Postmenopausal Estrogen Progestin Interventions
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Menopause, also known as the climacteric, is the time 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 makes pregnancy possible. The ovarian cycle controls the production and release of egg ...
permanently stop, marking the end of the reproductive stage for the female human. It typically occurs between the ages of 45 and 55, although the exact timing can vary. Menopause is usually a natural change related to a decrease in circulating blood
estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...
levels. It can occur earlier in those who smoke tobacco. Other causes include surgery that removes both
ovaries The ovary () is a gonad in the female reproductive system that produces ova; when released, an ovum travels through the fallopian tube/oviduct into the uterus. There is an ovary on the left and the right side of the body. The ovaries are endocr ...
, some types of
chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...
, or anything that leads to a decrease in hormone levels. At the physiological level, menopause happens because of a decrease in the ovaries' production of the hormones estrogen 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 ma ...
. While typically not needed, measuring hormone levels in the blood or urine can confirm a diagnosis. Menopause is the opposite of
menarche Menarche ( ; ) is the first menstrual cycle, or first menstruation, 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 fe ...
, the time when periods start. 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 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 may typically last from t ...
es; these typically last from 30 seconds to ten minutes and may be associated with shivering,
night sweats Night sweats or nocturnal hyperhydrosis is the repeated occurrence of excessive sweating during sleep. The person may or may not also perspire excessively while awake. One of the most common causes of night sweats in women over 40 is the horm ...
, and reddening of the skin. Hot flashes can recur for four to five years. Other symptoms may include
vaginal dryness Vaginal lubrication is a naturally produced fluid that lubricates the vagina. Vaginal lubrication production increases significantly during sexual arousal in anticipation of sexual intercourse. Vaginal dryness is the condition in which this l ...
, 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 ovarian failure or surgical removal of the ovaries before the age of 40 years is termed " premature ovarian insufficiency". In addition to symptoms (hot flushes/flashes, night sweats, mood changes,
arthralgia Arthralgia () literally means ' joint pain'. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication Medication (also called medicament, medicine, pharmaceuti ...
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 more porous bone, and consequent increase in Bone fracture, fracture risk. It is the most common reason f ...
and bone fracture, and of cardio-metabolic disease (
diabetes Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...
and
cardiovascular disease Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheumati ...
).
Medical professionals A health professional, healthcare professional (HCP), or healthcare worker (sometimes abbreviated as HCW) is a provider of health care treatment and advice based on formal training and experience. The field includes those who work as a nurse, physi ...
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 Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...
production by the
ovaries The ovary () is a gonad in the female reproductive system that produces ova; when released, an ovum travels through the fallopian tube/oviduct into the uterus. There is an ovary on the left and the right side of the body. The ovaries are endocr ...
. In those who have had
surgery Surgery is a medical specialty that uses manual and instrumental techniques to diagnose or treat pathological conditions (e.g., trauma, disease, injury, malignancy), to alter bodily functions (e.g., malabsorption created by bariatric surgery s ...
to remove their
uterus The uterus (from Latin ''uterus'', : uteri or uteruses) or womb () is the hollow organ, organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic development, embryonic and prenatal development, f ...
but still have functioning ovaries, menopause is not considered to have yet occurred. Following the removal of the uterus, symptoms of menopause typically occur earlier. Iatrogenic menopause occurs when both ovaries are surgically removed (
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 ...
) along with the uterus for medical reasons. Medical treatment of menopause is primarily to ameliorate symptoms and prevent bone loss. Mild symptoms may be improved with treatment. With respect to hot flashes, avoiding nicotine, 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. Effects of menopause can include symptoms such ...
(MHT). Non-hormonal therapies for hot flashes include
cognitive-behavioral therapy Cognitive behavioral therapy (CBT) is a form of psychotherapy that aims to reduce symptoms of various mental health conditions, primarily depression, PTSD, and anxiety disorders. Cognitive behavioral therapy focuses on challenging and chang ...
, clinical hypnosis,
gabapentin Gabapentin, sold under the brand name Neurontin among others, is an anticonvulsant medication primarily used to treat neuropathic pain and also for partial seizures of epilepsy. It is a commonly used medication for the treatment of neuropath ...
, fezolinetant 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 primarily work by blo ...
. 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 refers to practices that aim to achieve the healing effects of conventional medicine, but that typically lack biological plausibility, testability, repeatability, or supporting evidence of effectiveness. Such practices are ...
has not been found.


