Materiały źródłowe

• #1 Factors leading to primary ovarian insufficiency: a literature overview – GREM – Gynecological and Reproductive Endocrinology & Metabolism

  https://gremjournal.com/journal/02-2021/factors-leading-to-primary-ovarian-insufficiency-a-literature-overview/

  Premature ovarian insufficiency (POI) is a disease characterized by oligomenorrhea, hypoestrogenism and elevated gonadotropin levels that occurs in women younger than 40 years of age. There are several possible causes of POI, including chromosomal and genetic diseases, and autoimmune, infectious or iatrogenic events. POI can be classified as primary (spontaneous) or secondary (iatrogenic). […] Unfortunately, in about 75% of POI cases the cause remains unknown. […] From a pathogenetic point of view, primary ovarian insufficiency occurs through two major mechanisms: follicle dysfunction and follicle depletion. […] There are several causes of POI, including chromosomal and genetic diseases, and autoimmune, infectious or iatrogenic events. […] In a retrospective case series of 276 women with Turners syndrome, 1.4% experienced spontaneous pregnancy, 1.4% achieved pregnancy using assisted reproduction technology, and 0.4% both spontaneous and assisted pregnancy.

• #2 What causes POI? | NICHD – Eunice Kennedy Shriver National Institute of Child Health and Human Development

  http://www.nichd.nih.gov/health/topics/poi/conditioninfo/causes

  In most cases, the exact cause of POI is unknown. Research shows that POI is related to problems with the follicles—the small sacs in the ovaries in which eggs grow and mature. For a woman with POI, there are problems with the follicles: Follicle depletion. A woman with follicle depletion runs out of working follicles earlier than normal or expected. In the case of POI, the woman runs out of working follicles before natural menopause occurs around age 50. Presently there is no safe way for scientists today to make primordial follicles. Follicle dysfunction. A woman with follicle dysfunction has follicles remaining in her ovaries, but the follicles are not working properly. Scientists do not have a safe and effective way to make follicles start working normally again. Although the exact cause is unknown in a majority of cases, some causes of follicle depletion and dysfunction have been identified: Genetic and chromosomal disorders. Disorders such as Fragile X syndrome and Turner syndrome can cause follicle depletion. Low number of follicles. Some women are born with fewer primordial follicles, so they have a smaller pool of follicles to use throughout their lives. Autoimmune diseases. In the case of POI, the immune system may damage developing follicles in the ovaries. Several studies suggest that about one-fifth of women with POI have an autoimmune disease. Thyroiditis is the autoimmune disorder most commonly associated with POI. Addison’s disease is also associated with POI. Chemotherapy or radiation therapy. These strong treatments for cancer may damage the genetic material in cells, including follicle cells. Metabolic disorders. These disorders affect the body’s ability to create, store, and use the energy it needs. Toxins. Cigarette smoke, chemicals, and pesticides can speed up follicle depletion.

• #3 What causes POI? | NICHD – Eunice Kennedy Shriver National Institute of Child Health and Human Development

  http://www.nichd.nih.gov/health/topics/poi/conditioninfo/causes

  In most cases, the exact cause of POI is unknown. Research shows that POI is related to problems with the follicles—the small sacs in the ovaries in which eggs grow and mature. For a woman with POI, there are problems with the follicles: Follicle depletion. A woman with follicle depletion runs out of working follicles earlier than normal or expected. In the case of POI, the woman runs out of working follicles before natural menopause occurs around age 50. Presently there is no safe way for scientists today to make primordial follicles. Follicle dysfunction. A woman with follicle dysfunction has follicles remaining in her ovaries, but the follicles are not working properly. Scientists do not have a safe and effective way to make follicles start working normally again. Although the exact cause is unknown in a majority of cases, some causes of follicle depletion and dysfunction have been identified: Genetic and chromosomal disorders. Disorders such as Fragile X syndrome and Turner syndrome can cause follicle depletion. Low number of follicles. Some women are born with fewer primordial follicles, so they have a smaller pool of follicles to use throughout their lives. Autoimmune diseases. In the case of POI, the immune system may damage developing follicles in the ovaries. Several studies suggest that about one-fifth of women with POI have an autoimmune disease. Thyroiditis is the autoimmune disorder most commonly associated with POI. Addison’s disease is also associated with POI. Chemotherapy or radiation therapy. These strong treatments for cancer may damage the genetic material in cells, including follicle cells. Metabolic disorders. These disorders affect the body’s ability to create, store, and use the energy it needs. Toxins. Cigarette smoke, chemicals, and pesticides can speed up follicle depletion.

• #4 Factors leading to primary ovarian insufficiency: a literature overview – GREM – Gynecological and Reproductive Endocrinology & Metabolism

  https://gremjournal.com/journal/02-2021/factors-leading-to-primary-ovarian-insufficiency-a-literature-overview/

  Premature ovarian insufficiency (POI) is a disease characterized by oligomenorrhea, hypoestrogenism and elevated gonadotropin levels that occurs in women younger than 40 years of age. There are several possible causes of POI, including chromosomal and genetic diseases, and autoimmune, infectious or iatrogenic events. POI can be classified as primary (spontaneous) or secondary (iatrogenic). […] Unfortunately, in about 75% of POI cases the cause remains unknown. […] From a pathogenetic point of view, primary ovarian insufficiency occurs through two major mechanisms: follicle dysfunction and follicle depletion. […] There are several causes of POI, including chromosomal and genetic diseases, and autoimmune, infectious or iatrogenic events. […] In a retrospective case series of 276 women with Turners syndrome, 1.4% experienced spontaneous pregnancy, 1.4% achieved pregnancy using assisted reproduction technology, and 0.4% both spontaneous and assisted pregnancy.

• #5 What causes POI? | NICHD – Eunice Kennedy Shriver National Institute of Child Health and Human Development

  http://www.nichd.nih.gov/health/topics/poi/conditioninfo/causes

  In most cases, the exact cause of POI is unknown. Research shows that POI is related to problems with the follicles—the small sacs in the ovaries in which eggs grow and mature. For a woman with POI, there are problems with the follicles: Follicle depletion. A woman with follicle depletion runs out of working follicles earlier than normal or expected. In the case of POI, the woman runs out of working follicles before natural menopause occurs around age 50. Presently there is no safe way for scientists today to make primordial follicles. Follicle dysfunction. A woman with follicle dysfunction has follicles remaining in her ovaries, but the follicles are not working properly. Scientists do not have a safe and effective way to make follicles start working normally again. Although the exact cause is unknown in a majority of cases, some causes of follicle depletion and dysfunction have been identified: Genetic and chromosomal disorders. Disorders such as Fragile X syndrome and Turner syndrome can cause follicle depletion. Low number of follicles. Some women are born with fewer primordial follicles, so they have a smaller pool of follicles to use throughout their lives. Autoimmune diseases. In the case of POI, the immune system may damage developing follicles in the ovaries. Several studies suggest that about one-fifth of women with POI have an autoimmune disease. Thyroiditis is the autoimmune disorder most commonly associated with POI. Addison’s disease is also associated with POI. Chemotherapy or radiation therapy. These strong treatments for cancer may damage the genetic material in cells, including follicle cells. Metabolic disorders. These disorders affect the body’s ability to create, store, and use the energy it needs. Toxins. Cigarette smoke, chemicals, and pesticides can speed up follicle depletion.

• #6 Selected Genetic Factors Associated with Primary Ovarian Insufficiency

  https://www.mdpi.com/1422-0067/24/5/4423

  Although POI is heterogenous and the causes of many cases remain unclear, various types of etiologies, such as genetic, autoimmune, iatrogenic, infectious, environmental, chemotherapeutic, and radiotherapeutic causes, have been determined. […] The overall prevalence of genetic-associated POI is approximately 20–25%. […] Chromosomal abnormality is defined as a variation resulting from aneuploidy or structural defects in chromosomes. This can lead to many harmful and even lethal human genetic diseases, such as trisomies 21, 18, and 13 and sex chromosomes rearrangements. […] Recent studies have shown that chromosomal abnormalities are responsible for POI. […] The prevalence of POI caused by chromosomal abnormalities varies in different populations, with the values ranging from approximately 10% to 13%.

• #7 Primary Ovarian Insufficiency – Gynecology and Obstetrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/gynecology-and-obstetrics/menstrual-abnormalities/primary-ovarian-insufficiency

  In primary ovarian insufficiency, the ovaries stop functioning normally in women who are […] Primary ovarian insufficiency has various causes, including the following: […] The number of ovarian follicles present at birth is insufficient. […] The rate of follicular atresia is accelerated, as occurs when the ovaries are damaged during surgery, chemotherapy, or radiation therapy. […] The follicles are dysfunctional (as occurs in autoimmune ovarian dysfunction). […] Certain genetic disorders are present. […] Genetic disorders that can cause premature ovarian insufficiency include Turner syndrome (45,X or mosaic 45,X/46,XX or 45,X/47,XXX) and Fragile X syndrome (caused by a premutation in the FMR1 gene). […] Genetic disorders that confer a Y chromosome can also cause primary ovarian insufficiency. […] These disorders, which are usually evident by age 35, increase risk of ovarian germ cell cancer.

• #8 Selected Genetic Factors Associated with Primary Ovarian Insufficiency

  https://www.mdpi.com/1422-0067/24/5/4423

  Chromosomal disorders cause POI via the depletion of primordial oocytes during early female development. […] However, the mechanism involved in the loss of oocytes is not clearly understood. […] Moreover, defects in both the X chromosome and autosome can contribute to POI. […] Turner syndrome is a critical sex chromosomal disease in females with a 1 in 2500 incidence. It is caused by the complete or partial deletion of one sex chromosome. […] TS has many hallmarks, including ovarian failure, and it is the most common genetic cause of POI, accounting for 4–5% of all POI cases. […] A recent review suggested that TS-related POI was associated with the function and length of telomeres and epigenetic modifications. […] The increase in the POI cases, among which there is a vast number of POI women with unclear genetic diagnoses, justifies investigating the etiology of POI, which may be critical in the early diagnosis, treatment, and prevention.

