Menopause

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.

During early menopause transition, the

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)

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

The most common physical symptoms of menopause are heavy

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

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

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

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

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

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

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

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

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,

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,

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

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

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

• 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 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.
• 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 bisphosphonate 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.^[98]
• A surgical procedure where a part of one of the ovaries is removed earlier in life and frozen and then over time thawed and returned to the body (ovarian tissue cryopreservation) has been tried. While at least 11 women have undergone the procedure and paid over £6,000, there is no evidence it is safe or effective.^[99]

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

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 popular culture, law and politics

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 five other species in which females live substantially longer than their ability to reproduce. The others are all

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

• European Menopause and Andropause Society
• Menopause in the workplace
• Menopause in incarceration
• Pregnancy over age 50
• Biological clock
• Evolution of menopause

References

External links

Wikimedia Commons has media related to Menopause.

• Menopause: MedlinePlus
• What Is Menopause?, National Institute on Aging
• Menopause & Me, The North American Menopause Society