Menopause

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Menopause
Other namesClimacteric
Menopause symbol.jpg
Specialty Gynecology
Symptoms No menstrual periods for a year [1]
Duration~3 years
CausesUsually a natural change.
Can also be caused by surgery that removes both ovaries, and some types of chemotherapy. [2] [3]
TreatmentNone, lifestyle changes [4]
Medication Menopausal hormone therapy, clonidine, gabapentin, selective serotonin reuptake inhibitors [4] [5]

Menopause, also known as the climacteric, is the time when menstrual periods permanently stop, marking the end of reproduction. [1] [6] It typically occurs between the ages of 45 and 55, although the exact timing can vary. [7] Menopause is usually a natural change. [3] It can occur earlier in those who smoke tobacco. [2] [8] Other causes include surgery that removes both ovaries or some types of chemotherapy. [9] [2] 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 the blood or urine. [10] Menopause is the opposite of menarche, the time when a girl's periods start. [11]

Contents

In the years before menopause, a woman's periods typically become irregular, [12] [13] which means that periods may be longer or shorter in duration or be lighter or heavier in the amount of flow. [12] During this time, women often experience hot flashes; these typically last from 30 seconds to ten minutes and may be associated with shivering, night sweats, and reddening of the skin. [12] Hot flashes [12] can recur for four to five years. [6] Other symptoms may include vaginal dryness, trouble sleeping, and mood changes. [12] The severity of symptoms varies between women. [6] Menopause before the age of 45 years is considered to be "early menopause" and when ovarian failure/surgical removal of the ovaries occurs before the age of 40 years this is termed "premature ovarian insufficiency". [14]

In addition to symptoms (hot flushes/flashes, night sweats, mood changes, arthralgia and vaginal dryness), the physical consequences of menopause include bone loss, increased central abdominal fat, and adverse changes in a woman's cholesterol profile and vascular function. [14] These changes predispose postmenopausal women to increased risks of osteoporosis and bone fracture, and of cardio-metabolic disease (diabetes and cardiovascular disease). [14]

Medical professionals often define menopause as having occurred when a woman has not had any menstrual bleeding for a year. [2] It may also be defined by a decrease in hormone production by the ovaries. [15] In those who have had surgery to remove their uterus but still have functioning ovaries, menopause is not considered to have yet occurred. [14] Following the removal of the uterus, symptoms of menopause typically occur earlier. [16] Iatrogenic menopause occurs when both ovaries are surgically removed along with uterus for medical reasons.

The primary indications for treatment of menopause are symptoms and prevention of bone loss. [17] Mild symptoms may be improved with treatment. With respect to hot flashes, avoiding smoking, caffeine, and alcohol is often recommended; sleeping naked in a cool room and using a fan may help. The most effective treatment for menopausal symptoms is menopausal hormone therapy (MHT). [17] Non-hormonal therapies for hot flashes include cognitive-behavioral therapy, clinical hypnosis, gabapentin, fezolinetant or selective serotonin reuptake inhibitors. [18] [19] These will not improve symptoms such as joint pain or vaginal dryness which affect over 55% of women. [17] Exercise may help with sleeping problems. Many of the concerns about the use of MHT raised by older studies are no longer considered barriers to MHT in healthy women. [17] High-quality evidence for the effectiveness of alternative medicine has not been found. [6]

Signs and symptoms

Symptoms of menopause Symptoms of menopause (vector).svg
Symptoms of menopause

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. [20]

The term menopause refers to a point in time that follows one year after the last menstruation. [20] During the menopausal transition and after menopause, women can experience a wide range of symptoms. [12] However, for women who enter the menopause transition without having regular menstrual cycles (due to prior surgery, other medical conditions or ongoing hormonal contraception) the menopause cannot be identified by bleeding patterns and is defined as the permanent loss of ovarian function. [17]

Vagina, uterus and bladder (urogenital tract)

Size of the vaginal canal before and after menopause, demonstrating vaginal atrophy Vaginal Canal Normal vs. Menopause.png
Size of the vaginal canal before and after menopause, demonstrating vaginal atrophy

During the transition to menopause, menstrual patterns can show shorter cycling (by 2–7 days); [20] longer cycles remain possible. [20] There may be irregular bleeding [12] (lighter, heavier, spotting). [20] Dysfunctional uterine bleeding is often experienced by women approaching menopause due to the hormonal changes that accompany the menopause transition. 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. [21]

In post-menopausal women, however, any unscheduled vaginal bleeding is of concern and requires an appropriate investigation to rule out the possibility of malignant diseases.