Signs and symptoms

During early menopause transition, the menstrual cycles remain regular but the interval between cycles begins to lengthen. Hormone levels begin to fluctuate. Ovulation may not occur with each cycle. 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 Mucous membrane, mucosal tissue from the endometrium, inner lining of the uterus through the vagina. The menstrual cycle is characterized ...
. 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, uterus and bladder (urogenital tract)

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 is vaginal bleeding from the uterus that is abnormally frequent, lasts excessively long, is heavier than normal, or is irregular. The term "dysfunctional uterine bleeding" was used when no underlying cause was presen ...
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), malnutrition, poor nourishment, poor circulatory system, circulation, loss of hormone, ...
, a benign sore ( polyp or lesion), or may be a functional endometrial response. The
European Menopause and Andropause Society European, or Europeans, may refer to: In general * ''European'', an adjective referring to something of, from, or related to Europe ** Ethnic groups in Europe ** Demographics of Europe ** European cuisine, the cuisines of Europe and other We ...
has released guidelines for assessment of the
endometrium The endometrium is the inner epithelium, 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 funct ...
, 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, urethr ...
is of concern and requires an appropriate investigation to rule out the possibility of malignant diseases. Urogenital symptoms may appear during menopause and continue through
postmenopause Menopause, also known as the climacteric, is the time when menstrual periods permanently stop, marking the end of the reproductive stage for the female human. It typically occurs between the ages of 45 and 55, although the exact timing can ...
and include painful intercourse,
vaginal dryness Vaginal lubrication is a naturally produced fluid that lubricates the vagina. Vaginal lubrication production increases significantly during sexual arousal in anticipation of sexual intercourse. Vaginal dryness is the condition in which this l ...
and
atrophic vaginitis Atrophic vaginitis is inflammation of the vagina as a result of atrophy, tissue thinning due to low estrogen levels. Symptoms may include pain with sex, pain during penetrative sex, vaginal itchiness or dryness, and an urge to urinate or burning ...
(thinning of the membranes of the
vulva In mammals, the vulva (: vulvas or vulvae) comprises mostly external, visible structures of the female sex organ, genitalia leading into the interior of the female reproductive tract. For humans, it includes the mons pubis, labia majora, lab ...
, the
vagina In mammals and other animals, the vagina (: vaginas or vaginae) is the elastic, muscular sex organ, reproductive organ of the female genital tract. In humans, it extends from the vulval vestibule to the cervix (neck of the uterus). The #Vag ...
, the
cervix The cervix (: cervices) or cervix uteri is a dynamic fibromuscular sexual organ of the female reproductive system that connects the vagina with the uterine cavity. The human female cervix has been documented anatomically since at least the time ...
and the outer
urinary tract The human 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 pressu ...
). There may also be considerable shrinking and loss in elasticity of all of the outer and inner genital areas.
Urinary urgency Urination is the release of urine from the bladder through the urethra in placental mammals, or through the cloaca in other vertebrates. It is the urinary system's form of excretion. It is also known medically as micturition, voiding, uresi ...
may also occur and
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 significant effect on quality of life. Urinary incontinence is common in older women ...
in some women.


Other physical effects

The most common physical symptoms of menopause are heavy
night sweat Night sweats or nocturnal hyperhydrosis is the repeated occurrence of excessive sweating during sleep. The person may or may not also perspire excessively while awake. One of the most common causes of night sweats in women over 40 is the hormo ...
s, and
hot flash 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 may typically last from t ...
es (also known as vasomotor symptoms). Sleeping problems and
insomnia Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...
are also common. Other physical symptoms may be reported that are not specific to menopause but may be exacerbated by it, such as lack of energy, joint soreness,
stiffness 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 ...
,
back pain Back pain (Latin: ''dorsalgia'') 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 ...
, breast enlargement, breast pain,
heart palpitation Palpitations occur when a person becomes aware of their heartbeat. The heartbeat may feel hard, fast, or uneven in their chest. Symptoms include a very fast or irregular heartbeat. Palpitations are a sensory symptom. They are often described as ...
s,
headache A headache, also known as cephalalgia, 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 (mood), depression in those with severe ...
,
dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to Balance disorder, disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a ...
, dry,
itch An itch (also known as pruritus) is a sensation that causes a strong desire or reflex to scratch. Itches have resisted many attempts to be classified as any one type of sensory experience. Itches have many similarities to pain, and while both ...
y skin, thinning of the skin, tingling 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, en ...
,
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 ...
.


