|Classification and external resources|
Menopause is the cessation of a woman's reproductive ability, the opposite of menarche. Menopause is usually a natural change; it typically occurs in women in midlife, during their late 40s or early 50s, signalling the end of the fertile phase of a woman's life.
Menopause is commonly defined by the state of the uterus and the absence of menstrual flow or "periods", but it can instead be more accurately defined as the permanent cessation of the primary functions of the ovaries. What ceases is the ripening and release of ova and the release of hormones that cause both the build-up of the uterine lining, and the subsequent shedding of the uterine lining (the menses or period).
The transition from a potentially reproductive to a non-reproductive state is normally not sudden or abrupt, occurs over a number of years, and is a consequence of biological aging. For some women, during the transition years the accompanying signs and effects (including lack of energy, hot flashes, and mood changes) can be powerful enough to significantly disrupt their daily activities and sense of well-being. In those cases various different treatments can be tried.
Medically speaking, the date of menopause (in a woman with an intact uterus) is the day after the final episode of menstrual flow finishes. "Perimenopause" is a term for the menopause transition years, the time both before and after the last period ever, while hormone levels are still fluctuating erratically. "Premenopause" is a term for the years leading up to menopause. "Postmenopause" is the part of a woman's life that occurs after the date of menopause; once a woman with an intact uterus (who is not pregnant or lactating) has gone a year with no flow at all she is considered to be one year into post menopause.
Signs and effects 1
List of signs and effects 1.1
- General 1.1.1
- Urogenital atrophy 1.1.2
- Skeletal 1.1.3
- Skin, soft tissue 1.1.4
- Psychological 1.1.5
- Sexual 1.1.6
- List of signs and effects 1.1
- Age 2
- Premenopause 3.1.1
- Perimenopause 3.1.2
- Menopause 3.1.3
- Postmenopause 3.1.4
- Hormonal changes 3.2
- Terminology 3.1
- Hormone replacement therapy (HRT) 4.1
- Selective estrogen receptor modulators 4.2
- DHEA 4.3
- Antidepressants 4.4
- Gabapentin 4.5
- Blood pressure medicines 4.6
Alternative medicine 4.7
- Phytoestrogens 4.7.1
- Soy isoflavones 4.7.2
- Accupuncture and accupressure 4.7.3
- Red clover, Black cohosh 4.7.4
- Education 4.8
- Other therapies 4.9
Abnormalities, dysfunction, and surgery 5
- POF (premature ovarian failure) 5.1
- Surgical menopause 5.2
Society and culture 6
- Medicalization of menopause and society 6.1
- Etymology 7
- Evolutionary rationale 8
- Other animals 9
- See also 10
- References 11
- External links 12
Signs and effects
During the menopause transition years, as the body responds to the rapidly fluctuating and dropping levels of the body's own hormones, a number of effects may appear. Not every woman experiences bothersome levels of these effects; the degree to which they occur varies greatly from person to person.
The majority of women find that their menstrual periods are gradually becoming more erratic, and the timing of the start of the flow usually becomes more and more difficult to predict. In addition the duration of the flow may be considerably shorter or longer than normal, and the flow itself may be significantly heavier or lighter than was previously the case, including sometimes long episodes of spotting.
It is not uncommon to have a 2-week cycle when an ovulation has been skipped. Further into the process it is common to skip periods for months at a time, and these skipped periods may be followed by a heavier period. The number of skipped periods in a row often increases as the time of last period approaches. If a woman keeps a written record of all the erratic episodes of flow, she will know how many months have passed with no flow at all, and thus will be able to know at what date she reached postmenopause, which is important medical information that will subsequently frequently be requested by doctors.
Effects such as formication (crawling, itching, or tingling skin sensations), may be associated directly with hormone withdrawal. Effects that are caused by the extreme fluctuations in hormone levels (for example hot flashes and mood changes) will usually disappear or improve significantly once the perimenopause transition is completely over, however, effects that are due to low estrogen levels (for example vaginal atrophy and skin drying) will continue after the menopause transition years are over.
Hot flashes and mood changes are the most commonly mentioned symptoms of perimenopause, but in a 2007 study, lack of energy was identified by women as the most distressing effect. Other effects can include palpitations, psychological effects such as depression, anxiety, irritability, memory problems and lack of concentration, and atrophic effects such as vaginal dryness and urgency of urination.
List of signs and effects
- Hot flashes (aka hot flushes), also including night sweats, and, rarely, cold flashes. Technically known as vasomotor instability, i.e. the inability to regulate body temperature properly.
- Possible but contentious increased risk of atherosclerosis
- Rapid heartbeat
- Dysfunctional bleeding as part of menstruation. Women approaching menopause often experience this 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.
Also known as vaginal atrophy
- Thinning of the membranes of the vulva, the vagina, the cervix, and also the outer urinary tract, along with considerable shrinking and loss in elasticity of all of the outer and inner genital areas.
- Watery discharge
- Urinary frequency
- Urinary incontinence may worsen the menopause-related quality of life, although urinary incontinence is more related to obstetric events than to menopause
- Urinary urgency
- Increased susceptibility to inflammation and infection, for example vaginal candidiasis, and urinary tract infections
- Back pain
- Joint pain, Muscle pain
- Osteopenia and the risk of osteoporosis gradually developing over time
Skin, soft tissue
- Breast atrophy
- Breast tenderness ± swelling
- Decreased elasticity of the skin
- Formication (itching, tingling, burning, pins, and needles, or sensation of ants crawling)
- Skin thinning and becoming drier
- Depression and/or anxiety
- Memory loss, and problems with concentration
- Mood disturbance
- Sleep disturbances, poor or light sleep, insomnia, and daytime sleepiness
Cohort studies have reached mixed conclusions about medical conditions associated with the menopause. For example, a 2007 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. However, in contrast to this, a 2008 study did find an association with poor sleep quality.