Urogenital symptoms (that may appear during menopause and continue through postmenopause) include painful intercourse, vaginal dryness and atrophic vaginitis – thinning of the membranes of the vulva, the vagina, the cervix and the outer urinary tract, along with considerable shrinking and loss in elasticity of all of the outer and inner genital areas – urinary urgency and burning up to urinary incontinence. [20]

Other physical effects

Bone mineral density, especially of the vertebrae, decreases with menopause. Menopause - Osteoporosis -- Smart-Servier (cropped).jpg
Bone mineral density, especially of the vertebrae, decreases with menopause.

The most common physical symptoms of menopause are heavy night sweats, and hot flashes (also known as vasomotor symptoms). [22] Sleeping problems and insomnia are also common. [23] Other physical symptoms may be reported that are not specific to menopause but may be exacerbated by it, such as lack of energy, joint soreness, stiffness, back pain, breast enlargement, breast pain, heart palpitations, headache, dizziness, dry, itchy skin, thinning, tingling skin, rosacea, weight gain. [20] [24]

Mood and memory effects

Psychological symptoms are often reported but they are not specific to menopause and can be caused by other factors. [25] [26] They include anxiety, poor memory, inability to concentrate, depressive mood, irritability, mood swings, and less interest in sexual activity. [20] [27] [12]

Menopause-related cognitive impairment can be confused with the mild cognitive impairment that precedes dementia. [28] There is evidence of small decreases in verbal memory, on average, which may be caused by the effects of declining estrogen levels on the brain, [29] or perhaps by reduced blood flow to the brain during hot flashes. [30] However, these tend to resolve for most women during the postmenopause. Subjective reports of memory and concentration problems are associated with several factors, such as lack of sleep, and stress. [26] [25]

Long-term effects

Cardiovascular health

Exposure to endogenous estrogen during reproductive years provides women with protection against cardiovascular disease, which is lost around 10 years after the onset of menopause. The menopausal transition is associated with an increase in fat mass (predominantly in visceral fat), an increase in insulin resistance, dyslipidaemia, and endothelial dysfunction. [31] Women with vasomotor symptoms during menopause seem to have an especially unfavorable cardiometabolic profile, [32] as well as women with premature onset of menopause (before 45 years of age). [33] These risks can be reduced by managing risk factors, such as tobacco smoking, hypertension, increased blood lipids and body weight. [34] [35]

Bone health

The annual rates of bone mineral density loss are highest starting one year before the final menstrual period and continuing through the two years after it. [36] Thus, post menopausal women are at increased risk of osteopenia, osteoporosis and fractures.

Causes

Menopause can be induced or occur naturally. Induced menopause [37] occurs as a result of medical treatment such as chemotherapy, radiotherapy, oophorectomy, or complications of tubal ligation, hysterectomy, unilateral or bilateral salpingo-oophorectomy or leuprorelin usage. [38]

Age

Menopause typically occurs at some point between 47 and 54 years of age. [7] According to various data, more than 95% of women have their last period between the ages of 44–56 (median 49–50). 2% of women under the age of 40, 5% between the ages of 40–45 and the same number between the ages of 55–58 have their last bleeding. [39] The average age of the last period in the United States is 51 years, in Russia is 50 years, in Greece is 49 years, in Turkey is 47 years, in Egypt is 47 years and in India is 46 years. [40] The menopausal transition or perimenopause leading up to menopause usually lasts 3–4 years (sometimes as long as 5–14 years). [1] [13]

Undiagnosed and untreated coeliac disease is a risk factor for early menopause. Coeliac disease can present with several non-gastrointestinal symptoms, in the absence of gastrointestinal symptoms, and most cases escape timely recognition and go undiagnosed, leading to a risk of long-term complications. A strict gluten-free diet reduces the risk. Women with early diagnosis and treatment of coeliac disease present a normal duration of fertile life span. [41] [42]

Women who have undergone hysterectomy with ovary conservation go through menopause on average 1.5 years earlier than the expected age. [17]

Premature ovarian insufficiency

In rare cases, a woman's ovaries stop working at a very early age, ranging anywhere from the age of puberty to age 40. This is known as premature ovarian failure and affects 1 to 2% of women by age 40. [43] also called premature ovarian insufficiency (POI) [44] [45] It is diagnosed or confirmed by high blood levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) on at least three occasions at least four weeks apart. [46]