• #9 Primary Ovarian Insufficiency | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/136054

  Fragile X FMR1 premutation (59-199 CGG trinucleotide repeats) significantly increases a womans risk of POI in comparison to the general population. Interestingly, women with FMR1 premutation of 80-100 CGG repeats are at the highest risk of POI. Autoimmune diseases such as adrenal insufficiency (Addison disease), hypothyroidism (Hashimoto thyroiditis), rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, nontypical congenital adrenal hyperplasia, myasthenia gravis, and inflammatory bowel disease have also been associated with POI. Genetic mutations and autosomal recessive diseases such as galactosemia (reduction of galactose-1-phosphate), ataxia-telangiectasia (ATM gene), and blepharophimosis-ptosis-epicanthus-inversus syndrome (known as BPES, a mutation in FOXL2) have undefined effects on POI. Environmental exposures such as smoking, nicotine, and the various substances produced (dimethylbenzanthracene) are hypothesized to contribute to POI by binding to the receptors on ovarian granulosa cells. This leads to activation of proapoptotic genes and inhibits aromatase, ultimately leading to decreased circulating estradiol. Other environmental exposures, such as substances in plastic production (phthalates, bisphenol-A), may contribute to POI, but the exact mechanism remains unknown.

• #10 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

  Primary ovarian insufficiency may be associated with multiple endocrinopathies, including hypoparathyroidism and hypoadrenalism. […] Follicle depletion or dysfunction in adolescents may be caused by many different factors. It is often caused by chromosomal abnormalities or damage from chemotherapy or radiation therapy. […] Approximately 4% of women who have primary ovarian insufficiency will have adrenal or ovarian antibodies, which suggests an autoimmune mechanism for disease. […] A common cause of primary ovarian insufficiency in adolescents is gonadal dysgenesis, with or without Turner syndrome. […] The immediate loss of ovarian function after chemotherapy or radiation therapy is termed acute ovarian failure, which may be transient. […] Among females with primary ovarian insufficiency and a normal karyotype, 6% have a premutation in the FMR1 gene. […] In many cases, the etiology remains unknown.

• #11 Hormone Therapy in Primary Ovarian Insufficiency | ACOG

  https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/05/hormone-therapy-in-primary-ovarian-insufficiency

  Primary ovarian insufficiency describes a spectrum of declining ovarian function and reduced fecundity due to a premature decrease in initial follicle number, an increase in follicle destruction, or poor follicular response to gonadotropins. […] At least 90% of cases of primary ovarian insufficiency are idiopathic. […] Only a small number of genetic and molecular derangements have been described that damage human follicle number and function severely enough to result in overt primary ovarian insufficiency. […] Among the most notable conditions that result in primary ovarian insufficiency are those in which one X chromosome is damaged (isochromosome X), lost (Turner syndrome and Turner mosaics), or altered (FMR1 permutation carriers). […] A number of autoimmune disorders and single-gene defects also are associated with primary ovarian insufficiency.

• #12 Primary Ovarian Insufficiency | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/136054

  Fragile X FMR1 premutation (59-199 CGG trinucleotide repeats) significantly increases a womans risk of POI in comparison to the general population. Interestingly, women with FMR1 premutation of 80-100 CGG repeats are at the highest risk of POI. Autoimmune diseases such as adrenal insufficiency (Addison disease), hypothyroidism (Hashimoto thyroiditis), rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, nontypical congenital adrenal hyperplasia, myasthenia gravis, and inflammatory bowel disease have also been associated with POI. Genetic mutations and autosomal recessive diseases such as galactosemia (reduction of galactose-1-phosphate), ataxia-telangiectasia (ATM gene), and blepharophimosis-ptosis-epicanthus-inversus syndrome (known as BPES, a mutation in FOXL2) have undefined effects on POI. Environmental exposures such as smoking, nicotine, and the various substances produced (dimethylbenzanthracene) are hypothesized to contribute to POI by binding to the receptors on ovarian granulosa cells. This leads to activation of proapoptotic genes and inhibits aromatase, ultimately leading to decreased circulating estradiol. Other environmental exposures, such as substances in plastic production (phthalates, bisphenol-A), may contribute to POI, but the exact mechanism remains unknown.

• #13 Primary Ovarian Insufficiency | GLOWM

  https://www.glowm.com/section-view/heading/Primary%20Ovarian%20Insufficiency/item/755

  Primary ovarian insufficiency (POI), also known as premature ovarian failure, premature menopause, hypergonadotropic amenorrhea, hypergonadotropic hypogonadism, and ovarian insufficiency, refers to the loss of ovarian function before the age of 40 years. […] POI may be developed as a result of many pathogenic mechanisms such as chromosomal or genetic abnormalities, autoimmune, infectious, or iatrogenic causes. […] In 90% of cases no cause is found and they are classified as idiopathic. […] POI may be developed as a result of many pathogenic mechanisms such as chromosomal or genetic abnormalities, autoimmune, infectious, or iatrogenic causes. […] Chromosomal/genetic causes […] In 50% of patients with primary amenorrhea as a result of POI, an abnormal karyotype is associated. […] Among the genetic disorders than can be associated with POI the most frequent is galactosemia.

• #14 Primary Ovarian Insufficiency | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/136054

  Primary ovarian insufficiency is thought to arise from either follicular dysfunction or follicular depletion. However, the exact mechanisms in which POI develops remain unknown. Approximately 90% of all diagnosed cases of spontaneous POI do not have a determined underlying etiology. […] Starting at the level of the ovary, rare mutations in the genes for FSH and LH receptors can alter the ovaries response to these circulating gonadotropins leading to nonfunctional ovarian tissue. Iatrogenic causes of POI such as oophorectomy, chemotherapy, or radiation, as well as women with mumps, varicella, malaria, shigella, and TB can destroy healthy ovarian tissue and substantially decrease the amount of functioning tissue that remains. Chromosomal abnormalities such as Turner Syndrome (X,0) can lead to early oocyte apoptosis in utero, in addition to accelerated oocyte depletion early in life (before 10 years old). This leaves a woman with little to no ovarian reserve near reproductive age.

• #15 Primary Ovarian Insufficiency | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/136054

  Fragile X FMR1 premutation (59-199 CGG trinucleotide repeats) significantly increases a womans risk of POI in comparison to the general population. Interestingly, women with FMR1 premutation of 80-100 CGG repeats are at the highest risk of POI. Autoimmune diseases such as adrenal insufficiency (Addison disease), hypothyroidism (Hashimoto thyroiditis), rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, nontypical congenital adrenal hyperplasia, myasthenia gravis, and inflammatory bowel disease have also been associated with POI. Genetic mutations and autosomal recessive diseases such as galactosemia (reduction of galactose-1-phosphate), ataxia-telangiectasia (ATM gene), and blepharophimosis-ptosis-epicanthus-inversus syndrome (known as BPES, a mutation in FOXL2) have undefined effects on POI. Environmental exposures such as smoking, nicotine, and the various substances produced (dimethylbenzanthracene) are hypothesized to contribute to POI by binding to the receptors on ovarian granulosa cells. This leads to activation of proapoptotic genes and inhibits aromatase, ultimately leading to decreased circulating estradiol. Other environmental exposures, such as substances in plastic production (phthalates, bisphenol-A), may contribute to POI, but the exact mechanism remains unknown.

• #16 Primary Ovarian Insufficiency | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/136054

  Fragile X FMR1 premutation (59-199 CGG trinucleotide repeats) significantly increases a womans risk of POI in comparison to the general population. Interestingly, women with FMR1 premutation of 80-100 CGG repeats are at the highest risk of POI. Autoimmune diseases such as adrenal insufficiency (Addison disease), hypothyroidism (Hashimoto thyroiditis), rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, nontypical congenital adrenal hyperplasia, myasthenia gravis, and inflammatory bowel disease have also been associated with POI. Genetic mutations and autosomal recessive diseases such as galactosemia (reduction of galactose-1-phosphate), ataxia-telangiectasia (ATM gene), and blepharophimosis-ptosis-epicanthus-inversus syndrome (known as BPES, a mutation in FOXL2) have undefined effects on POI. Environmental exposures such as smoking, nicotine, and the various substances produced (dimethylbenzanthracene) are hypothesized to contribute to POI by binding to the receptors on ovarian granulosa cells. This leads to activation of proapoptotic genes and inhibits aromatase, ultimately leading to decreased circulating estradiol. Other environmental exposures, such as substances in plastic production (phthalates, bisphenol-A), may contribute to POI, but the exact mechanism remains unknown.

• #17 Homozygosity for a stop-gain variant in CCDC201 causes primary ovarian insufficiency | Nature Genetics

  https://www.nature.com/articles/s41588-024-01885-6

  Homozygosity for the stop-gain variant rs117316434(A) in CCDC201 (p.(Arg162Ter), minor allele frequency ~1%) reached menopause 9 years earlier than other women (P=1.31015). The genotype is present in one in 10,000 northern European women and leads to primary ovarian insufficiency in close to half of them. Consequently, homozygotes have fewer children, and the age at last childbirth is 5 years earlier (P=3.8105). Homozygosity for CCDC201 loss-of-function has a substantial impact on female reproductive health, and homozygotes would benefit from reproductive counseling and treatment for symptoms of early menopause. […] Homozygosity (n=27 women) for the low-frequency stop-gain variant p.(Arg162Ter) (rs117316434(A), chr7: 45863165; minor allele frequency (MAF) ~1%) in CCDC201 is associated with earlier AOM by 9 years than in heterozygotes and noncarriers (recessive effect=1.59 s.d.; 95% confidence interval (CI): 1.98, 1.20), recessive P=1.31015.