Normal range. In the Western world, the most typical age range for menopause (last period from natural causes) is between 40 and 61 and the average age for last period is 51 years. The average age of natural menopause in Australia is 51.7 years. In India and the Philippines, the median age of natural menopause is considerably earlier, at 44 years.
Youngest. 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.
Oldest. Due to vagaries in records systems throughout the world, an oldest age for which menopause has occurred in a female of the human species is not exactly known. Reports of normal conception and child birth around the age of 70 exist, but are usually subject to controversy. Reports of normal conception beyond age 70 are almost nonexistent. 
Additional factors. 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. 
The menopause transition, and postmenopause itself, is a natural life change, not a disease state or a disorder. The transition itself has a variable degree of effects, and for some it can be a difficult time of life.
Menopause can be understood as the opposite to menarche, the start of the monthly periods. However, menopause cannot be defined simply as the permanent "stopping of the monthly periods", because what is happening to the uterus is secondary; what is happening to the ovaries is the essential change.
For example, when the uterus is surgically removed (hysterectomy) in a younger woman, her periods will cease permanently, and she will be incapable of pregnancy, but as long as at least one of her ovaries is intact and still functioning, the woman will not have reached menopause; ovulation will continue until menopause is reached. In contrast, when a woman's ovaries are removed (oophorectomy), even if the uterus is intact, the woman will immediately experience a menopause which is both sudden and total; this is known as surgical menopause.
The first evidence of the onset of the menopause transition time is usually the appearance of slight variations in the length of the menstrual cycle. These variations become more pronounced over time, and eventually lead to: cycles that may be much longer or shorter than usual; flow that can be much lighter or heavier than usual, including prolonged spotting; skipped ovulations; skipped periods; and spans of time of many months with no flow at all, after which menstruation may resume. The transition is considered to be finished once a woman has experienced 12 months without any menstrual bleeding at all, even though the effects of the transition (such as hot flashes, etc.) may extend well beyond this point in time.
Terms used for the stages of the menopause transition can be confusing because some of the terms overlap in meaning:
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. Premenopause often starts some time before the monthly cycles become noticeably erratic 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. 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.
During perimenopause, estrogen levels average about 20-30% higher than during premenopause, often with wide fluctuations. These fluctuations cause many of the physical changes during perimenopause as well as menopause. Some of these changes are hot flashes, night sweats, difficulty sleeping, vaginal dryness or atrophy, incontinence, osteoporosis, and heart disease. 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.
During perimenopause, many women frequently experience "hot flashes" or "hot flushes", sudden temporary increases in body temperature due to hormone fluctuations. During a hot flash, the external body temperature peaks extremely rapidly, and then slowly returns to normal. These hot flashes cause flushing, sweating, and may also cause the woman to feel light-headed. Despite the discomfort, hot flashes are not considered harmful. In extreme cases, flashes can be treated to ease discomfort, using prescription medications or by using over-the-counter plant estrogens and herbal remedies. Many women attempt to manage hot flashes by dressing in ways that dissipate heat quickly (wearing several loose and removable layers of lightweight clothing made of natural fibers) as well as mechanical means that can help the body to remove excess heat, such as fans, drinking ice water, and staying in cool rooms. Other common effects encountered during perimenopause include mood changes, worsening of premenstrual syndrome, breast tenderness, irregular periods, urinary urgency, insomnia, fatigue, and problems with memory and concentration.
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:
- Caring for, and/or the death of, elderly parents
- Empty-nest syndrome when children leave home
- The birth of grandchildren, which places people of "middle age" into a new category of "older people" (especially in cultures where being older is a state that is looked down on)
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.
Clinically speaking, menopause is defined as a specific date; assuming the woman still has a uterus, the date is the day after the woman's final episode of menstrual flow finishes. However, this date can only be fixed retrospectively, once 12 months have gone by with no menstrual flow at all.
In common parlance, however, the word "menopause" usually refers not to just one day, but to the whole of the menopause transition years. This span of time is also called the "change of life", the "change", or the "climacteric" and more recently is known as "perimenopause", (literally meaning "around menopause"). The word "menopause" is also sometimes used in common parlance to mean all the years of postmenopause.
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. 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.
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.
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. 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.
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. 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. Thus specific tissue effects of natural menopause cannot be attributed to loss of androgenic hormone production.
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. 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. 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. (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. 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.
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.
HRT may be reasonable for the treatment of menopausal symptoms such as hot flashes. Its use appears to increase the risk of strokes and blood clots. When used for menopausal symptoms it should be used for the shortest time possible and at the lowest dose possible. 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.
It also appears effective for preventing bone loss and osteoporotic fracture. It is often seen as a second line agent for this purpose.
Selective estrogen receptor modulators
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. 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. While most SERMs are known to increase hot flushes, Femarelle (DT56a) decreases them. In addition to the relieving effects on menopausal symptoms, Femarelle also increases bone mass density (BMD), making it protective against osteoporotic fractures. 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 and uterus, has no effect on these tissues.
There is more promising data from an emerging SERM treatment based on a multibotanical compound MF-101 (trade name Menerba) can be located here.
In postmenopausal women, within a randomized placebo-controlled trial, no statistically significant effect of DHEA supplementation on muscle strength during a 12 week combined endurance and weight training program.
Of the non-hormonal therapies for hot flashes, some of the SSRIs appear to provide some pharmaceutical relief. For example, paroxetine is FDA-approved for hot moderate-to-severe vasomotor symptoms associated with menopause, after randomized controlled trials has shown modest relief.
Also, fluoxetine and venlafaxine have been used with some success in the treatment of hot flashes. However, paroxetine and venlafaxine may cause nausea and insomnia. In addition, venlafaxine may cause dry mouth, constipation, and decreased appetite whereas paroxetine may cause headaches.