Premature ovarian insufficiency may be auto immune and therefore might co occur with other autoimmune disorders such as thyroid disease, [adrenal insufficiency], and diabetes mellitus. Other causes include chemotherapy, being a carrier of the fragile X syndrome gene, and radiotherapy. [45] However, in about 50–80% of cases of premature ovarian insufficiency, the cause is unknown, i.e., it is generally idiopathic. [44] [46]

An early menopause can be related to cigarette smoking, higher body mass index, racial and ethnic factors, illnesses, and the removal of the uterus. [47]

Rates of premature menopause have been found to be significantly higher in fraternal and identical twins; about 5% of twins reach menopause before the age of 40.[ dubious ] The reasons for this are not completely understood. [48]

Surgical menopause

Menopause can be surgically induced by bilateral oophorectomy (removal of ovaries), [37] which is often, but not always, done in conjunction with removal of the fallopian tubes (salpingo-oophorectomy) and uterus (hysterectomy). [49] Cessation of menses as a result of removal of the ovaries is called "surgical menopause". Surgical treatments, such as the removal of ovaries, might cause periods to stop altogether. [50] The sudden and complete drop in hormone levels may produce extreme withdrawal symptoms such as hot flashes, etc. The symptoms of early menopause may be more severe. [50]

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.[ medical citation needed ] The time between surgery and possible early menopause is due to the fact that ovaries are still producing hormones. [50]

Mechanism

Bone loss due to menopause occurs due to changes in a woman's hormone levels. 615 Age and Bone Mass.jpg
Bone loss due to menopause occurs due to changes in a woman's hormone levels.

The menopausal transition, and postmenopause itself, is a natural change, not usually a disease state or a disorder. The main cause of this transition is the natural depletion and aging of the finite amount of oocytes (ovarian reserve). This process is sometimes accelerated by other conditions and is known to occur earlier after a wide range of gynecologic procedures such as hysterectomy (with and without ovariectomy), endometrial ablation and uterine artery embolisation. The depletion of the ovarian reserve causes an increase in circulating follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels because there are fewer oocytes and follicles responding to these hormones and producing estrogen.

The transition has a variable degree of effects. [51]

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. [52]

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 luteinizing hormone (LH), which are both produced by the pituitary gland. During perimenopause (approaching menopause), estradiol levels and patterns of production remain relatively unchanged or may increase compared to young women, but the cycles become frequently shorter or irregular. [53] The often observed increase in estrogen is presumed to be in response to elevated FSH levels that, in turn, is hypothesized to be caused by decreased feedback by inhibin. [54] Similarly, decreased inhibin feedback after hysterectomy is hypothesized to contribute to increased ovarian stimulation and earlier menopause. [55] [56]

The menopausal transition is characterized by marked, and often dramatic, variations in FSH and estradiol levels. Because of this, measurements of these hormones are not considered to be reliable guides to a woman's exact menopausal status. [54]

Menopause occurs because of the sharp decrease of estradiol and progesterone production by the ovaries. After menopause, estrogen continues to be produced mostly by aromatase in fat tissues and is produced in small amounts in many other tissues such as ovaries, bone, blood vessels, and the brain where it acts locally. [57] The substantial 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. [58] Thus specific tissue effects of natural menopause cannot be attributed to loss of androgenic hormone production. [59]

Hot flashes and other vasomotor and body symptoms accompanying the menopausal transition are associated with estrogen insufficiency and changes that occur in the brain, primarily the hypothalamus and involve complex interplay between the neurotransmitters kisspeptin, neurokinin B, and dynorphin, which are found in KNDy neurons in the infundibular nucleus. [60]

Ovarian aging

Decreased inhibin feedback after hysterectomy is hypothesized to contribute to increased ovarian stimulation and earlier menopause. Hastened ovarian aging has been observed after endometrial ablation. While it is difficult to prove that these surgeries are causative, it has been hypothesized that the endometrium may be producing endocrine factors contributing to the endocrine feedback and regulation of the ovarian stimulation. Elimination of these factors contributes to faster depletion of the ovarian reserve. Reduced blood supply to the ovaries that may occur as a consequence of hysterectomy and uterine artery embolisation has been hypothesized to contribute to this effect. [55] [56]

Impaired DNA repair mechanisms may contribute to earlier depletion of the ovarian reserve during aging. [61] 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; it appears to be an adaptation for efficiently removing damages in germ line DNA. [62]

Human primary oocytes are present at an intermediate stage of meiosis, termed prophase I (see Oogenesis). 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. [61] 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.