Mood and memory effects

Psychological symptoms are often reported but they are not specific to menopause and can be caused by other factors. They include
anxiety Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...
, poor memory, inability to concentrate, depressive mood,
irritability Irritability 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 excessive sensitivity to stimul ...
,
mood swing A mood swing is an extreme or sudden change of mood. Such changes can play a positive or a disruptive part in promoting problem solving and in producing flexible forward planning. When mood swings are severe, they may be categorized as part ...
s, and less interest in sexual activity. Menopause-related cognitive impairment can be confused with the
mild cognitive impairment Mild cognitive impairment (MCI) is a diagnosis that reflects an intermediate stage of cognitive impairment that is often, but not always, a transitional phase from cognitive changes in normal aging to those typically found in dementia, especially ...
that precedes
dementia Dementia is a syndrome associated with many neurodegenerative diseases, characterized by a general decline in cognitive abilities that affects a person's ability to perform activities of daily living, everyday activities. This typically invo ...
. 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, or perhaps by reduced blood flow to the brain during
hot flash 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 may typically last from t ...
es. 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.


Long-term effects


Cardiovascular health

Exposure to endogenous
estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...
during reproductive years provides women with protection against
cardiovascular disease Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheumati ...
, which is lost around 10 years after the onset of menopause. The menopausal transition is associated with an increase in
fat mass Adipose tissue (also known as body fat or simply fat) is a loose connective tissue composed mostly of adipocytes. It also contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular endothelial cells and ...
(predominantly in
visceral fat Adipose tissue (also known as body fat or simply fat) is a loose connective tissue composed mostly of adipocytes. It also contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, Blood vessel, vascular endothel ...
), an increase in
insulin resistance Insulin resistance (IR) is a pathological response in which cells in insulin-sensitive tissues in the body fail to respond normally to the hormone insulin or downregulate insulin receptors in response to hyperinsulinemia. Insulin is a horm ...
, dyslipidaemia, and
endothelial dysfunction In blood vessel diseases, endothelial dysfunction is an unhealthy state of the the cells that line the blood vessels (endothelium). The main cause of endothelial dysfunction is impaired bioavailability of nitric oxide. In addition to acting a ...
. Women with
vasomotor symptoms 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 may typically last from two ...
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, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...
, 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 phospholipid capsule, and the type of protein embedded in this outer shell determines the fate of the particle and its ...
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 opti ...
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 o ...
,
osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to more porous bone, and consequent increase in Bone fracture, fracture risk. It is the most common reason f ...
and
fracture Fracture is the appearance of a crack or complete separation of an object or material into two or more pieces under the action of stress (mechanics), stress. The fracture of a solid usually occurs due to the development of certain displacemen ...
s.


Causes

Menopause is a normal event in a woman's life and a natural part of aging. Menopause can also be induced early. Induced menopause occurs as a result of medical treatment such as
chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...
,
radiotherapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a treatment using ionizing radiation, generally provided as part of cancer therapy to either kill or control the growth of malignant cells. It is normally delivered by a linear particle ...
,
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 ...
, 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 the ...
,
hysterectomy Hysterectomy is the surgical removal of the uterus and cervix. Supracervical hysterectomy refers to removal of the uterus while the cervix is spared. These procedures may also involve removal of the ovaries (oophorectomy), fallopian tubes ( salpi ...
, 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, for early puberty, as part of transgender hormone therapy, or to perform chemical ca ...
usage.


Age

Menopause typically occurs at some point between 47 and 54 years of age. 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. 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. Beyond the influence of genetics, these differences are also due to early-life environmental conditions and associated with epigenetic effects. The menopausal transition or perimenopause leading up to menopause usually lasts 3–4 years (sometimes as long as 5–14 years). 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. Patients develop intolerance to gluten, which is present in foods such as wheat, rye, spelt ...
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 prolamin proteins found in wheat (and all of its species and hybrids, such as spelt, kamut, and triticale), as well as barley, rye, and oats ...
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 and cervix. Supracervical hysterectomy refers to removal of the uterus while the cervix is spared. These procedures may also involve removal of the ovaries (oophorectomy), fallopian tubes ( salpi ...
with ovary conservation go through menopause on average 1.5 years earlier than the expected age.


