Original Article
Primary ovarian insufficiency in cancer survivors: Keys to optimal management
Fallo ovárico prematuro en supervivientes a un tumor sólido: puntos clave de manejo
Carmen Garrido Colinoa,
, Paula González Urdialesb, Antonio Molinés Honrubiac, María José Ortega Acostad, Mirian García Abose
Corresponding author
a Servicio de Pediatría, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
b Servicio de Pediatría, Hospital Universitario de Cruces, Barakaldo, Bizkaia, Spain
c Servicio de Hematología, Hospital Insular Las Palmas de Gran Canarias, Las Palmas de Gran Canaria, Las Palmas, Spain
d Servicio de Pediatría, Hospital Universitario Virgen de las Nieves, Granada, Spain
e Servicio de Pediatría, Hospital Universitario Donostia, Donostia, Gipuzkoa, Spain
Read
1571
Timeswas read the article
468
Total PDF
1103
Total HTML
Share statistics
array:23 [ "pii" => "S2341287923002612" "issn" => "23412879" "doi" => "10.1016/j.anpede.2023.11.007" "estado" => "S300" "fechaPublicacion" => "2023-12-01" "aid" => "3526" "copyrightAnyo" => "2023" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "An Pediatr (Barc). 2023;99:385-92" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S1695403323002114" "issn" => "16954033" "doi" => "10.1016/j.anpedi.2023.09.018" "estado" => "S300" "fechaPublicacion" => "2023-12-01" "aid" => "3526" "copyright" => "Asociación Española de Pediatría" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "An Pediatr (Barc). 2023;99:385-92" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "es" => array:14 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original</span>" "titulo" => "Fallo ovárico prematuro en supervivientes a un tumor sólido: puntos clave de manejo" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:3 [ 0 => "es" 1 => "es" 2 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "385" "paginaFinal" => "392" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Primary ovarian insufficiency in cancer survivors: Keys to optimal management" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 1 "multimedia" => array:5 [ "identificador" => "fig0025" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 826 "Ancho" => 1333 "Tamanyo" => 179120 ] ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Carmen Garrido Colino, Paula González Urdiales, Antonio Molinés Honrubia, María José Ortega Acosta, Mirian García Abos" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Carmen" "apellidos" => "Garrido Colino" ] 1 => array:2 [ "nombre" => "Paula" "apellidos" => "González Urdiales" ] 2 => array:2 [ "nombre" => "Antonio" "apellidos" => "Molinés Honrubia" ] 3 => array:2 [ "nombre" => "María José" "apellidos" => "Ortega Acosta" ] 4 => array:2 [ "nombre" => "Mirian" "apellidos" => "García Abos" ] ] ] ] "resumen" => array:1 [ 0 => array:3 [ "titulo" => "Graphical abstract" "clase" => "graphical" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><elsevierMultimedia ident="fig0025"></elsevierMultimedia></p></span>" ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2341287923002612" "doi" => "10.1016/j.anpede.2023.11.007" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287923002612?idApp=UINPBA00005H" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1695403323002114?idApp=UINPBA00005H" "url" => "/16954033/0000009900000006/v1_202312041657/S1695403323002114/v1_202312041657/es/main.assets" ] ] "itemSiguiente" => array:18 [ "pii" => "S2341287923002600" "issn" => "23412879" "doi" => "10.1016/j.anpede.2023.11.006" "estado" => "S300" "fechaPublicacion" => "2023-12-01" "aid" => "3525" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "An Pediatr (Barc). 2023;99:393-402" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:14 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Acceptance and socioeconomic inequalities in meningococcal B vaccination in the community of Madrid prior to its inclusion in the immunization schedule" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:3 [ 0 => "en" 1 => "en" 2 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "393" "paginaFinal" => "402" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Aceptación y desigualdades socioeconómicas en la vacunación frente a meningococo B en la Comunidad de Madrid en el periodo anterior a su inclusión en el calendario" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 1 "multimedia" => array:5 [ "identificador" => "fig0040" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 825 "Ancho" => 1333 "Tamanyo" => 168756 ] ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Marta Ijalba Martínez, María Dolores Lasheras Carbajo, Sara Santos Sanz, Diana Gómez Barroso" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Marta" "apellidos" => "Ijalba Martínez" ] 1 => array:2 [ "nombre" => "María Dolores" "apellidos" => "Lasheras Carbajo" ] 2 => array:2 [ "nombre" => "Sara" "apellidos" => "Santos Sanz" ] 3 => array:2 [ "nombre" => "Diana" "apellidos" => "Gómez Barroso" ] ] ] ] "resumen" => array:1 [ 0 => array:3 [ "titulo" => "Graphical abstract" "clase" => "graphical" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall"><elsevierMultimedia ident="fig0040"></elsevierMultimedia></p></span>" ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S1695403323002138" "doi" => "10.1016/j.anpedi.2023.09.017" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1695403323002138?idApp=UINPBA00005H" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287923002600?idApp=UINPBA00005H" "url" => "/23412879/0000009900000006/v1_202312211250/S2341287923002600/v1_202312211250/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2341287923002624" "issn" => "23412879" "doi" => "10.1016/j.anpede.2023.11.008" "estado" => "S300" "fechaPublicacion" => "2023-12-01" "aid" => "3532" "copyright" => "Asociación Española de Pediatría" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "An Pediatr (Barc). 