Materiały źródłowe

• #1 Pathogenesis and Causes of Premature Ovarian Failure: An Update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4059950/

  Premature ovarian failure (POF) affects 1% of young women. […] Diverse etiologies are associated with POF. […] POF may be either spontaneous or induced. […] The known causes include: Genetic disorders, which could involve the X chromosome or autosomes. […] However, the growing body of literature demonstrates a list of newly discovered mutations that may be responsible for causing POF. […] Most of these mutations are extremely rare, and most cases of POF are still considered to be idiopathic. […] Autoimmune causes; there is some evidence of an association of POF with lymphocytic oophoritis and other autoimmune disorders. […] Antiovarian antibodies are reported in POF, but their specificity and pathogenic role are obscure. […] Iatrogenic causes; chemotherapy, radiotherapy and pelvic surgery can lead to POF.

• #2 Ovarian Insufficiency: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/271046-overview

  Ovarian insufficiency is a failure of the ovary to function adequately in a woman younger than 40 years, in its role either as an endocrine organ or as a reproductive organ. […] Primary ovarian insufficiency (POI) (premature ovarian failure, premature menopause, or early menopause) is a condition characterized by amenorrhea, hypoestrogenism, and elevated serum gonadotropin levels in women younger than 40 years. […] Overt primary ovarian insufficiency is the clinical condition that has previously been referred to as premature ovarian failure or premature menopause. This clinical state is characterized by elevated basal serum FSH levels in association with disordered menstrual cycles as demonstrated by oligomenorrhea, polymenorrhea, or metrorrhagia. […] Premature ovarian failure is the extreme state of complete primordial follicle depletion. This is an irreversible state characterized by the presence of amenorrhea, permanent infertility, and elevated menopausal gonadotropin levels.

• #3 Ovarian Insufficiency: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/271046-overview

  The pathogenesis of spontaneous POI/POF in most cases is unknown. Two mechanisms are presumed to play a role: follicle depletion and follicle dysfunction. […] Follicle depletion is a major pathogenetic mechanism for development of POI/POF. […] Pathological conditions that cause depletion or a reduction of the follicle number may lead to a disruption of the highly coordinated process of follicular growth and ovulation. […] The ovarian follicle reserve can be depleted prematurely because of a low initial number or an accelerated rate of follicle atresia. […] Primary ovarian insufficiency or premature ovarian failure can be subdivided into 2 major pathogenetic categories: induced (iatrogenic) POI/POF and spontaneous POI/POF. The focus of this article is on spontaneous POI/POF, a term that will be used as an equivalent to ovarian failure. […] Some patients with spontaneous POI/POF have numerous ovarian follicles with seemingly normal oocytes that fail to grow and ovulate in the presence of elevated gonadotropins. Most of these patients have idiopathic disease, but, in some cases, a specific cause can be found.

• #4 Pathogenesis and Causes of Premature Ovarian Failure: An Update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4059950/

  These can lead to ovarian failure by causing a decrease in the pool of primordial follicles, increased atresia of the ovarian follicles due to apoptosis, or failure of follicle maturation. […] Genetically, ovarian failure is associated with X chromosomal abnormalities. […] These abnormalities could include a small defect in chromosomal arrangement such as deletions, isochromosomes and balanced X chromosome-autosomal translocations. […] However, complete deletion of one X (Turners syndrome) has also been recorded. […] The identification of genes or critical regions responsible for individual Turners syndrome features has turned out to be problematic. […] The degrees of ovarian dysfunction and the extent of the somatic anomalies are variable. […] The association of POF and X chromosome deletions or X-autosomal translocations has been extensively reported in literature.

• #5 What is POI

  https://www.daisynetwork.org/about-poi/what-is-poi/

  Simply put, it means that the ovaries arent working properly. They stop producing eggs years, and in some cases even decades, before they should. In addition, the ovaries are unable to produce the hormones estrogen and progesterone, which have important roles in womens health and well-being. […] POI is different to menopause that occurs at around the average age (52 years). Not only does it occur at a very young age, but the ovaries often dont completely fail. This means that ovarian function can fluctuate over time, occasionally resulting in a period, ovulation or even pregnancy, several years after diagnosis. Because of this intermittent temporary return of ovarian function, approximately 5-10% of women with POI may still conceive. […] POI can occur for several reasons. Unfortunately there is still a lot that we dont understand about POI and in the majority of women (90%), no underlying cause will be found. This type of POI is usually called spontaneous or idiopathic POI.

• #6 Premature or Early Menopause: Causes, Risks, and Treatment

  https://www.health.com/condition/menopause/5-reasons-why-some-women-go-through-early-menopause

  Premature menopause happens when the ovaries stop functioning normally before age 40, Shawn Tassone, MD, an OB-GYN specializing in integrative medicine in Austin, Texas, told Health. Early menopause happens when menopause happens between ages 40 to 45. […] With premature and early menopause, your ovaries gradually make less of the hormones estrogen and progesterone at a younger age than average. […] Premature and early menopause share similarities with primary ovarian insufficiency (POI). POI is a condition where the ovaries stop working, usually before you naturally reach menopause. […] However, POI is distinct from any form of menopause. Although irregular, people with POI may still get periods and have the ability to become pregnant. In contrast, people who experience premature and early menopause have no periods and cannot become pregnant.

• #7

  https://www.who.int/news-room/fact-sheets/detail/menopause

  Menopause is caused by the loss of ovarian follicular function and a decline in circulating blood oestrogen levels. […] Some women experience menopause earlier (before 40 years of age). This premature menopause may be because of certain chromosomal abnormalities, autoimmune disorders or other unknown causes. […] Menopause can also be induced as a consequence of surgical procedures that involve removal of both ovaries or medical interventions that cause cessation of ovarian function (for example radiation therapy or chemotherapy).

• #8

  https://journals.lww.com/grh/fulltext/2018/06000/the_etiology_of_menopause__not_just_ovarian.1.aspx

  The hormonal changes which occur leading up to menopause have been described in multiple cross-sectional and longitudinal studies. […] However, the role of pituitary-hypothalamic function in the menopausal transition (MT) has been generally overlooked. […] During the MT, in addition to a reduction in the number of ovarian follicles, there is a marked reduction in the sensitivity of the central nervous system to both the positive and negative feedback effects of estrogen. […] On the basis of longitudinal hormone studies, it is clear that desensitization of the hypothalamic-pituitary-ovarian feedback loop plays an important role, in addition to a decrease in follicle number and insensitivity of remaining follicles to the positive feedback of estrogen, to trigger ovulation. […] The data which demonstrate that a reduction in pituitary sensitivity to estradiol occurs during the menopausal transition (MT), in addition to the dysfunction in the ovary and its response to endogenous hormone signals, are reviewed in the current report.

• #9

  https://journals.lww.com/grh/fulltext/2018/06000/the_etiology_of_menopause__not_just_ovarian.1.aspx

  The etiology of the MT is 2-fold, with alterations in the pituitary-hypothalamus pathway, along with changes in the ovary both playing roles. […] The hypothesis that there is a reduction in pituitary positive and negative feedback to estrogen is supported by the data that during the MT estradiol levels remain the same, or are increased, and that there is a reduction in ovulatory cycles. […] Results from this study lend significant support for the hypothesis that there is a relative hypothalamic-pituitary insensitivity to estrogen in aging women. […] While decreased sensitivity to estrogen and reduction of the number of ovarian follicles appear to drive the MT, GnRH production remains potent and robust well after menopause. […] The transition into menopause is frequently accompanied by significant distress for patients, due to symptoms including menstrual irregularities, hot flashes, and breast tenderness. […] Although the etiology of these changes has not yet been well determined, the data demonstrate that, not only there are deficiencies at the level of the ovary, but also quite meaningful desensitization to estrogen at the level of the pituitary.

