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Menopause, also known as the climacteric, is the time in women's lives when
menstrual periods The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that make pregnancy possible. The ovarian cycle controls the production and release of eggs a ...
stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often define menopause as having occurred when a woman has not had any menstrual bleeding for a year. It may also be defined by a decrease in
hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
production by the
ovaries The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body. T ...
. In those who have had
surgery Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical specialty that uses operative manual and instrumental techniques on a person to investigate or treat a pat ...
to remove their
uterus The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The uter ...
but still have functioning ovaries, menopause is not considered to have yet occurred. Following the removal of the uterus, symptoms typically occur earlier. In the years before menopause, a woman's periods typically become irregular, which means that periods may be longer or shorter in duration or be lighter or heavier in the amount of flow. During this time, women often experience
hot flash Hot flashes (also known as hot flushes) 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 ...
es; these typically last from 30 seconds to ten minutes and may be associated with shivering,
sweating Perspiration, also known as sweating, is the production of fluids secreted by the sweat glands in the skin of mammals. Two types of sweat glands can be found in humans: eccrine glands and apocrine glands. The eccrine sweat glands are distr ...
, and reddening of the skin. Hot flashes can last from four to five years. Other symptoms may include
vaginal dryness Vaginal lubrication is a naturally produced fluid that lubricates a vagina. Vaginal lubrication is always present, but production increases significantly near ovulation and during sexual arousal in anticipation of sexual intercourse. Vaginal ...
, trouble sleeping, and mood changes. The severity of symptoms varies between women. 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". 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. These changes predispose postmenopausal women to increased risks of
osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...
and bone fracture, and of cardio-metabolic disease (diabetes and cardiovascular disease). Menopause is usually a natural change. It can occur earlier in those who
smoke tobacco Tobacco smoking is the practice of burning tobacco and ingesting the resulting smoke. The smoke may be inhaled, as is done with cigarettes, or simply released from the mouth, as is generally done with pipes and cigars. The practice is believed ...
. Other causes include surgery that removes both
ovaries The ovary is an organ in the female reproductive system that produces an ovum. When released, this travels down the fallopian tube into the uterus, where it may become fertilized by a sperm. There is an ovary () found on each side of the body. T ...
or some types of
chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
. At the physiological level, menopause happens because of a decrease in the ovaries' production of the hormones
estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
and
progesterone Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...
. While typically not needed, a diagnosis of menopause can be confirmed by measuring hormone levels in the blood or urine. Menopause is the opposite of
menarche Menarche ( ; ) is the first menstrual cycle, or first menstrual bleeding, in female humans. From both social and medical perspectives, it is often considered the central event of female puberty, as it signals the possibility of fertility. Gir ...
, the time when a girl's periods start. The primary indications for treatment of menopause are symptoms and prevention of bone loss. 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 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. These symptoms can include hot flashes, vagina ...
(MHT). Non hormonal therapies for hot flashes include
clonidine Clonidine, sold under the brand name Catapres among others, is an α2-adrenergic agonist medication used to treat high blood pressure, ADHD, drug withdrawal ( alcohol, opioids, or nicotine), menopausal flushing, diarrhea, spasticity, and c ...
,
gabapentin Gabapentin, sold under the brand name Neurontin among others, is an anticonvulsant medication primarily used to treat partial seizures and neuropathic pain. It is a first-line medication for the treatment of neuropathic pain caused by diabet ...
, or
selective serotonin reuptake inhibitors Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extracell ...
. These will not improve symptoms such as joint pain or vaginal dryness which affect over 55% of women. 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. High-quality evidence for the effectiveness of
alternative medicine Alternative medicine is any practice that aims to achieve the healing effects of medicine despite lacking biological plausibility, testability, repeatability, or evidence from clinical trials. Complementary medicine (CM), complementary and alt ...
has not been found. There is tentative evidence for the use of
phytoestrogens A phytoestrogen is a plant-derived xenoestrogen (see estrogen) not generated within the endocrine system, but consumed by eating plants or manufactured foods. Also called a "dietary estrogen", it is a diverse group of naturally occurring nonstero ...
for symptomatic treatment.


Signs and symptoms

During early menopause transition, the
menstrual cycles The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that make pregnancy possible. The ovarian cycle controls the production and release of eggs a ...
remain regular but the interval between cycles begins to lengthen. Hormone levels begin to fluctuate. Ovulation may not occur with each cycle. The term ''menopause'' refers to a point in time that follows one year after the last
menstruation Menstruation (also known as a period, among other colloquial terms) is the regular discharge of blood and mucosal tissue from the inner lining of the uterus through the vagina. The menstrual cycle is characterized by the rise and fall of hor ...
. During the menopausal transition and after menopause, women can experience a wide range of symptoms. 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.


