood vessels and even in the brain.[32] However, the dramatic fall in circulating estradiol levels at menopause impacts many tissues, from brain to skin.
In contrast to the sudden fall in estradiol during menopause, the levels of total and free testosterone, as well as dehydroepiandrosterone sulfate (DHEAS) and androstenedione appear to decline more or less steadily with age. An effect of natural menopause on circulating androgen levels has not been observed.[33] Thus specific tissue effects of natural menopause cannot be attributed to loss of androgenic hormone production.[34]
Natural or physiological menopause occurs as a part of a woman's normal aging process. It is the result of the eventual depletion of almost all of the oocytes and ovarian follicles in the ovaries.[35] This causes an increase in circulating follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels because there are a decreased number of oocytes and follicles 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. Long-term effects may include osteoporosis and vaginal atrophy.
Titus et al. proposed an explanation for the depletion of the ovarian reserve during aging.[36] They found that as women age, double-strand breaks accumulate in the DNA of their primordial follicles. Primordial follicles are immature primary oocytes surrounded by a single layer of granulosa cells. An enzyme system is present in oocytes that ordinarily accurately repairs DNA double-strand breaks. This repair system is called “homologous recombinational repair”, and it is especially effective during meiosis. Meiosis is the general process by which germ cells are formed in all sexual eukaryotes, and it appears to be an adaptation for efficiently removing damages in germ line DNA.[37] (See Meiosis.)
Human primary oocytes are present at an intermediate stage of meiosis, termed prophase I (see Oogenesis). Titus et al. further demonstrated that expression of four key DNA repair genes that are necessary for homologous recombinational repair during meiosis (BRCA1, MRE11, Rad51, and ATM) decline with age in oocytes.[36] This age-related decline in ability to repair DNA double-strand damages can account for the accumulation of these damages, that then likely contributes to the depletion of the ovarian reserve.
Menopause confers:
One way of assessing the impact on women of some of these menopause effects are the Greene Climacteric Scale questionnaire,[41] the Cervantes Scale[42] and the Menopause Rating Scale.[16]
Premenopause is a term used to mean the years leading up to the last period, when the levels of reproductive hormones are already becoming more variable and lower, and the effects of hormone withdrawal are present.[27] Premenopause often starts some time before the monthly cycles become noticeably irregular in timing.
The term "perimenopause", which literally means "around the menopause", refers to the menopause transition years, a span of time both before and after the date of the final episode of flow. According to the North American Menopause Society, this transition can last for four to eight years.[43] The Centre for Menstrual Cycle and Ovulation Research describes it as a six to ten year phase ending 12 months after the last menstrual period.[44]
During perimenopause, estrogen levels average about 20-30% higher than during premenopause, often with wide fluctuations.[44] These fluctuations cause many of the physical changes during perimenopause as well as menopause.[45] Some of these changes are hot flashes, night sweats, difficulty sleeping, vaginal dryness or atrophy, incontinence, osteoporosis, and heart disease.[44] During this period, fertility diminishes, but is not considered to reach zero until the official date of menopause. The official date is determined retroactively, once 12 months have passed after the last appearance of menstrual blood.
Signs and effects of the menopause transition can begin as early as age 35, although most women become aware of the transition in their mid to late 40s, which is often many years after the actual beginning of the perimenopausal window. The duration of perimenopause with noticeable bodily effects can be as brief as a few years, but it is not unusual for the duration to last ten or more years. The actual duration and severity of perimenopause effects for any individual woman currently cannot be predicted in advance. Even though the process, or the course, of perimenopause or menopause can be difficult to predict, the age of onset is somewhat predictable: women will often, but not always, start these transitions (perimenopause and menopause) about the same time as their mother.[46]
In some women, menopause may bring about a sense of loss related to the end of fertility. In addition this change often occurs when other stressors may be present in a woman's life:
Some research appears to show that melatonin supplementation in perimenopausal women can improve thyroid function and gonadotropin levels, as well as restoring fertility and menstruation and preventing depression associated with the menopause.[47]
The term "postmenopausal" describes women who have not experienced any menstrual flow for a minimum of 12 months, assuming that they do still have a uterus, and are not pregnant or lactating.[27] In women without a uterus, menopause or postmenopause can be identified by a blood test showing a very high FSH level. Thus postmenopause is all of the time in a woman's life that take place after her last period, or more accurately, all of the time that follows the point when her ovaries become inactive.