2023;99:376-84" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:14 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Medication reconciliation on admission in paediatric chronic patients: A multicentre study" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:3 [ 0 => "en" 1 => "en" 2 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "376" "paginaFinal" => "384" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Conciliación de la medicación al ingreso en paciente crónico pediátrico: estudio multicéntrico" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 1 "multimedia" => array:5 [ "identificador" => "fig0020" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 832 "Ancho" => 1333 "Tamanyo" => 155501 ] ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Margarita Cuervas-Mons Vendrell, Dolores Pilar Iturgoyen Fuentes, Joëlle Arrojo Suárez, Inés Jimenez Lozano, Cecilia Martínez Fernandez-Llamazares, Angela Tristancho-Perez, Lucia Yunquera Romero, Cristina Martínez Roca, Cristina Otero Villalustre, Ana García Robles, Beatriz Garrido Corro, Belén Rodríguez Marrodán" "autores" => array:12 [ 0 => array:2 [ "nombre" => "Margarita" "apellidos" => "Cuervas-Mons Vendrell" ] 1 => array:2 [ "nombre" => "Dolores Pilar" "apellidos" => "Iturgoyen Fuentes" ] 2 => array:2 [ "nombre" => "Joëlle" "apellidos" => "Arrojo Suárez" ] 3 => array:2 [ "nombre" => "Inés" "apellidos" => "Jimenez Lozano" ] 4 => array:2 [ "nombre" => "Cecilia Martínez" "apellidos" => "Fernandez-Llamazares" ] 5 => array:2 [ "nombre" => "Angela" "apellidos" => "Tristancho-Perez" ] 6 => array:2 [ "nombre" => "Lucia" "apellidos" => "Yunquera Romero" ] 7 => array:2 [ "nombre" => "Cristina" "apellidos" => "Martínez Roca" ] 8 => array:2 [ "nombre" => "Cristina" "apellidos" => "Otero Villalustre" ] 9 => array:2 [ "nombre" => "Ana" "apellidos" => "García Robles" ] 10 => array:2 [ "nombre" => "Beatriz" "apellidos" => "Garrido Corro" ] 11 => array:2 [ "nombre" => "Belén" "apellidos" => "Rodríguez Marrodán" ] ] ] ] "resumen" => array:1 [ 0 => array:3 [ "titulo" => "Graphical abstract" "clase" => "graphical" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall"><elsevierMultimedia ident="fig0020"></elsevierMultimedia></p></span>" ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S1695403323002199" "doi" => "10.1016/j.anpedi.2023.10.004" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1695403323002199?idApp=UINPBA00005H" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287923002624?idApp=UINPBA00005H" "url" => "/23412879/0000009900000006/v1_202312211250/S2341287923002624/v1_202312211250/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Primary ovarian insufficiency in cancer survivors: Keys to optimal management" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "385" "paginaFinal" => "392" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Carmen Garrido Colino, Paula González Urdiales, Antonio Molinés Honrubia, María José Ortega Acosta, Mirian García Abos" "autores" => array:5 [ 0 => array:4 [ "nombre" => "Carmen" "apellidos" => "Garrido Colino" "email" => array:1 [ 0 => "cgarridoc@salud.madrid.org" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Paula" "apellidos" => "González Urdiales" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Antonio" "apellidos" => "Molinés Honrubia" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "María José" "apellidos" => "Ortega Acosta" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "Mirian" "apellidos" => "García Abos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Servicio de Pediatría, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Pediatría, Hospital Universitario de Cruces, Barakaldo, Bizkaia, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Hematología, Hospital Insular Las Palmas de Gran Canarias, Las Palmas de Gran Canaria, Las Palmas, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Pediatría, Hospital Universitario Virgen de las Nieves, Granada, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Servicio de Pediatría, Hospital Universitario Donostia, Donostia, Gipuzkoa, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Fallo ovárico prematuro en supervivientes a un tumor sólido: puntos clave de manejo" ] ] "resumenGrafico" => array:2 [ "original" => 1 "multimedia" => array:5 [ "identificador" => "fig0025" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 826 "Ancho" => 1333 "Tamanyo" => 181257 ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Survival in childhood and adolescent cancers has increased in recent years, exceeding 80%.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> However, the sequelae of cancer and the received treatments have a deleterious impact on the quality of life of survivors in adulthood.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Premature ovarian insufficiency (POI) is one of the possible sequelae. The term POI was proposed by the European Society of Human Reproduction and Embryology (ESHRE) for use in research and clinical practice. The condition is characterised by ovarian failure, deficient ovarian sex hormones and decreased ovarian reserve, which together cause significant morbidity, including infertility, sexual dysfunction, decreased bone density, cardiovascular risk, negative feelings and increased risk of early mortality.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The prevalence of POI in the general population is approximately 1.8%. It is greater in patients with cancer or diseases requiring chemotherapy and/or radiation therapy. In the current literature, some studies have reported that the incidence of POI is 3.5 times greater in girls and female adolescents who are cancer survivors compared to their peers.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The risk associated with radiation therapy depends on the field and dose of radiation and the age of the patient. When it comes to chemotherapy, alkylating agents are the drugs associated most strongly with POI in every age group.