Vagina and uterus

During the transition to menopause, menstrual patterns can show shorter cycling (by 2–7 days); longer cycles remain possible. There may be irregular bleeding (lighter, heavier, spotting).
Dysfunctional uterine bleeding Abnormal uterine bleeding (AUB), also known as (AVB) or as atypical vaginal bleeding, is vaginal bleeding from the uterus that is abnormally frequent, lasts excessively long, is heavier than normal, or is irregular. The term dysfunctional uterin ...
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 Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations (which can destroy the gene to build up the organ), poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply t ...
, a benign sore ( polyp or lesion), or may be a functional endometrial response. The
European Menopause and Andropause Society The European Menopause and Andropause Society is an institution that promotes the study, and encourages research, of midlife health. Mission EMAS "strives to encourage the study of Menopause and Andropause as well as promote the exchange of resea ...
has released guidelines for assessment of the
endometrium The endometrium is the inner epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The functional laye ...
, which is usually the main source of spotting or bleeding. In post-menopausal women, however, any unscheduled vaginal
bleeding Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vag ...
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 Dyspareunia ( ) is painful sexual intercourse due to medical or psychological causes. The term ''dyspareunia'' covers both female dyspareunia and male dyspareunia, but many discussions that use the term without further specification concern the f ...
*
vaginal dryness Vaginal lubrication is a naturally produced fluid that lubricates a vagina. Vaginal lubrication is always present, but production increases significantly near ovulation and during sexual arousal in anticipation of sexual intercourse. Vaginal ...
*
atrophic vaginitis Atrophic vaginitis is inflammation of the vagina as a result of tissue thinning due to not enough estrogen. Symptoms may include pain with sex, vaginal itchiness or dryness, and an urge to urinate or burning with urination. It generally does no ...
– thinning of the membranes of the
vulva The vulva (plural: vulvas or vulvae; derived from Latin for wrapper or covering) consists of the external sex organ, female sex organs. The vulva includes the mons pubis (or mons veneris), labia majora, labia minora, clitoris, bulb of vestibu ...
, the
vagina In mammals, the vagina is the elastic, muscular part of the female genital tract. In humans, it extends from the vestibule to the cervix. The outer vaginal opening is normally partly covered by a thin layer of mucosal tissue called the hymen ...
, the
cervix The cervix or cervix uteri (Latin, 'neck of the uterus') is the lower part of the uterus (womb) in the human female reproductive system. The cervix is usually 2 to 3 cm long (~1 inch) and roughly cylindrical in shape, which changes during ...
, and the outer
urinary tract The urinary system, also known as the urinary tract or renal system, consists of the kidneys, ureters, bladder, and the urethra. The purpose of the urinary system is to eliminate waste from the body, regulate blood volume and blood pressure, con ...
, along with considerable shrinking and loss in elasticity of all of the outer and inner genital areas. *
Urinary urgency Urination, also known as micturition, is the release of urine from the urinary bladder through the urethra to the outside of the body. It is the urinary system's form of excretion. It is also known medically as micturition, voiding, uresis, ...
and burning


Other physical effects

Other physical symptoms of menopause include lack of energy, joint soreness,
stiffness Stiffness is the extent to which an object resists deformation in response to an applied force. The complementary concept is flexibility or pliability: the more flexible an object is, the less stiff it is. Calculations The stiffness, k, of a b ...
,
back pain Back pain is pain felt in the back. It may be classified as neck pain (cervical), middle back pain (thoracic), lower back pain (lumbar) or coccydynia (tailbone or sacral pain) based on the segment affected. The lumbar area is the most common area ...
, breast enlargement,
breast pain Breast pain is the symptom of discomfort in either one or both breasts. Pain in both breasts is often described as ''breast tenderness'', is usually associated with the menstrual period and is not serious. Pain that involves only one part of a br ...
,
heart palpitation Palpitations are perceived abnormalities of the heartbeat characterized by awareness of cardiac muscle contractions in the chest, which is further characterized by the hard, fast and/or irregular beatings of the heart. Symptoms include a rapi ...
s,
headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...
,
dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a common medical c ...
, dry,
itch Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant ...
y skin, thinning,
tingling Paresthesia is an abnormal sensation of the skin (tingling, pricking, chilling, burning, numbness) with no apparent physical cause. Paresthesia may be transient or chronic, and may have any of dozens of possible underlying causes. Paresthesias ar ...
skin,
rosacea Rosacea is a long-term skin condition that typically affects the face. It results in redness, pimples, swelling, and small and superficial dilated blood vessels. Often, the nose, cheeks, forehead, and chin are most involved. A red, enlarge ...
,
weight gain Weight gain is an increase in body weight. This can involve an increase in muscle mass, fat deposits, excess fluids such as water or other factors. Weight gain can be a symptom of a serious medical condition. Description Weight gain occurs wh ...
,
urinary incontinence Urinary incontinence (UI), also known as involuntary urination, is any uncontrolled leakage of urine. It is a common and distressing problem, which may have a large impact on quality of life. It has been identified as an important issue in geria ...
,
urinary urgency Urination, also known as micturition, is the release of urine from the urinary bladder through the urethra to the outside of the body. It is the urinary system's form of excretion. It is also known medically as micturition, voiding, uresis, ...
, interrupted sleeping patterns,heavy
night sweat Night sweats, also referred to as nocturnal hyperhidrosis (Hyperhidrosis - a medical term for excessive sweating + nocturnal - night), is the repeated occurrence of excessive sweating during sleep. The person may or may not also perspire exces ...
s, and
hot flash Hot flashes (also known as hot flushes) 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 ...
es.


Mood and memory effects

Psychological symptoms include
anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
, poor memory, inability to concentrate, depressive mood,
irritability Irritability (also called as crankiness) is the excitatory ability that living organisms have to respond to changes in their environment. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessi ...
,
mood swing A mood swing is an extreme or sudden change of mood. Such changes can play a positive part in promoting problem solving and in producing flexible forward planning, or be disruptive. When mood swings are severe, they may be categorized as par ...
s, and less interest in sexual activity.
Menopause-related cognitive impairment Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often ...
can be confused with the
mild cognitive impairment Mild cognitive impairment (MCI) is a neurocognitive disorder which involves cognitive impairments beyond those expected based on an individual's age and education but which are not significant enough to interfere with instrumental activities of ...
that precedes
dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...
. Tentative evidence has found that forgetfulness affects about half of menopausal women and is probably caused by the effects of declining estrogen levels on the brain, or perhaps by reduced blood flow to the brain during
hot flash Hot flashes (also known as hot flushes) 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 ...
es.