The reason for this delay in declaring postmenopause is because periods are usually 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 completely. At this point a woman is considered infertile; however, the possibility of becoming pregnant has usually been very low (but not quite zero) for a number of years before this point is reached.
A woman's reproductive hormone levels continue to drop and fluctuate for some time into post-menopause, so hormone withdrawal effects such as hot flashes may take several years to disappear.
Any period-like flow during postmenopause, even spotting, must be reported to a doctor. The cause may be minor, but the possibility of endometrial cancer must be checked for.
Perimenopause is a natural stage of life. It is not a disease or a disorder, and therefore it does not automatically require any kind of medical treatment. However, in those cases where the physical, mental, and emotional effects of perimenopause are strong enough that they significantly disrupt the everyday life of the woman experiencing them, palliative medical therapy may sometimes be appropriate.
In the context of the menopause, hormone replacement therapy (HRT) is the use of estrogen, plus progestin in women who have an intact uterus and estrogen alone in those without a uterus.[48]
HRT may be reasonable for the treatment of menopausal symptoms such as hot flashes.[49] Its use appears to increase the risk of strokes and blood clots.[50] When used for menopausal symptoms it should be used for the shortest time possible and at the lowest dose possible.[50] The response to HRT in each postmenopausal women may not be the same. Genetic polymorphism in estrogen receptors appears to be associated with inter-individual variability in metabolic response to HRT in postmenopausal women.[51]
It also appears effective for preventing bone loss and osteoporotic fracture.[52] It is often seen as a second line agent for this purpose.[53] There is some concern that this treatment increases the risk of breast cancer.[54]
SERMs are a category of drugs, either synthetically produced or derived from a botanical source (phytoserms), that act selectively as agonists or antagonists on the estrogen receptors throughout the body. The most commonly prescribed SERMs are raloxifene and tamoxifen. Raloxifene exhibits oestrogen agonist activity on bone and lipids, and antagonist activity on breast and the endometrium.[55] Tamoxifen is in widespread use for treatment of hormone sensitive breast cancer. Raloxifene prevents vertebral fractures in postmenopausal, osteoporotic women and reduces the risk of invasive breast cancer.[56] While most SERMs are known to increase hot flushes, Femarelle (DT56a) decreases them.[57][58] In addition to the relieving effects on menopausal symptoms, Femarelle also increases bone mass density (BMD), making it protective against osteoporotic fractures.[59] These effects are achieved by an agonistic interaction with estrogen receptors in the brain and bone. On the other hand, an antagonist interaction with estrogen receptors in the breast[60] and uterus,[61][62] has no effect on these tissues.
Some of the SSRIs and SNRIs appear to provide some relief.[12] Low dose paroxetine has been FDA-approved for hot moderate-to-severe vasomotor symptoms associated with menopause.[63] They may however be associated with sleeping problems.[12]
Gabapentin or clonidine may help but does not work as well as hormone therapy.[12] Clonidine may be associated with constipation and sleeping problems.[12]
There is no evidence of consistent benefit of alternative therapies for menopausal symptoms despite their popularity.[64] The effect of soy isoflavones on menopausal symptoms is promising but not clear.[65] Evidence does not support a benefit from phytoestrogens such as coumestrol,[66] femarelle,[67] or black cohosh.[68] It is unclear if acupuncture is effective for menopausal hot flushes.[69] As of 2011 there is no support for herbal or dietary supplements in the prevention or treatment of the mental changes that occur around menopause.[70]
The cultural context within which a woman lives can have a significant impact on the way she experiences the menopausal transition. Menopause has been described as a subjective experience, with social and cultural factors playing a prominent role in the way menopause is experienced and perceived.
