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Last update 23 Jan 2025

Primary Ovarian Insufficiency

Last update 23 Jan 2025

Basic Info

Synonyms

FMR1 Related Primary Ovarian Insufficiency, FMR1-Related Primary Ovarian Insufficiency, FRAGILE X PREMATURE OVARIAN FAILURE

+ [72]

Introduction

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.

Drugs associated with Primary Ovarian Insufficiency

Estrone sodium sulfate/Sodium equilin sulfate

Target

ER x PR

Mechanism

ERs agonists [+1]

Active Org.

Pfizer Inc.

Originator Org.

Wyeth LLC

Active Indication

Menorrhagia [+5]

Inactive Indication-

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date15 Oct 2009

Methylnaltrexone Bromide

Target

μ opioid receptor

Mechanism

μ opioid receptor antagonists

Active Org.

Salix Pharmaceuticals, Inc. [+2]

Originator Org.

Progenics Pharmaceuticals, Inc.

Active Indication

Opioid-Induced Constipation

Inactive Indication

Advanced Pancreatic Adenocarcinoma [+12]

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date24 Apr 2008

Bevacizumab

Target

VEGF-A

Mechanism

VEGF-A inhibitors [+1]

Active Org.

National Cancer Institute [+23]

Originator Org.

Genentech, Inc.

Active Indication

Unresectable Hepatocellular Carcinoma [+190]

Inactive Indication

Acidemia, Isovaleric [+279]

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date26 Feb 2004

278

Clinical Trials associated with Primary Ovarian Insufficiency

ITMCTR2024000820

/ SuspendedNot Applicable

The Mechanism of Yangyin Shugan Capsule in Treating Premature Ovarian Insufficiency Based on Multi-Omics Analysis

Start Date01 Dec 2025

Sponsor / Collaborator

Guangdong Hospital of Traditional Chinese Medicine

NCT06673004

/ Not yet recruitingNot ApplicableIIT

Ovarian Tissue Allo-Transplantation in the Setting of Primary Ovarian Insufficiency Between Non-Genetically Identical Siblings With Use of Immunosuppression

Premature ovarian failure, also known as primary ovarian insufficiency (POI), or premature menopause, affects 1-2% of women under 40. The diagnosis is typically made based on high levels of follicle stimulating hormone (FSH) and absent or irregular menstrual periods. It leads to infertility and menopause-like effects (hot flashes and thin bones) due to low estrogen levels. POI can result from various factors such as genetic conditions, autoimmune diseases, or previous medical treatments like chemotherapy.
Treatment of POI usually involves hormone replacement therapy and, if pregnancy is desired, assisted reproductive technologies such as in vitro fertilization (IVF) using an egg donor. However, IVF may not be an option for everyone due to personal, religious, ethical or financial reasons. Recent advances in medicine have identified ovarian tissue transplantation (OTT) as a potential solution. OTT involves transplanting either fresh or frozen ovarian tissue into the pelvic area, where it can begin functioning again. Studies in animals and humans have shown success in restoring hormonal function and even achieving pregnancies in some cases. Initial human trials of ovarian tissue transplants from another individual began with identical twins and have since expanded to include non-identical siblings with compatible tissue matches using immunosuppression. Success rates of OTT have been promising, with multiple live births reported between identical twins. Long-term studies indicate that transplanted tissue can remain functional for up to eight years. Ovarian tissue transplantation offers a promising avenue for women with POI to help restore fertility and hormonal function. Continued research and refinement of tissue techniques are essential to improve outcomes and expand access to this innovative treatment option.
This study will enroll 10 participants who will undergo ovarian tissue transplantation donated by a non-identical sister using an immunosuppression protocol at University Hospitals.

Start Date30 May 2025

Sponsor / Collaborator

University Hospitals Cleveland Medical Center

NCT06754332

/ Not yet recruitingPhase 1IIT

The Research on the Role of Human Chorionic Gonadotropin (HCG) Activation in Vivo on the Dormant Follicles in Patients With Premature Ovarian Insufficiency (POI).

This project aims to activate dormant follicles in patients with premature ovarian insufficiency by injecting human chorionic gonadotropin (hCG) to explore the feasibility of a treatment plan that stimulates the growth of dormant follicles, not visible to the naked eye, to antral follicles visible under ultrasound, without visible follicle growth. The project also seeks to enable patients to conceive offspring carrying their own genetic material through in vitro fertilization (IVF) technology.