• #10 Early and premature menopause | NHS inform

  https://www.nhsinform.scot/healthy-living/womens-health/later-years-around-50-years-and-over/menopause-and-post-menopause-health/early-and-premature-menopause

  Menopause before the age of 45 is called early menopause. Menopause before the age of 40 is called premature menopause. […] Premature menopause, or premature ovarian insufficiency (POI), is defined as being menopause that happens before the age of 40. […] Premature menopause is different to menopause which occurs at around the average age (45 to 55 years), as premature menopause means that the ovaries arent working properly. They stop producing eggs years before they normally would. […] Women can experience early or premature menopause for lots of different reasons including certain surgeries or cancer treatments. […] In 90% of women who experience premature menopause, the reason will be unknown. […] Having an early or premature menopause can increase the risk of osteoporosis (weak bones) and cardiovascular (heart) disease. It is believed that HRT can reduce these risks, as well as controlling menopausal symptoms.

• #11 Pathogenesis and Causes of Premature Ovarian Failure: An Update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4059950/

  Premature ovarian failure (POF) affects 1% of young women. […] Diverse etiologies are associated with POF. […] POF may be either spontaneous or induced. […] The known causes include: Genetic disorders, which could involve the X chromosome or autosomes. […] However, the growing body of literature demonstrates a list of newly discovered mutations that may be responsible for causing POF. […] Most of these mutations are extremely rare, and most cases of POF are still considered to be idiopathic. […] Autoimmune causes; there is some evidence of an association of POF with lymphocytic oophoritis and other autoimmune disorders. […] Antiovarian antibodies are reported in POF, but their specificity and pathogenic role are obscure. […] Iatrogenic causes; chemotherapy, radiotherapy and pelvic surgery can lead to POF.

• #12 Pathogenesis and Causes of Premature Ovarian Failure: An Update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4059950/

  Infectious Causes; some viral and microbial infections can be followed by POF. […] Environmental toxins, such as cigarette smoking are reported as risk factors of spontaneous POF. […] Idiopathic; in most cases, no identifiable etiology can be recognized after complete evaluation. […] Although most cases of POF are idiopathic, with no identifiable etiology even after a thorough evaluation, diverse etiologies have been associated with POF: genetic aberrations, autoimmune ovarian damage, iatrogenic factors, infectious agents, toxins and environmental factors. […] The observation of familial cases with POF indicates the role of genetic aberrations in its pathogenesis. […] Various genetic mechanisms implicated in the pathogenesis of POF include reduced gene dosage and non-specific chromosome effects that impair meiosis.

• #13 Pathogenesis and Causes of Premature Ovarian Failure: An Update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4059950/

  These can lead to ovarian failure by causing a decrease in the pool of primordial follicles, increased atresia of the ovarian follicles due to apoptosis, or failure of follicle maturation. […] Genetically, ovarian failure is associated with X chromosomal abnormalities. […] These abnormalities could include a small defect in chromosomal arrangement such as deletions, isochromosomes and balanced X chromosome-autosomal translocations. […] However, complete deletion of one X (Turners syndrome) has also been recorded. […] The identification of genes or critical regions responsible for individual Turners syndrome features has turned out to be problematic. […] The degrees of ovarian dysfunction and the extent of the somatic anomalies are variable. […] The association of POF and X chromosome deletions or X-autosomal translocations has been extensively reported in literature.

• #14 Primary ovarian insufficiency – Wikipedia

  https://en.wikipedia.org/wiki/Primary_ovarian_insufficiency

  In some women FSH may bind to the FSH receptor site, but be inactive. By lowering the endogenous FSH levels with ethinylestradiol (EE) or with a GnRH-a the receptor sites are free and treatment with exogenous recombinant FSH activates the receptors and normal follicle growth and ovulation can occur. […] Mutations in FOXL2 cause blepharophimosis, ptosis, epicanthus inversus syndrome (BPES). Premature ovarian failure is part of the BPES Type I variant of the syndrome but not of the BPES Type II variant. […] BRCA1 protein plays an essential role in the repair of DNA double-strand breaks by homologous recombination. Women with a germline BRCA1 mutation tend to have premature menopause as evidenced by the final amenorrhea appearing at a younger age. […] Impairment of the repair of DNA double-strand breaks due to a BRCA1 defect leads to premature ovarian aging in both mice and humans. […] In addition to BRCA1, the MCM8-MCM9 protein complex also plays a crucial role in the recombinational repair of DNA double-strand breaks. In humans, an MCM8 mutation can give rise to premature ovarian failure, as well as chromosomal instability.

• #15 Menopause pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Menopause_pathophysiology

  There are genetic disorders involved in the premature menopause/early menopause include: […] Fragile X syndrome is a genetic disorder characterized by reduction of ovarian function, women that have Fragile X Syndrome go through early menopause an average 5 years early than other women. […] Turners syndrome: women born with missing X chromosome can go through menopause early, due to their ovaries do not form normally at birth.

• #16 What is POI

  https://www.daisynetwork.org/about-poi/what-is-poi/

  Auto-immune disorders are conditions in which the bodys immune system can attack its own tissues. If damage occurs to the ovaries it can result in POI. In around 5% of women with POI it is thought to occur due to auto-immune disease. […] Abnormalities in the female sex chromosome (the X chromosome) or other genes affecting sex hormone function can cause POI and many different genetic defects have been identified. The most common of these is Turner syndrome, where the one of the X chromosomes is missing. POI is also associated with some rare conditions which tend to run in families such as Fragile X syndrome and galactosaemia. […] Surgical removal of the ovaries before the age of 40 is another form of POI. This sudden removal of ovarian hormones can often lead to an abrupt onset of menopause symptoms.

• #17 Pathogenesis and Causes of Premature Ovarian Failure: An Update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4059950/

  The exact mechanism of ovarian failure has not been elucidated in patients with galactosemia and POF. […] The glycoprotein inhibin plays an important role in the recruitment and development of ovarian follicles by the negative feedback control of FSH. […] The published incidence of antiovarian antibodies in patients with POF ranges widely due to the heterogeneity of investigation methods, multiple ovarian antibody targets, the transient appearance of antiovarian antibodies, different stages of disease, as well as variations in antibody test format and antigen presentation. […] Theoretically, ovarian function might be restored if a safe and effective immunosuppressive regimen could be used, but the placebo-controlled randomized clinical trials, using corticosteroids as immunosuppressive therapy, failed to show a change in the course of the disease.

• #18 Premature Ovarian Failure (POF) Diagnosis & Treatment | CCRM

  https://www.ccrmivf.com/blog/premature-ovarian-failure-pof/

  It is estimated that up to 40% of Premature Ovarian Failure (POF) can be attributed to genetic causes, as the disorder has a tendency to be familial. […] Autoimmunity has also been shown to play a role, with the most common cause thought to be Hashimotos thyroiditis. […] The diagnosis of Premature Ovarian Failure (POF) can be emotionally devastating to patients, especially for women looking forward to their childbearing years. […] Chronic low levels of estrogen, needed for bone health, increase the risks of osteoporosis, leading to an increased risk of bone fractures and resulting complications. Other medical disorders that affect the heart, eyes, and neurologic systems can put Premature Ovarian Failure (POF) patients at a greater risk for serious health problems such as cardiovascular disease, glaucoma, Parkinsons disease, and Alzheimers disease.