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. Fluoxetine is also prescribed for premenstrual dysphoric disorder (PMDD), a mood disorder often exacerbated during perimenopause.
Gabapentin and other GABA analogs are anti-seizure medications. Several GABA analogs are prescribed off-label for a variety of other conditions (such as pregabalin being used to treat the symptoms of fibromyalgia; gabapentin itself has been shown to be as effective as estrogen at reducing hot flashes.
Blood pressure medicines
Blood pressure medicines including clonidine (Catapres) are about as effective as antidepressants for hot flashes, but do not have the other mind and mood benefits of antidepressants. However they may merit special consideration by women suffering both from high blood pressure and hot flashes.
Some botanical sources, referred to as phytoestrogens, do not simply mimic the effects of human steroidal estrogen but exhibit both similar and divergent actions. The ultimate actions of these compounds in specific cells is determined by many factors including the relative levels of the estrogen receptors ER alpha and beta and the diverse mix of coactivators and corepressors present in any given cell type. Thus they have been described to act somewhat like selective estrogen receptor modulators (SERMs). Effects vary according to the phytoestrogen studied, cell line, tissue, species, and response being evaluated.
Systematic reviews of intervention studies question the validity of the proposed benefits of phytoestrogen supplementation, with little data in postmenopausal women to support a role for phytoestrogens as an alternative for conventional HT. Femarelle is a mixture of DT56a soy derivative and ground flaxseed at a ratio of 3:1, for oral administration. Each capsule contains 344 mg soy and 108 mg flaxseed—altogether 430 mg powder. It is being promoted for the treatment of menopause and prevention of bone loss and has also been described as having SERM qualities, thereby reducing the safety risks involved in estrogenic-like treatments. In 2008 the European Food Safety Authority concluded that "a cause and effect relationship has not been established between the consumption of Femarelle and increased BMD, increased bone formation, or decreased risk of osteoporosis or other bone disorders in post-menopausal women".
There are regular claims that soy isoflavones are beneficial concerning some symptoms of menopause. Isoflavones are naturally occurring compounds, and daidzein and genistein are the main isoflavones found in soy. After consuming soy containing daidzein some, but not all, humans produce S-equol (7-hydroxy-3-(49-hydroxyphenyl)-chroman), which may have some health benefits, particularly the reduction of some menopausal symptoms.
The ability to transform daidzein into S-equol is based on the presence of certain intestinal bacteria. In fact, several studies indicate that only 25 to 30 percent of the adult population of Western countries produces S-equol after eating soy foods containing isoflavones, significantly lower than the reported 50 to 60 percent frequency of equol-producers in adults from Japan, Korea, or China. S-equol is not of plant origin. Kenneth Setchell, Ph.D., et al., proposed in 2002 that S-equol had potential for disease prevention and treatment. The scientists stated "There is good rationale for expecting greater efficacy in equol-producers because equol binds with greater affinity to estrogen receptor than daidzein."
Recent human clinical studies showed that S-equol provided as a standardized soygerm-based dietary supplement helped reduce menopausal symptoms, bone loss and crow's feet skin wrinkles in menopausal women. Studies of Japanese postmenopausal women documented that those who can produce S-equol after soy consumption had milder menopause symptoms than those who were equol nonproducers. Key basic animal and human studies, in both women in Japan and the United States, have documented the efficacy and safety of the soygerm-based supplement containing S-equol to modify menopause symptoms, particularly the reduction of the severity and frequency of hot flashes and neck and shoulder stiffness.
However, one study indicated that soy isoflavones did not improve or appreciably affect cognitive functioning in postmenopausal women.
Accupuncture and accupressure
In the area of complementary and alternative therapies, acupuncture and acupressure treatments are promising. Numerous studies indicate positive effects, especially on hot flashes  but also others showing no positive effects of acupuncture regarding menopause.
Red clover, Black cohosh
Other remedies which work in some studies, but in other studies appear to be no better than a placebo, include red clover isoflavone extracts and black cohosh (Cimicifuga racemosa, also known as Actaea racemosa), a plant native to North America. It has common usage internationally for the treatment of hot flushes and sweats experienced by postmenopausal women. However, study results do not support a benefit of black cohosh for the treatment of menopausal symptoms. Black cohosh has been associated with reports of acute liver toxicity and a concern has been raised regarding the stimulation of pre-existing breast cancer based on an animal study. One study found that when compared to a placebo, black cohosh and red clover did not reduce the number of vasomotor symptoms, although safety monitoring indicated that chemically and biologically standardized extracts of black cohosh and red clover were safe during daily administration for 12 months. Another study reported that black cohosh used in isolation, or as part of a multibotanical regimen, had little potential to relieve vasomotor symptoms.
There is promising data from an emerging treatment comprising a multibotanical compound MF-101 (trade name Menerba).
Many women arrive at their menopause transition 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; at least in the United States, it may often be the case that she has received no information from her physician, or from her older female family members, or from her social group. In the United States there appears to be a lingering taboo over this subject. As a result, a woman who happens to undergo a strong perimenopause with a large number of different effects, 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.
- Lack of lubrication is a common problem during and after perimenopause. Vaginal moisturizers can help women with overall dryness, and lubricants 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 complain that that their genitalia are uncomfortably dry all the time, and they may do better with moisturizers. Those who need only lubricants do well using them only during intercourse.
- Low-dose prescription vaginal estrogen products such as estrogen creams are generally a safe way to use estrogen topically, 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, 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.
- Individual counseling or support groups can sometimes be helpful to handle sad, depressed, anxious or confused feelings women may be having as they pass through what can be for some a very challenging transition time.
- Osteoporosis can be minimized by smoking cessation, adequate vitamin D intake and regular weight-bearing exercise. The bisphosphate drug alendronate may decrease the risk of a fracture, in women that have both bone loss and a previous fracture and less so for those with just osteoporosis.