Long-term effects


Cardiovascular health

Exposure to endogenous
estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
during reproductive years provides women with protection against
cardiovascular disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...
, which is lost around 10 years after the onset of menopause. The menopausal transition is associated with an increase in
fat mass Adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular e ...
(predominantly in
visceral fat Adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular en ...
), an increase in
insulin resistance Insulin resistance (IR) is a pathological condition in which cell (biology), cells fail to respond normally to the hormone insulin. Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood gluco ...
, dyslipidaemia, and
endothelial dysfunction In vascular diseases, endothelial dysfunction is a systemic pathological state of the endothelium. Along with acting as a semi-permeable membrane, the endothelium is responsible for maintaining vascular tone and regulating oxidative stress by ...
. Women with
vasomotor symptoms Hot flashes (also known as hot flushes) 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 ...
during menopause seem to have an especially unfavorable cardiometabolic profile, as well as women with premature onset of menopause (before 45 years of age). These risks can be reduced by managing risk factors, such as tobacco smoking,
hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
, increased
blood lipid Blood lipids (or blood fats) are lipids in the blood, either free or bound to other molecules. They are mostly transported in a protein capsule, and the density of the lipids and type of protein determines the fate of the particle and its influence ...
s and body weight.


Bone health

The annual rates of
bone mineral density Bone density, or bone mineral density, is the amount of bone mineral in bone tissue. The concept is of mass of mineral per volume of bone (relating to density in the physics sense), although clinically it is measured by proxy according to optica ...
loss are highest starting one year before the final menstrual period and continuing through the two years after it. Thus, post menopausal women are at increased risk of
osteopenia Osteopenia, known as "low bone mass" or "low bone density", is a condition in which bone mineral density is low. Because their bones are weaker, people with osteopenia may have a higher risk of fractures, and some people may go on to develop osteop ...
,
osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...
and
fractures Fracture is the separation of an object or material into two or more pieces under the action of stress. The fracture of a solid usually occurs due to the development of certain displacement discontinuity surfaces within the solid. If a displa ...
.


Causes

Menopause can be induced or occur naturally
Induced menopause
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occurs as a result of medical treatment such as
chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
,
radiotherapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...
,
oophorectomy Oophorectomy (; from Greek , , 'egg-bearing' and , , 'a cutting out of'), 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 ...
, or complications of
tubal ligation Tubal ligation (commonly known as having one's "tubes tied") is a surgical procedure for female sterilization in which the fallopian tubes are permanently blocked, clipped or removed. This prevents the fertilization of eggs by sperm and thus th ...
,
hysterectomy Hysterectomy is the surgical removal of the uterus. It may also involve removal of the cervix, ovaries (oophorectomy), Fallopian tubes (salpingectomy), and other surrounding structures. Usually performed by a gynecologist, a hysterectomy may b ...
, unilateral or bilateral salpingo-oophorectomy or
leuprorelin Leuprorelin, also known as leuprolide, is a manufactured version of a hormone used to treat prostate cancer, breast cancer, endometriosis, uterine fibroids, as part of transgender hormone therapy, for early puberty, or to perform chemical castra ...
usage.


Age

Menopause typically occurs between 47 and 54 years of age. According to various data, more than 85% of women have their last period between the ages of 47–54 (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. 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. The menopausal transition or perimenopause leading up to menopause usually lasts 3–4 years (sometimes as long as 5–14 years). In rare cases, a woman's ovaries stop working at a very early age, ranging anywhere from the age of
puberty Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a girl, the testes in a boy. ...
to age 40. This is known as
premature ovarian failure Primary ovarian insufficiency (POI) (also called premature ovarian insufficiency, premature menopause, and premature ovarian failure) is the partial or total loss of reproductive and hormonal function of the ovaries before age 40 because of fol ...
and affects 1 to 2% of women by age 40. Undiagnosed and untreated
coeliac disease Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barle ...
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 A gluten-free diet (GFD) is a nutritional plan that strictly excludes gluten, which is a mixture of proteins found in wheat (and all of its species and hybrids, such as spelt, kamut, and triticale), as well as barley, rye, and oats. The inclus ...
reduces the risk. Women with early diagnosis and treatment of coeliac disease present a normal duration of fertile life span. Women who have undergone
hysterectomy Hysterectomy is the surgical removal of the uterus. It may also involve removal of the cervix, ovaries (oophorectomy), Fallopian tubes (salpingectomy), and other surrounding structures. Usually performed by a gynecologist, a hysterectomy may b ...
with ovary conservation go through menopause on average 1.5 years earlier than the expected age. Another factor that can promote an earlier onset of menopause (usually 1 to 3 years early) is smoking cigarettes.


Premature ovarian insufficiency

Premature ovarian insufficiency Primary ovarian insufficiency (POI) (also called premature ovarian insufficiency, premature menopause, and premature ovarian failure) is the partial or total loss of reproductive and hormonal function of the ovaries before age 40 because of fol ...
(POI) is when the ovaries stop functioning before the age of 40 years. It is diagnosed or confirmed by high blood levels of
follicle stimulating hormone Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, pubertal maturation, an ...
(FSH) and
luteinizing hormone Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (GnRH) ...
(LH) on at least three occasions at least four weeks apart. Premature ovarian insufficiency may be auto immune and therefore co occur with other
autoimmune disorder An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...
s such as
thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thy ...
disease, drenal insufficiency and
diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
. Other causes include
chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
, being a carrier of the
fragile X syndrome Fragile X syndrome (FXS) is a genetic disorder characterized by mild-to-moderate intellectual disability. The average IQ in males with FXS is under 55, while about two thirds of affected females are intellectually disabled. Physical features may ...
gene, and
radiotherapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...
. However, in about 50–80% of cases of premature ovarian insufficiency, the cause is unknown, i.e., it is generally
idiopathic An idiopathic disease is any disease with an unknown cause or mechanism of apparent wikt:spontaneous, spontaneous origin. From Ancient Greek, Greek ἴδιος ''idios'' "one's own" and πάθος ''pathos'' "suffering", ''idiopathy'' means approxi ...
. An early menopause can be related to
cigarette A cigarette is a narrow cylinder containing a combustible material, typically tobacco, that is rolled into thin paper for smoking. The cigarette is ignited at one end, causing it to smolder; the resulting smoke is orally inhaled via the opp ...
smoking, higher
body mass index Body mass index (BMI) is a value derived from the mass (weight) and height of a person. The BMI is defined as the body mass divided by the square of the body height, and is expressed in units of kg/m2, resulting from mass in kilograms and he ...
, racial and ethnic factors, illnesses, and the removal of the uterus.Bucher, et al. 1930 Rates of premature menopause have been found to be significantly higher in fraternal and identical
twins Twins are two offspring produced by the same pregnancy.MedicineNet > Definition of TwinLast Editorial Review: 19 June 2000 Twins can be either ''monozygotic'' ('identical'), meaning that they develop from one zygote, which splits and forms two em ...
; 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.


