Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (907 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
Cessation of ovarian function after menarche but before the age of 40, without or with ovarian follicle depletion. It is characterized by the presence of oligomenorrhea or amenorrhea, elevated gonadotropins, and low estradiol levels. It is a state of female hypergonadotropic hypogonadism. Etiologies include genetic defects, autoimmune processes, chemotherapy, radiation, and infections. The most commonly known genetic cause is the expansion of a CGG repeat to 55 to 199 copies in the 5' untranslated region in the X-linked FMR1 gene.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Ovarian Insufficiency, Primary; Premature Ovarian Failure; Ovarian Failure, Premature; Gonadotropin-Resistant Ovary Syndrome; Gonadotropin Resistant Ovary Syndrome; Resistant Ovary Syndrome; Fragile X-Associated Primary Ovarian Insufficiency; Fragile X Associated Primary Ovarian Insufficiency.
Where it fits in the MeSH classification
- Broader topics
- Ovarian Diseases
- See also
- Menopause, Premature
Related concepts
- Menarche
- Ovarian Follicle
- Oligomenorrhea
- Amenorrhea
- Gonadotropins
- Estradiol
- Hypogonadism
Research landscape
PubMed indexes 4,461 records tagged with the MeSH heading “Primary Ovarian Insufficiency” (counts retrieved 2026-11-04). 1,816 of them (40.7%) were published from 2020 onward, and the busiest period so far is 2020 onward with 1,816 records.
Reviews account for 1,043 records (23.4%) and meta-analyses for 83. Randomized controlled trials number 85 (1.9%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 271 |
| 2000-2009 | 829 |
| 2010-2019 | 1,545 |
| 2020 onward | 1,816 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 1,043 | 23.4% |
| Meta-analyses | 83 | 1.9% |
| Randomized controlled trials | 85 | 1.9% |
Method: PubMed query "Primary Ovarian Insufficiency"[MeSH Terms] with publication-type and date filters, retrieved 2026-11-04.
Reading the evidence in metabolism and endocrine disease
Studies of diabetes, obesity and hormone disorders often follow blood tests such as glucose, HbA1c or hormone levels, which are stand-ins for outcomes that matter more, such as complications. Lifestyle and diet research is largely observational, and weight and diabetes trials can differ in how long people were followed. Nothing on this page is advice about medicines, insulin or diet; talk to a qualified clinician about your own situation. Check whether the outcome was a lab value or a clinical event, and the type and duration of the condition studied.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
Primary ovarian insufficiency: update on clinical and genetic findings [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Primary ovarian insufficiency (POI) is a disorder of insufficient ovarian follicle function before the age of 40 years with an estimated prevalence of 3.
- Closing excerpt
- We also provide current information on the management of the premature hypoestrogenic state as well as on fertility preservation in subjects at risk of POI.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (241 words)
Primary ovarian insufficiency (POI) is a disorder of insufficient ovarian follicle function before the age of 40 years with an estimated prevalence of 3.7% worldwide. Its relevance is emerging due to the increasing number of women desiring conception late or beyond the third decade of their lives. POI clinical presentation is extremely heterogeneous with a possible exordium as primary amenorrhea due to ovarian dysgenesis or with a secondary amenorrhea due to different congenital or acquired abnormalities. POI significantly impacts non only on the fertility prospect of the affected women but also on their general, psychological, sexual quality of life, and, furthermore, on their long-term bone, cardiovascular, and cognitive health. In several cases the underlying cause of POI remains unknown and, thus, these forms are still classified as idiopathic. However, we now know the age of menopause is an inheritable trait and POI has a strong genetic background. This is confirmed by the existence of several candidate genes, experimental and natural models. The most common genetic contributors to POI are the X chromosome-linked defects. Moreover, the variable expressivity of POI defect suggests it can be considered as a multifactorial or oligogenic defect. Here, we present an updated review on clinical findings and on the principal X-linked and autosomal genes involved in syndromic and non-syndromic forms of POI. We also provide current information on the management of the premature hypoestrogenic state as well as on fertility preservation in subjects at risk of POI.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 39391877 · DOI · PMC11466302
M6A demethylase FTO-stabilized exosomal circBRCA1 alleviates oxidative stress-induced granulosa cell damage via the miR-642a-5p/FOXO1 axis [2]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundPremature ovarian insufficiency (POI) is an important cause of female infertility and seriously impacts the physical and psychological health of patients.
