Research & Literature

Long-term health consequences of premature or early menopause and considerations for management.

Faubion SS, Kuhle CL, Shuster LT, Rocca WA

Climacteric : the journal of the International Menopause Society 2015; (18(4)):483-91 doi:10.3109/13697137.2015.1020484.

Neurological and endocrine phenotypes of fragile X carrier women.

Hall D, Todorova-Koteva K, Pandya S, et al.

Clinical genetics 2016; (89(1)):60-7 doi:10.1111/cge.12646.

Trajectory and Predictors of Depression and Anxiety Disorders in Mothers With the FMR1 Premutation.

Roberts JE, Tonnsen BL, McCary LM, et al.

Biological psychiatry 2016; (79(10)):850-857 doi:10.1016/j.biopsych.2015.07.015.

Presence of inclusions positive for polyglycine containing protein, FMRpolyG, indicates that repeat-associated non-AUG translation plays a role in fragile X-associated primary ovarian insufficiency.

Buijsen RA, Visser JA, Kramer P, et al.

Human reproduction (Oxford, England) 2016; (31(1)):158-68 doi:10.1093/humrep/dev280.

Granulosa cell and oocyte mitochondrial abnormalities in a mouse model of fragile X primary ovarian insufficiency.

Conca Dioguardi C, Uslu B, Haynes M, et al.

Molecular human reproduction 2016; (22(6)):384-96 doi:10.1093/molehr/gaw023.

Fragile X-associated tremor/ataxia syndrome - features, mechanisms and management.

Hagerman RJ, Hagerman P

Nature reviews. Neurology 2016; (12(7)):403-12 doi:10.1038/nrneurol.2016.82.

Reproductive and gynecologic care of women with fragile X primary ovarian insufficiency (FXPOI).

Hipp HS, Charen KH, Spencer JB, et al.

Menopause (New York, N.Y.) 2016; (23(9)):993-9 doi:10.1097/GME.0000000000000658.

A design thinking approach to primary ovarian insufficiency.

Martin LA, Porter AG, Pelligrini VA, et al.

Panminerva medica 2017; (59(1)):15-32 doi:10.23736/S0031-0808.16.03259-6.

Prognostic dilemmas and genetic counseling for prenatally detected fragile X gene expansions.

Finucane B, Lincoln S, Bailey L, Martin CL

Prenatal diagnosis 2017; (37(1)):37-42 doi:10.1002/pd.4963.

Endocrine Dysfunction in Female FMR1 Premutation Carriers: Characteristics and Association with Ill Health.

Campbell S, Eley SE, McKechanie AG, Stanfield AC

Genes 2016; (7(11)).

Hormone replacement therapy in young women with primary ovarian insufficiency and early menopause.

Sullivan SD, Sarrel PM, Nelson LM

Fertility and sterility 2016; (106(7)):1588-1599 doi:10.1016/j.fertnstert.2016.09.046.

Fragile X premutation in women: recognizing the health challenges beyond primary ovarian insufficiency.

Hoyos LR, Thakur M

Journal of assisted reproduction and genetics 2017; (34(3)):315-323 doi:10.1007/s10815-016-0854-6.

Impact of FMR1 Pre-Mutation Status on Blastocyst Development in Patients Undergoing Pre-Implantation Genetic Diagnosis.

Hutchinson AP, Pereira N, Lilienthal DP, et al.

Gynecologic and obstetric investigation 2018; (83(1)):23-28 doi:10.1159/000455849.

Committee Opinion No. 698: Hormone Therapy in Primary Ovarian Insufficiency.

Obstetrics and gynecology 2017; (129(5)):e134-e141 doi:10.1097/AOG.0000000000002044.

Fragile X syndrome: An overview and update of the FMR1 gene.

Mila M, Alvarez-Mora MI, Madrigal I, Rodriguez-Revenga L

Clinical genetics 2018; (93(2)):197-205 doi:10.1111/cge.13075.

FMR1 CGG repeat expansion mutation detection and linked haplotype analysis for reliable and accurate preimplantation genetic diagnosis of fragile X syndrome.

Rajan-Babu IS, Lian M, Cheah FSH, et al.

Expert reviews in molecular medicine 2017; (19()):e10 doi:10.1017/erm.2017.10.

Fragile X-Associated Diminished Ovarian Reserve and Primary Ovarian Insufficiency from Molecular Mechanisms to Clinical Manifestations.