Surgical menopause

Menopause can be surgically induced by bilateral
oophorectomy Oophorectomy (; from Greek , , 'egg-bearing' and , , 'a cutting out of'), 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 ...
(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". Surgical treatments, such as the removal of ovaries, might cause periods to stop altogether. 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. 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. The time between surgery and possible early menopause is due to the fact that ovaries are still producing hormones.


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
oocytes An oocyte (, ), oöcyte, or ovocyte is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The female ge ...
(
ovarian reserve Ovarian reserve is a term that is used to determine the capacity of the ovary to provide egg cells that are capable of fertilization resulting in a healthy and successful pregnancy. With advanced maternal age the number of egg cell that can be succe ...
). This process is sometimes accelerated by other conditions and is known to occur earlier after a wide range of gynecologic procedures such as
hysterectomy Hysterectomy is the surgical removal of the uterus. It may also involve removal of the cervix, ovaries (oophorectomy), Fallopian tubes (salpingectomy), and other surrounding structures. Usually performed by a gynecologist, a hysterectomy may b ...
(with and without
ovariectomy Oophorectomy (; from Greek , , 'egg-bearing' and , , 'a cutting out of'), 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 t ...
),
endometrial ablation Endometrial ablation is a surgical procedure that is used to remove (ablate) or destroy the endometrial lining of the uterus in people who have heavy menstrual bleeding. Endometrial ablation is not recommended for people who wish to have childre ...
and
uterine artery embolisation Uterine artery embolization is a procedure in which an interventional radiologist uses a catheter to deliver small particles that block the blood supply to the uterine body. The procedure is done for the treatment of uterine fibroids and adenomyos ...
. The depletion of the ovarian reserve causes an increase in circulating
follicle-stimulating hormone Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, pubertal maturation, an ...
(FSH) and
luteinizing hormone Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (GnRH) ...
(LH) levels because there are fewer
oocyte An oocyte (, ), oöcyte, or ovocyte is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The female ...
s and follicles responding to these hormones and producing estrogen. The transition has a variable degree of effects. 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 Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, pubertal maturation, an ...
(FSH) levels. In younger women, during a normal
menstrual cycle The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that make pregnancy possible. The ovarian cycle controls the production and release of eggs a ...
the ovaries produce
estradiol Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development of f ...
,
testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...
and
progesterone Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the m ...
in a cyclical pattern under the control of FSH and
luteinizing hormone Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (GnRH) ...
(LH), which are both produced by the
pituitary gland In vertebrate anatomy, the pituitary gland, or hypophysis, is an endocrine gland, about the size of a chickpea and weighing, on average, in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain. The ...
. During perimenopause (approaching menopause),
estradiol Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development of f ...
levels and patterns of production remain relatively unchanged or may increase compared to young women, but the cycles become frequently shorter or irregular. 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 Activin and inhibin are two closely related protein complexes that have almost directly opposite biological effects. Identified in 1986, activin enhances FSH biosynthesis and secretion, and participates in the regulation of the menstrual ...
. Similarly, decreased inhibin feedback after
hysterectomy Hysterectomy is the surgical removal of the uterus. It may also involve removal of the cervix, ovaries (oophorectomy), Fallopian tubes (salpingectomy), and other surrounding structures. Usually performed by a gynecologist, a hysterectomy may b ...
is hypothesized to contribute to increased ovarian stimulation and earlier menopause. 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. 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 Aromatase (), also called estrogen synthetase or estrogen synthase, is an enzyme responsible for a key step in the biosynthesis of estrogens. It is CYP19A1, a member of the cytochrome P450 superfamily, which are monooxygenases that catalyze many ...
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. 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 Dehydroepiandrosterone sulfate, abbreviated as DHEA sulfate or DHEA-S, also known as androstenolone sulfate, is an endogenous androstane steroid that is produced by the adrenal cortex. It is the 3β-sulfate ester and a metabolite of dehydroepi ...
(DHEAS) and
androstenedione Androstenedione, or 4-androstenedione (abbreviated as A4 or Δ4-dione), also known as androst-4-ene-3,17-dione, is an endogenous weak androgen steroid hormone and intermediate in the biosynthesis of estrone and of testosterone from dehydroepia ...
appear to decline more or less steadily with age. An effect of natural menopause on circulating
androgen An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This inc ...
levels has not been observed. Thus specific tissue effects of natural menopause cannot be attributed to loss of androgenic hormone production. 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 The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...
and involve complex interplay between the neurotransmitters
kisspeptin Kisspeptins (including kisspeptin-54 (KP-54), formerly known as metastin) are proteins encoded by the ''KISS1'' gene in humans. Kisspeptins are ligands of the G-protein coupled receptor, GPR54. ''Kiss1'' was originally identified as a human me ...
,
neurokinin B Neurokinin B (NKB) belongs in the family of tachykinin peptides. Neurokinin B is implicated in a variety of human functions and pathways such as the secretion of gonadotropin-releasing hormone. Additionally, NKB is associated with pregnancy in fem ...
, and
dynorphin Dynorphins (Dyn) are a class of opioid peptides that arise from the precursor protein prodynorphin. When prodynorphin is cleaved during processing by proprotein convertase 2 (PC2), multiple active peptides are released: dynorphin A, dynorphin B, a ...
, which are found in ‘KNDy’ neurons in the infundibular nucleus. Long-term effects of menopause may include
osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...
, vaginal atrophy as well as changed metabolic profile resulting in increased cardiac and metabolic disease (diabetes) risks.