• #19 Premature menopause and autoimmune primary ovarian insufficiency in two international multi-center cohorts in: Endocrine Connections Volume 11 Issue 5 (2022)

  https://ec.bioscientifica.com/view/journals/ec/11/5/EC-22-0024.xml

  Premature menopause was identified in 2.8% of women, and these women had higher frequencies of nulliparity (37.4% vs 19.7%), obesity (28.7% vs 21.4%), osteoporosis (17.1% vs 11.6%), hormone replacement therapy (59.1% vs 36.9%) and never smokers (60.1% vs 50.9%) (P 0.05), compared to women with menopause 40 years. […] Iatrogenic causes were found in 91 (47%) and non-ovarian causes in 27 (14%) women, while 77 (39%) women were classified as POI of unknown cause, resulting in a 1.1% prevalence of idiopathic POI. […] Based on the presence of autoantibodies against 21 OH and SCC, 4.5% of POI cases were of likely autoimmune origin. […] Autoimmunity explains 4.5% of these cases judged by positive steroidogenic autoantibodies. […] Important causes of POI include iatrogenic treatment (surgical, chemotherapy or radiation), genetic, infectious or autoimmune etiology.

• #20 Premature or Early Menopause: Causes, Risks, and Treatment

  https://www.health.com/condition/menopause/5-reasons-why-some-women-go-through-early-menopause

  In general, menopause that occurs at any age poses complications. The natural decline in estrogen puts many people at a higher risk of the following health conditions: Mood changes, Low libido, Depression and anxiety, Osteoporosis, Heart disease, Infertility. […] Specifically, research has found that estrogen helps protect your heart and bones against disease. Therefore, when your body makes less of the hormone, your risk of heart disease and osteoporosis increases. […] Premature and early menopause may happen for no apparent reason. But in some cases, certain factors may increase your risk. Specifically, some surgeries, medicines, or health conditions may cause the onset of menopause to occur earlier than average. […] With autoimmune diseases, your immune system may attack your ovarian follicles and small sacs in your ovaries. Ovarian follicles are where egg cells mature and grow. So, although rare, an abnormal immune response may interfere with the function of your ovarian follicles.

• #21 Pathogenesis and Causes of Premature Ovarian Failure: An Update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4059950/

  Premature ovarian failure (POF) affects 1% of young women. […] Diverse etiologies are associated with POF. […] POF may be either spontaneous or induced. […] The known causes include: Genetic disorders, which could involve the X chromosome or autosomes. […] However, the growing body of literature demonstrates a list of newly discovered mutations that may be responsible for causing POF. […] Most of these mutations are extremely rare, and most cases of POF are still considered to be idiopathic. […] Autoimmune causes; there is some evidence of an association of POF with lymphocytic oophoritis and other autoimmune disorders. […] Antiovarian antibodies are reported in POF, but their specificity and pathogenic role are obscure. […] Iatrogenic causes; chemotherapy, radiotherapy and pelvic surgery can lead to POF.

• #22 HealthtalkEarly (premature) menopause | Real People. Real life experiences. | Healthtalk

  https://healthtalk.org/experiences/menopause/early-premature-menopause/

  It can be hereditary. If your mum had an early menopause and I’ve got a few families whose mums had the menopause at 32 and they’ve gone through the menopause at 32. it’s actually very important to know because, obviously, you cut out twenty possible years of child bearing so you need to plan your life. they’re very rare but it has a strong hereditary familial risk. Other reasons for going through a premature menopause are all very rare. There are autoimmune ones, that’s your own body’s immune system attacking your body so it’s linked with other autoimmune diseases like thyroiditis or Addison’s disease of the adrenal gland. There are also genetic reasons like if you’re unfortunate enough to be born with Turner’s syndrome that’s an X0 chromosome, you may actually go through the menopause before you hit puberty but that’s incredibly rare. But that’s why it’s such a complex group of women and you need a proper diagnosis and treatment. So anyone with a premature menopause needs to seek specialist help.

• #23 Premature and early menopause | Jean Hailes

  https://www.jeanhailes.org.au/health-a-z/menopause/premature-early-menopause

  Premature ovarian insufficiency (POI) can cause premature and early menopause. […] The causes of POI are not always clear. In about 60% of women, a cause cant be found. […] POI is associated with autoimmune conditions such as Addisons disease, thyroid disease, type 1 diabetes, Crohns disease and coeliac disease. […] Some studies suggest women who have premature or early menopause may have a higher risk of developing heart disease and osteoporosis compared with women who reach menopause at the expected age. […] Women who experience premature or early menopause can start to lose bone density at an earlier age than women who experience menopause in their 50s. This puts them at a greater risk of developing osteoporosis earlier in life. […] Menopause can happen because of cancer treatment, such as chemotherapy or radiotherapy, that causes your ovaries to stop working. This is known as medically induced menopause.

• #24 Pathogenesis and Causes of Premature Ovarian Failure: An Update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4059950/

  Premature ovarian failure (POF) affects 1% of young women. […] Diverse etiologies are associated with POF. […] POF may be either spontaneous or induced. […] The known causes include: Genetic disorders, which could involve the X chromosome or autosomes. […] However, the growing body of literature demonstrates a list of newly discovered mutations that may be responsible for causing POF. […] Most of these mutations are extremely rare, and most cases of POF are still considered to be idiopathic. […] Autoimmune causes; there is some evidence of an association of POF with lymphocytic oophoritis and other autoimmune disorders. […] Antiovarian antibodies are reported in POF, but their specificity and pathogenic role are obscure. […] Iatrogenic causes; chemotherapy, radiotherapy and pelvic surgery can lead to POF.

• #25 Premature menopause and autoimmune primary ovarian insufficiency in two international multi-center cohorts in: Endocrine Connections Volume 11 Issue 5 (2022)

  https://ec.bioscientifica.com/view/journals/ec/11/5/EC-22-0024.xml

  However, in the majority of cases the cause remains unknown. […] Autoantibodies against the steroidogenic cell enzymes have shown consistent association with autoimmune POI, including autoantibodies against 21-hydroxylase (21-OH), side-chain cleavage enzyme (anti-SCC) and 17alpha-hydroxylase (17 OH), as well as NACHT leucine-rich-repeat protein 5 (NALP5), which are highly expressed in the ovaries. […] We found immunological markers suggesting an autoimmune etiology in 4.5% of women with POI, using specific autoantibody assays.

• #26 Pathogenesis and Causes of Premature Ovarian Failure: An Update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4059950/

  Premature ovarian failure (POF) affects 1% of young women. […] Diverse etiologies are associated with POF. […] POF may be either spontaneous or induced. […] The known causes include: Genetic disorders, which could involve the X chromosome or autosomes. […] However, the growing body of literature demonstrates a list of newly discovered mutations that may be responsible for causing POF. […] Most of these mutations are extremely rare, and most cases of POF are still considered to be idiopathic. […] Autoimmune causes; there is some evidence of an association of POF with lymphocytic oophoritis and other autoimmune disorders. […] Antiovarian antibodies are reported in POF, but their specificity and pathogenic role are obscure. […] Iatrogenic causes; chemotherapy, radiotherapy and pelvic surgery can lead to POF.