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Close monitoring of ovarian function in girls and women exposed to gonadotoxic treatments is important, as it offers the opportunity of pursuing fertility preservation options, especially in cases in which it was not possible to do so before initiation of treatment. It also allows early initiation of hormone replacement therapy, thereby optimizing health outcomes and quality of life in female patients.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In the case of prepubertal girls, the diagnosis of POI poses a greater challenge. A consensus guideline developed in Spain described the paediatric solid tumours associated with the highest risk of POI.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> In addition, the International Late Effects of Childhood Cancer Guideline Harmonization Group has published evidence-based guidelines regarding the risk of infertility and monitoring of cancer survivors.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> The levels of follicle-stimulating hormone (FSH) and oestradiol are the recommended tests for assessment of prepubertal girls with delayed puberty: absence of physical signs of puberty at age 13 years, primary amenorrhoea at age 16 years or failure to progress through puberty.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The Children’s Oncology Group (COG), the PanCare consortium and other institutions have published guidelines developed by experts for the surveillance and management of adverse events in survivors.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10–12</span></a> It is essential to raise awareness and educate survivors about the potential adverse events they may develop throughout adulthood. In this regard, girls and female adolescents at high risk of POI and their families should be aware of POI and know how to identify its warning signs and when to consult a specialist. Unfortunately, multiple studies in the literature show that informing patients about the sequelae of cancer and management of these sequelae continue to be inadequate.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Objective</span><p id="par0030" class="elsevierStylePara elsevierViewall">To describe the incidence and current management of POI in survivors of solid tumours developed in childhood or adolescence in Spain with the aim of improving surveillance, early detection, management and patient education.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Material and methods</span><p id="par0035" class="elsevierStylePara elsevierViewall">A multicentre observational study was conducted by the working group on adolescents with cancer of the Sociedad Española de Hematología y Oncología Pediátricas (SEHOP, Spanish Society of Paediatric Haematology and Oncology).</p><p id="par0040" class="elsevierStylePara elsevierViewall">The study was approved by the ethics committee overseeing research at the Hospital General Universitario Gregorio Marañón under file code GARFOP2021 and conducted in adherence to current regulations, Royal Decree 1090/2015 and Decree 39/94 of the Community of Madrid to uphold the ethics committee resolution.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Patients</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Inclusion criteria</span><p id="par0045" class="elsevierStylePara elsevierViewall">We included female patients aged 12–18 years at the time of the study with a diagnosis of solid tumour and a moderate/high risk of developing POI.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Exclusion criteria</span><p id="par0050" class="elsevierStylePara elsevierViewall">We excluded patients with blood tumours or who had undergone an allogeneic hematopoietic stem cell transplantation.</p><p id="par0055" class="elsevierStylePara elsevierViewall">The study was carried out in 5 referral hospitals in Spain that manage paediatric and/or adolescent patients with cancer. We selected the medical histories of 210 female patients who had solid tumours in childhood or adolescence with a moderate to high risk of POI managed between January 2010 and December 2022 and who had been in follow-up for a minimum of 2 years after completing treatment.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Data collection</span><p id="par0060" class="elsevierStylePara elsevierViewall">We reviewed the electronic health records of the 210 selected patients, collecting data only for those girls and/or adolescents with a history of cancer that met the criteria for diagnosis of POI. We collected data for relevant variables: age at diagnosis, type of tumour, end of treatment, date of event, history of fertility preservation before treatment or ovarian failure, risk group, menarche, follow-up by endocrinologist, follow-up by gynaecologist, hormone replacement therapy and POI criteria.</p><p id="par0065" class="elsevierStylePara elsevierViewall">We defined the risk groups according to the criteria established by the experts of the Pediatric Initiative Network (PIN) of the Oncofertility Consortium.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Then, we estimated the risk of POI cases with the following tool: <a href="https://fertilitypreservationpittsburgh.org/fertility-resources/fertility-risk-calculator/">https://fertilitypreservationpittsburgh.org/fertility-resources/fertility-risk-calculator/</a>.</p><p id="par0075" class="elsevierStylePara elsevierViewall">We defined POI, in adherence with the recommendations of the ESHRE, as clinical manifestations of menopause with amenorrhoea or oligomenorrhoea lasting at least 4 months and levels of FSH greater than 25 IU/L on 2 occasions at least 4 weeks apart or a level of FSH greater than 40 IU/L at a single timepoint. Measurement of FSH is the gold standard of diagnosis. Levels of anti-Müllerian hormone (AMH) need to be interpreted in relation to FSH and oestrogen levels.