Premature ovarian insufficiency

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 female, the testicles i ...
to age 40. This is known as
premature ovarian failure Primary ovarian insufficiency (POI), also called premature ovarian insufficiency and premature ovarian failure, is the partial or total loss of reproductive and hormonal function of the ovaries before age 40 because of follicular ( egg produc ...
or premature ovarian insufficiency (POI) and affects 1 to 2% of women by age 40. 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, ...
(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 (G ...
(LH) on at least three occasions at least four weeks apart. Premature ovarian insufficiency may be related to an auto immune disorder and therefore might co-occur with other
autoimmune disorder An autoimmune disease is a condition that results from an anomalous response of the adaptive immune system, wherein it mistakenly targets and attacks healthy, functioning parts of the body as if they were foreign organisms. It is estimated tha ...
s such as
thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans, it is a butterfly-shaped gland located in the neck below the Adam's apple. It consists of two connected lobes. The lower two thirds of the lobes are connected by ...
disease, drenal insufficiency and
diabetes mellitus Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained hyperglycemia, high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or th ...
. Other causes include
chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...
, being a carrier of the
fragile X syndrome Fragile X syndrome (FXS) is a genetic neurodevelopmental disorder. The average IQ in males with FXS is under 55, while affected females tend to be in the borderline to normal range, typically around 70–85. Physical features may include a lo ...
gene, and
radiotherapy Radiation therapy or radiotherapy (RT, RTx, or XRT) is a treatment using ionizing radiation, generally provided as part of cancer therapy to either kill or control the growth of malignant cells. It is normally delivered by a linear particle ...
. 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 spontaneous origin. For some medical conditions, one or more causes are somewhat understood, but in a certain percentage of people with the condition, the cause ...
. Early menopause can be related to
cigarette A cigarette is a narrow cylinder containing a combustible material, typically tobacco, that is rolled into Rolling paper, thin paper for smoking. The cigarette is ignited at one end, causing it to smolder; the resulting smoke is orally inhale ...
smoking, higher
body mass index Body mass index (BMI) is a value derived from the mass (Mass versus weight, weight) and height of a person. The BMI is defined as the human body weight, body mass divided by the square (algebra), square of the human height, body height, and is ...
, racial and ethnic factors, illnesses, and the removal of the uterus.Bucher, et al. 1930


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 ...
(removal of ovaries), which is often, but not always, done in conjunction with removal of the fallopian tubes (
salpingo-oophorectomy In medicine, salpingo-oophorectomy is the removal of an ovary and its fallopian tube. This procedure is most frequently associated with prophylactic surgery in response to the discovery of a BRCA mutation, particularly those of the normally tumo ...
) and uterus (
hysterectomy Hysterectomy is the surgical removal of the uterus and cervix. Supracervical hysterectomy refers to removal of the uterus while the cervix is spared. These procedures may also involve removal of the ovaries (oophorectomy), fallopian tubes ( salpi ...
). 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 ger ...
(
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 suc ...
). 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 and cervix. Supracervical hysterectomy refers to removal of the uterus while the cervix is spared. These procedures may also involve removal of the ovaries (oophorectomy), fallopian tubes ( salpi ...
(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 to ...
),
endometrial ablation Endometrial ablation is a surgical procedure that is used to remove ( ablate) or destroy the endometrial lining of the uterus. The goal of the procedure is to decrease the amount of blood loss during menstruation (periods). Endometrial ablation i ...
and uterine artery embolisation. 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, puberty, pubertal maturat ...
(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 (G ...
(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 ger ...
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, puberty, pubertal maturat ...
(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 makes pregnancy possible. The ovarian cycle controls the production and release of eg ...
the ovaries produce
estradiol Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...
,
testosterone Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...
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 ma ...
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 (G ...
(LH), which are both produced by the
pituitary gland The pituitary gland or hypophysis is an endocrine gland in vertebrates. In humans, the pituitary gland is located at the base of the human brain, brain, protruding off the bottom of the hypothalamus. The pituitary gland and the hypothalamus contr ...
. During perimenopause (approaching menopause),
estradiol Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...
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 c ...
. Similarly, decreased inhibin feedback after
hysterectomy Hysterectomy is the surgical removal of the uterus and cervix. Supracervical hysterectomy refers to removal of the uterus while the cervix is spared. These procedures may also involve removal of the ovaries (oophorectomy), fallopian tubes ( salpi ...
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 man ...
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 dehydroepia ...
(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 dehydroe ...
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 ) is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes ...
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 (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...
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 fe ...
, 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 ...
, which are found in KNDy neurons in the infundibular nucleus.


Ovarian aging

Decreased inhibin feedback after
hysterectomy Hysterectomy is the surgical removal of the uterus and cervix. Supracervical hysterectomy refers to removal of the uterus while the cervix is spared. These procedures may also involve removal of the ovaries (oophorectomy), fallopian tubes ( salpi ...
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. The goal of the procedure is to decrease the amount of blood loss during menstruation (periods). Endometrial ablation i ...
. While it is difficult to prove that these surgeries are causative, it has been hypothesized that the
endometrium The endometrium is the inner epithelium, 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 funct ...
may be producing endocrine factors contributing to the endocrine feedback and regulation of the ovarian stimulation. Elimination of these factors contributes to faster depletion of the ovarian reserve. Reduced blood supply to the ovaries that may occur as a consequence of hysterectomy and uterine artery embolisation has been hypothesized to contribute to this effect. Impaired
DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
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 Cell (biology), cellular organi ...
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 () or ovogenesis 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 before birth during embryonic devel ...
). 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.