Man L, Lekovich J, Rosenwaks Z, Gerhardt J

Frontiers in molecular neuroscience 2017; (10()):290 doi:10.3389/fnmol.2017.00290.

CGG repeat length and AGG interruptions as indicators of fragile X-associated diminished ovarian reserve.

Lekovich J, Man L, Xu K, et al.

Genetics in medicine : official journal of the American College of Medical Genetics 2018; (20(9)):957-964 doi:10.1038/gim.2017.220.

Fragile x-associated premature ovarian failure in a large Turkish cohort: Findings of Hacettepe Fragile X Registry.

Utine GE, Şimşek-Kiper PÖ, Akgün-Doğan Ö, et al.

European journal of obstetrics, gynecology, and reproductive biology 2018; (221()):76-80 doi:10.1016/j.ejogrb.2017.12.028.

Detecting AGG Interruptions in Females With a FMR1 Premutation by Long-Read Single-Molecule Sequencing: A 1 Year Clinical Experience.

Ardui S, Race V, de Ravel T, et al.

Frontiers in genetics 2018; (9()):150 doi:10.3389/fgene.2018.00150.

Menopausal Hormone Therapy and Cardiovascular Risk: Where are we Now?

Anagnostis P, Paschou SA, Katsiki N, et al.

Current vascular pharmacology 2019; (17(6)):564-572 doi:10.2174/1570161116666180709095348.

Managing Menopause by Combining Evidence With Clinical Judgment.

Flores VA, Pal L

Clinical obstetrics and gynecology 2018; (61(3)):496-507 doi:10.1097/GRF.0000000000000384.

FXPOI: Pattern of AGG Interruptions Does not Show an Association With Age at Amenorrhea Among Women With a Premutation.

Allen EG, Glicksman A, Tortora N, et al.

Frontiers in genetics 2018; (9()):292 doi:10.3389/fgene.2018.00292.

Preimplantation genetic diagnosis versus prenatal diagnosis-decision-making among pregnant FMR1 premutation carriers.

Haham LM, Avrahami I, Domniz N, et al.

Journal of assisted reproduction and genetics 2018; (35(11)):2071-2075 doi:10.1007/s10815-018-1293-3.

Premature ovarian insufficiency - aetiopathology, epidemiology, and diagnostic evaluation.

Rudnicka E, Kruszewska J, Klicka K, et al.

Przeglad menopauzalny = Menopause review 2018; (17(3)):105-108 doi:10.5114/pm.2018.78550.

Spontaneous pregnancy in a patient with premature ovarian insufficiency - case report.

Calik-Ksepka A, Grymowicz M, Bronkiewicz W, et al.

Przeglad menopauzalny = Menopause review 2018; (17(3)):139-140 doi:10.5114/pm.2018.78560.

Fragile X Associated Primary Ovarian Insufficiency (FXPOI): Case Report and Literature Review.

Fink DA, Nelson LM, Pyeritz R, et al.

Frontiers in genetics 2018; (9()):529 doi:10.3389/fgene.2018.00529.

Absence of AGG Interruptions Is a Risk Factor for Full Mutation Expansion Among Israeli FMR1 Premutation Carriers.

Domniz N, Ries-Levavi L, Cohen Y, et al.

Frontiers in genetics 2018; (9()):606 doi:10.3389/fgene.2018.00606.

HRT for women with premature ovarian insufficiency: a comprehensive review.

Webber L, Anderson RA, Davies M, et al.

Human reproduction open 2017; (2017(2)):hox007 doi:10.1093/hropen/hox007.

Hormonal management of menopausal symptoms in women with a history of gynecologic malignancy.

Harris BS, Bishop KC, Kuller JA, et al.

Menopause (New York, N.Y.) 2020; (27(2)):243-248 doi:10.1097/GME.0000000000001447.

Assessment of FMR1 triplet repeats in patients affected with mental retardation, fragile X syndrome and primary ovarian insufficiency.

Salimy Z, Akbari MT, Deilamani FK

Journal of genetics 2020; (99()).

FMRpolyG accumulates in FMR1 premutation granulosa cells.

Friedman-Gohas M, Elizur SE, Dratviman-Storobinsky O, et al.

Journal of ovarian research 2020; (13(1)):22 doi:10.1186/s13048-020-00623-w.

Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS): Pathophysiology and Clinical Implications.

Cabal-Herrera AM, Tassanakijpanich N, Salcedo-Arellano MJ, Hagerman RJ

International journal of molecular sciences 2020; (21(12)) doi:10.3390/ijms21124391.

Two Cases of Primary Ovarian Insufficiency Accompanied by High Serum Anti-Müllerian Hormone Levels and Preservation of Ovarian Follicles.

Chun S, Koo YH, Na YJ

Journal of menopausal medicine 2020; (26(2)):143-146 doi:10.6118/jmm.20004.

Cardiovascular Problems in the Fragile X Premutation.

Tassanakijpanich N, Cohen J, Cohen R, et al.

Frontiers in genetics 2020; (11()):586910 doi:10.3389/fgene.2020.586910.

Characterization of the Metabolic, Clinical and Neuropsychological Phenotype of Female Carriers of the Premutation in the X-Linked FMR1 Gene.

Napoli E, McLennan YA, Schneider A, et al.

Frontiers in molecular biosciences 2020; (7()):578640 doi:10.3389/fmolb.2020.578640.

Differential Progression of Motor Dysfunction Between Male and Female Fragile X Premutation Carriers Reveals Novel Aspects of Sex-Specific Neural Involvement.

Loesch DZ, Tassone F, Atkinson A, et al.

Frontiers in molecular biosciences 2020; (7()):577246 doi:10.3389/fmolb.2020.577246.

[Menopause and risk of thromboembolic events. Postmenopausal women management: CNGOF and GEMVi clinical practice guidelines].

Hugon-Rodin J, Perol S, Plu-Bureau G

Gynecologie, obstetrique, fertilite & senologie 2021; (49(5)):455-461 doi:10.1016/j.gofs.2021.03.018.

Ectopic expression of CGG-repeats alters ovarian response to gonadotropins and leads to infertility in a murine FMR1 premutation model.

Shelly KE, Candelaria NR, Li Z, et al.

Human molecular genetics 2021; (30(10)):923-938 doi:10.1093/hmg/ddab083.

Refining the risk for fragile X-associated primary ovarian insufficiency (FXPOI) by FMR1 CGG repeat size.

Allen EG, Charen K, Hipp HS, et al.

Genetics in medicine : official journal of the American College of Medical Genetics 2021; (23(9)):1648-1655 doi:10.1038/s41436-021-01177-y.

Hormone therapy regimens for managing the menopause and premature ovarian insufficiency.

Armeni E, Paschou SA, Goulis DG, Lambrinoudaki I

Best practice & research. Clinical endocrinology & metabolism 2021; (35(6)):101561 doi:10.1016/j.beem.2021.101561.

A decision tree model for predicting live birth in FMR1 premutation carriers undergoing preimplantation genetic testing for monogenic/single gene defects.

Cohen Y, Nattiv N, Avrham S, et al.

Reproductive biomedicine online 2021; (43(4)):680-686 doi:10.1016/j.rbmo.2021.06.009.

Population-based carrier screening and prenatal diagnosis of fragile X syndrome in East Asian populations.

Guo Q, Chang YY, Huang CH, et al.

Journal of genetics and genomics = Yi chuan xue bao 2021; (48(12)):1104-1110 doi:10.1016/j.jgg.2021.04.012.

Position statement on the diagnosis and management of premature/primary ovarian insufficiency (except Turner Syndrome).

Christin-Maitre S, Givony M, Albarel F, et al.

Annales d'endocrinologie 2021; (82(6)):555-571 doi:10.1016/j.ando.2021.09.001.

Approach to the Patient With New-Onset Secondary Amenorrhea: Is This Primary Ovarian Insufficiency?

Stuenkel CA, Gompel A, Davis SR, et al.

The Journal of clinical endocrinology and metabolism 2022; (107(3)):825-835 doi:10.1210/clinem/dgab766.

Female fragile X premutation carriers are at increased risk for metabolic syndrome from early adulthood.

Gruber N, Haham LM, Raanani H, et al.

Nutrition, metabolism, and cardiovascular diseases : NMCD 2022; (32(4)):1010-1018 doi:10.1016/j.numecd.2021.11.018.

Refining reproductive risk for FMR1 premutation carriers in the general obstetric population.

Owens KM, Terhaar C, Zdrodowski J, et al.