Within the United States, social location affects the way women perceive menopause and its related biological effects. Research indicates that whether a woman views menopause as a medical issue or an expected life change is correlated with her socio-economic status.[73] The paradigm within which a woman considers menopause also influences the way she views it: women who understand menopause as a medical condition rate it significantly more negatively than those who view it as a life transition or a symbol of aging.[74]
Ethnicity and geographical location also play a role in the experience of menopause. American women of different ethnicities report significantly different types of menopausal effects. One major study found Caucasian women most likely to report what are sometimes described as psychosomatic symptoms, while African-American women were more likely to report vasomotor symptoms.[75]
It seems that Japanese women experience menopause effects, or konenki in a different way from American women.[76] Japanese women report lower rates of hot flashes and night sweats; this can be attributed to a variety of factors, both biological and social. Historically, konenki was associated with wealthy middle-class housewives in Japan, i.e. it was a “luxury disease” that women from traditional, inter-generational rural households did not report. Menopause in Japan was viewed as a symptom of the inevitable process of aging, rather than a “revolutionary transition”, or a “deficiency disease” in need of management.[76]
However, within Japanese culture, reporting of vasomotor symptoms has been on the increase, with research conducted by Melissa Melby in 2005 finding that of 140 Japanese participants, hot flashes were prevalent in 22.1%.[77] This was almost double that of 20 years prior.[78] Whilst the exact cause for this is unknown, possible contributing factors include significant dietary changes, increased medicalisation of middle-aged women and increased media attention on the subject.[78] However, reporting of vasomotor symptoms is still significantly lower than North America.[79]
Additionally, while most women in the United States apparently have a negative view of menopause as a time of deterioration or decline, some studies seem to indicate that women from some Asian cultures have an understanding of menopause that focuses on a sense of liberation, and celebrates the freedom from the risk of pregnancy.[80] Postmenopausal Indian women can enter Hindu temples and participate in rituals, marking it as a celebration for reaching an age of wisdom and experience.
Diverging from these conclusions however, one study appeared to show that many American women "experience this time as one of liberation and self-actualization".[81]
Generally speaking, women raised in the Western world or developed countries in Asia live long enough so that a third of their life is spent in post-menopause. For some women, the menopausal transition represents a major life change, similar to menarche in the magnitude of its social and psychological significance. Although the significance of the changes that surround menarche is fairly well recognized, in countries such as the United States, the social and psychological ramifications of the menopause transition are frequently ignored or underestimated.[citation needed]
The medicalization of menopause within biomedical practice began in the early 19th century and has affected the way menopause is viewed within society. By the 1930s in North America and Europe, biomedicine practitioners began to think of menopause as a disease-like state. This idea coincided with the concept of the “standardization of the body.” The bodies of young premenopausal women began to be considered the “normal”, against which all female bodies were compared.[82]
Menopause literally means the "end of monthly cycles" (the end of monthly periods or menstruation), from the Greek word pausis ("pause") and mēn ("month"). This is a medical calque; the Greek word for menses is actually different. In Ancient Greek, the menses were described in the plural, ta emmēnia, ("the monthlies"), and its modern descendant has been clipped to ta emmēna. The Modern Greek medical term is emmenopausis in Katharevousa or emmenopausi in Demotic Greek.
The word "menopause" was coined specifically for human females, where the end of fertility is traditionally indicated by the permanent stopping of monthly menstruations. However, menopause also exists in some other animals, many of which do not have monthly menstruation;[83] in this case, the term means a natural end to fertility that occurs before the end of the natural lifespan.