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 Menopause Society, 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 and healthy aging. Base ...
, 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 (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...
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 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 may typically last from t ...
es,
night sweats Night sweats or nocturnal hyperhydrosis is the repeated occurrence of excessive sweating during sleep. The person may or may not also perspire excessively while awake. One of the most common causes of night sweats in women over 40 is the horm ...
, difficulty sleeping, mood swings,
vaginal dryness Vaginal lubrication is a naturally produced fluid that lubricates the vagina. Vaginal lubrication production increases significantly during sexual arousal in anticipation of sexual intercourse. Vaginal dryness is the condition in which this l ...
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), malnutrition, poor nourishment, poor circulatory system, circulation, loss of hormone, ...
,
incontinence Incontinence or Incontinent may refer to: * Urinary incontinence, the most commonly occurring type of incontinence, the involuntary excretion of urine *Fecal incontinence Fecal incontinence (FI), or in some forms, encopresis, is a lack of con ...
,
osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to more porous bone, and consequent increase in Bone fracture, fracture risk. It is the most common reason f ...
, 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 in colloquial terms refers the ability to have offspring. In demographic contexts, fertility refers to the actual production of offspring, rather than the physical capability to reproduce, which is termed fecundity. The fertility rate ...
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. Some research appears to show that
melatonin Melatonin, an indoleamine, is a natural compound produced by various organisms, including bacteria and eukaryotes. Its discovery in 1958 by Aaron B. Lerner and colleagues stemmed from the isolation of a substance from the pineal gland of cow ...
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'', : uteri or uteruses) or womb () is the hollow organ, organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic development, embryonic and prenatal development, f ...
and are not pregnant or
lactating Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process naturally occurs with all sexually mature female mammals, although it may predate mammals. The proces ...
. 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. 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 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, puberty, pubertal maturat ...
level, greater than 25 IU/L in a random blood draw; it rises as ovaries become inactive. 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. Finally, late postmenopause has been defined as the remainder of a woman's lifespan, when reproductive hormones do not change any more. 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 epithelium, lining of the uterus or womb). It is the result of the abnormal growth of cells (biology), cells that can invade or spread to other parts of the body. The first s ...
.


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. Effects of menopause can include symptoms such ...
(MHT) is the use of
estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...
in women without a uterus and estrogen plus
progestogen Progestogens, also sometimes written progestins, 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 progestoge ...
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 Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...
s and
blood clots A thrombus ( thrombi) is a solid or semisolid aggregate from constituents of the blood (platelets, fibrin, red blood cells, white blood cells) within the circulatory system during life. A blood clot is the final product of the blood coagulati ...
. 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 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 male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...
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.


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 proteins found in cell (biology), cells that function as receptor (biochemistry), receptors for the hormone estrogen (17β-estradiol). There are two main classes of ERs. The first includes the intracellular estrogen ...
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 ...
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 men. It is also being studied for other types of cancer. It has been used for Albright syndrome ...
. 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 primarily work by blo ...
and SNRIs appear to provide some relief from vasomotor symptoms. The most effective SSRIs and SNRIs are
paroxetine Paroxetine ( ), sold under the brand name Paxil among others, is an Antidepressant, antidepressant medication of the selective serotonin reuptake inhibitor (SSRI) class used to treat major depressive disorder, obsessive-compulsive disorder, o ...
,
escitalopram Escitalopram ( ), sold under the brand names Lexapro and Cipralex, among others, is an antidepressant medication of the selective serotonin reuptake inhibitor (SSRI) class. It is mainly used to treat major depressive disorder, generalized ...
,
citalopram Citalopram, sold under the brand name Celexa 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, and soci ...
,
venlafaxine Venlafaxine, sold under the brand name Effexor among others, is an antidepressant medication of the serotonin–norepinephrine reuptake inhibitor (SNRI) class. It is used to treat major depressive disorder, generalized anxiety disorder, pani ...
, and desvenlafaxine. 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 neuropathic pain and also for partial seizures of epilepsy. It is a commonly used medication for the treatment of neuropath ...
or fezolinetant can also improve the frequency and severity of vasomotor symptoms. Side effects of using gabapentin include drowsiness and headaches.


Therapy

Cognitive behavioural therapy Cognitive behavioral therapy (CBT) is a form of psychotherapy that aims to reduce symptoms of various mental health conditions, primarily depression, PTSD, and anxiety disorders. Cognitive behavioral therapy focuses on challenging and chang ...
and clinical hypnosis can decrease the amount women are affected by hot flashes.
Mindfulness Mindfulness is the cognitive skill, usually developed through exercises, of sustaining metacognitive awareness towards the contents of one's own mind and bodily sensations in the present moment. The term ''mindfulness'' derives from the Pali ...
is not yet proven to be effective in easing vasomotor symptoms.