American journal of medical genetics. Part A 2022; (188(5)):1476-1481 doi:10.1002/ajmg.a.62666.

Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS): A Gender Perspective.

Orsucci D, Lorenzetti L, Baldinotti F, et al.

Journal of clinical medicine 2022; (11(4)) doi:10.3390/jcm11041002.

Menopause-associated risk of cardiovascular disease.

Anagnostis P, Lambrinoudaki I, Stevenson JC, Goulis DG

Endocrine connections 2022; (11(4)).

Expression of FMRpolyG in Peripheral Blood Mononuclear Cells of Women with Fragile X Mental Retardation 1 Gene Premutation.

Nguyen XP, Vilkaite A, Messmer B, et al.

Genes 2022; (13(3)) doi:10.3390/genes13030451.

Hormone therapy in women with premature ovarian insufficiency: a systematic review and meta-analysis.

Gonçalves CR, Vasconcellos AS, Rodrigues TR, et al.

Reproductive biomedicine online 2022; (44(6)):1143-1157 doi:10.1016/j.rbmo.2022.02.006.

Both cis and trans-acting genetic factors drive somatic instability in female carriers of the FMR1 premutation.

Hwang YH, Hayward BE, Zafarullah M, et al.

Scientific reports 2022; (12(1)):10419 doi:10.1038/s41598-022-14183-0.

Hormone therapy for uterine and endometrial development in women with premature ovarian insufficiency.

Craciunas L, Zdoukopoulos N, Vinayagam S, Mohiyiddeen L

The Cochrane database of systematic reviews 2022; (10()):CD008209 doi:10.1002/14651858.CD008209.pub2.

Evidence for a fragile X messenger ribonucleoprotein 1 (FMR1) mRNA gain-of-function toxicity mechanism contributing to the pathogenesis of fragile X-associated premature ovarian insufficiency.

Rosario R, Stewart HL, Choudhury NR, et al.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2022; (36(11)):e22612 doi:10.1096/fj.202200468RR.

The diagnostic experience of women with fragile X-associated primary ovarian insufficiency (FXPOI).

Poteet B, Ali N, Bellcross C, et al.

Journal of assisted reproduction and genetics 2023; (40(1)):179-190 doi:10.1007/s10815-022-02671-1.

Clinical implications of somatic allele expansion in female FMR1 premutation carriers.

Aishworiya R, Hwang YH, Santos E, et al.

Scientific reports 2023; (13(1)):7050 doi:10.1038/s41598-023-33528-x.

Management of menopause.

Magraith K, Jang C

Australian prescriber 2023; (46(3)):48-53 doi:10.18773/austprescr.2023.014.

Primary ovarian insufficiency: a toolkit for the busy clinician.

Kapoor E

Menopause (New York, N.Y.) 2024; (31(1)):65-67 doi:10.1097/GME.0000000000002275.

PGT-M for Premature Ovarian Failure Related to CGG Repeat Expansion of the FMR1 Gene.

Persico T, Tranquillo ML, Seracchioli R, et al.

Genes 2023; (15(1)) doi:10.3390/genes15010006.

Ovarian reserve in patients with FMR1 gene premutation and the role of fertility preservation.

Le Poulennec T, Dubreuil S, Grynberg M, et al.

Annales d'endocrinologie 2024; (85(4)):269-275 doi:10.1016/j.ando.2024.04.004.

The association between primary ovarian insufficiency and increased multimorbidity in a large prospective cohort (Canadian Longitudinal Study on Aging).

Kirubarajan A, Sohel N, Mayhew A, et al.

Fertility and sterility 2025; (123(2)):289-299 doi:10.1016/j.fertnstert.2024.08.345.

Dysregulation of the actin cytoskeleton and FMRP causes polar body protrusion defects in human fragile X premutation and aged oocytes.

McCarter K, Deshpande M, Romanski P, et al.

bioRxiv : the preprint server for biology 2025; doi:10.1101/2025.02.23.639319.

Premutation Females with preFXTAS.

Liani V, Torrents C, Rolleri E, et al.

International journal of molecular sciences 2025; (26(6)) doi:10.3390/ijms26062825.

Premature ovarian insufficiency: When ovaries retire early.

Sugianto SRS, Webber L, Safdar Husain F, et al.