- The risk of acute myocardial infarction and other cardiovascular diseases rises sharply after menopause, but the risk can be reduced by managing risk factors, such as tobacco smoking, hypertension, increased blood lipids and body weight.
Abnormalities, dysfunction, and surgery
POF (premature ovarian failure)
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.
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.
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). 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.
Society and culture
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. 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.
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.
It seems that Japanese women experience menopause effects, or konenki in a different way from American women. 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.
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%. This was almost double that of 20 years prior. 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. However, reporting of vasomotor symptoms is still significantly lower than North America.
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. 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".
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.
Medicalization of menopause and society
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.
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; 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:
- Non-adaptive hypotheses:
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 and the available data does not support this.
A recent increase in female longevity due to improvements in the standard of living and social care has also been suggested. It is difficult for selection, however, to favour aid to offspring from parents and grandparents. Irrespective of living standards, adaptive responses are limited by physiological mechanisms. In other words senescence is programmed and regulated by specific genes.
- Adaptive hypotheses:
- The "survival of the fittest" hypothesis
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.  One problem with this hypothesis is that we would expect to see menopause exhibited more often throughout the animal kingdom.
- The mother hypothesis:
The mother hypothesis suggests that menopause was selected for in 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.
- The grandmother hypothesis:
The Grandmother hypothesis suggests that menopause was selected for 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 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. 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). Differing assistance strategies for maternal and paternal grandmothers have also been demonstrated. Maternal grandmothers concentrate on offspring survival, whereas paternal grandmothers increase birth rates.
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. However, there is disagreement split along ideological lines about whether patrilineality would have existed before modern times. 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). 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. 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. 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. However, there is evidence that the physical risks of childbirth were more dangerous to women than menopause during the Medieval period in Europe, with survival statistics relative to men 10% worse during fertile ages 14–40, but 10% better after age 40.
Menopause in the animal kingdom appears to be uncommon, but the presence of this phenomenon in different species has not been thoroughly researched. 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, including rhesus monkeys, and chimpanzees. Menopause also has been reported in a variety of other vertebrate species including elephants, short-finned pilot whales and other cetaceans, the guppy, 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. Similar observations have been made in cats.
- Twiss JJ, Wegner J, Hunter M, Kelsay M, Rathe-Hart M, Salado W (2007). "Perimenopausal symptoms, quality of life, and health behaviors in users and nonusers of hormone therapy". J Am Acad Nurse Pract 19 (11): 602–13.
- Greene JG (1998). "Constructing a standard climacteric scale". Maturitas 29 (1): 25–31.
- Monterrosa-Castro A, Romero-Pérez I, Marrugo-Flórez M, Fernández-Alonso AM, Chedraui P, Pérez-López FR (2012). "Quality of life in a large cohort of mid-aged Colombian women assessed using the Cervantes Scale.". Menopause 19 (8): 924–30.
- Chedraui P, Pérez-López FR, Mendoza M, Leimberg ML, Martínez MA, Vallarino V, Hidalgo L. (2010). "Factors related to increased daytime sleepiness during the menopausal transition as evaluated by the Epworth sleepiness scale". Maturitas 65 (1). pp. 75–80.
- Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson (2007). Robbins Basic Pathology: With Student Consult Online Access. Philadelphia: Saunders. p. 344. 8th edition.
- Dreisler E, Poulsen LG, Antonsen SL, Ceausu I, Depypere H, Erel CT, Lambrinoudaki I, Pérez-López FR, Simoncini T, Tremollieres F, Rees M, Ulrich LG (2013). "EMAS clinical guide: Assessment of the endometrium in peri and postmenopausal women". Maturitas 75 (2): 181–90.
- Pérez-López FR, Cuadros JL, Fernández-Alonso AM, Chedraui P, Sánchez-Borrego R, Monterrosa-Castro A (2012). "Quality of life in a large cohort of mid-aged Colombian women assessed using the Cervantes Scale.". Maturitas 73 (4): 369–72.
- Llaneza P, García-Portilla MP, Llaneza-Suárez D, Armott B, Pérez-López FR (2012). "Depressive disorders and the menopause transition.". Maturitas 71 (2): 120–30.
- Arakane M, Castillo C, Rosero MF, Peñafiel R, Pérez-López FR, Chedraui P. (2011). "Factors relating to insomnia during the menopausal transition as evaluated by the Insomnia Severity Index.". Maturitas 69 (2). pp. 157–161.
- Monterrosa-Castro A, Marrugo-Flórez M, Romero-Pérez I, Chedraui P, Fernández-Alonso AM, Pérez-López FR (2013). "Prevalence of insomnia and related factors in a large mid-aged female Colombian sample.". Maturitas 74 (4): 346–51.
- Llaneza P, Fernández-Iñarrea JM, Arnott B, García-Portilla MP, Chedraui P, Pérez-López FR (2011). "Sexual function assessment in postmenopausal women with the 14-item changes in sexual functioning questionnaire.". J Sex Med 8 (8): 2144–51.
- Pérez-López FR, Fernández-Alonso AM, Trabalón-Pastor M, Vara C, Chedraui P (2012). "Assessment of sexual function and related factors in mid-aged sexually active Spanish women with the six-item Female Sex Function Index.". Menopause 19 (11): 1224–30.
- Ornat L, Martínez-Dearth R, Muñoz A, Franco P, Alonso B, Tajada M, Pérez-López FR (2012). "Sexual function, satisfaction with life and menopausal symptoms in middle-aged women.". Maturitas 75 (3): 261–9.
- Freeman EW, Sammel MD, Lin H, Gracia CR, Pien GW, Nelson DB, Sheng L (2007). "Symptoms associated with menopausal transition and reproductive hormones in midlife women". Obstetrics and gynecology 110 (2 Pt 1): 230–40.
- Pien GW, Sammel MD, Freeman EW, Lin H, DeBlasis TL (July 2008). "Predictors of sleep quality in women in the menopausal transition". Sleep 31 (7): 991–9.