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Statistical analysis</span><p id="par0080" class="elsevierStylePara elsevierViewall">Data were anonymised upon retrieval in adherence with good clinical practice guidelines before being entered in a database for subsequent analysis, which was performed with the software IBM SPSS version 26 (IBM Corp, Armonk, NY, USA). We summarised categorical data as absolute frequencies and percentages and continuous data as mean and standard deviation. Statistical significance was defined as a <span class="elsevierStyleItalic">P</span> value of less than 0.05. We generated Kaplan-Meier curves to analyse the time elapsed to the development of the adverse event after diagnosis and various factors.</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Results</span><p id="par0085" class="elsevierStylePara elsevierViewall">Of the 210 patients who met the criteria for moderate to high risk, we excluded 170 patients who had not developed POI by the data collection period. We included 30 patients in the study, which corresponded to an incidence of 1.5 in the sample.</p><p id="par0090" class="elsevierStylePara elsevierViewall">The mean age at diagnosis of the tumour was 10 years (SD, 3.88) and the mean age at the time of the event was 14 years (SD, 2.09). As for the type of solid tumour, Ewing sarcoma, central nervous system tumours and germ cell tumours accounted for 70% of POI cases in our study. Eighty-three percent of patients had not undergone preservation of oocytes or ovarian cortex tissue before initiation of treatment and/or development of POI. Sixty-three percent (19) had not gone through menarche at the time ovarian failure was diagnosed. The most frequent stage of pubertal development at the time of the examination was Tanner stage 1 (<span class="elsevierStyleItalic">n</span> = 13) followed by stage 5 (<span class="elsevierStyleItalic">n</span> = 14), which together amounted to 90% of the cases.</p><p id="par0095" class="elsevierStylePara elsevierViewall">At the time of diagnosis of POI, 14 patients had gone through puberty, while the rest were prepubertal and most frequently at stage 1.</p><p id="par0100" class="elsevierStylePara elsevierViewall">A transvaginal ultrasound scan was performed in only 10 patients (33%), and the results were abnormal, with fewer than 10 follicles, in 90%. A transabdominal pelvic ultrasound scan was performed in 23 cases, with normal findings in 11 (37%) and abnormal findings, with visualization of small-sized ovaries and absence of follicles, in 12 (40%).</p><p id="par0105" class="elsevierStylePara elsevierViewall">Hormone level tests evinced FSH levels above 40 IU/L in a single measurement in 78% of the sample and above 25 IU/L in two measurements in the remaining 21%. The level of oestradiol was less than 28 ng/L in 90% of cases. The level of luteinizing hormone (LH) was elevated in 25 measurements (83% of tests). Measurement of AMA levels was not considered necessary for diagnosis. It was carried out in 7 patients (23%) and found decreased values in all.</p><p id="par0110" class="elsevierStylePara elsevierViewall">Sixteen patients (53%) exhibited symptoms of menopause and 23 (77%) had oligomenorrhoea or amenorrhoea of at least 4 months’ duration.</p><p id="par0115" class="elsevierStylePara elsevierViewall">When it came to the risk factors for POI, 20% (<span class="elsevierStyleItalic">n</span> = 8) had received alkylating agents at intermediate doses and 53% (<span class="elsevierStyleItalic">n</span> = 16) at high doses. Thirteen (43%) had received high-dose chemotherapy followed by haematopoietic stem cell transplantation as consolidation therapy. Forty percent of patients received platinum-based antineoplastic drugs. Eight patients (27%) received abdominal irradiation at a dose greater than 10 Gy. Six patients (20%) received cranial irradiation at a dose greater than 40 Gy. Five patients (17%) underwent oophorectomy.</p><p id="par0120" class="elsevierStylePara elsevierViewall">Combining the different risks in each of the patients included in the sample according to the criteria described in the material and methods section and using the risk calculator, 97% of patients were at high risk of POI and the rest were at moderate-to-high risk.</p><p id="par0125" class="elsevierStylePara elsevierViewall">Concerning the monitoring of adverse events recommended in this at-risk population, we found that14 patients (47%) were not followed up by an endocrinologist, 5 (17%) had attended 1–5 follow-up visits at irregular intervals, and 11 (37%) were being monitored for adverse events by endocrinology and/or gynaecology care teams.</p><p id="par0130" class="elsevierStylePara elsevierViewall">A paediatric oncologist made the diagnosis of POI in 33% of the patients, and in many of the other patients made a referral to a gynaecologist and/or endocrinologist. At the time of the study, 26 of the patients (87%) were receiving hormone replacement therapy.</p><p id="par0135" class="elsevierStylePara elsevierViewall">The median time elapsed to the occurrence of the adverse event was 43.5 months from the diagnosis of the tumour and 29.5 months from the completion of treatment.