Diagnosis

Ways of assessing the impact on women of some of these menopause effects, include the Greene climacteric scale questionnaire, [63] the Cervantes scale [64] and the Menopause rating scale. [65]

Perimenopause

The term "perimenopause", which literally means "around the menopause", refers to the menopause transition years before the date of the final episode of flow. [1] [13] [66] [67] According to the North American Menopause Society, this transition can last for four to eight years. [68] 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. [69]

During perimenopause, estrogen levels average about 20–30% higher than during premenopause, often with wide fluctuations. [69] These fluctuations cause many of the physical changes during perimenopause as well as menopause, especially during the last 1–2 years of perimenopause (before menopause). [66] [70] Some of these changes are hot flashes, night sweats, difficulty sleeping, mood swings, vaginal dryness or atrophy, incontinence, osteoporosis, and heart disease. [69] Perimenopause is also associated with a higher likelihood of depression (affecting from 45 percent to 68 percent of perimenopausal women), which is twice as likely to affect those with a history of depression. [71]

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.

The menopause transition typically begins between 40 and 50 years of age (average 47.5). [72] [73] The duration of perimenopause may be for up to eight years. [73] Women will often, but not always, start these transitions (perimenopause and menopause) about the same time as their mother did. [74]

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 menopause. [75]

Postmenopause

The term "postmenopausal" describes women who have not experienced any menstrual flow for a minimum of 12 months, assuming that they have a uterus and are not pregnant or lactating. [49] The reason for this delay in declaring postmenopause is that periods are usually erratic during menopause. Therefore, a reasonably long stretch of time is necessary to be sure that the cycling has ceased. 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.[ citation needed ]

In women with or without a uterus, menopause or postmenopause can also be identified by a blood test showing a very high Follicle-stimulating hormone level, greater than 25 IU/L in a random blood draw; it rises as ovaries become inactive. [49] FSH continues to rise, as its counterpart estradiol continues to drop for about 2 years after the last menstrual period, after which the levels of each of these hormones stabilize. The stabilization period after the begin of early postmenopause has been estimated to last 3 to 6 years, so early postmenopause lasts altogether about 5 to 8 years, during which hormone withdrawal effects such as hot flashes disappear. [49] Finally, late postmenopause has been defined as the remainder of a woman s lifespan, when reproductive hormones do not change any more.[ citation needed ]

A period-like flow during postmenopause, even spotting, may be a sign of endometrial cancer.

Management

Perimenopause is a natural stage of life. It is not a disease or a disorder. 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 life of the woman experiencing them, palliative medical therapy may sometimes be appropriate.

Menopausal hormone therapy

In the context of the menopause, menopausal hormone therapy (MHT) is the use of estrogen in women without a uterus and estrogen plus progestogen in women who have an intact uterus. [76]

MHT may be reasonable for the treatment of menopausal symptoms, such as hot flashes. [77] It is the most effective treatment option, especially when delivered as a skin patch. [78] [79] Its use, however, appears to increase the risk of strokes and blood clots. [80] When used for menopausal symptoms the global recommendation is MHT should be prescribed for a long as there are defined treatment effects and goals for the individual woman. [17]

MHT is also effective for preventing bone loss and osteoporotic fracture, [81] but it is generally recommended only for women at significant risk for whom other therapies are unsuitable. [82]

MHT may be unsuitable for some women, including those at increased risk of cardiovascular disease, increased risk of thromboembolic disease (such as those with obesity or a history of venous thrombosis) or increased risk of some types of cancer. [82] There is some concern that this treatment increases the risk of breast cancer. [83] Women at increased risk of cardiometabolic disease and VTE may be able to use transdermal estradiol which does not appear to increase risks in low to moderate doses. [17]

Adding testosterone to hormone therapy has a positive effect on sexual function in postmenopausal women, although it may be accompanied by hair growth or acne if used in excess. Transdermal testosterone therapy in appropriate dosing is generally safe. [84]

Selective estrogen receptor modulators

SERMs are a category of drugs, either synthetically produced or derived from a botanical source, 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. [85] 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. [86]

Other medications

Some of the SSRIs and SNRIs appear to provide some relief from vasomotor symptoms. [19] [18] The most effective SSRIs and SNRIs are paroxetine, escitalopram, citalopram, venlafaxine, and desvenlafaxine. [18] They may, however, be associated with appetite and sleeping problems, constipation and nausea. [19] [87]