Start Date01 Jan 2025

Sponsor / Collaborator-

100 Clinical Results associated with Primary Ovarian Insufficiency

100 Translational Medicine associated with Primary Ovarian Insufficiency

0 Patents (Medical) associated with Primary Ovarian Insufficiency

6,364

Literatures (Medical) associated with Primary Ovarian Insufficiency

01 Dec 2025·Molecular Biology Reports

Human umbilical cord mesenchymal stem cells improve the ovarian function through oxidative stress-mediated PERK/eIF-2α/ATF4/CHOP signaling in premature ovarian insufficiency mice

Article

Author: Zhang, Hong-Mei ; Peng, Lu ; Liu, Yao ; Yang, Yuan ; Zheng, Chun-Bing ; Tang, Shi-Huan ; Zhang, Xian-Ping ; Wang, Han-Yue ; Wu, Pei-Ling

BACKGROUNDPremature ovarian insufficiency (POI) is a refractory disease that severely affects female fertility. The PERK/eIF-2α/ATF4/CHOP pathway is one of the classical pathways involved in the unfolded protein response to endoplasmic reticulum stress by regulating protein synthesis and promoting apoptosis. This study aimed to investigate the functional role and mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs) in the POI animal model through the PERK/eIF-2α/ATF4/CHOP pathway.METHODS AND RESULTSForty-five sexually mature female C57 mice were divided into a blank control group, POI model group, and hUCMSCs intervention group. To establish the POI model, mice received intraperitoneal injections of cyclophosphamide (CTX) (70 mg/kg) daily for 14 consecutive days, while the control group received saline only. In the hUCMSC intervention group, mice were given hUCMSCs on days 14 and 28, based on CTX modeling in the POI model group. The hUCMSCs were isolated, labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR) fluorescent dye, and tail vein-injected, and the distribution of the DiR signal was monitored in the mice using a fluorescence imaging detection method. The ovarian tissues were hematoxylin and eosin stained to observe the ovarian structure, and the number of primordial follicles were counted. An enzyme-linked immunosorbent assay was used to detect the serum levels of estradiol, anti-mullerian hormone, and follicle-stimulating hormone. Terminal deoxynucleotidyl transferase dUTP nick end labeling was used to detect the apoptosis of granulosa cells (GCs). The reactive oxygen species (ROS) content of ovarian tissue was detected by flow cytometry assay. The RNA expression of PERK, eIF-2α, ATF4, and CHOP was determined by quantitative real-time polymerase chain reaction, and protein levels of the targets were determined by western blot and immunohistochemistry. We identified hUCMSCs using surface antigenic markers (CD90, CD44, CD105, and CD73), and osteoblasts and chondroplast differentiation assays. Our studies demonstrated that hUCMSC intervention significantly restored ovarian function by improving the irregular estrous cycle, increasing the number of follicles, decreasing ROS, and inhibiting GC apoptosis in POI mice. Moreover, hUCMSCs suppressed CTX-induced PERK/eIF-2a/ATF4/CHOP pathway activation.CONCLUSIONSHUCMSCs can migrate to the damaged ovaries of POI mice, and improve the ovarian function of POI mice by inhibiting oxidative stress, down-regulating the expression of the PERK/eIF-2α/ATF4/CHOP pathway, and reducing the apoptosis of GCs.

01 Apr 2025·Mechanisms of Ageing and Development

Insights into age-related osteoporosis from senescence-based preclinical models and human accelerated aging paradigms

Article

Author: Pignolo, Robert J ; Chandra, Abhishek

Preclinical models of age-related osteoporosis have been developed based on the accumulation and clearance of senescent cells. The former include animal models based on telomere dysfunction and focal radiation; the latter based on genetic and pharmacological targeting (i.e., removal) of senescent cells. The weight of evidence using these models suggests that cellular senescence plays a key role in the pathophysiology of aging-onset bone loss with the senescence-associated secretory phenotype (SASP) mediating local and systemic deleterious effects on the skeleton. Mitochondrial dysfunction has also been implicated in senescence and age-related comorbidities, including osteoporosis, and knock-in mutations in the mtDNA polymerase gamma (Polg) gene in mice may recapitulate similar respiratory chain complex defects in aged individual with osteoporosis. This and other contributions to senile osteoporosis may also be identified by the careful evaluation of non-genetic paradigms of human accelerated aging. Premature aging syndromes, especially those with a prominent bone loss phenotype, include clinical scenarios of skeletal unloading, premature ovarian failure and survival from childhood cancers. These non-hereditary progeroid syndromes implicate the involvement of lineage switching to an adipogenic fate, inhibition of Wnt signaling, increased osteoclastogenesis and activation frequency of osteoclasts, as well as the substantial burden of senescent cell accumulation.

01 Apr 2025·Endocrine, Metabolic & Immune Disorders - Drug Targets

A Glimpse of Research Trends and Frontiers in the Etiology of Premature Ovarian Insufficiency via Bibliometric Analysis

Article

Author: Li, Duan ; Hui, Yameng ; Li, Bing ; Liu, Yingxue ; Hao, Cuifang

Introduction:Premature Ovarian Insufficiency (POI) is the most common reproductive aging disorder in women of reproductive age, which is characterized by decreased ovarian function in women before the age of 40. Etiology research of POI has garnered interest and attention from scholars worldwide over the past decades.Methods:However, to the best of our knowledge, no comprehensive survey with bibliometric analysis has been conducted yet on the research trends of POI etiology. This article aimed to analyze current scientific findings on the etiology of POI, offering innovative ideas for further research. Research articles on the etiology of POI from 1994 to 2023 were collected from the Web of Science Core Collection. A total of 456 research articles were included, and the total number of publications increased annually. We used VOSviewer and bibliometric.com to analyze the keywords, terms, institution, publication country/region, author name, publication journal, and the sum of times the articles have been cited.Results:This study has shown that a research hotspot is the genetic etiology of POI; however, there is still a lack of research on the impact of epigenetic alterations, iatrogenic injuries, environmental pollution, social stress, and unhealthy lifestyles on the pathogenesis of POI.Conclusion:The factors illustrated here represent potential future directions for POI etiology research and warrant more attention from researchers.