Various theories have been suggested that attempt to suggest evolutionary benefits to the human species stemming from the cessation of women's reproductive capability before the end of their natural lifespan. Explanations can be categorized as adaptive and non-adaptive:
The high cost of female investment in offspring may lead to physiological deteriorations that amplify susceptibility to becoming infertile. This hypothesis suggests the reproductive lifespan in humans has been optimized, but it has proven more difficult in females and thus their reproductive span is shorter. If this hypothesis were true however, age at menopause should be negatively correlated with reproductive effort[84] and the available data does not support this.[85]
A recent increase in female longevity due to improvements in the standard of living and social care has also been suggested.[86] It is difficult for selection, however, to favour aid to offspring from parents and grandparents.[87] Irrespective of living standards, adaptive responses are limited by physiological mechanisms. In other words senescence is programmed and regulated by specific genes.[88]
This hypothesis suggests that younger mothers and offspring under their care will fare better in a difficult and predatory environment because a younger mother will be stronger and more agile in providing protection and sustenance for herself and a nursing baby. The various biological factors associated with menopause had the effect of male members of the species investing their effort with the most viable of potential female mates.[89] One problem with this hypothesis is that we would expect to see menopause exhibited in the animal kingdom.[83]
The mother hypothesis suggests that menopause was selected for humans because of the extended development period of human offspring and high costs of reproduction so that mothers gain an advantage in reproductive fitness by redirecting their effort from new offspring with a low survival chance to existing children with a higher survival chance.[90]
The Grandmother hypothesis suggests that menopause was selected for 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 of their 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. Arguably, however, there is no firm consensus on the supposed evolutionary advantages (or simply neutrality) of menopause to the survival of the species in the evolutionary past.
Indeed, analysis of historical data found that the length of a female's post-reproductive lifespan was reflected in the reproductive success of her offspring and the survival of her grandchildren.[91] Interestingly, another study found comparative effects but only in the maternal grandmother – paternal grandmothers had a detrimental effect on infant mortality (probably due to paternity uncertainty).[92] Differing assistance strategies for maternal and paternal grandmothers have also been demonstrated. Maternal grandmothers concentrate on offspring survival, whereas paternal grandmothers increase birth rates.[93]
Some believe a problem concerning the grandmother hypothesis is that it requires a history of female philopatry while in the present day the majority of hunter-gatherer societies are patriarchal.[94] However, there is disagreement split along ideological lines about whether patrilineality would have existed before modern times.[95] Some believe variations on the mother, or grandmother effect fail to explain longevity with continued spermatogenesis in males (oldest verified paternity is 94 years, 35 years beyond the oldest documented birth attributed to females).[96] Notably, the survival time past menopause is roughly the same as the maturation time for a human child. That a mother's presence could aid in the survival of a developing child, while an unidentified father's absence might not have affected survival, could explain the paternal fertility near the end of the father's lifespan.[97] A man with no certainty of which children are his may merely attempt to father additional children, with support of existing children present but small. Note the existence of partible paternity supporting this.[98] Some argue that the mother and grandmother hypotheses fail to explain the detrimental effects of losing ovarian follicular activity, such as osteoporosis, osteoarthritis, Alzheimer's disease and coronary artery disease.[99]
The theories discussed above assume that evolution directly selected for menopause. Another theory states that menopause is the byproduct of the evolutionary selection for follicular atresia, which is a factor that causes menopause. Menopause results from having too few ovarian follicles to produce enough estrogen to maintain the ovarian-pituitary-hypothalamic loop, which results in the cessation of menses and the beginning of menopause. Human females are born with approximately two million oocytes, and approximately 400 oocytes are lost to ovulation throughout life.[100]
Menopause in the animal kingdom appears to be uncommon, but the presence of this phenomenon in different species has not been thoroughly researched. Life histories show a varying degree of senescence; rapid senescing organisms (e.g., Pacific salmon and annual plants) do not have a post-reproductive life-stage. Gradual senescence is exhibited by all placental mammalian life histories.
Menopause has been observed in several species of nonhuman primates,[83] including rhesus monkeys,[101] and chimpanzees.[102] Menopause also has been reported in a variety of other vertebrate species including elephants,[103] short-finned pilot whales[104] and other cetaceans,[105][106] the guppy,[107] the platyfish, the budgerigar, the laboratory rat and mouse, and the opossum. However, with the exception of the short-finned pilot whale, such examples tend to be from captive individuals, and thus they are not necessarily representative of what happens in natural populations in the wild.
Dogs do not experience menopause; the canine estrus cycle simply becomes irregular and infrequent. Although older female dogs are not considered good candidates for breeding, offspring have been produced by older animals.[108] Similar observations have been made in cats.[109]
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リンク元 | 「閉経期」 |
拡張検索 | 「postmenopausal hemorrhage」「postmenopausal period」「premenopausal」 |