• #18 Homozygosity for a stop-gain variant in CCDC201 causes primary ovarian insufficiency | Nature Genetics

  https://www.nature.com/articles/s41588-024-01885-6

  Homozygotes are also at high risk of POI (OR=27.3 (95% CI: 9.38, 82.6), P=2.2109; Table 2), with 33% of homozygotes (9 of 27 women) entering menopause before the age of 40 compared with 3% of heterozygotes and noncarriers. […] We performed a GWAS of AOM under the recessive model in 174,329 postmenopausal women from four European countries, we discovered that homozygosity of the low-frequency p.(Arg162Ter) in CCDC201 causes menopause to occur 9 years earlier than in noncarrier or heterozygotes and leads to POI of close to half of carriers.

• #19

  https://journals.lww.com/abhs/fulltext/2024/03030/overview_of_prevalence,_etiology,_clinical.2.aspx

  Approximately one-fourth of all POI cases are categorized as iatrogenic and are linked to cancer treatment. […] Autoimmune diseases comprise 4%30% of cases. […] Prolonged exposure to chemotherapy and radiotherapy, as experienced by cancer survivors, can lead to POI at a later age. […] A major risk factor for POI is tobacco use, specifically cigarette smoking, of which the most common toxic components are polycyclic aromatic hydrocarbons. […] Aging-associated inflammation is related to the etiology of POI. […] Mumps oophoritis caused by the epidemic parotitis virus and human immunodeficiency virus are the most common viruses that impair ovarian function and cause POI. […] Furthermore, a link between POI and COVID-19 has been recognized in women who are being investigated for infertility after recovering from the infection.

• #20 Primary ovarian insufficiency: Symptoms, treatment, and fertility

  https://www.medicalnewstoday.com/articles/primary-ovarian-insufficiency

  Primary ovarian insufficiency (POI) is a condition that occurs when a person stops ovulating regularly before the age of 40 years. […] Scientists are not completely sure how POI develops, but they believe that it occurs due to problems with the follicles inside the ovaries. Follicles are tiny sacs in which eggs grow. […] However, if there is an early decrease in the number of working follicles, or the follicles are not functioning as they should, this may cause POI. […] About 10-20% of people with POI have a family member who also has the condition, which suggests that genetics are an important factor in POI. Several genetic mutations and medical conditions are associated with POI, including fragile X syndrome and Turner syndrome. […] A 2019 study estimates that autoimmunity may account for 4-30% of all POI cases. […] Chemotherapy, radiation therapy, and toxins can damage follicles in the ovaries and stop them from working. […] Most females with a metabolic disorder known as galactosemia also have POI.

• #21 Primary ovarian insufficiency // Middlesex Health

  https://middlesexhealth.org/learning-center/diseases-and-conditions/primary-ovarian-insufficiency

  An immune system response to ovarian tissue. This also is called autoimmune disease. In this rare form, the immune system makes protective proteins that attack ovary tissue by mistake. This harms sacs in the ovaries that each contain an egg, called follicles. It also damages the egg. What triggers the immune response is unclear. But being exposed to a virus may play a role. […] Unknown factors. Most often, the cause of primary ovarian insufficiency isn’t clear. You might hear this called an idiopathic cause. Your health care professional may recommend more testing to try to find the cause.

• #22 Primary Ovarian Insufficiency | GLOWM

  https://www.glowm.com/section-view/heading/Primary%20Ovarian%20Insufficiency/item/755

  Autoimmune diseases are characterized by the presences of organ and non-organ specific autoantibodies. […] The association of POI with autoimmune Addison disease (adrenal insufficiency) can occur in the context of two types of autoimmune polyendocrine syndromes (APS): type I (autoimmune polyendocrinopathy candidiasis ectodermal dystrophy) and type II (a polygenic syndrome with Addison disease and hypothyroidism). […] Almost any pelvic surgery that affects the ovarian blood supply can be responsible of the development of POI. […] Mumps oophoritis has been considered to be a cause of POI.

• #23 Primary Ovarian Insufficiency | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/136054

  Fragile X FMR1 premutation (59-199 CGG trinucleotide repeats) significantly increases a womans risk of POI in comparison to the general population. Interestingly, women with FMR1 premutation of 80-100 CGG repeats are at the highest risk of POI. Autoimmune diseases such as adrenal insufficiency (Addison disease), hypothyroidism (Hashimoto thyroiditis), rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, nontypical congenital adrenal hyperplasia, myasthenia gravis, and inflammatory bowel disease have also been associated with POI. Genetic mutations and autosomal recessive diseases such as galactosemia (reduction of galactose-1-phosphate), ataxia-telangiectasia (ATM gene), and blepharophimosis-ptosis-epicanthus-inversus syndrome (known as BPES, a mutation in FOXL2) have undefined effects on POI. Environmental exposures such as smoking, nicotine, and the various substances produced (dimethylbenzanthracene) are hypothesized to contribute to POI by binding to the receptors on ovarian granulosa cells. This leads to activation of proapoptotic genes and inhibits aromatase, ultimately leading to decreased circulating estradiol. Other environmental exposures, such as substances in plastic production (phthalates, bisphenol-A), may contribute to POI, but the exact mechanism remains unknown.

• #24 Primary Ovarian Insufficiency | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/136054

  Fragile X FMR1 premutation (59-199 CGG trinucleotide repeats) significantly increases a womans risk of POI in comparison to the general population. Interestingly, women with FMR1 premutation of 80-100 CGG repeats are at the highest risk of POI. Autoimmune diseases such as adrenal insufficiency (Addison disease), hypothyroidism (Hashimoto thyroiditis), rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, nontypical congenital adrenal hyperplasia, myasthenia gravis, and inflammatory bowel disease have also been associated with POI. Genetic mutations and autosomal recessive diseases such as galactosemia (reduction of galactose-1-phosphate), ataxia-telangiectasia (ATM gene), and blepharophimosis-ptosis-epicanthus-inversus syndrome (known as BPES, a mutation in FOXL2) have undefined effects on POI. Environmental exposures such as smoking, nicotine, and the various substances produced (dimethylbenzanthracene) are hypothesized to contribute to POI by binding to the receptors on ovarian granulosa cells. This leads to activation of proapoptotic genes and inhibits aromatase, ultimately leading to decreased circulating estradiol. Other environmental exposures, such as substances in plastic production (phthalates, bisphenol-A), may contribute to POI, but the exact mechanism remains unknown.

• #25 Primary Ovarian Insufficiency | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/136054

  Fragile X FMR1 premutation (59-199 CGG trinucleotide repeats) significantly increases a womans risk of POI in comparison to the general population. Interestingly, women with FMR1 premutation of 80-100 CGG repeats are at the highest risk of POI. Autoimmune diseases such as adrenal insufficiency (Addison disease), hypothyroidism (Hashimoto thyroiditis), rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, nontypical congenital adrenal hyperplasia, myasthenia gravis, and inflammatory bowel disease have also been associated with POI. Genetic mutations and autosomal recessive diseases such as galactosemia (reduction of galactose-1-phosphate), ataxia-telangiectasia (ATM gene), and blepharophimosis-ptosis-epicanthus-inversus syndrome (known as BPES, a mutation in FOXL2) have undefined effects on POI. Environmental exposures such as smoking, nicotine, and the various substances produced (dimethylbenzanthracene) are hypothesized to contribute to POI by binding to the receptors on ovarian granulosa cells. This leads to activation of proapoptotic genes and inhibits aromatase, ultimately leading to decreased circulating estradiol. Other environmental exposures, such as substances in plastic production (phthalates, bisphenol-A), may contribute to POI, but the exact mechanism remains unknown.

• #26 Primary Ovarian Insufficiency | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/136054

  Fragile X FMR1 premutation (59-199 CGG trinucleotide repeats) significantly increases a womans risk of POI in comparison to the general population. Interestingly, women with FMR1 premutation of 80-100 CGG repeats are at the highest risk of POI. Autoimmune diseases such as adrenal insufficiency (Addison disease), hypothyroidism (Hashimoto thyroiditis), rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, nontypical congenital adrenal hyperplasia, myasthenia gravis, and inflammatory bowel disease have also been associated with POI. Genetic mutations and autosomal recessive diseases such as galactosemia (reduction of galactose-1-phosphate), ataxia-telangiectasia (ATM gene), and blepharophimosis-ptosis-epicanthus-inversus syndrome (known as BPES, a mutation in FOXL2) have undefined effects on POI. Environmental exposures such as smoking, nicotine, and the various substances produced (dimethylbenzanthracene) are hypothesized to contribute to POI by binding to the receptors on ovarian granulosa cells. This leads to activation of proapoptotic genes and inhibits aromatase, ultimately leading to decreased circulating estradiol. Other environmental exposures, such as substances in plastic production (phthalates, bisphenol-A), may contribute to POI, but the exact mechanism remains unknown.

• #27 Primary Ovarian Insufficiency | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/136054

  Fragile X FMR1 premutation (59-199 CGG trinucleotide repeats) significantly increases a womans risk of POI in comparison to the general population. Interestingly, women with FMR1 premutation of 80-100 CGG repeats are at the highest risk of POI. Autoimmune diseases such as adrenal insufficiency (Addison disease), hypothyroidism (Hashimoto thyroiditis), rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, nontypical congenital adrenal hyperplasia, myasthenia gravis, and inflammatory bowel disease have also been associated with POI. Genetic mutations and autosomal recessive diseases such as galactosemia (reduction of galactose-1-phosphate), ataxia-telangiectasia (ATM gene), and blepharophimosis-ptosis-epicanthus-inversus syndrome (known as BPES, a mutation in FOXL2) have undefined effects on POI. Environmental exposures such as smoking, nicotine, and the various substances produced (dimethylbenzanthracene) are hypothesized to contribute to POI by binding to the receptors on ovarian granulosa cells. This leads to activation of proapoptotic genes and inhibits aromatase, ultimately leading to decreased circulating estradiol. Other environmental exposures, such as substances in plastic production (phthalates, bisphenol-A), may contribute to POI, but the exact mechanism remains unknown.