</p><p id="par0140" class="elsevierStylePara elsevierViewall">The analysis of Kaplan-Meier curves (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) showed that approximately 30% of POI cases developed within 2 years of the diagnosis of solid tumour and some cases had late onset several years after the diagnosis. When the Tanner stage of development was included as a factor in the same analysis, we found significant differences in the development of POI between prepubertal (Tanner 1) and postpubertal patients (Tanner 5) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). On the other hand, we found no differences based on the type of tumour (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Discussion</span><p id="par0145" class="elsevierStylePara elsevierViewall">As the number of childhood/adolescence cancer survivor increases,<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> the importance of the management of long-term adverse events cannot be neglected. The gonadotoxic effect of treatment has been identified as one of the greatest concerns of childhood cancer survivors and their parents.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> It has also been found to have a deleterious impact on the quality of life of childhood cancer survivors.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">The risk of POI in the general female population is approximately 1%.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> This risk increases in childhood and adolescent cancer survivors, with a prevalence of 5.4% in adolescents with a history of cancer compared to 2.2% in the general adolescent population.<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20,21</span></a> The risk of developing POI before age 40 years in childhood/adolescent cancer survivors is variable. Different studies have found cumulative incidences ranging from 8% to 10.9%.<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22,23</span></a> In our study, we found a cumulative incidence of 1.5%. We ought to underscore that POI may develop in the paediatric age group following cancer treatment, so monitoring should be initiated early, as the risk of POI increases progressively in the following decades until peaking at approximately 34 years of age.<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">23,24</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">In our study, the median time elapsed to the occurrence of the event was 43.5 months from diagnosis and 29.5 months from completion of treatment. The Kaplan-Meier survival curves show that 30% of cases of POI developed within 2 years of diagnosis of the tumour and that some cases had delayed onset, with development of POI several years after the diagnosis.</p><p id="par0160" class="elsevierStylePara elsevierViewall">We also found a statistically significant difference in the time elapsed to the development of POI based on the stage of pubertal development at the time of the cancer diagnosis, with substantially earlier development of POI in patients diagnosed after puberty compared to patients diagnosed in prepubertal stages. There is published evidence of a lower probability of POI in female patients treated at earlier ages, which is associated with the greater number of primordial follicles.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> This could also explain the delay in the development of POI in younger patients, although the data currently available are not sufficient to confirm this hypothesis.</p><p id="par0165" class="elsevierStylePara elsevierViewall">It is important to highlight that while menstruation and oocytes are intimately related, it is possible for menstruation to occur in anovulatory cycles in association with abnormalities in the hypothalamic-pituitary-ovarian axis. The presence of menstruation after cancer treatment is not indicative of an adequate ovarian reserve and may be misinterpreted in some cases.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> Therefore, it should not be the basis for failing to provide adequate follow-up in patients at risk. In our study, menarche had taken place before the development of POI in 36% of cases, and menstrual cycles continued in 23%.</p><p id="par0170" class="elsevierStylePara elsevierViewall">In our study, we analysed risk factors based on the classification of the Pediatric Interest Network of the Oncofertility Consortium.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">At present, multiple tools are available to establish uniform risk group definitions and assist clinicians in risk stratification. Green et al<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> developed the Cyclophosphamide Equivalent Dose (CED) calculator to facilitate universal risk stratification independent of the population (<a href="https://fertilitypreservationpittsburgh.org/fertility-resources/fertility-risk-calculator/">https://fertilitypreservationpittsburgh.org/fertility-resources/fertility-risk-calculator/</a>). Clark et al. developed an online tool to predict the risk of ovarian failure after treatment.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> Knowledge and use of these tools by specialists allows the identification girls/adolescents at risk following diagnosis and development of a treatment plan. The retrospective use of these tools in our study indicated that 97% of survivors in the sample were at high risk of POI.</p><p id="par0180" class="elsevierStylePara elsevierViewall">In our study, POI was diagnosed in 19 girls that had not undergone puberty or menarche, of who 47% were not in follow-up by an endocrinologist nor undergoing monitoring or hormone levels due to a lack of suspicion. Introducing the routine use of the tools and guidelines described above would contribute substantially to early diagnosis, which carries significant benefits.</p><p id="par0185" class="elsevierStylePara elsevierViewall">The findings in our study were consistent with the predictions of these tools, as all patients with POI had abnormal levels of FSH and oestradiol 63% (<span class="elsevierStyleItalic">n</span> = 19) had no signs of puberty.