• #27 Primary Ovarian Insufficiency in Adolescents and Young Women | ACOG

  https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2014/07/primary-ovarian-insufficiency-in-adolescents-and-young-women

  ABSTRACT: Primary ovarian insufficiency is the depletion or dysfunction of ovarian follicles with cessation of menses before age 40 years. […] Primary ovarian insufficiency is the depletion or dysfunction of ovarian follicles with cessation of menses before age 40 years, and it has previously been referred to as premature menopause or primary ovarian failure. […] Primary ovarian insufficiency may be associated with multiple endocrinopathies, including hypoparathyroidism and hypoadrenalism. […] Approximately 4% of women who have primary ovarian insufficiency will have adrenal or ovarian antibodies, which suggests an autoimmune mechanism for disease. […] The immediate loss of ovarian function after chemotherapy or radiation therapy is termed acute ovarian failure, which may be transient.

• #28 Premature or Early Menopause: Causes, Risks, and Treatment

  https://www.health.com/condition/menopause/5-reasons-why-some-women-go-through-early-menopause

  Some health conditions may increase your risk of premature or early menopause. For example, if untreated, human immunodeficiency virus (HIV), which is a sexually transmitted infection, may bring about menopause earlier than expected. […] Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis, may also increase the risk of premature or early menopause. […] Cancer treatments, like chemotherapy and radiation, may damage the genetic material in your egg cells. […] People who are born with missing, extra, or atypical chromosomes may experience menopause earlier than average. […] If your mother went through menopause earlier than average, your chances of premature or early menopause might increase. […] Research has found that people who smoke are more likely to experience menopause nearly two years earlier than others.

• #29 Premature and early menopause | Jean Hailes

  https://www.jeanhailes.org.au/health-a-z/menopause/premature-early-menopause

  Premature ovarian insufficiency (POI) can cause premature and early menopause. […] The causes of POI are not always clear. In about 60% of women, a cause cant be found. […] POI is associated with autoimmune conditions such as Addisons disease, thyroid disease, type 1 diabetes, Crohns disease and coeliac disease. […] Some studies suggest women who have premature or early menopause may have a higher risk of developing heart disease and osteoporosis compared with women who reach menopause at the expected age. […] Women who experience premature or early menopause can start to lose bone density at an earlier age than women who experience menopause in their 50s. This puts them at a greater risk of developing osteoporosis earlier in life. […] Menopause can happen because of cancer treatment, such as chemotherapy or radiotherapy, that causes your ovaries to stop working. This is known as medically induced menopause.

• #30 Menopause: Definition, Symptoms, Causes, Treatment, and Complications

  https://www.webmd.com/menopause/menopause-basics

  Induced menopause. This happens when your doctor takes out your ovaries for medical reasons, such as uterine cancer or endometriosis. It can also happen when radiation or chemotherapy damages your ovaries. […] A lack of essential nutrients such as Vitamin D, calcium, and omega-3- fatty acids may negatively impact your hormonal balance and reproductive health, according to Susan Treiser, MD, a reproductive endocrinologist. Not having enough protein, especially with strict vegetarian or vegan diets, can affect how your body produces hormones, which can affect the timing of menopause. […] Eating disorders can also play a role in early menopause. […] The extreme physical stress, hormone changes, and nutritional deficiencies caused by anorexia (an eating disorder that causes you not to eat enough calories) can significantly impact menstrual health and disrupt hormonal balance, potentially leading to early menopause or other reproductive issues, Treiser said.

• #31 Early or premature menopause | Office on Women’s Health

  https://womenshealth.gov/menopause/early-or-premature-menopause

  Menopause that happens before age 40 is called premature menopause (which is also medically called primary ovarian insufficiency [POI]). Menopause that happens between 40 and 45 is called early menopause. About 5% of women naturally go through early menopause. Smoking and certain medicines or treatments can cause menopause to come earlier than usual. […] Early or premature menopause can happen on their own for no clear reason, or they can happen because of certain surgeries, medicines, or health conditions. […] Reasons for early or premature menopause can include: Family history. Women with a family history of early or premature menopause are more likely to have early or premature menopause. Smoking. Women who smoke may reach menopause as many as two years before nonsmokers. They may also get more severe menopause symptoms. Research suggests that women who have early or premature menopause and smoke may die earlier than nonsmoking women. Chemotherapy or pelvic radiation treatments for cancer. These treatments can damage your ovaries and cause your periods to stop forever or just for a while. You also may have trouble getting pregnant or not be able to get pregnant again. Not all women who have chemotherapy or radiation will go through menopause. The younger a woman is at the time of chemotherapy or radiation, the less likely she is to go through menopause. Surgery to remove the ovaries. A bilateral oophorectomy may cause menopausal symptoms right away. Your periods will stop after this surgery, and your hormone levels will drop quickly. You may have strong menopausal symptoms, like hot flashes and less sexual desire. Surgery to remove the uterus. Some women who have a hysterectomy can keep their ovaries. If this happens, you will no longer have periods, and you cannot get pregnant, but you are not menopausal. You will probably not go through menopause right away because your ovaries will continue to make hormones. Later on, you might have natural menopause a year or two earlier than expected.

• #32 Primary Ovarian Insufficiency in Adolescents and Young Women | ACOG

  https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2014/07/primary-ovarian-insufficiency-in-adolescents-and-young-women

  Although the highest incidence of acute ovarian failure occurs after the use of alkylating agents or procarbazine, the younger the patient at the time of receiving the chemotherapy, the more likely it is that some follicles will survive. […] Patients with primary ovarian insufficiency are estrogen deficient. […] The goals of hormonal therapy extend beyond simply symptom relief to levels that support bone, cardiovascular (CV), and sexual health. […] For adolescents with primary ovarian insufficiency, the objective of treatment is to replace the hormones that the ovary would be producing before the age of menopause, making the treatment distinctly different from hormonal therapy for menopause that focuses on the treatment of menopausal symptoms. […] Primary ovarian insufficiency increases the risk of bone loss, CV disease, and endocrine disorders.

• #33 Pathogenesis and Causes of Premature Ovarian Failure: An Update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4059950/

  Infectious Causes; some viral and microbial infections can be followed by POF. […] Environmental toxins, such as cigarette smoking are reported as risk factors of spontaneous POF. […] Idiopathic; in most cases, no identifiable etiology can be recognized after complete evaluation. […] Although most cases of POF are idiopathic, with no identifiable etiology even after a thorough evaluation, diverse etiologies have been associated with POF: genetic aberrations, autoimmune ovarian damage, iatrogenic factors, infectious agents, toxins and environmental factors. […] The observation of familial cases with POF indicates the role of genetic aberrations in its pathogenesis. […] Various genetic mechanisms implicated in the pathogenesis of POF include reduced gene dosage and non-specific chromosome effects that impair meiosis.

• #34 Risk factors for natural menopause before the age of 45: evidence from two British population-based birth cohort studies | BMC Women’s Health | Full Text

  https://bmcwomenshealth.biomedcentral.com/articles/10.1186/s12905-022-02021-4

  Gynaecological problems are another potential risk factor for early menopause. […] Behavioural factors such as smoking, drinking and exercise affect endocrine function and women’s reproductive hormones, and thus may have an impact on the timing of menopause. […] It has been suggested that the lack of consensus on the factors affecting the timing of natural menopause could be explained by methodological differences, e.g., differences in study populations and designs, differences in the definition of menopause, and varying use of controls in the analyses. […] We found that multiple factors from birth, childhood and adulthood are associated with menopause before 45 years of age. The early life factors associated with early menopause were father in a manual job, or no father figure at birth, mother smoking during pregnancy, and the absence of or short duration of breastfeeding. Childhood factors increasing the likelihood of early menopause were poor cognitive ability and smoking. Early adulthood factors associated with an increased probability of early menopause were smoking, no alcohol consumption, lower levels of exercise, problems with periods or other gynaecological issues, and not being in paid work. […] Our findings support the hypothesis that fetal and early life experiences are associated with age at menopause.