• #28 Primary Ovarian Insufficiency | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/136054

  Fragile X FMR1 premutation (59-199 CGG trinucleotide repeats) significantly increases a womans risk of POI in comparison to the general population. Interestingly, women with FMR1 premutation of 80-100 CGG repeats are at the highest risk of POI. Autoimmune diseases such as adrenal insufficiency (Addison disease), hypothyroidism (Hashimoto thyroiditis), rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, nontypical congenital adrenal hyperplasia, myasthenia gravis, and inflammatory bowel disease have also been associated with POI. Genetic mutations and autosomal recessive diseases such as galactosemia (reduction of galactose-1-phosphate), ataxia-telangiectasia (ATM gene), and blepharophimosis-ptosis-epicanthus-inversus syndrome (known as BPES, a mutation in FOXL2) have undefined effects on POI. Environmental exposures such as smoking, nicotine, and the various substances produced (dimethylbenzanthracene) are hypothesized to contribute to POI by binding to the receptors on ovarian granulosa cells. This leads to activation of proapoptotic genes and inhibits aromatase, ultimately leading to decreased circulating estradiol. Other environmental exposures, such as substances in plastic production (phthalates, bisphenol-A), may contribute to POI, but the exact mechanism remains unknown.

• #29 Primary Ovarian Insufficiency | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/136054

  Fragile X FMR1 premutation (59-199 CGG trinucleotide repeats) significantly increases a womans risk of POI in comparison to the general population. Interestingly, women with FMR1 premutation of 80-100 CGG repeats are at the highest risk of POI. Autoimmune diseases such as adrenal insufficiency (Addison disease), hypothyroidism (Hashimoto thyroiditis), rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, nontypical congenital adrenal hyperplasia, myasthenia gravis, and inflammatory bowel disease have also been associated with POI. Genetic mutations and autosomal recessive diseases such as galactosemia (reduction of galactose-1-phosphate), ataxia-telangiectasia (ATM gene), and blepharophimosis-ptosis-epicanthus-inversus syndrome (known as BPES, a mutation in FOXL2) have undefined effects on POI. Environmental exposures such as smoking, nicotine, and the various substances produced (dimethylbenzanthracene) are hypothesized to contribute to POI by binding to the receptors on ovarian granulosa cells. This leads to activation of proapoptotic genes and inhibits aromatase, ultimately leading to decreased circulating estradiol. Other environmental exposures, such as substances in plastic production (phthalates, bisphenol-A), may contribute to POI, but the exact mechanism remains unknown.

• #30 Primary ovarian insufficiency // Middlesex Health

  https://middlesexhealth.org/learning-center/diseases-and-conditions/primary-ovarian-insufficiency

  An immune system response to ovarian tissue. This also is called autoimmune disease. In this rare form, the immune system makes protective proteins that attack ovary tissue by mistake. This harms sacs in the ovaries that each contain an egg, called follicles. It also damages the egg. What triggers the immune response is unclear. But being exposed to a virus may play a role. […] Unknown factors. Most often, the cause of primary ovarian insufficiency isn’t clear. You might hear this called an idiopathic cause. Your health care professional may recommend more testing to try to find the cause.

• #31 Primary ovarian insufficiency // Middlesex Health

  https://middlesexhealth.org/learning-center/diseases-and-conditions/primary-ovarian-insufficiency

  An immune system response to ovarian tissue. This also is called autoimmune disease. In this rare form, the immune system makes protective proteins that attack ovary tissue by mistake. This harms sacs in the ovaries that each contain an egg, called follicles. It also damages the egg. What triggers the immune response is unclear. But being exposed to a virus may play a role. […] Unknown factors. Most often, the cause of primary ovarian insufficiency isn’t clear. You might hear this called an idiopathic cause. Your health care professional may recommend more testing to try to find the cause.

• #32 Primary ovarian insufficiency // Middlesex Health

  https://middlesexhealth.org/learning-center/diseases-and-conditions/primary-ovarian-insufficiency

  Primary ovarian insufficiency may be caused by: […] Chromosome changes. Chromosomes are thread-like structures that contain genes. Most often, people assigned female at birth have two X chromosomes in their cells. But some people with primary ovarian insufficiency have one typical X chromosome and one altered X chromosome. This can be a sign of genetic conditions such as mosaic Turner syndrome. Other people with primary ovarian insufficiency have X chromosomes that are fragile and break. This is called fragile X syndrome. […] Toxins. Chemotherapy and radiation therapy are common causes of toxin-induced ovarian insufficiency. These treatments can damage genetic material in cells. Other toxins such as cigarette smoke, chemicals, pesticides and viruses might speed up ovarian insufficiency.

• #33 Primary Ovarian Insufficiency | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/136054

  Primary ovarian insufficiency is thought to arise from either follicular dysfunction or follicular depletion. However, the exact mechanisms in which POI develops remain unknown. Approximately 90% of all diagnosed cases of spontaneous POI do not have a determined underlying etiology. […] Starting at the level of the ovary, rare mutations in the genes for FSH and LH receptors can alter the ovaries response to these circulating gonadotropins leading to nonfunctional ovarian tissue. Iatrogenic causes of POI such as oophorectomy, chemotherapy, or radiation, as well as women with mumps, varicella, malaria, shigella, and TB can destroy healthy ovarian tissue and substantially decrease the amount of functioning tissue that remains. Chromosomal abnormalities such as Turner Syndrome (X,0) can lead to early oocyte apoptosis in utero, in addition to accelerated oocyte depletion early in life (before 10 years old). This leaves a woman with little to no ovarian reserve near reproductive age.

• #34 Primary ovarian insufficiency // Middlesex Health

  https://middlesexhealth.org/learning-center/diseases-and-conditions/primary-ovarian-insufficiency

  Primary ovarian insufficiency may be caused by: […] Chromosome changes. Chromosomes are thread-like structures that contain genes. Most often, people assigned female at birth have two X chromosomes in their cells. But some people with primary ovarian insufficiency have one typical X chromosome and one altered X chromosome. This can be a sign of genetic conditions such as mosaic Turner syndrome. Other people with primary ovarian insufficiency have X chromosomes that are fragile and break. This is called fragile X syndrome. […] Toxins. Chemotherapy and radiation therapy are common causes of toxin-induced ovarian insufficiency. These treatments can damage genetic material in cells. Other toxins such as cigarette smoke, chemicals, pesticides and viruses might speed up ovarian insufficiency.

• #35 Primary Ovarian Insufficiency | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/136054

  Fragile X FMR1 premutation (59-199 CGG trinucleotide repeats) significantly increases a womans risk of POI in comparison to the general population. Interestingly, women with FMR1 premutation of 80-100 CGG repeats are at the highest risk of POI. Autoimmune diseases such as adrenal insufficiency (Addison disease), hypothyroidism (Hashimoto thyroiditis), rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, nontypical congenital adrenal hyperplasia, myasthenia gravis, and inflammatory bowel disease have also been associated with POI. Genetic mutations and autosomal recessive diseases such as galactosemia (reduction of galactose-1-phosphate), ataxia-telangiectasia (ATM gene), and blepharophimosis-ptosis-epicanthus-inversus syndrome (known as BPES, a mutation in FOXL2) have undefined effects on POI. Environmental exposures such as smoking, nicotine, and the various substances produced (dimethylbenzanthracene) are hypothesized to contribute to POI by binding to the receptors on ovarian granulosa cells. This leads to activation of proapoptotic genes and inhibits aromatase, ultimately leading to decreased circulating estradiol. Other environmental exposures, such as substances in plastic production (phthalates, bisphenol-A), may contribute to POI, but the exact mechanism remains unknown.

• #36 Factors leading to primary ovarian insufficiency: a literature overview – GREM – Gynecological and Reproductive Endocrinology & Metabolism

  https://gremjournal.com/journal/02-2021/factors-leading-to-primary-ovarian-insufficiency-a-literature-overview/

  Some authors noted that ovarian insufficiency is correlated with adrenal insufficiency. […] Cigarette smoke contains polycyclic aromatic hydrocarbons (PAHs), which bind to the aryl hydrocarbon receptor present on the surface of granulosa cells. […] There is still little evidence that a viral infection may cause POI; indeed, a real cause-and-effect relationship has not yet been established. […] At present, there is considerable interest in the possible influence on ovarian function of three different factors: endocrine-disrupting chemicals (EDCs), oxidative stress and epigenetics. […] Some uncommon cases of POI may be related to genetic defects of the enzymes involved in the biosynthesis of androstenedione, estradiol and cortisol. […] Some cases of POI have been associated with defects in FSH receptor (FSHR) production. […] In this narrative review, we have provided an overview of possible causes associated with primary POI. There are many possible causes of POI, including chromosomal and genetic diseases, and autoimmune, infectious or iatrogenic events. In about 75% of POI cases, however, the cause remains unknown.

• #37 Primary Ovarian Insufficiency | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/136054

  Fragile X FMR1 premutation (59-199 CGG trinucleotide repeats) significantly increases a womans risk of POI in comparison to the general population. Interestingly, women with FMR1 premutation of 80-100 CGG repeats are at the highest risk of POI. Autoimmune diseases such as adrenal insufficiency (Addison disease), hypothyroidism (Hashimoto thyroiditis), rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus, nontypical congenital adrenal hyperplasia, myasthenia gravis, and inflammatory bowel disease have also been associated with POI. Genetic mutations and autosomal recessive diseases such as galactosemia (reduction of galactose-1-phosphate), ataxia-telangiectasia (ATM gene), and blepharophimosis-ptosis-epicanthus-inversus syndrome (known as BPES, a mutation in FOXL2) have undefined effects on POI. Environmental exposures such as smoking, nicotine, and the various substances produced (dimethylbenzanthracene) are hypothesized to contribute to POI by binding to the receptors on ovarian granulosa cells. This leads to activation of proapoptotic genes and inhibits aromatase, ultimately leading to decreased circulating estradiol. Other environmental exposures, such as substances in plastic production (phthalates, bisphenol-A), may contribute to POI, but the exact mechanism remains unknown.

• #38 Primary ovarian insufficiency – Wikipedia

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

  Certain environmental toxins such as phthalates, bisphenols, and dioxins are also associated with POI. […] 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.