Gabapentin or fezolinetant can also improve the frequency and severity of vasomotor symptoms. [19] [18] Side effects of using gabapentin include drowsiness and headaches. [19] [87]

Therapy

Cognitive behavioural therapy and clinical hypnosis can decrease the amount women are affected by hot flashes. [18] Mindfulness is not yet proven to be effective in easing vasomotor symptoms. [88] [89] [18]

Lifestyle and exercise

Exercise has been thought to reduce postmenopausal symptoms through the increase of endorphin levels, which decrease as estrogen production decreases. [90] However, there is insufficient evidence to suggest that exercise helps with the symptoms of menopause. [18] Similarly, yoga has not been shown to be useful as a treatment for vasomotor symptoms. [18]

However a high BMI is a risk factor for vasomotor symptoms in particular. Weight loss may help with symptom management. [91] [18]

There is no strong evidence that cooling techniques such as using specific clothing or environment control tools (for example fans) help with symptoms. [18] Paced breathing and relaxation are not effective in easing symptoms. [18]

Dietary supplements

There is no evidence of consistent benefit of taking any dietary supplements or herbal products for menopausal symptoms. [18] [92] [93] These widely marketed but ineffective supplements include soy isoflavones, pollen extracts, black cohosh, omega-3 among many others. [18] [94] [95]

Alternative medicine

There is no evidence of consistent benefit of alternative therapies for menopausal symptoms despite their popularity. [93] [18]

As of 2023, there is no evidence to support the efficacy of acupuncture as a management for menopausal symptoms. [18] [96] [93] The Cochrane review found not enough evidence in 2016 to show a difference between Chinese herbal medicine and placebo for the vasomotor symptoms. [97]

Other efforts

Society and culture

Attitudes and experiences

The menopause transition is a process, involving hormonal, menstrual, and typically vasomotor changes. However, the experience of the menopause as a whole is very much influenced by psychological and social factors, such as past experience, lifestyle, social and cultural meanings of menopause, and a woman's social and material circumstances. Menopause has been described as a biopsychosocial experience, with social and cultural factors playing a prominent role in the way menopause is experienced and perceived.[ citation needed ]

The paradigm within which a woman considers menopause 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. [100] There is some evidence that negative attitudes and expectations, held before the menopause, predict symptom experience during the menopause, [101] and, interestingly, beliefs and attitudes toward menopause tend to be more positive in postmenopausal than in premenopausal women. [102] Women with more negative attitudes towards the menopause report more symptoms during this transition. [101]

Menopause is a stage of life experienced in different ways. It can be characterized by personal challenges, changes in personal roles within the family and society. Women's approaches to changes during menopause are influenced by their personal, family and sociocultural background. [103] Women from different regions and countries also have different attitudes. Postmenopausal women had more positive attitudes toward menopause compared with peri- or premenopausal women. Other influencing factors of attitudes toward menopause include age, menopausal symptoms, psychological and socioeconomical status, and profession and ethnicity. [104]

Ethnicity and geography play roles 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. [105]

There may be variations in experiences of women from different ethnic backgrounds regarding menopause and care. Immigrant women reported more vasomotor symptoms and other physical symptoms and poorer mental health than non-immigrant women and were mostly dissatisfied with the care they had received. Self-management strategies for menopausal symptoms were also influenced by culture. [106]

Two multinational studies of Asian women, found that hot flushes were not the most commonly reported symptoms, instead body and joint aches, memory problems, sleeplessness, irritability and migraines were. [107] In another study comparing experiences of menopause amongst White Australian women and women in Laos, Australian women reported higher rates of depression, as well as fears of aging, weight gain and cancer – fears not reported by Laotian women, who positioned menopause as a positive event. [108] Japanese women experience menopause effects, or konenki, in a different way from American women. [109] 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. [109]

As of 2005, in Japanese culture, reporting of vasomotor symptoms has been on the increase, with research finding that of 140 Japanese participants, hot flashes were prevalent in 22.1%. [110] This was almost double that of 20 years prior. [111] Whilst the exact cause for this is unknown, possible contributing factors include dietary changes, increased medicalisation of middle-aged women and increased media attention on the subject. [111] However, reporting of vasomotor symptoms is still "significantly" lower than in North America. [112]

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. [113] Diverging from these conclusions, one study appeared to show that many American women "experience this time as one of liberation and self-actualization". [114]

In some women, menopause may bring about a sense of loss related to the end of fertility. In addition, this change often aligns with other stressors, such as the responsibility of looking after elderly parents or dealing with the emotional challenges of "empty nest syndrome" when children move out of the family home. This situation can be accentuated in cultures where being older is negatively perceived.