Ovarian aging

Decreased inhibin feedback after
hysterectomy Hysterectomy is the surgical removal of the uterus. It may also involve removal of the cervix, ovaries (oophorectomy), Fallopian tubes (salpingectomy), and other surrounding structures. Usually performed by a gynecologist, a hysterectomy may b ...
is hypothesized to contribute to increased ovarian stimulation and earlier menopause. Hastened ovarian aging has been observed after
endometrial ablation Endometrial ablation is a surgical procedure that is used to remove (ablate) or destroy the endometrial lining of the uterus in people who have heavy menstrual bleeding. Endometrial ablation is not recommended for people who wish to have childre ...
. While it is difficult to prove that these surgeries are causative, it has been hypothesized that the
endometrium The endometrium is the inner epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The functional laye ...
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 Uterine artery embolization is a procedure in which an interventional radiologist uses a catheter to deliver small particles that block the blood supply to the uterine body. The procedure is done for the treatment of uterine fibroids and adenomyos ...
has been hypothesized to contribute to this effect. Impaired DNA repair mechanisms may contribute to earlier depletion of the ovarian reserve during aging. 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 recombination Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in cellular organisms but may ...
al 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. Human primary oocytes are present at an intermediate stage of meiosis, termed prophase I (see
Oogenesis Oogenesis, ovogenesis, or oögenesis is the differentiation of the ovum (egg cell) into a cell competent to further develop when fertilized. It is developed from the primary oocyte by maturation. Oogenesis is initiated in the embryonic stage. O ...
). 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.


Diagnosis

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


Premenopause

Premenopause is a term used to mean the years leading up to the last period, when the levels of reproductive hormones are becoming more variable and lower, and the effects of hormone withdrawal are present. Premenopause starts some time before the monthly cycles become noticeably irregular in timing.


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. According to the
North American Menopause Society The North American Menopause Society (NAMS), founded in 1989, is a nonprofit, multidisciplinary organization with the mission of promoting the health and quality of life of women during midlife and beyond through an understanding of menopause an ...
, this transition can last for four to eight years. The
Centre for Menstrual Cycle and Ovulation Research The Centre for Menstrual Cycle and Ovulation Research (CeMCOR) is a health research centre in Vancouver. According to the University of British Columbia, CeMCOR is the only centre in the world that focuses on ovulation and the causes and consequenc ...
describes it as a six- to ten-year phase ending 12 months after the last menstrual period. During perimenopause,
estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
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, especially during the last 1–2 years of perimenopause (before menopause). Some of these changes are
hot flash Hot flashes (also known as hot flushes) 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 ...
es, night sweats, difficulty sleeping, mood swings,
vaginal dryness Vaginal lubrication is a naturally produced fluid that lubricates a vagina. Vaginal lubrication is always present, but production increases significantly near ovulation and during sexual arousal in anticipation of sexual intercourse. Vaginal ...
or
atrophy Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations (which can destroy the gene to build up the organ), poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply t ...
,
incontinence Incontinence or Incontinent may refer to: *Fecal incontinence, the involuntary excretion of bowel contents *Urinary incontinence, the involuntary excretion of urine * Lack of moderation or self-control, especially related to sexual desire - see I ...
,
osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...
, and heart disease. 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. During this period,
fertility Fertility is the capability to produce offspring through reproduction following the onset of sexual maturity. The fertility rate is the average number of children born by a female during her lifetime and is quantified demographically. Fertili ...
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). The duration of perimenopause may be for up to eight years. Women will often, but not always, start these transitions (perimenopause and menopause) about the same time as their mother did. 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 Empty nest syndrome is a feeling of grief and loneliness parents may feel when their children move out of the family home, such as to live on their own or to attend a college or university. It is not a clinical condition. Since young adults movin ...
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 Melatonin is a natural product found in plants and animals. It is primarily known in animals as a hormone released by the pineal gland in the brain at night, and has long been associated with control of the sleep–wake cycle. In vertebrates ...
supplementation in perimenopausal women can improve thyroid function and gonadotropin levels, as well as restoring fertility and menstruation and preventing depression associated with menopause.


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 The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The uter ...
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 the time in a woman's life that takes place after her last period or, more accurately, after the point when her ovaries become inactive. The reason for this delay in declaring
postmenopause Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...
is that periods are usually erratic at this time of life. 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. 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. A period-like flow during postmenopause, even spotting, may be a sign of
endometrial cancer Endometrial cancer is a cancer that arises from the endometrium (the lining of the uterus or womb). It is the result of the abnormal growth of cells that have the ability to invade or spread to other parts of the body. The first sign is most o ...
.