</p><p id="par0190" class="elsevierStylePara elsevierViewall">The level of AMH is not recommended as a criterion for diagnosis of POI, as low values may be due to toxicity and to the disease in general. Low values of AMH adolescents or young adults do not preclude the possibility of pregnancy. Furthermore, the interpretation of AMH values in the paediatric population is complicated, as the levels increase throughout childhood until adulthood to then decrease with menopause. Overall, with the exception of a study conducted by Van der Kooi et al.,<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> there have been no differences in AMH levels after treatment in prepubertal vs postpubertal patients. Most published studies have also found no differences in the levels of adult survivors of childhood or adolescent cancers compared to the general population.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">The combination of FSH elevation and undetectable or low levels of AMH is associated with POI. This was confirmed in our study in the patients in whom AMH levels had been measured (23%), in whom AMH levels were decreased and FSH levels elevated.</p><p id="par0200" class="elsevierStylePara elsevierViewall">In the follow-up of female cancer survivors, AMH levels have been found to be useful to detect poor ovarian reserve and identify the need for close monitoring.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> Another method used to monitor ovarian reserve in adult women is the transvaginal ultrasound scan. As is the case of AMH, transvaginal sonography is not recommended as a criterion for the definition of POI. Its applicability in childhood and adolescence is limited. In our study, this test had only been performed in 10 of the patients (33%), and the findings were pathological, with fewer than 10 follicles, in 90% of them.</p><p id="par0205" class="elsevierStylePara elsevierViewall">Despite advances in oncofertility, such as the development of guidelines or tools to identify patients at risk,<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> as noted above, our study found that the monitoring of the risk of POI was only adequate in 11 patients (37%), even though the entire sample consisted of patients at high risk. In addition, the proportion that had undergone fertility preservation interventions before starting treatment or developing POI was low (17%). <a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a> summarises the recommendations and the tools currently available for the follow-up of women at risk of developing POI.</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Limitations of the study</span><p id="par0210" class="elsevierStylePara elsevierViewall">At presence, there is preliminary evidence on the use of anthracyclines and the increased risk of POI,<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> while the effect on the gonads of novel treatments like monoclonal antibodies, bevacizumab or tyrosine-kinase inhibitors, among others, is unknown.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> These risk factors were not taken into account in our study and could be analysed in future studies.</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conclusion</span><p id="par0215" class="elsevierStylePara elsevierViewall">The use of the tools currently available to estimate the risk of POI allows the education of patients and/or families regarding potential adverse events and can guide the development of a follow-up plan, including monitoring and referral to the appropriate specialists. There is significant room for improvement in this field in Spain, and improvement could yield substantial health benefits. Chief among them is the possibility of fertility preservation prior to the development of POI in survivors of childhood cancer in which such an intervention was not contemplated or possible before initiation of treatment.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> It would also allow early initiation of hormone replacement therapy, which has been found to decrease the morbidity secondary to cardiovascular disease, decreased bone density and psychological distress. The involvement of endocrinology and gynaecology specialists in the follow-up of these patients is essential.</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Funding</span><p id="par0220" class="elsevierStylePara elsevierViewall">This research did not receive any external funding.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conflicts of interest</span><p id="par0225" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:15 [ 0 => array:3 [ "identificador" => "xres2054687" "titulo" => "Graphical abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:3 [ "identificador" => "xres2054686" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0010" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0015" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0020" "titulo" => "Material and methods" ] 3 => array:2 [ "identificador" => "abst0025" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0030" "titulo" => "Conclusions" ] ] ] 2 => array:2 [ "identificador" => "xpalclavsec1754408" "titulo" => "Keywords" ] 3 => array:3 [ "identificador" => "xres2054688" "titulo" => "Resumen" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0035" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0040" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0045" "titulo" => "Material y métodos" ] 3 => array:2 [ "identificador" => "abst0050" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0055" "titulo" => "Conclusiones" ] ] ] 4 => array:2 [ "identificador" => "xpalclavsec1754409" "titulo" => "Palabras clave" ] 5 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 6 => array:2 [ "identificador" => "sec0010" "titulo" => "Objective" ] 7 => array:2 [ "identificador" => "sec0015" "titulo" => "Material and methods" ] 8 => array:3 [ "identificador" => "sec0020" "titulo" => "Patients" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Inclusion criteria" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Exclusion