- Closing excerpt
- Exosomal circBRCA1 supplementation may be a general prospect for the prevention and treatment of POI.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (298 words)
BackgroundPremature ovarian insufficiency (POI) is an important cause of female infertility and seriously impacts the physical and psychological health of patients. Human umbilical cord mesenchymal stem cell-derived exosomes (HucMSCs-Exs, H-Exs) have exhibited protective effects on ovarian function with unclear mechanisms.MethodsA comprehensive analysis of the Gene Expression Omnibus (GEO) database were used to identify POI-associated circRNAs and miRNAs. The relationship between HucMSC-derived exosomal circBRCA1/miR-642a-5p/FOXO1 axis and POI was examined by RT-qPCR, Western blotting, reactive oxygen species (ROS) staining, senescence-associated β-gal (SA-β-gal) staining, JC-1 staining, TEM, oxygen consumption rate (OCR) measurements and ATP assay in vivo and in vitro. RT-qPCR detected the expression of circBRCA1 in GCs and serum of patients with normal ovarian reserve function (n = 50) and patients with POI (n = 50); then, the correlation of circBRCA1 with ovarian reserve function indexes was analyzed.ResultsHerein, we found that circBRCA1 was decreased in the serum and ovarian granulosa cells (GCs) of patients with POI and was associated with decreased ovarian reserve. H-Exs improved the disorder of the estrous cycles and reproductive hormone levels, reduced the number of atretic follicles, and alleviated the apoptosis and senescence of GCs in rats with POI. Moreover, H-Exs mitigated mitochondrial damage and reversed the reduced circBRCA1 expression induced by oxidative stress in GCs. Mechanistically, FTO served as an eraser to increase the stability and expression of circBRCA1 by mediating the m6A demethylation of circBRCA1, and exosomal circBRCA1 sponged miR-642a-5p to block its interaction with FOXO1. CircBRCA1 insufficiency aggravated mitochondrial dysfunction, mimicking FTO or FOXO1 depletion effects, which was counteracted by miR-642a-5p inhibition.ConclusionH-Exs secreted circBRCA1 regulated by m6A modification, directly sponged miR-642a-5p to upregulate FOXO1, resisted oxidative stress injuries in GCs and protected ovarian function in rats with POI. Exosomal circBRCA1 supplementation may be a general prospect for the prevention and treatment of POI.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 38918838 · DOI · PMC11197183
Human mesenchymal stem cells derived exosomes improve ovarian function in chemotherapy-induced premature ovarian insufficiency mice by inhibiting ferroptosis through Nrf2/GPX4 pathway [3]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundChemotherapy exposure has become a main cause of premature ovarian insufficiency (POI).
- Closing excerpt
- ConclusionhUMSC-Exos inhibit ferroptosis and protect against CTX-induced ovarian damage and granulosa cell apoptosis through the Nrf2/GPX4 signaling pathway, revealing a novel mechanism of hUMSC-Exos in POI therapy.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (211 words)
BackgroundChemotherapy exposure has become a main cause of premature ovarian insufficiency (POI). This study aimed to evaluate the role and molecular mechanism of human umbilical cord mesenchymal stem cell-derived exosomes (hUMSC-Exos) in ovarian function protection after chemotherapy.MethodshUMSC-Exos were applied to cyclophosphamide-induced premature ovarian insufficiency mice and human ovarian granulosa tumor cells (KGN) to determine their effects on follicular development and granulosa cell apoptosis. Evaluation was done for iron ion and reactive oxygen species (ROS) production, lipid peroxidation levels, and changes in iron death-related molecules (nuclear factor (erythroid-derived 2)-like 2 (Nrf2), Glutathione Peroxidase enzyme 4 (GPX4), and Solute carrier family 7 member 11 cystine glutamate transporter (SLC7A11; xCT)). Furthermore, rescue experiments using an Nrf2 inhibitor were performed to assess the therapeutic effects of hUMSC-Exos on granulosa cells.ResultshUMSC-Exos promoted ovarian hormone levels and primary follicle development in POI mice and reduced granulosa cell apoptosis. After hUMSC-Exos treatment, the ROS production, free iron ions and lipid peroxidation levels of granulosa cells decreased, and the iron death marker proteins Nrf2, xCT and GPX4 also decreased. Furthermore, the Nrf2 inhibitor ML385 significantly attenuated the effects of hUMSC-Exos on granulosa cells.ConclusionhUMSC-Exos inhibit ferroptosis and protect against CTX-induced ovarian damage and granulosa cell apoptosis through the Nrf2/GPX4 signaling pathway, revealing a novel mechanism of hUMSC-Exos in POI therapy.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 38622725 · DOI · PMC11017636
SIRT5-RAC2 Axis Drives Monocyte-to-Macrophage Differentiation to Promote Inflammatory Injury in Premature Ovarian Insufficiency [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Premature ovarian insufficiency (POI) is a major cause of infertility and endocrine dysfunction, in which chronic inflammation plays a critical role.