Lifestyle and exercise

Exercise has been thought to reduce postmenopausal symptoms through the increase of endorphin levels, which decrease as estrogen production decreases. However, there is insufficient evidence to suggest that exercise helps with the symptoms of menopause. Similarly, yoga has not been shown to be useful as a treatment for vasomotor symptoms. However a high BMI is a risk factor for vasomotor symptoms in particular. Weight loss may help with symptom management. There is no strong evidence that cooling techniques such as using specific clothing or environment control tools (for example fans) help with symptoms. Paced breathing and relaxation are not effective in easing symptoms.


Dietary supplements

There is no evidence of consistent benefit of taking any
dietary supplement A dietary supplement is a manufactured product intended to supplement a person's diet by taking a pill (pharmacy), pill, capsule (pharmacy), capsule, tablet (pharmacy), tablet, powder, or liquid. A supplement can provide nutrients eithe ...
s or herbal products for menopausal symptoms. These widely marketed but ineffective supplements include
soy isoflavones Isoflavones are a type of naturally-occurring isoflavonoids, many of which act as phytoestrogens in mammals. Isoflavones occur in many plant species, but are especially high in soybeans. Although isoflavones and closely-related phytoestrogens are ...
, pollen extracts,
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 ext ...
,
omega-3 Omega−3 fatty acids, also called omega−3 oils, ω−3 fatty acids or ''n''−3 fatty acids, are polyunsaturated fatty acids (PUFAs) characterized by the presence of a double bond three atoms away from the terminal methyl group in their ...
among many others.


Alternative medicine

There is no evidence of consistent benefit of alternative therapies for menopausal symptoms despite their popularity. As of 2023, 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 scientif ...
as a management for menopausal symptoms. The
Cochrane review Cochrane is a British international charitable organisation formed to synthesize medical research findings to facilitate evidence-based choices about health interventions involving health professionals, patients and policy makers. It includes ...
found not enough evidence in 2016 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 ...
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 Atrophic vaginitis is inflammation of the vagina as a result of tissue thinning due to low estrogen levels. Symptoms may include pain during penetrative sex, vaginal itchiness or dryness, and an urge to urinate or burning with urination. It ...
) 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 Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to more porous bone, and consequent increase in Bone fracture, fracture risk. It is the most common reason f ...
can be minimized by
smoking cessation Smoking cessation, usually called quitting smoking or stopping smoking, is the process of discontinuing tobacco smoking. Tobacco smoke contains nicotine, which is Addiction, addictive and can cause Substance dependence, dependence. As a resu ...
, adequate
vitamin D Vitamin D is a group of structurally related, fat-soluble compounds responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, along with numerous other biological functions. In humans, the most important compo ...
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 ( 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.


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 Biopsychosocial models (BPSM) are a class of trans-disciplinary models which look at the interconnection between biology, psychology, and socio- environmental factors. These models specifically examine how these aspects play a role in a range o ...
experience, with social and cultural factors playing a prominent role in the way menopause is experienced and perceived. 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. There is some evidence that negative attitudes and expectations, held before the menopause, predict symptom experience during the menopause, and beliefs and attitudes toward menopause tend to be more positive in postmenopausal than in premenopausal women. Women with more negative attitudes towards the menopause report more symptoms during this transition. 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. 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. 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. 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. 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. 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. Japanese women experience menopause effects, or ''kōnenki'' (更年期), 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, ''kōnenki'' 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. 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%. This was almost double that of 20 years prior. 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. However, reporting of vasomotor symptoms is still "significantly" lower than in 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 Self-actualization, in Maslow's hierarchy of needs, is the highest personal aspirational human need in the hierarchy. It represents where one's potential is fully realized after more basic needs, such as for the body and the ego, have been fulfill ...
". 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 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 pursue a higher education. It is not a clinical condition. Since the departure of their ...
" 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. Hot flashes are often reported to be particularly distressing at work and lead to embarrassment and worry about potential stigmatisation. 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. This was one of the largest studies to date examining the impact of menopause symptoms on work outcomes. The research concluded there was a strong need to improve medical treatment for menopausal women and make the workplace environment more supportive to avoid such productivity losses.