• #39

  https://journals.lww.com/abhs/fulltext/2024/03030/overview_of_prevalence,_etiology,_clinical.2.aspx

  Approximately one-fourth of all POI cases are categorized as iatrogenic and are linked to cancer treatment. […] Autoimmune diseases comprise 4%30% of cases. […] Prolonged exposure to chemotherapy and radiotherapy, as experienced by cancer survivors, can lead to POI at a later age. […] A major risk factor for POI is tobacco use, specifically cigarette smoking, of which the most common toxic components are polycyclic aromatic hydrocarbons. […] Aging-associated inflammation is related to the etiology of POI. […] Mumps oophoritis caused by the epidemic parotitis virus and human immunodeficiency virus are the most common viruses that impair ovarian function and cause POI. […] Furthermore, a link between POI and COVID-19 has been recognized in women who are being investigated for infertility after recovering from the infection.

• #40 Primary Ovarian Insufficiency | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/136054

  Primary ovarian insufficiency is thought to arise from either follicular dysfunction or follicular depletion. However, the exact mechanisms in which POI develops remain unknown. Approximately 90% of all diagnosed cases of spontaneous POI do not have a determined underlying etiology. […] Starting at the level of the ovary, rare mutations in the genes for FSH and LH receptors can alter the ovaries response to these circulating gonadotropins leading to nonfunctional ovarian tissue. Iatrogenic causes of POI such as oophorectomy, chemotherapy, or radiation, as well as women with mumps, varicella, malaria, shigella, and TB can destroy healthy ovarian tissue and substantially decrease the amount of functioning tissue that remains. Chromosomal abnormalities such as Turner Syndrome (X,0) can lead to early oocyte apoptosis in utero, in addition to accelerated oocyte depletion early in life (before 10 years old). This leaves a woman with little to no ovarian reserve near reproductive age.

• #41

  https://journals.lww.com/abhs/fulltext/2024/03030/overview_of_prevalence,_etiology,_clinical.2.aspx

  Approximately one-fourth of all POI cases are categorized as iatrogenic and are linked to cancer treatment. […] Autoimmune diseases comprise 4%30% of cases. […] Prolonged exposure to chemotherapy and radiotherapy, as experienced by cancer survivors, can lead to POI at a later age. […] A major risk factor for POI is tobacco use, specifically cigarette smoking, of which the most common toxic components are polycyclic aromatic hydrocarbons. […] Aging-associated inflammation is related to the etiology of POI. […] Mumps oophoritis caused by the epidemic parotitis virus and human immunodeficiency virus are the most common viruses that impair ovarian function and cause POI. […] Furthermore, a link between POI and COVID-19 has been recognized in women who are being investigated for infertility after recovering from the infection.

• #42 Primary Ovarian Insufficiency | GLOWM

  https://www.glowm.com/section-view/heading/Primary%20Ovarian%20Insufficiency/item/755

  Autoimmune diseases are characterized by the presences of organ and non-organ specific autoantibodies. […] The association of POI with autoimmune Addison disease (adrenal insufficiency) can occur in the context of two types of autoimmune polyendocrine syndromes (APS): type I (autoimmune polyendocrinopathy candidiasis ectodermal dystrophy) and type II (a polygenic syndrome with Addison disease and hypothyroidism). […] Almost any pelvic surgery that affects the ovarian blood supply can be responsible of the development of POI. […] Mumps oophoritis has been considered to be a cause of POI.

• #43

  https://journals.lww.com/abhs/fulltext/2024/03030/overview_of_prevalence,_etiology,_clinical.2.aspx

  Approximately one-fourth of all POI cases are categorized as iatrogenic and are linked to cancer treatment. […] Autoimmune diseases comprise 4%30% of cases. […] Prolonged exposure to chemotherapy and radiotherapy, as experienced by cancer survivors, can lead to POI at a later age. […] A major risk factor for POI is tobacco use, specifically cigarette smoking, of which the most common toxic components are polycyclic aromatic hydrocarbons. […] Aging-associated inflammation is related to the etiology of POI. […] Mumps oophoritis caused by the epidemic parotitis virus and human immunodeficiency virus are the most common viruses that impair ovarian function and cause POI. […] Furthermore, a link between POI and COVID-19 has been recognized in women who are being investigated for infertility after recovering from the infection.

• #44 Primary Ovarian Insufficiency | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/136054

  Primary ovarian insufficiency is thought to arise from either follicular dysfunction or follicular depletion. However, the exact mechanisms in which POI develops remain unknown. Approximately 90% of all diagnosed cases of spontaneous POI do not have a determined underlying etiology. […] Starting at the level of the ovary, rare mutations in the genes for FSH and LH receptors can alter the ovaries response to these circulating gonadotropins leading to nonfunctional ovarian tissue. Iatrogenic causes of POI such as oophorectomy, chemotherapy, or radiation, as well as women with mumps, varicella, malaria, shigella, and TB can destroy healthy ovarian tissue and substantially decrease the amount of functioning tissue that remains. Chromosomal abnormalities such as Turner Syndrome (X,0) can lead to early oocyte apoptosis in utero, in addition to accelerated oocyte depletion early in life (before 10 years old). This leaves a woman with little to no ovarian reserve near reproductive age.

• #45 Primary Ovarian Insufficiency | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/136054

  Primary ovarian insufficiency is thought to arise from either follicular dysfunction or follicular depletion. However, the exact mechanisms in which POI develops remain unknown. Approximately 90% of all diagnosed cases of spontaneous POI do not have a determined underlying etiology. […] Starting at the level of the ovary, rare mutations in the genes for FSH and LH receptors can alter the ovaries response to these circulating gonadotropins leading to nonfunctional ovarian tissue. Iatrogenic causes of POI such as oophorectomy, chemotherapy, or radiation, as well as women with mumps, varicella, malaria, shigella, and TB can destroy healthy ovarian tissue and substantially decrease the amount of functioning tissue that remains. Chromosomal abnormalities such as Turner Syndrome (X,0) can lead to early oocyte apoptosis in utero, in addition to accelerated oocyte depletion early in life (before 10 years old). This leaves a woman with little to no ovarian reserve near reproductive age.

• #46 Primary Ovarian Insufficiency | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/136054

  Primary ovarian insufficiency is thought to arise from either follicular dysfunction or follicular depletion. However, the exact mechanisms in which POI develops remain unknown. Approximately 90% of all diagnosed cases of spontaneous POI do not have a determined underlying etiology. […] Starting at the level of the ovary, rare mutations in the genes for FSH and LH receptors can alter the ovaries response to these circulating gonadotropins leading to nonfunctional ovarian tissue. Iatrogenic causes of POI such as oophorectomy, chemotherapy, or radiation, as well as women with mumps, varicella, malaria, shigella, and TB can destroy healthy ovarian tissue and substantially decrease the amount of functioning tissue that remains. Chromosomal abnormalities such as Turner Syndrome (X,0) can lead to early oocyte apoptosis in utero, in addition to accelerated oocyte depletion early in life (before 10 years old). This leaves a woman with little to no ovarian reserve near reproductive age.

• #47 Primary Ovarian Insufficiency | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/136054

  Primary ovarian insufficiency is thought to arise from either follicular dysfunction or follicular depletion. However, the exact mechanisms in which POI develops remain unknown. Approximately 90% of all diagnosed cases of spontaneous POI do not have a determined underlying etiology. […] Starting at the level of the ovary, rare mutations in the genes for FSH and LH receptors can alter the ovaries response to these circulating gonadotropins leading to nonfunctional ovarian tissue. Iatrogenic causes of POI such as oophorectomy, chemotherapy, or radiation, as well as women with mumps, varicella, malaria, shigella, and TB can destroy healthy ovarian tissue and substantially decrease the amount of functioning tissue that remains. Chromosomal abnormalities such as Turner Syndrome (X,0) can lead to early oocyte apoptosis in utero, in addition to accelerated oocyte depletion early in life (before 10 years old). This leaves a woman with little to no ovarian reserve near reproductive age.

• #48

  https://journals.lww.com/abhs/fulltext/2024/03030/overview_of_prevalence,_etiology,_clinical.2.aspx

  Approximately one-fourth of all POI cases are categorized as iatrogenic and are linked to cancer treatment. […] Autoimmune diseases comprise 4%30% of cases. […] Prolonged exposure to chemotherapy and radiotherapy, as experienced by cancer survivors, can lead to POI at a later age. […] A major risk factor for POI is tobacco use, specifically cigarette smoking, of which the most common toxic components are polycyclic aromatic hydrocarbons. […] Aging-associated inflammation is related to the etiology of POI. […] Mumps oophoritis caused by the epidemic parotitis virus and human immunodeficiency virus are the most common viruses that impair ovarian function and cause POI. […] Furthermore, a link between POI and COVID-19 has been recognized in women who are being investigated for infertility after recovering from the infection.

• #49 Factors leading to primary ovarian insufficiency: a literature overview – GREM – Gynecological and Reproductive Endocrinology & Metabolism

  https://gremjournal.com/journal/02-2021/factors-leading-to-primary-ovarian-insufficiency-a-literature-overview/

  Some authors noted that ovarian insufficiency is correlated with adrenal insufficiency. […] Cigarette smoke contains polycyclic aromatic hydrocarbons (PAHs), which bind to the aryl hydrocarbon receptor present on the surface of granulosa cells. […] There is still little evidence that a viral infection may cause POI; indeed, a real cause-and-effect relationship has not yet been established. […] At present, there is considerable interest in the possible influence on ovarian function of three different factors: endocrine-disrupting chemicals (EDCs), oxidative stress and epigenetics. […] Some uncommon cases of POI may be related to genetic defects of the enzymes involved in the biosynthesis of androstenedione, estradiol and cortisol. […] Some cases of POI have been associated with defects in FSH receptor (FSHR) production. […] In this narrative review, we have provided an overview of possible causes associated with primary POI. There are many possible causes of POI, including chromosomal and genetic diseases, and autoimmune, infectious or iatrogenic events. In about 75% of POI cases, however, the cause remains unknown.