• #35 Early or premature menopause | Office on Women’s Health

  https://womenshealth.gov/menopause/early-or-premature-menopause

  Menopause that happens before age 40 is called premature menopause (which is also medically called primary ovarian insufficiency [POI]). Menopause that happens between 40 and 45 is called early menopause. About 5% of women naturally go through early menopause. Smoking and certain medicines or treatments can cause menopause to come earlier than usual. […] Early or premature menopause can happen on their own for no clear reason, or they can happen because of certain surgeries, medicines, or health conditions. […] Reasons for early or premature menopause can include: Family history. Women with a family history of early or premature menopause are more likely to have early or premature menopause. Smoking. Women who smoke may reach menopause as many as two years before nonsmokers. They may also get more severe menopause symptoms. Research suggests that women who have early or premature menopause and smoke may die earlier than nonsmoking women. Chemotherapy or pelvic radiation treatments for cancer. These treatments can damage your ovaries and cause your periods to stop forever or just for a while. You also may have trouble getting pregnant or not be able to get pregnant again. Not all women who have chemotherapy or radiation will go through menopause. The younger a woman is at the time of chemotherapy or radiation, the less likely she is to go through menopause. Surgery to remove the ovaries. A bilateral oophorectomy may cause menopausal symptoms right away. Your periods will stop after this surgery, and your hormone levels will drop quickly. You may have strong menopausal symptoms, like hot flashes and less sexual desire. Surgery to remove the uterus. Some women who have a hysterectomy can keep their ovaries. If this happens, you will no longer have periods, and you cannot get pregnant, but you are not menopausal. You will probably not go through menopause right away because your ovaries will continue to make hormones. Later on, you might have natural menopause a year or two earlier than expected.

• #36 Early and Premature Menopause: Causes, Symptoms, and Management

  https://bywinona.com/journal/early-premature-menopause?srsltid=AfmBOoqVztCIsKYI5Kv01qpzN85fc2-eArlMB-6a6P61iHc_rotXokR-

  Early and premature menopause can occur spontaneously due to underlying biological factors or can be induced by medical treatments or surgical procedures. […] While spontaneous premature menopause can occur without a clear cause, several known factors contribute to ovarian dysfunction: Genetic Disorders: Chromosomal abnormalities and inherited metabolic disorders are common causes of early menopause. Autoimmune Diseases: The immune system can mistakenly attack ovarian tissue, leading to early ovarian failure. Autoimmune conditions like rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes are responsible for 30%60% of spontaneous early menopause cases. Infections: Certain infections like mumps and pelvic tuberculosis can cause ovarian damage to increase the risk of early menopause. Smoking: Studies indicate that smoking can increase the risk of early menopause by 40%60%. Heavy smoking can cause menopause to occur up to two years earlier than it might naturally. Poor Health and Nutrition: Research suggests that malnutrition and low body weight can increase the risk of early menopause.

• #37 Menopause is hereditary: here’s the latest research

  https://helloclue.com/articles/menopause/menopause-is-hereditary-here-s-the-latest-research

  The age you reach menopause may be a trait you inherit from your mom (1). […] Some people experience early or premature menopause, which is when someone reaches menopause before the age of 40 (12). […] Your mothers experience could determine if you may be more likely to reach menopause earlier, as early and premature menopause can run in families (12). […] According to one study, around one in three women who had early menopause had a family history of early menopause (12). […] In fact, youre six times more likely to have early or premature menopause if your mother or siblings experienced it (12). […] Perimenopause is a natural process that all women and people with ovaries will experience as they age. During perimenopause, reproductive hormones like estrogen and progesterone fluctuate and then decline (2,5). The declining hormone levels lead to experiences like hot flashes, night sweats, vaginal dryness, and changes to cycle length and period flow (2).

• #38 Early or premature menopause | Office on Women’s Health

  https://womenshealth.gov/menopause/early-or-premature-menopause

  Women with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have extreme tiredness, weakness, muscle and joint pain, memory loss, headache, unrefreshing sleep, and other symptoms. Research has found that women with ME/CFS are more likely to have early or premature menopause. […] Women who go through menopause early may have symptoms or health problems similar to those of regular menopause. But some women with early or premature menopause may also have: Higher risk of serious health problems, such as heart disease and osteoporosis, since women will live longer without the health benefits of higher estrogen levels. Talk to your health care provider about steps to lower your risk for these health problems. More severe menopause symptoms. Talk to your health care provider about treatments to help with symptoms if they affect your daily life. Sadness or depression over the early loss of fertility or the change in their bodies. Talk to your health care provider if you have symptoms of depression, including less energy or a lack of interest in things you once enjoyed that lasts longer than a few weeks. They can recommend specialists to help you understand and cope with your feelings. Your health care provider can also discuss options, such as adoption or donor egg programs, if you want to have children.

• #39 Early Menopause: Causes, Symptoms, and More

  https://www.healthline.com/health/menopause/causes-early

  Early menopause usually refers to onset before age 45. Premature menopause or premature ovarian insufficiency occurs before age 40. […] Anything that damages your ovaries or stops estrogen production can cause early menopause. This includes chemotherapy for cancer or an oophorectomy (removal of the ovaries). […] If there’s no obvious medical reason for early menopause, the cause is likely genetic. Your age at menopause onset is likely inherited. […] Some lifestyle factors may have an impact on when you begin menopause. Smoking affects estrogen and can contribute to early menopause. […] Some chromosomal issues can lead to early menopause. For example, Turner syndrome (also called monosomy X and gonadal dysgenesis) involves being born with an incomplete chromosome. […] Premature menopause can be a symptom of an autoimmune disease, such as thyroid disease or rheumatoid arthritis. […] Epilepsy is a seizure disorder that stems from the brain. Someone with epilepsy is more likely to experience primary ovarian insufficiency, which leads to menopause.

• #40 Risk factors for natural menopause before the age of 45: evidence from two British population-based birth cohort studies | BMC Women’s Health | Full Text

  https://bmcwomenshealth.biomedcentral.com/articles/10.1186/s12905-022-02021-4

  Several studies have indicated an association between disadvantaged childhood socioeconomic position and earlier menopause, and the impact of socioeconomic disadvantage has been considered to act through the effects of hardship experience throughout life and health behaviours. […] Psychological health in early life has been linked to the onset of menopause, potentially acting through the function of the hypothalamic-pituitary-adrenal axis, which affects the reproduction function. […] Several studies have found that lower cognitive ability in childhood is associated with early menopause with earlier measures of cognitive ability being more strongly related to age at menopause than tests taken later in life. […] It has been hypothesized that both young and old maternal age at birth may increase the risk of earlier menopause in the daughter.