- Kato I, Toniolo P, Akhmedkhanov A, Koenig KL, Shore R, Zeleniuch-Jacquotte A (1998). "Prospective study of factors influencing the onset of natural menopause". J Clin Epidemiol 51 (12): 1271–1276.
- Do KA, Treloar SA, Pandeya N, Purdie D, Green AC, Heath AC, Martin NG (1998). "Predictive factors of age at menopause in a large Australian twin study". Hum Biol 70 (6): 1073–91.
- Ringa, V. (2000). "Menopause and treatments". Quality of Life Research 9 (6): 695–707.
- et al.
- Healthline. "What causes early menopause". Healthline.
- et al. "Risk for New Onset of Depression During the Menopausal TransitionThe Harvard Study of Moods and Cycles". JAMA. Retrieved 28 September 2013.
- Harlow SD, Gass M, Hall JE, Lobo R, Maki P, Rebar RW, Sherman S, Sluss PM, de Villiers TJ (2012). "Executive summary of the Stages of Reproductive Aging Workshop +10: addressing the unfinished agenda of staging reproductive aging.". Fertility and Sterility 97 (4): 398–406.
- "Menopause 101". A primer for the perimenopausal. The North American Menopause Society. Retrieved 11 April 2013.
- Prior, Jerilynn. "Perimenopause". Centre for Menstrual Cycle and Ovulation Research (CeMCOR). Retrieved 10 May 2013.
- Chichester, Melanie; Ciranni, Patricia (August–September 2011). "Approaching Menopause (But Not There Yet!)". Nursing for Women's Health 15 (4): 320.
- Kessenich, Cathy. "Inevitalbe Menopause". Retrieved 11 April 2013.
- Bellipanni G, DI Marzo F, Blasi F, Di Marzo A. "Effects of melatonin in perimenopausal and menopausal women: our personal experience. 2005". Annals of the New York Academy of Sciences 1057: 393–402.
- Soules MR, Sherman S, Parrott E, Rebar R, Santoro N, Utian W, Woods N (2001). "Executive summary: Stages of Reproductive Aging Workshop (STRAW)". Climacteric 4 (4): 267–72.
- Burger HG (1994). "Diagnostic role of follicle stimulating hormone (FSH) measurements during menopausal transition – an analysis of FSH, oestradiol and inhibin". European Journal of Endocrinology 130 (1): 38–42.
- Burger HG (1994). "Diagnostic role of follicle stimulating hormone (FSH) measurements during menopausal transition – an analysis of FSH, oestraiol and inhibim". European Journal of Endocrinology 130 (1): 38–42.
- Simpson ER, Davis SR (2001). "Minireview: aromatase and the regulation of estrogen biosynthesis – some new perspectives". Endocrinology 142 (11): 4589–94.
- Davison SL, Bell R, Donath S, Montalto JG, Davis SR (2005). "Androgen levels in adult females: changes with age, menopause, and oophorectomy". J Clin Endocrinol Metab 90 (7): 3847–53.
- JCEM. "Ovarian Androgen Production in Postmenopausal Women". JCEM. Retrieved 27 September 2013.
- Angela M Cheung, Perimenopausal and Postmenopausal Health
- Titus S, Li F, Stobezki R, Akula K, Unsal E, Jeong K, Dickler M, Robson M, Moy F, Goswami S, Oktay K (2013). "Impairment of BRCA1-related DNA double-strand break repair leads to ovarian aging in mice and humans". Science Translational Medicine 5 (172): 172ra21.
- Harris Bernstein, Carol Bernstein and Richard E. Michod (2011). Meiosis as an Evolutionary Adaptation for DNA Repair. Chapter 19 in DNA Repair. Inna Kruman editor. InTech Open Publisher. DOI: 10.5772/25117 http://www.intechopen.com/books/dna-repair/meiosis-as-an-evolutionary-adaptation-for-dna-repair
- The Woman's Health Program Monash University, Oestrogen and Progestin as hormone therapy; http://med.monash.edu.au/sphpm/womenshealth/docs/postmenopausal-hormone-therapy.pdf.
- "Estrogen and progestogen use in postmenopausal women: 2010 position statement of The North American Menopause Society.". Menopause (New York, N.Y.) 17 (2): 242–55. Mar 2010.
- Main C, Knight B, Moxham T, Gabriel Sanchez R, Sanchez Gomez LM, Roqué i Figuls M, Bonfill Cosp X (Apr 30, 2013). "Hormone therapy for preventing cardiovascular disease in post-menopausal women.". The Cochrane database of systematic reviews 4: CD002229.
- de Villiers TJ, Stevenson JC (Jun 2012). "The WHI: the effect of hormone replacement therapy on fracture prevention.". Climacteric : the journal of the International Menopause Society 15 (3): 263–6.
- Marjoribanks J, Farquhar C, Roberts H, Lethaby A (Jul 11, 2012). "Long term hormone therapy for perimenopausal and postmenopausal women.". The Cochrane database of systematic reviews 7: CD004143.
- Davis SR, Dinatale I, Rivera-Woll L, Davison S (2005). "Postmenopausal hormone therapy: from monkey glands to transdermal patches". JEndocrinol 185 (2): 207–22.
- Bevers TB (2007). "The STAR Trial: Evidence for Raloxifene as a Breast Cancer Risk Reduction Agent for Postmenopausal Women". J Natl Compr Canc Netw 5 (8): 817–22.
- Yoles I, Yogev Y, Frenkel Y, Hirsch M, Nahum R, Kaplan B (2004). "menopausal symptoms". Clin Exp Obstet Gynecol 31 (2): 123–6.
- Somjen D, Katzburg S, Knoll E, Hendel D, Stern N, Kaye AM, Yoles I (May 2007). "DT56a (Femarelle): a natural selective estrogen receptor modulator (SERM)". J. Steroid Biochem. Mol. Biol. 104 (3–5): 252–8.