Etymology

Menopause literally means the "end of monthly cycles" (the end of monthly periods or
menstruation Menstruation (also known as a period, among other colloquial terms) is the regular discharge of blood and Mucous membrane, mucosal tissue from the endometrium, inner lining of the uterus through the vagina. The menstrual cycle is characterized ...
), from the Greek word ''pausis'' ("pause") and ''mēn'' ("month"). This is a medical coinage; the Greek word for
menses Menstruation (also known as a period, among other colloquial terms) is the regular discharge of blood and Mucous membrane, mucosal tissue from the endometrium, inner lining of the uterus through the vagina. The menstrual cycle is characterized ...
is actually different. In Ancient Greek, the menses were described in the plural, ("the monthlies"), and its modern descendant has been clipped to ''ta emmēna''. The Modern Greek medical term is ''emmenopausis'' in
Katharevousa Katharevousa (, , literally "purifying anguage) is a conservative form of the Modern Greek language conceived in the late 18th century as both a literary language and a compromise between Ancient Greek and the contemporary vernacular, Demotic ...
or ''emmenopausi'' in
Demotic Greek Demotic Greek (, , , ) is the standard spoken language of Greece in modern times and, since the resolution of the Greek language question in 1976, the official language of Greece. "Demotic Greek" (with a capital D) contrasts with the conservat ...
. The Ancient Greeks did not produce medical concepts about any symptoms associated with end of menstruation and did not use a specific word to refer to this time of a woman's life. The word menopause was invented by French doctors at the beginning of the nineteenth century. Greek etymology was reconstructed at this time and it was the Parisian student doctor Charles-Pierre-Louis de Gardanne who invented a variation of the word in 1812, which was edited to its final French form in 1821. 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. The word "menopause" was coined specifically for female humans, 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.


In popular culture, law and politics

In the 21st 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 Lorraine Kelly (born 30 November 1959) is a Scottish television presenter. She has presented various television shows for ITV and STV, including '' Good Morning Britain'' (1988–1992), ''GMTV'' (1993–2010), ''This Morning'' (2003–2005, ...
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.
Davina McCall Davina Lucy Pascale McCall (born 16 October 1967) is an English television presenter. She has presented various television shows for Channel 4, including ''Streetmate'' (1998–2001, 2016), ''Big Brother (British TV series), Big Brother'' (2 ...
also led an awareness campaign based on a documentary on
Channel 4 Channel 4 is a British free-to-air public broadcast television channel owned and operated by Channel Four Television Corporation. It is state-owned enterprise, publicly owned but, unlike the BBC, it receives no public funding and is funded en ...
. In the UK,
Carolyn Harris Carolyn Harris (born 18 September 1960) is a Welsh politician serving as Deputy Leader of Welsh Labour since 2018. She has been Member of Parliament (MP) for Neath and Swansea East, previously Swansea East since 2015. Harris served as Sha ...
sponsored the Menopause (Support and Services) Bill in June 2021. It was to exempt hormone replacement therapy from National Health Service
prescription charges In the United Kingdom most medicines are supplied via the National Health Service at either no charge, or for a fixed charge for up to three months' worth of any medicine. Charges for prescriptions for medicines and some medical appliances are pay ...
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. In the US,
David McKinley David Bennett McKinley (born March 28, 1947) is an American businessman and politician who served as the U.S. representative for from 2011 to 2023. A member of the Republican Party, McKinley was a member of the West Virginia House of Delegates f ...
, Republican from West Virginia introduced the Menopause Research Act in September 2022 for $100 million in 2023 and 2024, but it stalled.