• #41

  https://journals.lww.com/grh/fulltext/2018/06000/the_etiology_of_menopause__not_just_ovarian.1.aspx

  The hormonal changes which occur leading up to menopause have been described in multiple cross-sectional and longitudinal studies. […] However, the role of pituitary-hypothalamic function in the menopausal transition (MT) has been generally overlooked. […] During the MT, in addition to a reduction in the number of ovarian follicles, there is a marked reduction in the sensitivity of the central nervous system to both the positive and negative feedback effects of estrogen. […] On the basis of longitudinal hormone studies, it is clear that desensitization of the hypothalamic-pituitary-ovarian feedback loop plays an important role, in addition to a decrease in follicle number and insensitivity of remaining follicles to the positive feedback of estrogen, to trigger ovulation. […] The data which demonstrate that a reduction in pituitary sensitivity to estradiol occurs during the menopausal transition (MT), in addition to the dysfunction in the ovary and its response to endogenous hormone signals, are reviewed in the current report.

• #42

  https://journals.lww.com/grh/fulltext/2018/06000/the_etiology_of_menopause__not_just_ovarian.1.aspx

  The etiology of the MT is 2-fold, with alterations in the pituitary-hypothalamus pathway, along with changes in the ovary both playing roles. […] The hypothesis that there is a reduction in pituitary positive and negative feedback to estrogen is supported by the data that during the MT estradiol levels remain the same, or are increased, and that there is a reduction in ovulatory cycles. […] Results from this study lend significant support for the hypothesis that there is a relative hypothalamic-pituitary insensitivity to estrogen in aging women. […] While decreased sensitivity to estrogen and reduction of the number of ovarian follicles appear to drive the MT, GnRH production remains potent and robust well after menopause. […] The transition into menopause is frequently accompanied by significant distress for patients, due to symptoms including menstrual irregularities, hot flashes, and breast tenderness. […] Although the etiology of these changes has not yet been well determined, the data demonstrate that, not only there are deficiencies at the level of the ovary, but also quite meaningful desensitization to estrogen at the level of the pituitary.

• #43 Primary ovarian insufficiency – Wikipedia

  https://en.wikipedia.org/wiki/Primary_ovarian_insufficiency

  In some women FSH may bind to the FSH receptor site, but be inactive. By lowering the endogenous FSH levels with ethinylestradiol (EE) or with a GnRH-a the receptor sites are free and treatment with exogenous recombinant FSH activates the receptors and normal follicle growth and ovulation can occur. […] Mutations in FOXL2 cause blepharophimosis, ptosis, epicanthus inversus syndrome (BPES). Premature ovarian failure is part of the BPES Type I variant of the syndrome but not of the BPES Type II variant. […] BRCA1 protein plays an essential role in the repair of DNA double-strand breaks by homologous recombination. Women with a germline BRCA1 mutation tend to have premature menopause as evidenced by the final amenorrhea appearing at a younger age. […] Impairment of the repair of DNA double-strand breaks due to a BRCA1 defect leads to premature ovarian aging in both mice and humans. […] In addition to BRCA1, the MCM8-MCM9 protein complex also plays a crucial role in the recombinational repair of DNA double-strand breaks. In humans, an MCM8 mutation can give rise to premature ovarian failure, as well as chromosomal instability.

• #44 Premature & Early Menopause: Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/21138-premature-and-early-menopause

  Additionally, people who experience premature or early menopause spend more years without the benefits of estrogen. Without typical amounts of estrogen, youre at greater risk for certain health conditions like osteoporosis, heart disease, depression, and various neurological diseases like dementia and Parkinsons disease.

• #45 4 Things to Know About Early and Premature Menopause > News > Yale Medicine

  https://www.yalemedicine.org/news/early-and-premature-menopause

  Women with a family history of early or premature menopause are more likely to go through the transition early. […] Notably, women who experience premature or early menopause have a higher risk of heart disease and osteoporosis because they will spend more years of their lives without the benefits of estrogen. […] Because of this, women who are going to use MHT should do so within six to 10 years of their last menstrual period, Dr. Minkin says. […] Unless there’s a reason a woman can’t safely take hormones, medical experts recommend menopausal hormonal therapy for women going through premature or early menopause. […] The risks of MHT are very small for younger, healthy women who don’t have contraindications against taking it and are experiencing bothersome menopause symptoms, Dr. Pal says. […] Women with early menopause before age 40 without a history of breast cancer risk can take hormone therapy until the typical age of menopause at 51 if there is no reason not to take it.

• #46 Early and premature menopause | NHS inform

  https://www.nhsinform.scot/healthy-living/womens-health/later-years-around-50-years-and-over/menopause-and-post-menopause-health/early-and-premature-menopause

  Menopause before the age of 45 is called early menopause. Menopause before the age of 40 is called premature menopause. […] Premature menopause, or premature ovarian insufficiency (POI), is defined as being menopause that happens before the age of 40. […] Premature menopause is different to menopause which occurs at around the average age (45 to 55 years), as premature menopause means that the ovaries arent working properly. They stop producing eggs years before they normally would. […] Women can experience early or premature menopause for lots of different reasons including certain surgeries or cancer treatments. […] In 90% of women who experience premature menopause, the reason will be unknown. […] Having an early or premature menopause can increase the risk of osteoporosis (weak bones) and cardiovascular (heart) disease. It is believed that HRT can reduce these risks, as well as controlling menopausal symptoms.

• #47 Cognitive Decline in Early and Premature Menopause

  https://www.mdpi.com/1422-0067/24/7/6566

  Early and premature menopause, or premature ovarian insufficiency (POI), affects 1% of women under the age of 40 years. […] A premature reduction in estrogen puts women at a higher risk for cardiovascular disease, parkinsonism, depression, osteoporosis, hypertension, weight gain, midlife diabetes, as well as cognitive disorders and dementia, such as Alzheimer’s disease (AD). […] Estrogens seem to prevent cognitive disorders arising from a cholinergic deficit in women and female animals in middle age premature menopause that affects the central nervous system (CNS) directly and indirectly, both transiently and in the long term, leads to cognitive impairment or even dementia, mainly due to the decrease in estrogen levels and comorbidity with cardiovascular risk factors, autoimmune diseases, and aging.

• #48 Early and Premature Menopause: Causes, Symptoms, and Management

  https://bywinona.com/journal/early-premature-menopause?srsltid=AfmBOoqVztCIsKYI5Kv01qpzN85fc2-eArlMB-6a6P61iHc_rotXokR-

  Induced menopause occurs due to medical interventions, including cancer treatments, radiation exposure, surgical removal of ovaries, and prolonged use of certain medications. […] Cancer treatments, particularly chemotherapy and radiation therapy, can damage ovarian function and lead to premature menopause. The risk of ovarian damage depends on the age at which treatment is received, as well as the type and dosage of the therapy. […] Women who experience menopause before the age of 40 have a 50% higher risk of coronary heart disease compared to those who reach menopause after 45. […] Some women who undergo early menopause may be at an increased risk of cognitive impairment and dementia. The risk is higher in women who experience menopause due to surgical removal of the ovaries and don’t pursue estrogen replacement.

• #49 Premature ovarian insufficiency in general practice: Meeting the needs of women

  https://www.racgp.org.au/afp/2017/june/premature-ovarian-insufficiency-in-general-practic

  Although the exact mechanism is unclear, adverse changes in lipid profile and impaired endothelial function related to oestrogen deficiency may lead to premature atherosclerosis. […] Osteoporosis is considered one of the most feared consequences by patients with POI. […] The prevalence of osteoporosis is estimated to be 8-14% in women with POI, and bone loss of up to 26% at the lumbar spine, compared with a control population, has been reported. […] Studies have also suggested a possible link between cognitive impairment, dementia and Parkinsons disease and POI. […] Women with POI are at risk of premature mortality, largely due to CVD, and may be worsened by the presence of other modifiable CVD risk factors.