Annals of the Academy of Medicine, Singapore 2025; (54(3)):178-191 doi:10.47102/annals-acadmedsg.2024227.

No association between FMR1 premutation and either ADHD or anxiety in 53,707 women undergoing genetic testing for family planning purposes.

Klausner L, Carmi S, Ben-Shachar S, et al.

Genetics in medicine : official journal of the American College of Medical Genetics 2025; (27(7)):101428 doi:10.1016/j.gim.2025.101428.

Premature ovarian insufficiency: Updated concepts in diagnosis and hormonal treatment strategies.

Pravatta-Rezende G, Benetti-Pinto CL, Yela DA, et al.

Clinics (Sao Paulo, Brazil) 2025; (80()):100745 doi:10.1016/j.clinsp.2025.100745.

Advances in exploring the association between FMR1 premutation and fibromyalgia: a pilot study with a more effective sample definition.

Pinheiro MMLS, Antunes MD, Carvalho LML, et al.

Clinics (Sao Paulo, Brazil) 2025; (80()):100758 doi:10.1016/j.clinsp.2025.100758.

European society of endocrinology clinical practice guideline for evaluation and management of menopause and the perimenopause.

Lumsden MA, Dekkers OM, Faubion SS, et al.

European journal of endocrinology 2025; (193(4)):G49-G81 doi:10.1093/ejendo/lvaf206.

Expert opinion by the Italian Society of Gynecology of the Third Age (SIGiTE) and the Italian Society of Menopause (SIM) on diagnosis and treatment of premature ovarian insufficiency.

Capozzi A, Ambroggio S, Cagnacci A, et al.

Minerva endocrinology 2026; (51(1)):88-95 doi:10.23736/S2724-6507.25.04422-7.

Improving Treatment of Radiation-Induced Premature Ovarian Insufficiency After Cervical Cancer: A Practice Quality Improvement Initiative.

Smith EE, Heintz JR, Chesnokova A, Taunk NK

International journal of radiation oncology, biology, physics 2026; (126(1)):48-54 doi:10.1016/j.ijrobp.2026.02.211.

Psychiatric and Cognitive Features in Italian Women With the FMR1 Premutation: A Comprehensive Assessment Using SCID-5 and Standardized Cognitive Measures.

Montanaro FAM, Hagerman RJ, Spano G, et al.

American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2026; (201(6)):406-419 doi:10.1002/ajmg.b.70014.

Isolated β-Human Chorionic Gonadotropin Elevation-From Pregnancy to Fragile X-associated Premature Ovarian Insufficiency.

Sharma PP

AACE endocrinology and diabetes 2026; (13(2)):308-312 doi:10.1016/j.aed.2025.11.008.

Comprehensive, multidisciplinary care for fragile X-associated tremor/ataxia syndrome.

Bourgeois JA, Schneider A, Klusek J, et al.

Frontiers in neurology 2026; (17()):1746002 doi:10.3389/fneur.2026.1746002.

Large-scale analysis of FMR1 CGG repeat length and risk of premature ovarian insufficiency in over 92 000 women.

Morbey EJ, Day FR, Wright DJ, et al.

Human reproduction (Oxford, England) 2026; (41(6)):998-1007 doi:10.1093/humrep/deag061.

Hormone replacement therapy in gynecologic cancer survivors: bridging the gap between evidence and clinical practice.

Gil-Ibáñez B, Luzarraga Aznar A, Barretina-Ginesta MP, et al.

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 2026; 104881 doi:10.1016/j.ijgc.2026.104881.

Ovarian microenvironment remodeling in premature ovarian insufficiency: From hormone replacement to regenerative strategies with mesenchymal stem cells and exosomes.

Feng M, Su J, Yu G, et al.

Journal of reproductive immunology 2026; (177()):104959 doi:10.1016/j.jri.2026.104959.

Spontaneous conception and successful live birth during hormone replacement therapy in a patient with iatrogenic premature ovarian insufficiency: a case report.

Lee JM, Yang JS, Park JE, et al.

Frontiers in medicine 2026; (13()):1929801 doi:10.3389/fmed.2026.1929801.

FMR1-Associated Diminished Ovarian Reserve: Reduced Oocyte Yield Without Loss of Per-Embryo Ploidy.

Fouks Y, Morse B, Stern C, et al.

Fertility and sterility 2026; doi:10.1016/j.fertnstert.2026.09.010.