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 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. These symptoms can include hot flashes, vagina ...
(MHT) is the use of
estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...
in women without a uterus and estrogen plus
progestogen Progestogens, also sometimes written progestagens or gestagens, are a class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR). Progesterone is the major and most important progestogen in the body. ...
in women who have an intact uterus. MHT may be reasonable for the treatment of menopausal symptoms, such as hot flashes. It is the most effective treatment option, especially when delivered as a skin patch. Its use, however, appears to increase the risk of
stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
s and
blood clots A thrombus (plural thrombi), colloquially called a blood clot, is the final product of the blood coagulation step in hemostasis. There are two components to a thrombus: aggregated platelets and red blood cells that form a plug, and a mesh of cr ...
. 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. MHT is also effective for preventing bone loss and
osteoporotic Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone am ...
fracture, but it is generally recommended only for women at significant risk for whom other therapies are unsuitable. 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. There is some concern that this treatment increases the risk of breast cancer. 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. Adding
testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...
to hormone therapy has a positive effect on sexual function in postmenopausal women, although it may be accompanied by hair growth, acne if used in excess. Transdermal testosterone therapy in appropriate dosing is generally safe


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 receptor Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen ( 17β-estradiol). Two classes of ER exist: nuclear estrogen receptors (ERα and ERβ), which are members of the ...
s throughout the body. The most commonly prescribed SERMs are
raloxifene Raloxifene, sold under the brand name Evista among others, is a medication used to prevent and treat osteoporosis in postmenopausal women and those on glucocorticoids. For osteoporosis it is less preferred than bisphosphonates. It is also used to ...
and
tamoxifen Tamoxifen, sold under the brand name Nolvadex among others, is a selective estrogen receptor modulator used to prevent breast cancer in women and treat breast cancer in women and men. It is also being studied for other types of cancer. It has b ...
. 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.


Other medications

Some of the
SSRIs Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extracellul ...
and SNRIs appear to provide some relief from vasomotor symptoms. Low dose
paroxetine Paroxetine, sold under the brand names Paxil and Seroxat among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive-compulsive disorder, panic disorder ...
is the only non-hormonal medication that was
FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
-approved to treat moderate-to-severe vasomotor symptoms associated with menopause as of 2016. They may, however, be associated with appetite and sleeping problems, constipation and nausea.
Gabapentin Gabapentin, sold under the brand name Neurontin among others, is an anticonvulsant medication primarily used to treat partial seizures and neuropathic pain. It is a first-line medication for the treatment of neuropathic pain caused by diabet ...
or
clonidine Clonidine, sold under the brand name Catapres among others, is an α2-adrenergic agonist medication used to treat high blood pressure, ADHD, drug withdrawal ( alcohol, opioids, or nicotine), menopausal flushing, diarrhea, spasticity, and c ...
may help but do not work as well as hormone therapy. Gabapentin can decrease the amount of hot flashes. Side effects associated with its use include drowsiness and headaches. Clonidine is used to improve vasomotor symptoms and may be associated with constipation, dizziness, nausea and sleeping problems.


Therapy

One review found
mindfulness Mindfulness is the practice of purposely bringing one's attention to the present-moment experience without evaluation, a skill one develops through meditation or other training. Mindfulness derives from ''sati'', a significant element of Hind ...
and
cognitive behavioural therapy Cognitive behavioral therapy (CBT) is a psycho-social intervention that aims to reduce symptoms of various mental health conditions, primarily depression and anxiety disorders. CBT focuses on challenging and changing cognitive distortions (su ...
decreases the amount women are affected by hot flashes. Another review found not enough evidence to make a conclusion. A 2018 study found that 85% of study participants reported reduced hot flashes and night sweats when using a climate control system in their beds.


Exercise

Exercise has been thought to reduce postmenopausal symptoms through the increase of endorphin levels, which decrease as estrogen production decreases. Additionally, high BMI is a risk factor for vasomotor symptoms in particular. However, there is insufficient evidence to support the benefits of weight loss for symptom management. There are mixed perspectives on the benefits of physical exercise. While one review found that there was a lack of quality evidence supporting a benefit of exercise, another review recommended regular healthy exercise to reduce comorbidities, improve mood and anxiety symptoms, enhance cognition, and decrease the risk of fractures.
Yoga Yoga (; sa, योग, lit=yoke' or 'union ) is a group of physical, mental, and spiritual practices or disciplines which originated in ancient India and aim to control (yoke) and still the mind, recognizing a detached witness-consciou ...
may help with postmenopausal symptoms similar to other exercise. There is insufficient evidence to suggest that relaxation techniques reduce menopausal symptoms.


Alternative medicine

There is no evidence of consistent benefit of alternative therapies for menopausal symptoms despite their popularity. The effect of
soy isoflavones The soybean, soy bean, or soya bean (''Glycine max'') is a species of legume native to East Asia, widely grown for its edible bean, which has numerous uses. Traditional unfermented food uses of soybeans include soy milk, from which tofu and ...
on menopausal symptoms is promising for reduction of hot flashes and vaginal dryness. Evidence does not support a benefit from
phytoestrogens A phytoestrogen is a plant-derived xenoestrogen (see estrogen) not generated within the endocrine system, but consumed by eating plants or manufactured foods. Also called a "dietary estrogen", it is a diverse group of naturally occurring nonstero ...
such as
coumestrol Coumestrol is a natural organic compound in the class of phytochemicals known as coumestans. Coumestrol was first identified as a compound with estrogenic properties by E. M. Bickoff in ladino clover and alfalfa in 1957. It has garnered research ...
,
femarelle Femarelle is a dietary supplement that is a mixture of DT56a (a tofu extract) and flaxseed powder, that may act as a selective estrogen receptor modulator (SERM).Bedell S, et al. The pros and cons of plant estrogens for menopause. J Steroid Bioch ...
, or the non-phytoestrogen
black cohosh ''Actaea racemosa'', the black cohosh, black bugbane, black snakeroot, rattle-top, or fairy candle ( syn. ''Cimicifuga racemosa''), is a species of flowering plant of the family Ranunculaceae. It is native to eastern North America from the extrem ...
. As of 2011 there is no support for herbal or dietary supplements in the prevention or treatment of the mental changes that occur around menopause. Hypnosis may reduce the severity of hot flashes. In addition, relaxation training with at-home relaxation audiotapes such as deep breathing, paced respiration, and guided imagery may have positive effects on relaxing muscles and reducing stress. There is no evidence to support the efficacy of
acupuncture Acupuncture is a form of alternative medicine and a component of traditional Chinese medicine (TCM) in which thin needles are inserted into the body. Acupuncture is a pseudoscience; the theories and practices of TCM are not based on scientifi ...
as a management for menopausal symptoms. A 2016
Cochrane review Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health professi ...
found not enough evidence to show a difference between Chinese herbal medicine and placebo for the
vasomotor Vasomotor refers to actions upon a blood vessel which alter its diameter. More specifically, it can refer to vasodilator action and vasoconstrictor action. Control Sympathetic innervation Sympathetic nerve fibers travel around the tunica media of ...
symptoms.