• #50 Early and Premature Menopause: Causes, Symptoms, and Management

  https://bywinona.com/journal/early-premature-menopause?srsltid=AfmBOoqVztCIsKYI5Kv01qpzN85fc2-eArlMB-6a6P61iHc_rotXokR-

  Earlier menopause is associated with faster bone loss and a higher risk of osteoporosis and fractures. […] The primary approach to managing early and premature menopause is to identify the underlying cause and tailor treatment accordingly. HRT is widely recommended for women experiencing early or premature menopause, as it helps in replacing declining hormone levels, especially estrogen.

• #51 Premature ovarian insufficiency in general practice: Meeting the needs of women

  https://www.racgp.org.au/afp/2017/june/premature-ovarian-insufficiency-in-general-practic

  Although the exact mechanism is unclear, adverse changes in lipid profile and impaired endothelial function related to oestrogen deficiency may lead to premature atherosclerosis. […] Osteoporosis is considered one of the most feared consequences by patients with POI. […] The prevalence of osteoporosis is estimated to be 8-14% in women with POI, and bone loss of up to 26% at the lumbar spine, compared with a control population, has been reported. […] Studies have also suggested a possible link between cognitive impairment, dementia and Parkinsons disease and POI. […] Women with POI are at risk of premature mortality, largely due to CVD, and may be worsened by the presence of other modifiable CVD risk factors.

• #52 Cognitive Decline in Early and Premature Menopause

  https://www.mdpi.com/1422-0067/24/7/6566

  Early and premature menopause, or premature ovarian insufficiency (POI), affects 1% of women under the age of 40 years. […] A premature reduction in estrogen puts women at a higher risk for cardiovascular disease, parkinsonism, depression, osteoporosis, hypertension, weight gain, midlife diabetes, as well as cognitive disorders and dementia, such as Alzheimer’s disease (AD). […] Estrogens seem to prevent cognitive disorders arising from a cholinergic deficit in women and female animals in middle age premature menopause that affects the central nervous system (CNS) directly and indirectly, both transiently and in the long term, leads to cognitive impairment or even dementia, mainly due to the decrease in estrogen levels and comorbidity with cardiovascular risk factors, autoimmune diseases, and aging.

• #53 Linkage of premature and early menopause with psychosocial well-being: a moderated multiple mediation approach | BMC Psychology | Full Text

  https://bmcpsychology.biomedcentral.com/articles/10.1186/s40359-023-01267-3

  The findings emphasize the fact that smoking is associated with premature menopause, depression and insomnia. Women who experienced premature menopause has lower cognitive scores, depressive symptoms and insomnia symptoms, which were higher among those who consumed tobacco. […] The study has shown significant results from premature menopause, while for early menopause the hypothesis was rejected. This indicates the severity of lower menopausal age and its effect on psychosocial health. […] The direct effect of a premature menopause on cognitive health, without any mediators or moderators, and controlling for the possible confounders, have shown that there is a negative impact. […] A woman experiencing menopause have decreased production of estrogen which leads to symptoms of sleep problems or insomnia along with other prominent one like vaginal dryness, hot flushes, joint pain etc.

• #54 Essential Guide to Premature and Early Menopause – Stella

  https://www.onstella.com/the-latest/your-body/the-essential-guide-to-premature-and-early-menopause/

  Early and premature menopause can be slightly different from the menopause which occurs at a more usual time. Hormone levels tend to be more unstable, and even after diagnosis women may go through periods of relatively normal ovarian function, including having normal menstrual periods and even getting pregnant. […] After the menopause, you are at greater risk of cardiovascular disease (including heart disease, stroke and blood clots) due to hormonal changes. Some studies have suggested that this risk is increased further in those who go through menopause early. […] Premature menopause in particular has been linked with thinning of the bones (osteoporosis and osteopenia) and a subsequent increased risk of fractures. […] Surgery to remove the ovaries before the usual age of menopause has been linked to an increased risk of cognitive impairment, dementia and Parkinsons disease in later life. […] If you smoke, it is worth making a real effort to stop as soon as possible. Smokers have been found to go through menopause on average just under two years earlier than non-smokers.

• #55 Premature ovarian insufficiency in general practice: Meeting the needs of women

  https://www.racgp.org.au/afp/2017/june/premature-ovarian-insufficiency-in-general-practic

  Although the exact mechanism is unclear, adverse changes in lipid profile and impaired endothelial function related to oestrogen deficiency may lead to premature atherosclerosis. […] Osteoporosis is considered one of the most feared consequences by patients with POI. […] The prevalence of osteoporosis is estimated to be 8-14% in women with POI, and bone loss of up to 26% at the lumbar spine, compared with a control population, has been reported. […] Studies have also suggested a possible link between cognitive impairment, dementia and Parkinsons disease and POI. […] Women with POI are at risk of premature mortality, largely due to CVD, and may be worsened by the presence of other modifiable CVD risk factors.

• #56 Cognitive Decline in Early and Premature Menopause

  https://www.mdpi.com/1422-0067/24/7/6566

  The early and prolonged loss of ovarian-derived 17β-estradiol (E2) is the main cause of the negative neurological outcomes associated with premature menopause. […] These studies suggest that the decrease in midlife estrogen levels results in changes to cholinergic and serotonergic activity, thereby contributing to emotional and cognitive disorders. […] Estrogen may improve cerebral blood flow and increase glucose transport across the blood–brain barrier (BBB). […] Estrogen prevents Aβ from inducing a rise in the intracellular calcium level and protects against mitochondrial damage. […] Estrogen, apart from its effect on the levels and activity of neurotransmitters, promote the growth of neurons and the formation of synapses acting as antioxidants and regulating the homeostasis of calcium and the secondary messenger system. […] Premature menopause affects the central nervous system (CNS) directly and indirectly, as well as both transiently and in the long term, in many complex pathways which are already discovered or yet to be.

• #57 Early and premature menopause | NHS inform

  https://www.nhsinform.scot/healthy-living/womens-health/later-years-around-50-years-and-over/menopause-and-post-menopause-health/early-and-premature-menopause

  The current recommendation is that women experiencing an early or premature menopause should be offered hormonal therapy, unless there is a medical reason not to take it, and should continue until at least the average age of the menopause. By doing this, the hormones that would usually have been produced are being replaced. […] Early and premature menopause can affect your ability to have children naturally. […] Women experiencing early or premature menopause do not ovulate (release an egg) every month. This makes it difficult to get pregnant. […] Studies have shown that a small percentage of women (5-10%) experiencing premature menopause (where the cause is unknown) do sometimes ovulate and become pregnant.

• #58 Premature Menopause: Causes, Symptoms, and Treatments

  https://www.webmd.com/menopause/premature-menopause-symptoms

  The symptoms and health risks of premature menopause, as well as the emotional issues that may result from it, can be managed with methods similar to those used for natural menopause. Women dealing with infertility that is brought on by premature ovarian insufficiency may want to discuss their options with their doctor or with a reproductive specialist. […] With premature ovarian insufficiency, women who have been tested and have 46 XX chromosomes have some intermittent ovarian function later (can be 50%) and about 5%-10% may be able to get pregnant even after the diagnosis. In general, however, POI is unlikely to ever be completely reversed.