• #50

  https://journals.lww.com/abhs/fulltext/2024/03030/overview_of_prevalence,_etiology,_clinical.2.aspx

  Approximately one-fourth of all POI cases are categorized as iatrogenic and are linked to cancer treatment. […] Autoimmune diseases comprise 4%30% of cases. […] Prolonged exposure to chemotherapy and radiotherapy, as experienced by cancer survivors, can lead to POI at a later age. […] A major risk factor for POI is tobacco use, specifically cigarette smoking, of which the most common toxic components are polycyclic aromatic hydrocarbons. […] Aging-associated inflammation is related to the etiology of POI. […] Mumps oophoritis caused by the epidemic parotitis virus and human immunodeficiency virus are the most common viruses that impair ovarian function and cause POI. […] Furthermore, a link between POI and COVID-19 has been recognized in women who are being investigated for infertility after recovering from the infection.

• #51 Primary Ovarian Insufficiency | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/136054

  Primary ovarian insufficiency is thought to arise from either follicular dysfunction or follicular depletion. However, the exact mechanisms in which POI develops remain unknown. Approximately 90% of all diagnosed cases of spontaneous POI do not have a determined underlying etiology. […] Starting at the level of the ovary, rare mutations in the genes for FSH and LH receptors can alter the ovaries response to these circulating gonadotropins leading to nonfunctional ovarian tissue. Iatrogenic causes of POI such as oophorectomy, chemotherapy, or radiation, as well as women with mumps, varicella, malaria, shigella, and TB can destroy healthy ovarian tissue and substantially decrease the amount of functioning tissue that remains. Chromosomal abnormalities such as Turner Syndrome (X,0) can lead to early oocyte apoptosis in utero, in addition to accelerated oocyte depletion early in life (before 10 years old). This leaves a woman with little to no ovarian reserve near reproductive age.

• #52 Primary Ovarian Insufficiency | GLOWM

  https://www.glowm.com/section-view/heading/Primary%20Ovarian%20Insufficiency/item/755

  Autoimmune diseases are characterized by the presences of organ and non-organ specific autoantibodies. […] The association of POI with autoimmune Addison disease (adrenal insufficiency) can occur in the context of two types of autoimmune polyendocrine syndromes (APS): type I (autoimmune polyendocrinopathy candidiasis ectodermal dystrophy) and type II (a polygenic syndrome with Addison disease and hypothyroidism). […] Almost any pelvic surgery that affects the ovarian blood supply can be responsible of the development of POI. […] Mumps oophoritis has been considered to be a cause of POI.

• #53 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

  Premature ovarian insufficiency (POI), defined as amenorrhoea due to the loss of ovarian function before 40 years of age, can occur spontaneously or be secondary to medical therapies. […] The aetiology of POI is diverse, and it can occur spontaneously or be secondary to medical therapies. It is estimated that spontaneous POI affects 1% of the female population. […] Spontaneous POI can be associated with chromosomal and genetic defects, environmental factors, autoimmune diseases (most commonly adrenal and thyroid disease) and various infections, but is idiopathic in the majority of cases. […] The most clinically important autoimmune conditions associated with POI are autoimmune adrenal disease (Addisons disease) and thyroid autoimmunity. […] A family history of POI and cigarette smoking are well recognised risk factors for the development of POI, as is bilateral ovarian surgery for endometriomas, with a reported 2.3% of women developing POI. […] Importantly, the combined oral contraceptive pill (COCP), fertility drugs and prior hormone replacement therapy (HRT) do not cause POI, but cessation of these therapies may unmask undiagnosed POI.

• #54 Primary Ovarian Insufficiency | GLOWM

  https://www.glowm.com/section-view/heading/Primary%20Ovarian%20Insufficiency/item/755

  Autoimmune diseases are characterized by the presences of organ and non-organ specific autoantibodies. […] The association of POI with autoimmune Addison disease (adrenal insufficiency) can occur in the context of two types of autoimmune polyendocrine syndromes (APS): type I (autoimmune polyendocrinopathy candidiasis ectodermal dystrophy) and type II (a polygenic syndrome with Addison disease and hypothyroidism). […] Almost any pelvic surgery that affects the ovarian blood supply can be responsible of the development of POI. […] Mumps oophoritis has been considered to be a cause of POI.

• #55 What causes POI? | NICHD – Eunice Kennedy Shriver National Institute of Child Health and Human Development

  http://www.nichd.nih.gov/health/topics/poi/conditioninfo/causes

  In most cases, the exact cause of POI is unknown. Research shows that POI is related to problems with the follicles—the small sacs in the ovaries in which eggs grow and mature. For a woman with POI, there are problems with the follicles: Follicle depletion. A woman with follicle depletion runs out of working follicles earlier than normal or expected. In the case of POI, the woman runs out of working follicles before natural menopause occurs around age 50. Presently there is no safe way for scientists today to make primordial follicles. Follicle dysfunction. A woman with follicle dysfunction has follicles remaining in her ovaries, but the follicles are not working properly. Scientists do not have a safe and effective way to make follicles start working normally again. Although the exact cause is unknown in a majority of cases, some causes of follicle depletion and dysfunction have been identified: Genetic and chromosomal disorders. Disorders such as Fragile X syndrome and Turner syndrome can cause follicle depletion. Low number of follicles. Some women are born with fewer primordial follicles, so they have a smaller pool of follicles to use throughout their lives. Autoimmune diseases. In the case of POI, the immune system may damage developing follicles in the ovaries. Several studies suggest that about one-fifth of women with POI have an autoimmune disease. Thyroiditis is the autoimmune disorder most commonly associated with POI. Addison’s disease is also associated with POI. Chemotherapy or radiation therapy. These strong treatments for cancer may damage the genetic material in cells, including follicle cells. Metabolic disorders. These disorders affect the body’s ability to create, store, and use the energy it needs. Toxins. Cigarette smoke, chemicals, and pesticides can speed up follicle depletion.

• #56 What causes POI? | NICHD – Eunice Kennedy Shriver National Institute of Child Health and Human Development

  http://www.nichd.nih.gov/health/topics/poi/conditioninfo/causes

  In most cases, the exact cause of POI is unknown. Research shows that POI is related to problems with the follicles—the small sacs in the ovaries in which eggs grow and mature. For a woman with POI, there are problems with the follicles: Follicle depletion. A woman with follicle depletion runs out of working follicles earlier than normal or expected. In the case of POI, the woman runs out of working follicles before natural menopause occurs around age 50. Presently there is no safe way for scientists today to make primordial follicles. Follicle dysfunction. A woman with follicle dysfunction has follicles remaining in her ovaries, but the follicles are not working properly. Scientists do not have a safe and effective way to make follicles start working normally again. Although the exact cause is unknown in a majority of cases, some causes of follicle depletion and dysfunction have been identified: Genetic and chromosomal disorders. Disorders such as Fragile X syndrome and Turner syndrome can cause follicle depletion. Low number of follicles. Some women are born with fewer primordial follicles, so they have a smaller pool of follicles to use throughout their lives. Autoimmune diseases. In the case of POI, the immune system may damage developing follicles in the ovaries. Several studies suggest that about one-fifth of women with POI have an autoimmune disease. Thyroiditis is the autoimmune disorder most commonly associated with POI. Addison’s disease is also associated with POI. Chemotherapy or radiation therapy. These strong treatments for cancer may damage the genetic material in cells, including follicle cells. Metabolic disorders. These disorders affect the body’s ability to create, store, and use the energy it needs. Toxins. Cigarette smoke, chemicals, and pesticides can speed up follicle depletion.

• #57 Primary Ovarian Insufficiency | Cedars-Sinai

  https://www.cedars-sinai.org/health-library/diseases-and-conditions/p/primary-ovarian-insufficiency.html

  When the ovaries stop working normally in women younger than age 40, it’s called primary ovarian insufficiency (POI). […] Researchers are working to fully understand the causes of POI. It can result from any cause that reduces the number of eggs in the ovaries. It can also happen if your ovaries dont make enough hormones, even with a normal number of eggs. […] Some of the known causes of POI include: autoimmune disease in which the woman makes antibodies that attack their own ovaries, eating disorders, genetic conditions, such as Turner syndrome, Fragile X syndrome, or galactosemia, infections that damage the ovaries, such as mumps, problems with hormones that regulate the ovaries, such as follicle-stimulating hormone (FSH), surgery on the ovaries, thyroid disease, toxins that affect the ovaries, such as from radiation or chemotherapy. […] In most cases, the cause of the condition isnt known.

• #58 Primary ovarian insufficiency (POI) in girls – Children’s Health Gynecology

  https://www.childrens.com/specialties-services/conditions/primary-ovarian-insufficiency

  This inherited (passed down through generations) disease causes intellectual and developmental disabilities in both boys and girls. […] This disorder affects how the body processes galactose (a simple sugar). […] A rare condition caused by the complete or partial absence of one of the two X chromosomes. […] This includes too high (hyperthyroidism) or too low thyroid levels (hypothyroidism) that can lead to an imbalance of hormones and POI.

• #59 Primary ovarian insufficiency (POI) in girls – Children’s Health Gynecology

  https://www.childrens.com/specialties-services/conditions/primary-ovarian-insufficiency

  Primary ovarian insufficiency (POI) is a rare condition where young girls and teenagers prematurely reach menopause. […] The exact cause of most cases of POI is unknown. However, it can also occur as a result of a known condition, such as those noted below. […] Nutrient deficiencies and lower levels of key hormones can trigger POI. […] Chemotherapy or radiation These treatments can sometimes damage the ovaries, leading to POI. […] Triggers like cigarette smoke, pesticides and viruses related to autoimmune diseases have been linked to, but not shown to directly cause, POI. […] Girls with family members who have the disease are more likely to have POI, but they are not guaranteed to get it. […] This rare disease is inherited (passed down through generations) and is the most common form of aplastic anemia.

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

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

  Causes of secondary ovarian insufficiency include the following: Eating disorders, exercise, psychiatric disorders, chronic debilitating disease, Drugs, Pituitary tumors, such as prolactinomas, or other tumors that secrete pituitary hormone, such as with Cushing syndrome or acromegaly, Pituitary necrosis (Sheehan syndrome), Hypothalamic tumor, Craniopharyngioma, Kallmann syndrome, Infiltrative hypothalamic process, such as sarcoidosis.