Other efforts

* 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. * 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 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. * 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 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.


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. The word menopause was invented by French doctors at the beginning of the nineteenth century. 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. 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 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 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. 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. In Japanese culture, reporting of vasomotor symptoms has been on the increase, with research conducted 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. Diverging from these conclusions, one study appeared to show that many American women "experience this time as one of liberation and self-actualization".


Etymology

Menopause literally means the "end of monthly cycles" (the end of monthly periods or
menstruation Menstruation (also known as a period, among other colloquial terms) is the regular discharge of blood and mucosal tissue from the inner lining of the uterus through the vagina. The menstrual cycle is characterized by the rise and fall of hor ...
), 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 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; in this case, the term means a natural end to fertility that occurs before the end of the natural lifespan.


Menopause in popular culture

In recent years 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. This has led to TV shows 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


Evolutionary rationale

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, narwhals, orcas and short-finned pilot whales. 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 the amount of energy expended to maintain the reproductive organs, 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 favor 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.


Early human selection shadow

While it is fairly common for extant hunter-gatherers to live past age 50 provided that they survive childhood, fossil evidence shows that mortality in adults has decreased over the last 30,000 to 50,000 years and that it was extremely unusual for early ''Homo sapiens'' to live to age 50. This discovery has led some biologists to argue that there was no selection for or against menopause at the time at which the ancestor of all modern humans lived in Africa, suggesting that menopause is instead a random evolutionary effect of a selection shadow regarding aging in early ''Homo sapiens''. It is also argued that since the population fraction of post-menopausal women in early ''Homo sapiens'' was so low, menopause had no evolutionary effect on mate selection or social behaviors related to mate selection.


Adaptive hypotheses


"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. A problem with this hypothesis is that, if true, we would expect to see menopause exhibited among many species in the animal kingdom, and another problem is that in the case of extended child development, even a female who was relatively young, still agile, and attractive when producing a child would lose future support from her male partner due to him seeking out fertile mates when she reaches menopause, while the child is still not independent. This would be counterproductive to the supposed adaptation of getting male support, as it would significantly decrease the survival for children produced over much of the female's fertile and agile life, unless children were raised in ways that did not rely on support from a male partner, which would eliminate the supposed evolutionary benefit anyway.


Young female preference hypothesis

The young female preference hypothesis proposes that changes in male preferences for younger mates allowed late-age acting fertility mutations to accumulate in females without any evolutionary penalty, giving rise to menopause. A computer model was constructed to test this hypothesis, and showed that it was feasible. However, in order for deleterious mutations that affect fertility past roughly age fifty to accumulate, human maximum lifespan had to first be extended to about its present value. As of 2016 it was unclear if there has been sufficient time since that happened for such an evolutionary process to occur.


Male-biased philopatry hypothesis

The male-biased philopatry theory proposes that if human social groups were originally based around men leaving their birth communities more frequently than women, then this leads to increased relatedness to the group in relation to female age, making inclusive fitness benefits older females receive from helping the group greater than what they would receive from continued reproduction, which in turn eventually led to the evolution of menopause. In a pattern of male-biased dispersal and local mating, the relatedness of the individuals in the group decreases with female age, leading to a decrease in kin selection with female age. This occurs because a female will stay with her father in her birth community throughout life, initially being closely related to the males and females. Females are born and stay in the group, so relatedness to the females stays about the same. However, throughout time, the older male relatives will die and any sons she gives birth to will disperse, so that local relatedness to males, and therefore the whole group, declines. The situation is reversed in species where males are philopatric and either females disperse, or mating is non-local. Under these conditions, a female's reproductive life begins away from her father and paternal relatives because she was either born into a new group from non-local mating or because she dispersed. In the case of female-biased dispersal, the female is initially equally unrelated with every individual in the group, and with non-local mating, the female is closely related to the females of the group, but not the males since her paternal relatives are in another group. As she gives birth, her sons will stay with her, increasing her relatedness to males in the group over time and thus her relatedness with the overall group. The common feature that connects these two otherwise different behaviors is male-biased philopatry, which leads to an increase in kin selection with female age. While not conclusive, evidence does exist to support the idea that female-biased dispersal existed in pre-modern humans. The closest living relatives to humans, Common chimpanzee, chimpanzees, bonobos, and both mountain gorillas and western lowland gorillas, are female-biased dispersers. Analysis of sex specific genetic material, the non-recombining portions of the Y chromosome and mitochondrial DNA, show evidence of a prevalence of female-biased dispersal as well; however, these results could also be affected by the effective breeding numbers of males and females in local populations. Evidence of female-biased dispersion in hunter-gatherers is not definitive, with some studies supporting the idea, and others suggesting there is no strong bias towards either sex. In orcas, both sexes mate non-locally with members of a different pod but return to the pod after copulation. Demographic data shows that a female's mean relatedness to the group does increase over time due to increasing relatedness to males. While less well-studied, there is evidence that short-finned pilot whales, another menopausal species, also display this behavior. However, mating behavior that increases local relatedness with female age is prevalent in non-menopausal species, making it unlikely that it is the only factor that determines if menopause will evolve in a species.