Impact on work

Midlife is typically a life stage when men and women may be dealing with demanding life events and responsibilities, such as work, health problems, and caring roles. For example, in 2018 in the UK women aged 45–54 report more work-related stress than men or women of any other age group. [115] Hot flashes are often reported to be particularly distressing at work and lead to embarrassment and worry about potential stigmatisation. [116] A June 2023 study by the Mayo Clinic estimated an annual loss of $1.8 billion in the United States due to workdays missed as a result of menopause symptoms. [117] This was one of the largest studies to date examining the impact of menopause symptoms on work outcomes. The research concluded there was a strong need to improve medical treatment for menopausal women and make the workplace environment more supportive to avoid such productivity losses.

Etymology

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 coinage; 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 Ancient Greeks did not produce medical concepts about any symptoms associated with end of menstruation and did not use a specific word to refer to this time of a woman's life. The word menopause was invented by French doctors at the beginning of the nineteenth century. Greek etymology was reconstructed at this time and it was the Parisian student doctor Charles-Pierre-Louis de Gardanne who invented the a variation of the word in 1812, which was edited to its final French form in 1821. [118]

Some of them noted that peasant women had no complaints about the end of menses, while urban middle-class women had many troubling symptoms. Doctors at this time considered the symptoms to be the result of urban lifestyles of sedentary behaviour, alcohol consumption, too much time indoors, and over-eating, with a lack of fresh fruit and vegetables. [119]

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 exists in some other animals, many of which do not have monthly menstruation; [120] in this case, the term means a natural end to fertility that occurs before the end of the natural lifespan.

In the 21 st century, celebrities have spoken out about their experiences of the menopause, which has led to it becoming less of a taboo as it has boosted awareness of the debilitating symptoms. Subsequently, TV shows have been running features on the menopause to help women experiencing symptoms. In the UK Lorraine Kelly has been an advocate for getting women to speak about their experiences including sharing her own. This has led to an increase in women seeking treatment such as HRT. [121] Davina McCall also led an awareness campaign based on a documentary on Channel 4. [122]

In the UK, Carolyn Harris sponsored the Menopause (Support and Services) Bill in June 2021. It was to exempt hormone replacement therapy from National Health Service prescription charges and to make provisions about menopause support and services, including public education and communication in supporting perimenopausal and post-menopausal women, and to raise awareness of menopause and its effects. The bill was withdrawn on 29 October 2021. [123]

In the US, David McKinley, Republican from West Virginia introduced the Menopause Research Act in September 2022 for $100 million in 2023 and 2024, but it stalled. [124]

Other animals

Few animals have a menopause: humans are joined by just four other species in which females live substantially longer than their ability to reproduce. The others are all cetaceans: beluga whales, [125] narwhals, [125] orcas, [126] false killer whales [127] and short-finned pilot whales. [128]

Menopause has been reported in a variety of other vertebrate species, but these examples tend to be from captive individuals, and thus are not necessarily representative of what happens in natural populations in the wild. Menopause in captivity has been observed in several species of nonhuman primates, [120] including rhesus monkeys [129] and chimpanzees. [130] Some research suggests that wild chimpanzees do not experience menopause, as their fertility declines are associated with declines in overall health. [131] Menopause has been reported in elephants in captivity [132] and guppies. [133] 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, see Canine reproduction. Similar observations have been made in cats. [134]

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.[ original research? ]

Evolution

There are various theories on the origin and process of the evolution of the menopause. These 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. It is conjectured that in highly social groups natural selection favors females that stop reproducing and devote that post-reproductive life span to continuing to care for existing offspring, both their own and those of others to whom they are related, especially their granddaughters and grandsons. [135]

See also

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<span class="mw-page-title-main">Estradiol</span> Chemical compound

Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible for the development of female secondary sexual characteristics such as the breasts, widening of the hips and a female pattern of fat distribution. It is also important in the development and maintenance of female reproductive tissues such as the mammary glands, uterus and vagina during puberty, adulthood and pregnancy. It also has important effects in many other tissues including bone, fat, skin, liver, and the brain.

<span class="mw-page-title-main">Progestogen (medication)</span> Medication producing effects similar to progesterone

A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural female sex hormone progesterone in the body. A progestin is a synthetic progestogen. Progestogens are used most commonly in hormonal birth control and menopausal hormone therapy. They can also be used in the treatment of gynecological conditions, to support fertility and pregnancy, to lower sex hormone levels for various purposes, and for other indications. Progestogens are used alone or in combination with estrogens. They are available in a wide variety of formulations and for use by many different routes of administration. Examples of progestogens include natural or bioidentical progesterone as well as progestins such as medroxyprogesterone acetate and norethisterone.