News (Medical) associated with Primary Ovarian Insufficiency

16 Dec 2024

·www.drugs.com

Recommendations Updated on Diagnosis, Management of Premature/Primary Ovarian Insufficiency

MONDAY, Dec. 16, 2024 -- In an evidence-based guideline issued by the Centre for Research Excellence in Women's Health in Reproductive Life and published online Dec. 8 in Climacteric , updated recommendations are presented for the diagnosis and management of premature/primary ovarian insufficiency (POI). Nick Panay, M.D., from Queen Charlotte's and Chelsea Hospital at Imperial College London, and colleagues developed guidelines relating to diagnosis and management of POI based on evidence collected from literature searches and assessment. In general, the recommendations were informed by women with lived experience of POI. The authors note that the prevalence of POI is 3.5 percent, which is higher than previously thought. The updated guidelines included 145 recommendations. The list of clinical questions addressed in this guideline was expanded, including in relation to the role of anti-Müllerian hormone (AMH) in the diagnosis of POI and fertility preservation. The topic of complementary treatments was extended, focusing on nonhormone treatments and lifestyle management. Significant changes from the previous guideline include the recommendation that only follicle stimulating hormone (FSH) >25 IU is required for POI diagnosis and guidance that AMH testing, repeat FSH measurement, and/or AMH may be necessary in cases of diagnostic uncertainty. Recommendations relating to genetic testing, estrogen doses and regimens, use of the combined oral contraceptive, and testosterone therapy were also updated. "The guideline group concluded that there is still an urgent need for more research on the most appropriate diagnostic and treatment options, but also to further elaborate the impact of estrogen deficiency on the health and life expectancy of the women diagnosed with POI," the authors write. Several authors disclosed ties to the pharmaceutical industry. Abstract/Full Text Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

01 Oct 2024

·www.drugs.com

Premature Ovarian Insufficiency Linked to Autoimmune Diseases

TUESDAY, Oct. 1, 2024 -- Women diagnosed with premature ovarian insufficiency (POI) have an increased prevalence of severe autoimmune diseases, according to a study published online Sept. 25 in Human Reproduction . Susanna M. Savukoski, M.D., from Oulu University Hospital in Finland, and colleagues conducted a population-based registry study of 3,972 women diagnosed with spontaneous POI between 1988 and 2017 and 15,708 female population controls to examine the association with severe autoimmune diseases before and after POI diagnosis. The researchers found that the prevalence of having at least one severe autoimmune disease was 5.6 percent in women with POI. Compared with controls, women with POI had an increased prevalence of several specific autoimmune diseases prior to the index date including polyglandular autoimmune diseases, Addison disease, vasculitis, systemic lupus erythematosus, rheumatoid arthritis, sarcoidosis, inflammatory bowel diseases, and hyperthyroidism. No difference was seen in the prevalence of type 1 diabetes or ankylosing spondylitis. During the first three years after POI diagnosis, the standardized incidence ratio for being diagnosed for the first time with a severe autoimmune disease was 2.8, which decreased to 1.3 after 12 years. "The study results strengthen the hypothesis that autoimmune mechanisms play an important role in the pathogenesis of POI," the authors write. Abstract/Full Text Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

Clinical Result

03 Sep 2024

·www.drugs.com

Researchers Pinpoint Genes Behind Form of Early Menopause

TUESDAY, Sept. 3, 2024 -- Cases of menopause occurring before the age of 40 can be a major cause of distress and discomfort for women, but researchers now believe they've homed in on the condition's genetic cause. A team at deCODE genetics sought to understand the origins of what's known as primary ovarian insufficiency, which triggers menopause an average of nine years before it typically occurs in women. The deCODE team worked with colleagues in Iceland, Denmark, the UK and Norway to analyze the collected DNA of 174,000 women living in those countries. They focused especially on a gene called CCDC201. In 2022, CCDC201 was identified as a protein-producing gene and was later found to be "highly expressed in egg cells," according to a deCODE news release. Just how CCDC201 might go awry to trigger menopause early hasn't been known, however. The new research revealed the specific change in a snippet of CCDC201 gene coding that seems to effectively terminate its function. However, a woman needed to carry two copies of this defective variant for primary ovarian insufficiency to occur, the researchers noted. That seems to happen in about 1 in every 10,000 women of Northern European descent, the deCODE group found. This "leads to primary ovarian insufficiency, defined as age at menopause before the age of 40, in nearly half of carriers," according to the deCODE news release. The discovery might be important for women who are considering having children. Testing for this newly discovered genetic link could help women make better decisions around their odds for early menopause and the appropriate timing of childbearing, the researchers said. The findings were published Aug. 27 in the journal Nature Genetics . Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

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