• #61 Primary Ovarian Insufficiency | POI | MedlinePlus

  https://medlineplus.gov/primaryovarianinsufficiency.html

  Primary ovarian insufficiency (POI), also known as premature ovarian failure, happens when a woman’s ovaries stop working normally before she is 40. […] In about 90% of cases, the exact cause of POI is unknown. […] Research shows that POI is related to problems with the follicles. […] One type of follicle problem is that you run out of working follicles earlier than normal. […] Another is that the follicles are not working properly. […] But sometimes the cause may be: Genetic disorders such as Fragile X syndrome and Turner syndrome, a low number of follicles, autoimmune diseases, including thyroiditis and Addison disease, chemotherapy or radiation therapy, metabolic disorders, toxins, such as cigarette smoke, chemicals, and pesticides. […] Certain factors can raise a woman’s risk of POI: Family history, genes, certain diseases, cancer treatments, age. […] In most cases of POI, the cause is unknown.

• #62 How Primary Ovarian Insufficiency Affects Health and Fertility

  https://www.verywellhealth.com/what-is-primary-ovarian-insufficiency-5220953

  Primary ovarian insufficiency (POI), also known as premature ovarian failure, occurs when your ovaries stop working normally before age 40. […] The exact cause of primary ovarian insufficiency is usually unknown. In fact, the cause can only be determined in about 10% of cases. […] Experts believe that the risk of primary ovarian insufficiency is linked to the health of the follicles, small sacs in the ovaries where eggs form and grow. In primary ovarian insufficiency, the follicles either do not function properly or run out earlier than expected. […] Known risk factors of primary ovarian insufficiency include: Family history: Having a mother or sister who has primary ovarian insufficiency raises your risk. Genetic conditions: Having the genetic diseases Turner’s syndrome and fragile X syndrome raises your risk of primary ovarian insufficiency. Autoimmune disorders: Both thyroiditis (inflammation of the thyroid gland) and Addison’s disease (an insufficient production of cortisol) have been found to raise risk. Cancer treatments: Chemotherapy and radiation therapy can damage the follicles and affect fertility. Environmental factors: Toxins found in cigarette smoke and pesticides may affect the number and health of the follicles. […] Primary ovarian insufficiency occurs when an individuals ovaries stop working normally before age 40. Its believed that primary ovarian insufficiency is caused by a change in the follicles.

• #63 How Common Is Primary Ovarian Insufficiency? Life Expectancy

  https://www.medicinenet.com/how_common_is_primary_ovarian_insufficiency/article.htm

  POI can be caused by genetic changes in the female sex chromosome (the X chromosome) or other genes that control sex hormones. […] There have been cases of POI appearing after diseases such as mumps, tuberculosis, and malaria; however, these are rare instances. […] An additional form of POI is surgical ovarian removal before the age of 40 years. […] In addition to surgery, cancer treatments such as chemotherapy or radiotherapy can harm the ovaries permanently or temporarily, leading to POI. […] Viruses, chemicals, pesticides, and cigarette smoke can hasten ovarian failure. […] Risk increases with age (35 to 40 years). POI can occur in younger women, even in teens, despite being uncommon before the age of 30 years.

• #64 Understanding Primary Ovarian Insufficiency: Causes & Treatment – The Kingsley Clinic

  https://thekingsleyclinic.com/resources/understanding-primary-ovarian-insufficiency-causes-treatment/

  Primary ovarian insufficiency (POI) is a condition in which the ovaries stop functioning properly before the age of 40. […] The underlying cause of POI is often unclear but may involve genetic factors, autoimmune disorders, or certain medical treatments. […] POI may be linked to genetic abnormalities, autoimmune disorders, or medical treatments such as chemotherapy or radiation. However, in many cases, the exact cause remains unknown. […] Genetics play a significant role in the development of POI. Women with a family history of early menopause or POI are at a higher risk of experiencing the condition. […] Certain genetic disorders, such as Turner syndrome or fragile X syndrome, are also linked to POI. […] Age is another critical factor; while POI can occur at any age, the likelihood increases as women approach their late 30s.

• #65 Primary Ovarian Insufficiency Causes & Diagnosis | Baptist Health

  https://cd.baptisthealth.com/care-services/conditions-treatments/primary-ovarian-insufficiency

  Issues with hormones that regulate the ovaries, such as follicle-stimulating hormone (FSH). […] In many cases, the cause of POI is unknown. […] Known risk factors for POI are age, family history, and ovarian surgery. Despite this, the precise cause of POI is only identified in about 25 percent of all diagnosed cases.

• #66 Primary Ovarian Insufficiency (POI): Symptoms, Causes, & Treatment | HealthFocus SA | University Health

  https://www.universityhealth.com/blog/primary-ovarian-insufficiency

  Approximately 1-2% of women aged 40 or younger experience POI, which is when the ovaries stop working normally before age 40. […] In the vast majority of casesup to 90%, in factthe cause is unknown. […] POI is associated with a low number of follicles, which are the egg sacs in the ovaries. Various problems can affect the follicles causing early loss or destruction. There may be no known cause or there may be a known issue such as: Autoimmune diseases, Certain genetic disorders, Chemotherapy or radiation therapy, Exposure to toxins such as chemicals or pesticides, Low number of follicles, Metabolic disorders. […] Certain factors can increase a womans risk of developing POI, including genetic changes, a family history of POI, or cancer treatments.

• #67 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

  Premature ovarian insufficiency (POI), defined as amenorrhoea due to the loss of ovarian function before 40 years of age, can occur spontaneously or be secondary to medical therapies. […] The aetiology of POI is diverse, and it can occur spontaneously or be secondary to medical therapies. It is estimated that spontaneous POI affects 1% of the female population. […] Spontaneous POI can be associated with chromosomal and genetic defects, environmental factors, autoimmune diseases (most commonly adrenal and thyroid disease) and various infections, but is idiopathic in the majority of cases. […] The most clinically important autoimmune conditions associated with POI are autoimmune adrenal disease (Addisons disease) and thyroid autoimmunity. […] A family history of POI and cigarette smoking are well recognised risk factors for the development of POI, as is bilateral ovarian surgery for endometriomas, with a reported 2.3% of women developing POI. […] Importantly, the combined oral contraceptive pill (COCP), fertility drugs and prior hormone replacement therapy (HRT) do not cause POI, but cessation of these therapies may unmask undiagnosed POI.

• #68 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 causes of POI are heterogeneous and are unknown in 90% of cases. It can be associated with genetic causes, autoimmune disease, enzyme deficiency, infection, environmental factors, radiation, or surgery in 10%. […] The cause of POI is idiopathic in 39-67% of cases. Some cases of POI are attributed to autoimmune disorders such as autoimmune oophoritis, Hashimoto thyroiditis, Addison disease, type I diabetes mellitus, pernicious anemia, genetic disorders such as Turner syndrome and Fragile X syndrome, metabolic defects, and enzyme defects.

• #69 Factors leading to primary ovarian insufficiency: a literature overview – GREM – Gynecological and Reproductive Endocrinology & Metabolism

  https://gremjournal.com/journal/02-2021/factors-leading-to-primary-ovarian-insufficiency-a-literature-overview/

  Premature ovarian insufficiency (POI) is a disease characterized by oligomenorrhea, hypoestrogenism and elevated gonadotropin levels that occurs in women younger than 40 years of age. There are several possible causes of POI, including chromosomal and genetic diseases, and autoimmune, infectious or iatrogenic events. POI can be classified as primary (spontaneous) or secondary (iatrogenic). […] Unfortunately, in about 75% of POI cases the cause remains unknown. […] From a pathogenetic point of view, primary ovarian insufficiency occurs through two major mechanisms: follicle dysfunction and follicle depletion. […] There are several causes of POI, including chromosomal and genetic diseases, and autoimmune, infectious or iatrogenic events. […] In a retrospective case series of 276 women with Turners syndrome, 1.4% experienced spontaneous pregnancy, 1.4% achieved pregnancy using assisted reproduction technology, and 0.4% both spontaneous and assisted pregnancy.

• #70 Factors leading to primary ovarian insufficiency: a literature overview – GREM – Gynecological and Reproductive Endocrinology & Metabolism

  https://gremjournal.com/journal/02-2021/factors-leading-to-primary-ovarian-insufficiency-a-literature-overview/

  Some authors noted that ovarian insufficiency is correlated with adrenal insufficiency. […] Cigarette smoke contains polycyclic aromatic hydrocarbons (PAHs), which bind to the aryl hydrocarbon receptor present on the surface of granulosa cells. […] There is still little evidence that a viral infection may cause POI; indeed, a real cause-and-effect relationship has not yet been established. […] At present, there is considerable interest in the possible influence on ovarian function of three different factors: endocrine-disrupting chemicals (EDCs), oxidative stress and epigenetics. […] Some uncommon cases of POI may be related to genetic defects of the enzymes involved in the biosynthesis of androstenedione, estradiol and cortisol. […] Some cases of POI have been associated with defects in FSH receptor (FSHR) production. […] In this narrative review, we have provided an overview of possible causes associated with primary POI. There are many possible causes of POI, including chromosomal and genetic diseases, and autoimmune, infectious or iatrogenic events. In about 75% of POI cases, however, the cause remains unknown.

• #71 Selected Genetic Factors Associated with Primary Ovarian Insufficiency

  https://www.mdpi.com/1422-0067/24/5/4423

  Various types of etiologies, such as genetic, autoimmune, iatrogenic, infectious, environmental, chemotherapeutic, and radiotherapeutic causes, have been determined. […] The genetic factors that can be found in POI cases include chromosomal abnormalities, single gene mutations, defects in mitochondrial functions, and non-coding RNAs.

• #72 Primary ovarian insufficiency – Wikipedia

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

  Certain environmental toxins such as phthalates, bisphenols, and dioxins are also associated with POI. […] 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.