- Yoles I, Yogev Y, Frenkel Y, Nahum R, Hirsch M, Kaplan B (2003). "Tofupill/Femarelle (DT56a): a new phyto-selective estrogen receptor modulator-like substance for the treatment of postmenopausal bone loss". Menopause 10 (6): 522–5.
- Yoles I, Lilling G (January 2007). "Pharmacological doses of the natural phyto-SERM DT56a (Femarelle) have no effect on MCF-7 human breast cancer cell-line". Eur. J. Obstet. Gynecol. Reprod. Biol. 130 (1): 140–1.
- Somjen D, Yoles I (July 2003). "DT56a (Tofupill/Femarelle) selectively stimulates creatine kinase specific activity in skeletal tissues of rats but not in the uterus". J. Steroid Biochem. Mol. Biol. 86 (1): 93–8.
- Oropeza MV, Orozco S, Ponce H, Campos MG (2005). "Tofupill lacks peripheral estrogen-like actions in the rat reproductive tract". Reprod. Toxicol. 20 (2): 261–6.
- Igwebuike A, Irving BA, Bigelow ML, Short KR, McConnell JP, Nair KS (2008). "Lack of DHEA effect on a combined endurance and resistance exercise program in postmenopausal women". Journal of Clinical Endocrinology and Metabolism 95 (12): 534–538.
- Brainum, J. (2009). "DHEA Fountain of Youth or Washout". Iron Man Magazine: 534–538.
- Evans ML, Pritts E, Vittinghoff E, McClish K, Morgan KS, Jaffe RB (2005). "Management of postmenopausal hot flushes with venlafaxine hydrochloride: a randomized, controlled trial". Obstet Gynecol 105 (1): 161–6.
- Orleans RJ, Li L, Kim MJ, Guo J, Sobhan M, Soule L, Joffe HV (2014). "FDA approval of paroxetine for menopausal hot flushes". The New England Journal of Medicine 370 (19): 1777–9.
- *Rosack, Jim. "Antidepressants May Prevent Hippocampus From Shrinking", Psychiatric News, Volume 38 Number 17 Page 24, September 5, 2003.
- Thacker HL (2011). "Assessing risks and benefits of nonhormonal treatments for vasomotor symptoms in perimenopausal and postmenopausal women.". J. Womens Health 20 (7): 1007–16.
- Murkies AL, Wilcox G, Davis SR (1998). "Clinical review 92: Phytoestrogens". The Journal of Clinical Endocrinology and Metabolism 83 (2): 297–303.
- Lethaby A, Brown J, Marjoribanks J, Kronenberg F, Roberts H, Eden J. Phytoestrogens for vasomotor menopausal symptoms" Cochrane Database Syst Rev 2007(4) CD001395.
- Somjen D, Katzburg S, Knoll E, Hendel D, Stern N, Kaye AM, Yoles I (May 2007). "DT56a (Femarelle): a natural selective estrogen receptor modulator (SERM)". J. Steroid Biochem. Mol. Vol. 104 (3–5): 252–258.
- Scientific Opinion of the Panel on Dietetic Products Nutrition and Allergies on a request from the Se-Cure Pharmaceuticals Ltd on Femarelle and bone mineral density. The EFSA Journal (2008) 785, 1–10
- Murphy PA, Farmakalidis E, Johnson LD (June 1982). "Isoflavone content of soya-based laboratory animal diets.". Food and chemical toxicology 20 (3): 315–7.
- Setchell KD, Clerici C (July 2010). "Equol: history, chemistry, and formation.". The Journal of nutrition 140 (7): 1355S–62S.
- Atkinson C, Frankenfeld CL, Lampe JW (March 2005). "Gut bacterial metabolism of the soy isoflavone daidzein: exploring the relevance to human health.". Experimental biology and medicine (Maywood, N.J.) 230 (3): 155–70.
- Lampe JW, Karr SC, Hutchins AM, Slavin JL (March 1998). "Urinary equol excretion with a soy challenge: influence of habitual diet.". Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.) 217 (3): 335–9.
- Setchell KD, Cole SJ (August 2006). "Method of defining equol-producer status and its frequency among vegetarians.". The Journal of nutrition 136 (8): 2188–93.
- Rowland IR, Wiseman H, Sanders TA, Adlercreutz H, Bowey EA (2000). "Interindividual variation in metabolism of soy isoflavones and lignans: influence of habitual diet on equol production by the gut microflora.". Nutrition and cancer 36 (1): 27–32.
- Watanabe S, Yamaguchi M, Sobue T, Takahashi T, Miura T, Arai Y, Mazur W, Wähälä K, Adlercreutz H (October 1998). "Pharmacokinetics of soybean isoflavones in plasma, urine and feces of men after ingestion of 60 g baked soybean powder (kinako).". The Journal of nutrition 128 (10): 1710–5.
- Arai Y, Uehara M, Sato Y, Kimira M, Eboshida A, Adlercreutz H, Watanabe S (March 2000). "Comparison of isoflavones among dietary intake, plasma concentration and urinary excretion for accurate estimation of phytoestrogen intake.". Journal of epidemiology / Japan Epidemiological Association 10 (2): 127–35.
- Akaza H, Miyanaga N, Takashima N, Naito S, Hirao Y, Tsukamoto T, Fujioka T, Mori M, Kim WJ, Song JM, Pantuck AJ (February 2004). "Comparisons of percent equol producers between prostate cancer patients and controls: case-controlled studies of isoflavones in Japanese, Korean and American residents.". Japanese journal of clinical oncology 34 (2): 86–9.
- Song KB, Atkinson C, Frankenfeld CL, Jokela T, Wähälä K, Thomas WK, Lampe JW (May 2006). "Prevalence of daidzein-metabolizing phenotypes differs between Caucasian and Korean American women and girls.". The Journal of nutrition 136 (5): 1347–51.