Other animals

The majority of mammal species reach menopause when they cease the production of ovarian follicles, which contain eggs (oocytes), between one-third and two-thirds of their maximum possible lifespan. However, few live long enough in the wild to reach this point. Humans are joined by a limited number of other species in which females live substantially longer than their ability to reproduce. Examples of others include
cetaceans Cetacea (; , ) is an infraorder of aquatic mammals belonging to the order Artiodactyla that includes whales, dolphins and porpoises. Key characteristics are their fully aquatic lifestyle, streamlined body shape, often large size and exclusively c ...
: beluga whales,
narwhal The narwhal (''Monodon monoceros'') is a species of toothed whale native to the Arctic. It is the only member of the genus ''Monodon'' and one of two living representatives of the family Monodontidae. The narwhal is a stocky cetacean with a ...
s,
orca The orca (''Orcinus orca''), or killer whale, is a toothed whale and the largest member of the oceanic dolphin family. The only extant species in the genus '' Orcinus'', it is recognizable by its black-and-white-patterned body. A cosmopol ...
s,
false killer whale The false killer whale (''Pseudorca crassidens'') is a species of oceanic dolphin that is the only extant representative of the genus ''Pseudorca''. It is found in oceans worldwide but mainly in tropical regions. It was first species descriptio ...
sArticle , Reuters
, Why did menopause evolve? New study of whales gives some clues
/ref> and
short-finned pilot whale The short-finned pilot whale (''Globicephala macrorhynchus'') is one of the two species of cetaceans in the genus ''Pilot whale, Globicephala'', which it shares with the long-finned pilot whale (''G. melas''). It is part of the oceanic dolphin ...
s. Menopause has been reported in a variety of other vertebrate species, but these examples tend to be from captive individuals, and thus are not necessarily representative of what happens in natural populations in the wild. Menopause in captivity has been observed in several species of nonhuman
primates Primates is an order of mammals, which is further divided into the strepsirrhines, which include lemurs, galagos, and lorisids; and the haplorhines, which include tarsiers and simians ( monkeys and apes). Primates arose 74–63  ...
, including rhesus monkeys and
chimpanzees The chimpanzee (; ''Pan troglodytes''), also simply known as the chimp, is a species of great ape native to the forests and savannahs of tropical Africa. It has four confirmed subspecies and a fifth proposed one. When its close relative the ...
. Some research suggests that wild chimpanzees do not experience menopause, as their fertility declines are associated with declines in overall health. Menopause has been reported in elephants in captivity and guppies. Dogs do not experience menopause; the canine estrus cycle simply becomes irregular and infrequent. Although older female dogs are not considered good candidates for breeding, offspring have been produced by older animals, see
Canine reproduction Canine reproduction is the process of sexual reproduction in domestic dogs, wolves, coyotes and other canine species. Canine sexual anatomy and development Male reproductive system Erectile tissue As with all mammals, a dog's penis is made up ...
. Similar observations have been made in cats. Life histories show a varying degree of
senescence Senescence () or biological aging is the gradual deterioration of Function (biology), functional characteristics in living organisms. Whole organism senescence involves an increase in mortality rate, death rates or a decrease in fecundity with ...
; rapid senescing organisms (e.g.,
Pacific salmon ''Oncorhynchus'', from Ancient Greek ὄγκος (''ónkos''), meaning "bend", and ῥύγχος (''rhúnkhos''), meaning "snout", is a genus of ray-finned fish in the subfamily Salmoninae of the family Salmonidae, native to coldwater tributarie ...
and
annual plants An annual plant is a plant that completes its life cycle, from germination to the production of seeds, within one growing season, and then dies. Globally, 6% of all plant species and 15% of herbaceous plants (excluding trees and shrubs) are an ...
) do not have a post-reproductive life-stage. Gradual senescence is exhibited by all
placental mammal Placental mammals ( infraclass Placentalia ) are one of the three extant subdivisions of the class Mammalia, the other two being Monotremata and Marsupialia. Placentalia contains the vast majority of extant mammals, which are partly distinguish ...
ian life histories.


Evolution

There are various theories on the origin and process of the evolution of the menopause. These attempt to suggest evolutionary benefits to the human species stemming from the cessation of women's reproductive capability before the end of their natural lifespan. It is conjectured that in highly social groups
natural selection Natural selection is the differential survival and reproduction of individuals due to differences in phenotype. It is a key mechanism of evolution, the change in the Heredity, heritable traits characteristic of a population over generation ...
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.


See also

*
European Menopause and Andropause Society European, or Europeans, may refer to: In general * ''European'', an adjective referring to something of, from, or related to Europe ** Ethnic groups in Europe ** Demographics of Europe ** European cuisine, the cuisines of Europe and other We ...
*
Menopause in the workplace Menopause in the workplace is a social and human resources campaigning issue in which people work to raise awareness of the impact menopause symptoms can have on attendance and performance in the workplace. Activism Campaigners, journalists, pe ...
* Menopause in incarceration * Pregnancy over age 50 * Biological clock *
Evolution of menopause There are various theories on the origin and process of the evolution of 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 l ...


References


Further reading

* Rebecca Mead, "If You Can't Stand the Heat: Why menopause never gets old", ''
The New Yorker ''The New Yorker'' is an American magazine featuring journalism, commentary, criticism, essays, fiction, satire, cartoons, and poetry. It was founded on February 21, 1925, by Harold Ross and his wife Jane Grant, a reporter for ''The New York T ...
'', 10 March 2025, pp. 28–31. "If you've got
ovaries The ovary () is a gonad in the female reproductive system that produces ova; when released, an ovum travels through the fallopian tube/oviduct into the uterus. There is an ovary on the left and the right side of the body. The ovaries are endocr ...
, you'll go through it. Why do so many feel so blindsided?" (p. 28.)


External links


Menopause: MedlinePlus

What Is Menopause?
National Institute on Aging
Menopause & Me
The North American Menopause Society {{Authority control Developmental stages Endocrinology Gynaecological endocrinology Menstrual cycle Middle age Senescence Wikipedia medicine articles ready to translate Human female endocrine system