Oophorectomy, historically also called ovariotomy, is the surgical removal of an ovary or ovaries. The surgery is also called ovariectomy, but this term is mostly used in reference to non-human animals, e.g. the surgical removal of ovaries from laboratory animals. Removal of the ovaries of females is the biological equivalent of castration of males; the term castration is only occasionally used in the medical literature to refer to oophorectomy of women. In veterinary medicine, the removal of ovaries and uterus is called ovariohysterectomy (spaying) and is a form of sterilization.

Hot flashes are a form of flushing, often caused by the changing hormone levels that are characteristic of menopause. They are typically experienced as a feeling of intense heat with sweating and rapid heartbeat, and may typically last from two to 30 minutes for each occurrence.

<span class="mw-page-title-main">Estradiol acetate</span> Chemical compound

Estradiol acetate (EA), sold under the brand names Femtrace, Femring, and Menoring, is an estrogen medication which is used in hormone therapy for the treatment of menopausal symptoms in women. It is taken by mouth once daily or given as a vaginal ring once every three months.

<span class="mw-page-title-main">Estradiol valerate</span> Chemical compound

Estradiol valerate (EV), sold for use by mouth under the brand name Progynova and for use by injection under the brand names Delestrogen and Progynon Depot among others, is an estrogen medication. It is used in hormone therapy for menopausal symptoms and low estrogen levels, hormone therapy for transgender people, and in hormonal birth control. It is also used in the treatment of prostate cancer. The medication is taken by mouth or by injection into muscle or fat once every 1 to 4 weeks.

<span class="mw-page-title-main">Drospirenone</span> Medication drug

Drospirenone is a progestin and antiandrogen medication which is used in birth control pills to prevent pregnancy and in menopausal hormone therapy, among other uses. It is available both alone under the brand name Slynd and in combination with an estrogen under the brand name Yasmin among others. The medication is an analog of the drug spironolactone. Drospirenone is taken by mouth.

Hypoestrogenism, or estrogen deficiency, refers to a lower than normal level of estrogen. It is an umbrella term used to describe estrogen deficiency in various conditions. Estrogen deficiency is also associated with an increased risk of cardiovascular disease, and has been linked to diseases like urinary tract infections and osteoporosis.

<span class="mw-page-title-main">Tibolone</span> Chemical compound

Tibolone, sold under the brand name Livial among others, is a medication which is used in menopausal hormone therapy and in the treatment of postmenopausal osteoporosis and endometriosis. The medication is available alone and is not formulated or used in combination with other medications. It is taken by mouth.

<span class="mw-page-title-main">Dydrogesterone</span> Chemical compound

Dydrogesterone, sold under the brand name Dydroboon & Duphaston among others, is a progestin medication which is used for a variety of indications, including threatened or recurrent miscarriage during pregnancy, dysfunctional bleeding, infertility due to luteal insufficiency, dysmenorrhea, endometriosis, secondary amenorrhea, irregular cycles, premenstrual syndrome, and as a component of menopausal hormone therapy. It is taken by mouth.

<span class="mw-page-title-main">Estrone sulfate</span> Chemical compound

Estrone sulfate, also known as E1S, E1SO4 and estrone 3-sulfate, is a natural, endogenous steroid and an estrogen ester and conjugate.

Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. Effects of menopause can include symptoms such as hot flashes, accelerated skin aging, vaginal dryness, decreased muscle mass, and complications such as osteoporosis, sexual dysfunction, and vaginal atrophy. They are mostly caused by low levels of female sex hormones that occur during menopause.

Postmenopausal confusion, also commonly referred to as postmenopausal brain fog, is a group of symptoms of menopause in which women report problems with cognition at a higher frequency during postmenopause than before.

<span class="mw-page-title-main">Conjugated estrogens</span> Estrogen medication

Conjugated estrogens (CEs), or conjugated equine estrogens (CEEs), sold under the brand name Premarin among others, is an estrogen medication which is used in menopausal hormone therapy and for various other indications. It is a mixture of the sodium salts of estrogen conjugates found in horses, such as estrone sulfate and equilin sulfate. CEEs are available in the form of both natural preparations manufactured from the urine of pregnant mares and fully synthetic replications of the natural preparations. They are formulated both alone and in combination with progestins such as medroxyprogesterone acetate. CEEs are usually taken by mouth, but can also be given by application to the skin or vagina as a cream or by injection into a blood vessel or muscle.