- Setchell KD, Brown NM, Lydeking-Olsen E (December 2002). "The clinical importance of the metabolite equol-a clue to the effectiveness of soy and its isoflavones.". The Journal of nutrition 132 (12): 3577–84.
- Jou HJ, Wu SC, Chang FW, Ling PY, Chu KS, Wu WH (July 2008). "Effect of intestinal production of equol on menopausal symptoms in women treated with soy isoflavones.". International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 102 (1): 44–9.
- Uchiyama, S.; Ueno T; Masaki K; Shimizu S; Aso T; Shirota T. (2007). "The cross-sectional study of the relationship between soy isoflavones, equol and the menopausal symptoms in Japanese women". J Jpn Menopause Soc 15: 28–37.
- Oyama A, Ueno T, Uchiyama S, Aihara T, Miyake A, Kondo S, Matsunaga K (Feb 2012). "The effects of natural S-equol supplementation on skin aging in postmenopausal women: a pilot randomized placebo-controlled trial.". Menopause (New York, N.Y.) 19 (2): 202–10.
- Tousen Y, Ezaki J, Fujii Y, Ueno T, Nishimuta M, Ishimi Y (May 2011). "Natural S-equol decreases bone resorption in postmenopausal, non-equol-producing Japanese women: a pilot randomized, placebo-controlled trial.". Menopause (New York, N.Y.) 18 (5): 563–74.
- Aso T (July 2010). "Equol improves menopausal symptoms in Japanese women.". The Journal of nutrition 140 (7): 1386S–9S.
- Jenks, B.; Iwashita S; Nakagawa Y; Ragland K; Lee J; Carson W; Ueno T; Uchiyama S. (2012). "A Pilot Study on The Effects of S-equol When Compared to Soy Isoflavones on Menopausal Hot Flash Frequency and other menopausal symptoms". J Women's Health: In Press.
- Aso T, Uchiyama S, Matsumura Y, Taguchi M, Nozaki M, Takamatsu K, Ishizuka B, Kubota T, Mizunuma H, Ohta H (January 2012). "A natural S-equol supplement alleviates hot flushes and other menopausal symptoms in equol nonproducing postmenopausal Japanese women.". Journal of women's health (2002) 21 (1): 92–100.
- Yoneda T, Ueno T, Uchiyama S (July 2011). "S-equol and the fermented soy product SE5-OH containing S-equol similarly decrease ovariectomy-induced increase in rat tail skin temperature in an animal model of hot flushes.". Menopause (New York, N.Y.) 18 (7): 814–20.
- Fournier LR, Ryan Borchers TA, Robison LM, Wiediger M, Park JS, Chew BP, McGuire MK, Sclar DA, Skaer TL, Beerman KA (2007). "The effects of soy milk and isoflavone supplements on cognitive performance in healthy, postmenopausal women". J Nutr Health Aging. 11 (2): 155–164.
- Nir Y, Huang MI, Schnyer R, Chen B, Manber R (April 2007). "Acupuncture for postmenopausal hot flashes". Maturitas 56 (4): 383–95.
- Cohen SM, Rousseau ME, Carey BL (2003). "Can acupuncture ease the symptoms of menopause?". Holistic Nursing Practice 17 (6): 295–9.
- Zaborowska E, Brynhildsen J, Damberg S, Fredriksson M, Lindh-Astrand L, Nedstrand E, Wyon Y, Hammar M (February 2007). "Effects of acupuncture, applied relaxation, estrogens and placebo on hot flushes in postmenopausal women: an analysis of two prospective, parallel, randomized studies". Climacteric 10 (1): 38–45.
- Vincent A, Barton DL, Mandrekar JN, Cha SS, Zais T, Wahner-Roedler DL, Keppler MA, Kreitzer MJ, Loprinzi C (2007). "Acupuncture for hot flashes: a randomized, sham-controlled clinical study". Menopause 14 (1): 45–52.
- Krebs EE, Ensrud KE, MacDonald R, Wilt TJ (2004). "Phytoestrogens for treatment of menopausal symptoms: a systematic review". Obstetrics and Gynecology 104 (4): 824–36.
- Nedrow A, Miller J, Walker M, Nygren P, Huffman LH, Nelson HD (2006). "Complementary and alternative therapies for the management of menopause-related symptoms: a systematic evidence review". Arch Intern Med 166 (14): 1453–65.
- Lontos S, Jones RM, Angus PW, Gow PJ (2003). "Acute liver failure associated with the use of herbal preparations containing black cohosh". The Medical Journal of Australia 179 (7): 390–1.
- Davis VL, Jayo MJ, Ho A, Kotlarczyk MP, Hardy ML, Foster WG, Hughes CL (2008). "Black cohosh increases metastatic mammary cancer in transgenic mice expressing c-erbB2". Cancer Research 68 (20): 8377–83.
- Geller SE, Shulman LP, van Breemen RB, Banuvar S, Zhou Y, Epstein G, Hedayat S, Nikolic D, Krause EC, Piersen CE, Bolton JL, Pauli GF, Farnsworth NR (Nov–Dec 2009). "Safety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomized controlled trial.". Menopause (New York, N.Y.) 16 (6): 1156–66.
- Newton KM, Reed SD, LaCroix AZ, Grothaus LC, Ehrlich K, Guiltinan J (2006-12-19). "Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: a randomized trial.". Annals of Internal Medicine 145 (12): 869–79.
- Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Robinson V, Coyle D, Tugwell P (Jan 23, 2008). "Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women.". The Cochrane database of systematic reviews (1): CD001155.
- Pérez-López FR, Chedraui P, Gilbert JJ, Pérez-Roncero G (2009). "Cardiovascular risk in menopausal women and prevalent related co-morbid conditions: facing the post-Women's Health Initiative era.". Fertil Steril 92 (4). pp. 1171–1186.