criteria" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Data collection" ] 3 => array:2 [ "identificador" => "sec0040" "titulo" => "Statistical analysis" ] ] ] 9 => array:2 [ "identificador" => "sec0045" "titulo" => "Results" ] 10 => array:3 [ "identificador" => "sec0050" "titulo" => "Discussion" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0055" "titulo" => "Limitations of the study" ] ] ] 11 => array:2 [ "identificador" => "sec0060" "titulo" => "Conclusion" ] 12 => array:2 [ "identificador" => "sec0065" "titulo" => "Funding" ] 13 => array:2 [ "identificador" => "sec0070" "titulo" => "Conflicts of interest" ] 14 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2023-05-22" "fechaAceptado" => "2023-09-24" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1754408" "palabras" => array:9 [ 0 => "Primary ovarian insufficiency" 1 => "Solid tumours" 2 => "Childhood" 3 => "Adolescence" 4 => "Cancer" 5 => "Survivors" 6 => "Fertility" 7 => "Menopause" 8 => "Gonadal dysfunction" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1754409" "palabras" => array:9 [ 0 => "Insuficiencia ovárica prematura" 1 => "Tumor sólido" 2 => "Infancia" 3 => "Adolescencia" 4 => "Cáncer" 5 => "Supervivientes" 6 => "Fertilidad" 7 => "Menopausia" 8 => "Disfunción gonadal" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introduction</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Primary ovarian insufficiency (POI) carries significant morbidity, causing infertility, sexual disfunction, decreased bone density, cardiovascular risk, emotional distress and early mortality.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Objective</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">To know the incidence and current management of POI in childhood/adolescent solid tumour survivors.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Material and methods</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">We conducted a multicentre observational study. It included female patients aged 12–18 years with a diagnosis of solid tumour and meeting clinical or biochemical criteria for POI. The risk was estimated based on the criteria of the Pediatric Initiative Network of the Oncofertility Consortium.</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Results</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">We found an incidence of 1.5 (30 cases of POI): The median age at the time of the event was 14 years (standard deviation, 2.09). The solid tumours associated most frequently with POI were Ewing sarcoma and brain and germ cell tumours. Eighty-three percent of patients did not undergo fertility preservation. Sixty-three percent reported not having undergone menarche at the time of ovarian failure. Ninety-seven percent were at high risk of gonadal toxicity, yet 47% were not monitored before the diagnosis. The median time elapsed to the occurrence of the event was 43.5 months after diagnosis and 29.5 months after completing treatment. The Kaplan-Meier curves showed that approximately 30% of POI cases developed within 2 years of diagnosis and that women at Tanner stage 1 developed insufficiency later than women at Tanner stage 5.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclusions</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">There is room for improvement in the follow-up of women at risk of POI in Spain. The tools currently available facilitate risk assessment at the time of treatment planning and allow the implementation of monitoring, education, early diagnosis, fertility preservation, and replacement therapy as needed. All of this would achieve significant improvement in health outcomes.</p></span>" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0010" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0015" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0020" "titulo" => "Material and methods" ] 3 => array:2 [ "identificador" => "abst0025" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0030" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Introducción</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">La insuficiencia ovárica prematura (POI) conlleva importante morbilidad, causando infertilidad, disfunción sexual, disminución de la densidad ósea, riesgo cardiovascular, alteraciones emocionales y mortalidad precoz.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Objetivo</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Conocer la incidencia y manejo actual de POI en supervivientes a un tumor sólido en la infancia y / o adolescencia en nuestro medio.</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Material y métodos</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Estudio observacional multicéntrico. Mujeres entre 12 y 18 años con diagnóstico de tumor sólido y criterios clínicos y/o analíticos de POI. El riesgo se estima según los criterios” The Pediatric Initiative Network of the Oncofertility Consortium”.</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Resultados</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Incidencia de 1.5 (30 casos de POI). Mediana de edad 14 ± 2,09. Los tumores sólidos que más se asociaron a POI fueron: sarcoma de Ewing, tumores cerebrales y germinales. El 83% de los casos no realizó preservación previa al tratamiento. Un 63% no referían menarquia al diagnóstico de POI. 97% cumplían criterios de alto riesgo de toxicidad gonadal, a pesar de ello el 47% no realizó ninguna vigilancia previa al diagnóstico. La mediana de tiempo tras el diagnóstico y la aparición del evento es de 43,5 y 29,5 meses tras finalizar tratamiento. Las curvas de Kaplan- Meier, muestran que a el 30% de los casos, aparecen en los dos años tras el diagnóstico y las mujeres con estadio puberal 1 desarrollan insuficiencia más tardíamente que aquellas con estadio 5.