Mother hypothesis

The mother hypothesis suggests that menopause was selected for humans because of the extended development period of human offspring and high costs of reproduction so that mothers gain an advantage in reproductive fitness by redirecting their effort from new offspring with a low survival chance to existing children with a higher survival chance.


Grandmother hypothesis

The Grandmother hypothesis suggests that menopause was selected for humans because it promotes the survival of grandchildren. According to this hypothesis, post-reproductive women feed and care for children, adult nursing daughters, and grandchildren whose mothers have weaned them. Human babies require large and steady supplies of glucose to feed the growing brain. In infants in the first year of life, the brain consumes 60% of all calories, so both babies and their mothers require a dependable food supply. Some evidence suggests that hunters contribute less than half the total food budget of most hunter-gatherer societies, and often much less than half, so that foraging grandmothers can contribute substantially to the survival of grandchildren at times when mothers and fathers are unable to gather enough food for all of their children. In general, selection operates most powerfully during times of famine or other privation. So although grandmothers might not be necessary during good times, many grandchildren cannot survive without them during times of famine. Post-reproductive female orcas tend to lead their pods, especially during years of food scarcity. Furthermore, the increased mortality risk of an orca due to losing a grandmother is stronger in years of food scarcity 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. 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 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 Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...
, osteoarthritis, Alzheimer's disease and coronary artery disease. The theories discussed above assume that evolution directly selected for menopause. Another theory states that menopause is the byproduct of the evolutionary selection for follicular atresia, a factor that causes menopause. Menopause results from having too few ovarian follicles to produce enough estrogen to maintain the ovarian-pituitary-hypothalamic loop, which results in the cessation of menses and the beginning of menopause. Human females are born with approximately a million oocytes, and approximately 400 oocytes are lost to ovulation throughout life.


= Reproductive conflict hypothesis

= In social vertebrates, the sharing of resources among the group places limits on how many offspring can be produced and supported by members of the group. This creates a situation in which each female must compete with others of the group to ensure they are the one that reproduces. The reproductive conflict hypothesis proposes that this female reproductive conflict favors the cessation of female reproductive potential in older age to avoid reproductive conflict, increasing the older female's fitness through Inclusive fitness, inclusive benefits. Female-biased dispersal or non-local mating leads to an increase in relatedness to the social group with female age. In the human case of female-biased dispersal, when a young female enters a new group, she is not related to any individual and she reproduces to produce an offspring with a Coefficient of relationship, relatedness of 0.5. An older female could also choose to reproduce, producing an offspring with a relatedness of 0.5, or she could refrain from reproducing and allow another pair to reproduce. Because her relatedness to males in the group is high, there is a fair probability that the offspring will be her grandchild with a relatedness of 0.25. The younger female experiences no cost to her inclusive fitness from using the resources necessary to successfully rear offspring since she is not related to members of the group, but there is a cost for the older female. As a result, the younger female has the advantage in reproductive competition. Although a female orca born into a social group is related to some members of the group, the whale case of non-local mating leads to similar outcomes because the younger female relatedness to the group as a whole is less than the relatedness of the older female. This behavior makes more likely the cessation of reproduction late in life to avoid reproductive conflict with younger females. Research using both human and orca demographic data has been published that supports the role of reproductive conflict in the evolution of menopause. Analysis of demographic data from pre-industrial Finnish populations found significant reductions in offspring survivorship when mothers-in-laws and daughters-in-laws had overlapping births, supporting the idea that avoiding reproductive conflict is beneficial to offspring survivorship. Humans, more so than other primates, rely on food sharing for survival, so the large survivorship reduction values could be caused by a straining of community resources. Avoiding such straining is a possible explanation for why the reproductive overlap seen in humans is much lower than other primates. Food sharing is also prevalent among another menopausal species, orcas. Reproductive conflict has also been observed in orcas, with increased calf mortality seen when reproductive overlap between a younger and older generational female occurred.


Other animals

Menopause in the animal kingdom appears to be uncommon, but the presence of this phenomenon in different species has not been thoroughly researched. Biological life cycle, Life histories show a varying degree of senescence; rapid senescing organisms (e.g., Pacific salmon and annual plants) do not have a post-reproductive life-stage. Gradual senescence is exhibited by all placental mammalian life histories. Menopause has been observed in several species of nonhuman primates, including rhesus monkeys and Common chimpanzee, chimpanzees. Some research suggests that wild chimpanzees do not experience menopause, as their fertility declines are associated with declines in overall health. Menopause also has been reported in a variety of other vertebrate species including elephants, short-finned pilot whales, orcas, narwhals, beluga whales, and the guppy. However, with the exception of the short-finned pilot whale, killer whale, narwhals, and beluga whales, 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 reproduction#The female reproductive cycle, 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.


See also

*
European Menopause and Andropause Society The European Menopause and Andropause Society is an institution that promotes the study, and encourages research, of midlife health. Mission EMAS "strives to encourage the study of Menopause and Andropause as well as promote the exchange of resea ...
* Menopause in the workplace * Menopause in incarceration * Pregnancy over age 50


References


External links


Menopause: MedlinePlus

Menopause and Menopause Treatments
{{Authority control Menopause, Developmental stages Endocrinology Menstrual cycle Middle age Senescence Wikipedia medicine articles ready to translate Human female endocrine system