- "Perimenopausal risk factors and future health". Human Reproduction Update 17 (5): 706–717. 2011.
- Kalantaridou SN, Davis SR, Nelson LM. Endocrinol Metab Clin North Am. 1998 Dec;27(4) 989–1006.
- Bucher, et al. 1930
- Winterich, J. (August, 2008). "Gender, medicine, and the menopausal body: How biology and culture influence women's experiences with menopause". Paper presented at the annual meeting of the American Sociological Association, New York. Retrieved November 11, 2008 from Allacademic.com
- Gannon L, Ekstrom B (1993). "Attitudes toward menopause: The influence of sociocultural paradigms". Psychology of Women Quarterly 17: 275–288.
- Avis N., Stellato R. Crawford, Bromberger J., Gan P., Cain V., Kagawa-Singer M. (2001). "Is there a menopausal syndrome? Menopausal status and symptoms across racial/ethnic group". Social Science & Medicine 52 (3): 345–356.
- Lock M (1998). "Menopause: lessons from anthropology". Psychosomatic Medicine 60 (4): 410–9.
- Melby MK (2005). "Factor analysis of climacteric symptoms in Japan". Maturitas 52 (3-4): 205–22.
- Lock, M. & Nguyen, V. (2010) ‘An Anthropology of Biomedicine’, Chapter 4 "Local Biologies and Human Difference" (84-89), West Sussex, Wiley-Blackwell
- Gold EB, Block G, Crawford S, Lachance L, FitzGerald G, Miracle H, Sherman S (2004). "Lifestyle and demographic factors in relation to vasomotor symptoms: baseline results from the Study of Women's Health Across the Nation". American Journal of Epidemiology 159 (12): 1189–99.
- Maoz B., Dowty N., Antonovsky A., Wisjenbeck H. (1970). "Female attitudes to menopause". Social Psychiatry 5: 35–40.
- Stotland N.L. (2002). "Menopause: Social expectations, women's realities". Archives of Women's Mental Health 5: 5–8.
- Lock, Margaret M., and Vinh-Kim Nguyen. "Chapter 2." An Anthropology of Biomedicine. Chichester, West Sussex: Wiley-Blackwell, 2010. 32-56. Print.
- Walker ML, Herndon JG (2008). "Menopause in nonhuman primates?". Biology of Reproduction 79 (3): 398–406.
- Gaulin SJ (1980). "Sexual Dimorphism in the Human Post-reproductive Life-span: Possible Causes". Journal of Human Evolution 9 (3): 227–232.
- Holmberg, I. (1970), "Fecundity, Fertility and Family Planning". Demography Institute University of Gothenburg Reports. 10: 1–109
- Washburn, S.L. (1981). "Longevity in Primates". In: Aging: Biology and Behavior by McGaugh, J.L. and S. B. Kiesler, S.B. (eds). Pp. 11–29. Academic Press.
- Hawkes K (2004). "Human longevity: The grandmother effect". Nature 428 (6979): 128–129.
- Ricklefs RE, Wikelski M (2002). "The Physiology/Life-history Nexus". Trends in Ecology & Evolution 17 (10): 462–468.
- Darwin, Charles. "Origin of Species". Retrieved 24 September 2013.
- Peccei JS (2001). "Menopause: Adaptation or Epiphenomenon?". 'Evolutionary Anthropology 10 (2): 43–57.
- Lahdenperä M, Lummaa V, Helle S, Tremblay M, Russell AF (2004). "Fitness benefits of prolonged post-reproductive lifespan in women". Nature 428 (6979): 178–181.
- Voland, E. and Beise, J. (2002). "Opposite Effects of Maternal and Paternal Grandmothers on Infant Survival in Historical Krummörn". MPIDR WP 2001–026.
- Mace, R and Sear, R. (2004). Are Humans Communal Breeders? In: Voland, E., Chasiotis, A. and Schiefenhoevel, W. (eds). Grandmotherhood – the Evolutionary Significance of the Second Half of Female Life. Rutgers University Press.
- Peccei JS (2001). "A critique of the grandmother hypotheses: Old and new". American Journal of Human Biology 13 (4): 434–452.
- 10. Finch, C.E. 1990. Longevity senescence and the genome. University of Chicago Press. London.
- Pavard S, Sibert A, Heyer E (2007). "The effect of maternal care on child survival: a demographic, genetic, and evolutionary perspective". Evolution; International Journal of Organic Evolution 61 (5): 1153–61.
- Walker RS, Flinn MV, Hill KR (2010). "Evolutionary history of partible paternity in lowland South America". Proceedings of the National Academy of Sciences of the United States of America 107 (45): 19195–200.
- Massart F, Reginster JY, Brandi ML (2001). "Genetics of Menopause-Associatred Diseases". Maturitas 40 (2): 103–116.
- Walker ML (1995). "Menopause in female rhesus monkeys". Am J Primatol 35: 59–71.
- Bowden, D.M. and Williams, D.D. (1985). Aging. Adv.Vet.Sci.Comp.Med. 28: 306–341
- Marsh, H and Kasuya, T. (1986). Evidence for Reproductive Senescence in Female Cetaceans. Report of the International Whaling Commission. 8: 57–74.
- McAuliffe K, Whitehead H (2005). "Eusociality, menopause and information in matrilineal whales". Trends Ecol Evolution 20 (12): 650.
- Reznick D, Bryant M, Holmes D (January 2006). "The evolution of senescence and post-reproductive lifespan in guppies (Poecilia reticulata)". PLoS Biology 4 (1): e7.
- Canine reproduction
- European Menopause and Andropause Society
- Menopause: MedlinePlus
- Menopause and Menopause Treatments
- Menopause.org, The Official Website of The North American Menopause Society
- Menopause Symptoms