• #73 Primary ovarian insufficiency – Wikipedia

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

  Certain environmental toxins such as phthalates, bisphenols, and dioxins are also associated with POI. […] 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.

• #74 Primary Ovarian Insufficiency | Concise Medical Knowledge

  https://www.lecturio.com/concepts/primary-ovarian-insufficiency/

  Primary ovarian insufficiency can be caused by chromosomal and genetic defects, an autoimmune process, or ovarian toxins; however, in the vast majority of cases, a clear cause is never identified. […] Turner syndrome is a genetic condition affecting women, in which 1 X chromosome is partly or completely missing. […] FMR1 gene premutations: Gene that causes fragile X syndrome. […] Autoimmune oophoritis: Lymphocytic infiltration of theca cells inflammation follicular dysfunction. […] Polyglandular autoimmune failure (types I and II): syndromes associated with autoantibodies to multiple endocrine and other organs. […] Ovarian toxins: Chemotherapy, Radiation, Environmental toxins.

• #75 Hormone Therapy in Primary Ovarian Insufficiency | ACOG

  https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/05/hormone-therapy-in-primary-ovarian-insufficiency

  Young women with cancer or other serious illnesses that require chemotherapy or pelvic radiation are at risk of primary ovarian insufficiency because these agents may cause profound and rapid follicular atresia. […] Regardless of the underlying cause of primary ovarian insufficiency, the consequences of ovarian dysfunction and hypoestrogenism can be dire for affected individuals. […] The sequelae of primary ovarian insufficiency include vasomotor symptoms, urogenital atrophy, osteoporosis and fracture, cardiovascular disease, and increased all-cause mortality. […] In women with primary ovarian insufficiency, systemic HT is an effective approach to treat the symptoms of hypoestrogenism and mitigate long-term health risks if there are no contraindications to treatment. […] Hormone therapy is indicated to reduce the risk of osteoporosis, cardiovascular disease, and urogenital atrophy and to improve the quality of life of women with primary ovarian insufficiency.

• #76 Hormone Therapy in Primary Ovarian Insufficiency | ACOG

  https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/05/hormone-therapy-in-primary-ovarian-insufficiency

  Young women with cancer or other serious illnesses that require chemotherapy or pelvic radiation are at risk of primary ovarian insufficiency because these agents may cause profound and rapid follicular atresia. […] Regardless of the underlying cause of primary ovarian insufficiency, the consequences of ovarian dysfunction and hypoestrogenism can be dire for affected individuals. […] The sequelae of primary ovarian insufficiency include vasomotor symptoms, urogenital atrophy, osteoporosis and fracture, cardiovascular disease, and increased all-cause mortality. […] In women with primary ovarian insufficiency, systemic HT is an effective approach to treat the symptoms of hypoestrogenism and mitigate long-term health risks if there are no contraindications to treatment. […] Hormone therapy is indicated to reduce the risk of osteoporosis, cardiovascular disease, and urogenital atrophy and to improve the quality of life of women with primary ovarian insufficiency.

• #77 Hormone Therapy in Primary Ovarian Insufficiency | ACOG

  https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/05/hormone-therapy-in-primary-ovarian-insufficiency

  A number of large, well-designed prospective studies have provided strong evidence that early age at menopause, especially when occurring at 45 years or younger, is associated with a risk of fracture that is 1.53-fold higher than the risk for women who experience menopause after age 50 years. […] Women who develop primary ovarian insufficiency are also at increased risk of cardiovascular events and cardiovascular mortality compared with women who do not experience early menopause. […] The association between primary ovarian insufficiency and cardiovascular disease risk may be explained in part by metabolic and endothelial changes that occur with estrogen deprivation. […] Epidemiologic evidence supporting the use of HT to prevent cardiovascular events in women with primary ovarian insufficiency is currently lacking.

• #78 Hormone Therapy in Primary Ovarian Insufficiency | ACOG

  https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/05/hormone-therapy-in-primary-ovarian-insufficiency

  A number of large, well-designed prospective studies have provided strong evidence that early age at menopause, especially when occurring at 45 years or younger, is associated with a risk of fracture that is 1.53-fold higher than the risk for women who experience menopause after age 50 years. […] Women who develop primary ovarian insufficiency are also at increased risk of cardiovascular events and cardiovascular mortality compared with women who do not experience early menopause. […] The association between primary ovarian insufficiency and cardiovascular disease risk may be explained in part by metabolic and endothelial changes that occur with estrogen deprivation. […] Epidemiologic evidence supporting the use of HT to prevent cardiovascular events in women with primary ovarian insufficiency is currently lacking.

• #79 Primary Ovarian Insufficiency | Endocrine Society

  https://www.endocrine.org/patient-engagement/endocrine-library/primary-ovarian-insuffiency

  Primary ovarian insufficiency (POI), also called premature ovarian failure, occurs when the ovaries have a decrease in estrogen production and ovulation before a woman turns 40. The condition often leads to infertility. […] In most cases, the cause of POI is unknown. Women with certain genetic disorders, such as Turner syndrome and fragile X premutation carriers, are more likely to develop POI. Also, exposure to chemotherapy and radiation therapy can lead to POI. Last, autoimmune disease when your immune system attacks your ovarian tissue may be responsible for POI. The risk of developing POI increases if you have a family history of the disorder. […] If you have POI, you may also be more likely to develop other hormone-related disorders. Women with POI should be checked periodically for deficiencies in thyroid and adrenal gland hormones.

• #80 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

  Primary ovarian insufficiency may be associated with multiple endocrinopathies, including hypoparathyroidism and hypoadrenalism. […] Follicle depletion or dysfunction in adolescents may be caused by many different factors. It is often caused by chromosomal abnormalities or damage from chemotherapy or radiation therapy. […] Approximately 4% of women who have primary ovarian insufficiency will have adrenal or ovarian antibodies, which suggests an autoimmune mechanism for disease. […] A common cause of primary ovarian insufficiency in adolescents is gonadal dysgenesis, with or without Turner syndrome. […] The immediate loss of ovarian function after chemotherapy or radiation therapy is termed acute ovarian failure, which may be transient. […] Among females with primary ovarian insufficiency and a normal karyotype, 6% have a premutation in the FMR1 gene. […] In many cases, the etiology remains unknown.

• #81 Premature ovarian failure | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-1-9

  Premature ovarian failure (POF) is a primary ovarian defect characterized by absent menarche (primary amenorrhea) or premature depletion of ovarian follicles before the age of 40 years (secondary amenorrhea). […] POF has a strong genetic component. X chromosome abnormalities (e.g. Turner syndrome) represent the major cause of primary amenorrhea associated with ovarian dysgenesis. […] The causes of POF are extremely heterogeneous. Acquired forms such as those occurring after treatments for neoplastic diseases or autoimmune diseases account for many cases. […] POF has a strong genetic component with X chromosome abnormalities playing a primary role mainly in the cases with ovarian dysgenesis. […] Despite the description of several candidate genes, the cause of POF still remains undetermined in the majority of the cases (idiopathic).

• #82 Primary Ovarian Insufficiency | Kaiser Permanente

  https://healthy.kaiserpermanente.org/health-wellness/health-encyclopedia/he.primary-ovarian-insufficiency.uf6200spec

  Primary ovarian insufficiency (sometimes called premature ovarian failure) occurs when your ovaries-which store and release eggs-stop working before age 40. […] Although the exact cause of primary ovarian insufficiency may be unknown, a genetic factor or a problem with the body’s immune system may play a role. […] Primary ovarian insufficiency may develop after a hysterectomy or other pelvic surgery or from radiation or chemotherapy treatment for cancer. […] Very low estrogen with a high FSH is a sign of primary ovarian insufficiency. […] At this time, there is no way to prevent primary ovarian insufficiency.

• #83

• #84 Hormone Therapy in Primary Ovarian Insufficiency | ACOG

  https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/05/hormone-therapy-in-primary-ovarian-insufficiency

  The results from the Womens Health Initiative trials related to menopause therapy are not applicable to young women with primary ovarian insufficiency whose exposure to physiologic estrogen has been withdrawn prematurely. […] When HT is withheld from women with primary ovarian insufficiency because of extrapolation of good epidemiologic evidence from the wrong population, those women may experience many negative health consequences. […] Primary ovarian insufficiency is a pathologic condition that should not be considered a hastening of natural menopause. […] Although women with primary ovarian insufficiency share common health risks with naturally menopausal women, the approach to health maintenance in these women is distinct. […] In contrast to the treatment of postmenopausal osteopenia or osteoporosis, which focuses on bisphosphonates as first-line therapy, low bone mass in women with primary ovarian insufficiency is managed most appropriately with HT.

• #85 Selected Genetic Factors Associated with Primary Ovarian Insufficiency

  https://www.mdpi.com/1422-0067/24/5/4423

  Various types of etiologies, such as genetic, autoimmune, iatrogenic, infectious, environmental, chemotherapeutic, and radiotherapeutic causes, have been determined. […] The genetic factors that can be found in POI cases include chromosomal abnormalities, single gene mutations, defects in mitochondrial functions, and non-coding RNAs.

• #86 Selected Genetic Factors Associated with Primary Ovarian Insufficiency

  https://www.mdpi.com/1422-0067/24/5/4423

  Chromosomal disorders cause POI via the depletion of primordial oocytes during early female development. […] However, the mechanism involved in the loss of oocytes is not clearly understood. […] Moreover, defects in both the X chromosome and autosome can contribute to POI. […] Turner syndrome is a critical sex chromosomal disease in females with a 1 in 2500 incidence. It is caused by the complete or partial deletion of one sex chromosome. […] TS has many hallmarks, including ovarian failure, and it is the most common genetic cause of POI, accounting for 4–5% of all POI cases. […] A recent review suggested that TS-related POI was associated with the function and length of telomeres and epigenetic modifications. […] The increase in the POI cases, among which there is a vast number of POI women with unclear genetic diagnoses, justifies investigating the etiology of POI, which may be critical in the early diagnosis, treatment, and prevention.

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