<span class="mw-page-title-main">Estradiol (medication)</span> Steroidal hormone medication

Estradiol (E2) is a medication and naturally occurring steroid hormone. It is an estrogen and is used mainly in menopausal hormone therapy and to treat low sex hormone levels in women. It is also used in hormonal birth control for women, in feminizing hormone therapy for transgender women, and in the treatment of hormone-sensitive cancers like prostate cancer in men and breast cancer in women, among other uses. Estradiol can be taken by mouth, held and dissolved under the tongue, as a gel or patch that is applied to the skin, in through the vagina, by injection into muscle or fat, or through the use of an implant that is placed into fat, among other routes.

<span class="mw-page-title-main">Estrogen (medication)</span> Type of medication

An estrogen (E) is a type of medication which is used most commonly in hormonal birth control and menopausal hormone therapy, and as part of feminizing hormone therapy for transgender women. They can also be used in the treatment of hormone-sensitive cancers like breast cancer and prostate cancer and for various other indications. Estrogens are used alone or in combination with progestogens. They are available in a wide variety of formulations and for use by many different routes of administration. Examples of estrogens include bioidentical estradiol, natural conjugated estrogens, synthetic steroidal estrogens like ethinylestradiol, and synthetic nonsteroidal estrogens like diethylstilbestrol. Estrogens are one of three types of sex hormone agonists, the others being androgens/anabolic steroids like testosterone and progestogens like progesterone.

The timing hypothesis, gap hypothesis, gap theory, or critical window hypothesisfor menopausal hormone therapy is a scientific theory that the benefits and risks of menopausal hormone therapy vary depending on the amount of time a woman has been in menopause upon initiation of treatment. More specifically, it is thought that hormone therapy may be protective against coronary heart disease in women who initiate it in early menopause but may be harmful in women who start it in late menopause. The timing hypothesis may also extend to risks of breast cancer and dementia with hormone therapy. It is thought that the increase in breast cancer risk may be greater in women who start hormone therapy in early menopause but may be lower or that even decreased risk of breast cancer may occur in women who start in late menopause. The influence of hormone therapy on depressive symptoms may additionally be influenced by menopausal stage, with significant benefit seen in perimenopausal women but not in postmenopausal women. The timing hypothesis is potentially able to resolve conflicting findings between large observational studies and randomized controlled trials on long-term health outcomes with menopausal hormone therapy.

The Estrogen in Venous Thromboembolism Trial (EVTET) was a randomized controlled trial (RCT) of menopausal hormone therapy in 140 postmenopausal women with previous history of venous thromboembolism (VTE). It was a double-blind RCT of the estrogen, oral estradiol 2 mg/day, plus the progestogen, norethisterone acetate (NETA) (n=71) 1 mg/day versus placebo (n=69). The results of the trial were published in 2000 and 2001. The incidence of VTE was 10.7% in the hormone therapy group and 2.3% in the placebo group, with all events occurring within 261 days after study inclusion. The difference did not reach statistical significance in the sequential analysis, but was statistically significant if the sequential design was ignored. Markers of coagulation were likewise increased by hormone therapy. As a result of the high incidence of VTE in the treatment group, the trial was terminated prematurely. The researchers concluded on the basis of their findings that menopausal hormone therapy should not be used in women with a previous history of VTE.

The Menopause, Estrogen and Venous Events (MEVE) study was a retrospective observational study of menopausal hormone therapy and venous thromboembolism (VTE) in postmenopausal women with a previous history of VTE. It found that transdermal estradiol was not associated with increased risk of VTE whereas oral estrogens were associated with a large increase in risk. The mean dose of transdermal estradiol in the study was 50 μg/day, although data on dose were missing for around 50% of women. Similarly, a small study found that transdermal estradiol did not influence coagulation in women with prior VTE. These findings are similar to studies in menopausal women without prior history of VTE which have found that transdermal estradiol has minimal influence on coagulation and is not associated with increased risk of VTE at doses of up to 100 μg/day. Menopausal hormone therapy guidelines have cited the MEVE study and recommended use of transdermal estradiol over oral estrogens in women at high risk for VTE. However, randomized controlled trials (RCTs) are still needed to definitively confirm findings that transdermal estradiol is safer than oral estrogens in terms of VTE risk.

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