- Closing excerpt
- Our findings identify the SIRT5-RAC2 axis as a key regulator of ovarian immune homeostasis and establish SIRT5 as a proof-of-concept therapeutic target for POI.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (157 words)
Premature ovarian insufficiency (POI) is a major cause of infertility and endocrine dysfunction, in which chronic inflammation plays a critical role. The homeostasis of tissue-resident macrophages and monocyte-differentiated macrophages from peripheral blood serves as a key mechanism of inflammation across organs, yet their phenotypic plasticity in ovarian pathologies, including POI, remains poorly understood. Here, we identify that SIRT5 deficiency decreases macrophage count by attenuating monocyte-macrophage differentiation. SIRT5 deficiency markedly attenuated follicular depletion and granulosa cell apoptosis, coinciding with reduced M1 macrophage infiltration and cytokine expression in the POI model. Mechanistically, we uncovered RAC2 as a novel succinylation substrate of SIRT5. SIRT5 deficiency elevated RAC2 succinylation, promoting its proteasomal degradation and thereby impairing CSF1R-driven macrophage differentiation and M1 polarization. Pharmacological inhibition of SIRT5 recapitulated these protective effects, preserving follicular integrity and suppressing macrophage-mediated inflammation. Our findings identify the SIRT5-RAC2 axis as a key regulator of ovarian immune homeostasis and establish SIRT5 as a proof-of-concept therapeutic target for POI.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41498691 · DOI · PMC12970288
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Ovarian damage from chemotherapy and current approaches to its protection [5]
- Research article Hormone replacement therapy in young women with primary ovarian insufficiency and early menopause [6]
- Research article The global prevalence of primary ovarian insufficiency and early menopause: a meta-analysis [7]
- Research article Gonadotropin-Releasing Hormone Agonists During Chemotherapy for Preservation of Ovarian Function and Fertility in Premenopausal Patients With Early Breast Cancer: A Systematic Review and Meta-Analysis of Individual Patient-Level Data [8]
- Research article Current Understanding of the Etiology, Symptomatology, and Treatment Options in Premature Ovarian Insufficiency (POI) [9]
- Research article Premature ovarian insufficiency: an International Menopause Society White Paper [10]
References
- Federici S, Rossetti R, Moleri S, Munari EV, Frixou M, Bonomi M, et al.. Primary ovarian insufficiency: update on clinical and genetic findings. . 2024. PMID 39391877 · DOI · PMC11466302
- Zhu X, Li W, Lu M, Shang J, Zhou J, Lin L, et al.. M6A demethylase FTO-stabilized exosomal circBRCA1 alleviates oxidative stress-induced granulosa cell damage via the miR-642a-5p/FOXO1 axis. . 2024. PMID 38918838 · DOI · PMC11197183
- Zhou Y, Huang J, Zeng L, Yang Q, Bai F, Mai Q, et al.. Human mesenchymal stem cells derived exosomes improve ovarian function in chemotherapy-induced premature ovarian insufficiency mice by inhibiting ferroptosis through Nrf2/GPX4 pathway. . 2024. PMID 38622725 · DOI · PMC11017636
- TanTai W, Li Y, Liu S, Wu M, Liu Z, Jiang J, et al.. SIRT5-RAC2 Axis Drives Monocyte-to-Macrophage Differentiation to Promote Inflammatory Injury in Premature Ovarian Insufficiency. . 2026. PMID 41498691 · DOI · PMC12970288
- Spears N, Lopes F, Stefansdottir A, Rossi V, De Felici M, Anderson RA, et al.. Ovarian damage from chemotherapy and current approaches to its protection. Hum Reprod Update. 2019. PMID 31600388 · DOI · PMC6847836
- Sullivan SD, Sarrel PM, Nelson LM. Hormone replacement therapy in young women with primary ovarian insufficiency and early menopause. Fertil Steril. 2016. PMID 27912889 · DOI · PMC5137796
- Golezar S, Ramezani Tehrani F, Khazaei S, Ebadi A, Keshavarz Z. The global prevalence of primary ovarian insufficiency and early menopause: a meta-analysis. Climacteric. 2019. PMID 30829083 · DOI
- Lambertini M, Moore HCF, Leonard RCF, Loibl S, Munster P, Bruzzone M, et al.. Gonadotropin-Releasing Hormone Agonists During Chemotherapy for Preservation of Ovarian Function and Fertility in Premenopausal Patients With Early Breast Cancer: A Systematic Review and Meta-Analysis of Individual Patient-Level Data. J Clin Oncol. 2018. PMID 29718793 · DOI · PMC6804855
- Ishizuka B. Current Understanding of the Etiology, Symptomatology, and Treatment Options in Premature Ovarian Insufficiency (POI). Front Endocrinol (Lausanne). 2021. PMID 33716979 · DOI · PMC7949002
- Panay N, Anderson RA, Nappi RE, Nappi RE, Vincent AJ, Vujovic S, et al.. Premature ovarian insufficiency: an International Menopause Society White Paper. Climacteric. 2020. PMID 32896176 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-11-04; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-11-04.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.