• #59 Essential Guide to Premature and Early Menopause – Stella

  https://www.onstella.com/the-latest/your-body/the-essential-guide-to-premature-and-early-menopause/

  Early and premature menopause can be slightly different from the menopause which occurs at a more usual time. Hormone levels tend to be more unstable, and even after diagnosis women may go through periods of relatively normal ovarian function, including having normal menstrual periods and even getting pregnant. […] After the menopause, you are at greater risk of cardiovascular disease (including heart disease, stroke and blood clots) due to hormonal changes. Some studies have suggested that this risk is increased further in those who go through menopause early. […] Premature menopause in particular has been linked with thinning of the bones (osteoporosis and osteopenia) and a subsequent increased risk of fractures. […] Surgery to remove the ovaries before the usual age of menopause has been linked to an increased risk of cognitive impairment, dementia and Parkinsons disease in later life. […] If you smoke, it is worth making a real effort to stop as soon as possible. Smokers have been found to go through menopause on average just under two years earlier than non-smokers.

• #60 Ovarian Insufficiency: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/271046-overview

  The pathogenesis of spontaneous POI/POF in most cases is unknown. Two mechanisms are presumed to play a role: follicle depletion and follicle dysfunction. […] Follicle depletion is a major pathogenetic mechanism for development of POI/POF. […] Pathological conditions that cause depletion or a reduction of the follicle number may lead to a disruption of the highly coordinated process of follicular growth and ovulation. […] The ovarian follicle reserve can be depleted prematurely because of a low initial number or an accelerated rate of follicle atresia. […] Primary ovarian insufficiency or premature ovarian failure can be subdivided into 2 major pathogenetic categories: induced (iatrogenic) POI/POF and spontaneous POI/POF. The focus of this article is on spontaneous POI/POF, a term that will be used as an equivalent to ovarian failure. […] Some patients with spontaneous POI/POF have numerous ovarian follicles with seemingly normal oocytes that fail to grow and ovulate in the presence of elevated gonadotropins. Most of these patients have idiopathic disease, but, in some cases, a specific cause can be found.

• #61 Ovarian Insufficiency: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/271046-overview

  Ovarian insufficiency is a failure of the ovary to function adequately in a woman younger than 40 years, in its role either as an endocrine organ or as a reproductive organ. […] Primary ovarian insufficiency (POI) (premature ovarian failure, premature menopause, or early menopause) is a condition characterized by amenorrhea, hypoestrogenism, and elevated serum gonadotropin levels in women younger than 40 years. […] Overt primary ovarian insufficiency is the clinical condition that has previously been referred to as premature ovarian failure or premature menopause. This clinical state is characterized by elevated basal serum FSH levels in association with disordered menstrual cycles as demonstrated by oligomenorrhea, polymenorrhea, or metrorrhagia. […] Premature ovarian failure is the extreme state of complete primordial follicle depletion. This is an irreversible state characterized by the presence of amenorrhea, permanent infertility, and elevated menopausal gonadotropin levels.

• #62 Premature Ovarian Failure (POF) Diagnosis & Treatment | CCRM

  https://www.ccrmivf.com/blog/premature-ovarian-failure-pof/

  Premature Ovarian Failure (POF) is defined as the cessation of ovarian function prior to the age of 40. It is diagnosed in women under age 40 when ovarian function ceases, menstruation stops, the onset of menopausal symptoms, estrogen levels falling to a menopausal range (less than 20 pg/ml) and resulting infertility. […] Although the symptoms are often similar and Premature Ovarian Failure (POF) was once thought to be a form of premature menopause, there are differences in the two conditions. […] With Premature Ovarian Failure (POF), up to 50% of patients may ovulate once in any given year and 5% may become pregnant, leading to a theory that there is a follicular dysfunction rather than complete ovarian failure. […] A syndrome known as Resistant Ovary Syndrome (ROS) is a medical condition that presents, clinically, identical to Premature Ovarian Failure (POF); but the ovary has the normal amount of eggs, and it is thought to be secondary to a receptor block on the surface of the ovary to FSH, antibodies to gonadotrophins (FSH and LH) or a post receptor defect, that prevents the ovary from responding.

• #63 Primary ovarian insufficiency – Wikipedia

  https://en.wikipedia.org/wiki/Primary_ovarian_insufficiency

  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 producing area) dysfunction or early loss of eggs. […] The pathogenic mechanisms of POI are highly heterogeneous and can be divided into four major categories: follicular migration defect early in embryogenesis; an early decrease in the primordial follicles; increased follicular death; and altered maturation or recruitment of primordial follicles. […] Genetic causes such as Turner syndrome have initial ovarian development but then ovaries degenerate rapidly during prenatal life, often leading to gonadal dysgenesis with streak ovaries. In those cases where POI is associated with adrenal autoimmunity, histological examination almost always confirms the presence of an autoimmune oophoritis in which follicles are infiltrated by lymphocytes, plasma cells, and macrophages that attack mainly steroid-producing cells and eventually result in follicular depletion.

• #64 Primary ovarian insufficiency – Wikipedia

  https://en.wikipedia.org/wiki/Primary_ovarian_insufficiency

  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 producing area) dysfunction or early loss of eggs. […] The pathogenic mechanisms of POI are highly heterogeneous and can be divided into four major categories: follicular migration defect early in embryogenesis; an early decrease in the primordial follicles; increased follicular death; and altered maturation or recruitment of primordial follicles. […] Genetic causes such as Turner syndrome have initial ovarian development but then ovaries degenerate rapidly during prenatal life, often leading to gonadal dysgenesis with streak ovaries. In those cases where POI is associated with adrenal autoimmunity, histological examination almost always confirms the presence of an autoimmune oophoritis in which follicles are infiltrated by lymphocytes, plasma cells, and macrophages that attack mainly steroid-producing cells and eventually result in follicular depletion.

• #65

  https://journals.lww.com/grh/fulltext/2018/06000/the_etiology_of_menopause__not_just_ovarian.1.aspx

  The etiology of the MT is 2-fold, with alterations in the pituitary-hypothalamus pathway, along with changes in the ovary both playing roles. […] The hypothesis that there is a reduction in pituitary positive and negative feedback to estrogen is supported by the data that during the MT estradiol levels remain the same, or are increased, and that there is a reduction in ovulatory cycles. […] Results from this study lend significant support for the hypothesis that there is a relative hypothalamic-pituitary insensitivity to estrogen in aging women. […] While decreased sensitivity to estrogen and reduction of the number of ovarian follicles appear to drive the MT, GnRH production remains potent and robust well after menopause. […] The transition into menopause is frequently accompanied by significant distress for patients, due to symptoms including menstrual irregularities, hot flashes, and breast tenderness. […] Although the etiology of these changes has not yet been well determined, the data demonstrate that, not only there are deficiencies at the level of the ovary, but also quite meaningful desensitization to estrogen at the level of the pituitary.

• #66 Pathogenesis and Causes of Premature Ovarian Failure: An Update

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4059950/

  Premature ovarian failure (POF) affects 1% of young women. […] Diverse etiologies are associated with POF. […] POF may be either spontaneous or induced. […] The known causes include: Genetic disorders, which could involve the X chromosome or autosomes. […] However, the growing body of literature demonstrates a list of newly discovered mutations that may be responsible for causing POF. […] Most of these mutations are extremely rare, and most cases of POF are still considered to be idiopathic. […] Autoimmune causes; there is some evidence of an association of POF with lymphocytic oophoritis and other autoimmune disorders. […] Antiovarian antibodies are reported in POF, but their specificity and pathogenic role are obscure. […] Iatrogenic causes; chemotherapy, radiotherapy and pelvic surgery can lead to POF.

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