</p></span> <span id="abst0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conclusiones</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">El seguimiento de mujeres en riesgo de POI, es susceptible de mejora. Las herramientas actuales facilitan conocer el riesgo al planificar los tratamientos del tumor y realizar vigilancia, educación, diagnóstico precoz, preservación e instauración de tratamiento sustitutivo. Todo ello, supondría importantes mejoras en salud.</p></span>" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0035" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0040" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0045" "titulo" => "Material y métodos" ] 3 => array:2 [ "identificador" => "abst0050" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0055" "titulo" => "Conclusiones" ] ] ] ] "multimedia" => array:5 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 930 "Ancho" => 1675 "Tamanyo" => 57029 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Kaplan-Meier curve showing the time elapsed from diagnosis of the solid tumour to the development of premature ovarian insufficiency.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1051 "Ancho" => 1675 "Tamanyo" => 88807 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Differences in the occurrence of the event based on stage of pubertal development of the patient at the time of diagnosis of the solid tumour.</p>" ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 997 "Ancho" => 1675 "Tamanyo" => 96883 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Curve showing the time of development of premature ovarian insufficiency based on the type of solid tumour.</p>" ] ] 3 => array:8 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 4090 "Ancho" => 2925 "Tamanyo" => 838384 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Recommendations for the management of girls and female adolescents at risk of developing premature ovarian insufficiency following treatment for a solid tumour.</p>" ] ] 4 => array:5 [ "identificador" => "fig0025" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 826 "Ancho" => 1333 "Tamanyo" => 181257 ] ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:33 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cancer statistics for adolescents and young adults, 2020" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "K.D. Miller" 1 => "M. Fidler-Benaoudia" 2 => "T.H. Keegan" 3 => "H.S. Hipp" 4 => "A. Jemal" 5 => "R.L. Siegel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3322/caac.21637" "Revista" => array:5 [ "tituloSerie" => "CA A Cancer J Clin" "fecha" => "2020" "volumen" => "70" "paginaInicial" => "443" "paginaFinal" => "459" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Health-related quality-of-life among patients with premature ovarian insufficiency: A systematic review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "X.T. Li" 1 => "P.Y. Li" 2 => "Y. Liu" 3 => "H.S. Yang" 4 => "L.Y. He" 5 => "Y.G. Fang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s11136-019-02326-2" "Revista" => array:6 [ "tituloSerie" => "Qual Life Res" "fecha" => "2020" "volumen" => "29" "paginaInicial" => "19" "paginaFinal" => "36" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31620985" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Premature Ovarian Insufficiency: Past, Present, and Future" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S.J. Chon" 1 => "Z. Umair" 2 => "M.S. Yoon" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3389/fcell.2021.672890" "Revista" => array:3 [ "tituloSerie" => "Front Cell Dev Biol" "fecha" => "2021" "volumen" => "9" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chronic Health Conditions in Adult Survivors of Childhood Cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.C. Oeffinger" 1 => "A.C. Mertens" 2 => "C.A. Sklar" 3 => "T. Kawashima" 4 => "M.H. Hudson" 5 => "A.T. Meadows" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMsa060185" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2006" "volumen" => "355" "paginaInicial" => "1572" "paginaFinal" => "1582" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17035650" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chemotherapy-related late adverse effects on ovarian function in female survivors of childhood and young adult cancer: A systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Overbeek" 1 => "M.H. van den Berg" 2 => "F.E. van Leeuwen" 3 => "G.J.L. Kaspers" 4 => "C.B. Lambalk" 5 => "E. van Dulmen-den Broeder" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ctrv.2016.11.006" "Revista" => array:6 [ "tituloSerie" => "Cancer Treat Rev" "fecha" => "2017" "volumen" => "53" "paginaInicial" => "10" "paginaFinal" => "24" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28056411" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Current Understanding of the Etiology, Symptomatology, and Treatment Options in Premature Ovarian Insufficiency (POI)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "B. Ishizuka" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3389/fendo.2021.626924" "Revista" => array:3 [ "tituloSerie" => "Front Endocrinol" "fecha" => "2021" "volumen" => "12" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fertility Preservation and Long-Term Monitoring of Gonadotoxicity in Girls, Adolescents and Young Adults Undergoing Cancer Treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "K. Michalczyk" 1 => "A. Cymbaluk-Płoska" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3390/cancers13020202" "Revista" => array:5 [ "tituloSerie" => "Cancers" "fecha" => "2021" "volumen" => "13" "paginaInicial" => "202" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33429908" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Multidisciplinary consensus on the criteria for fertility preservation in cancer patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Santaballa" 1 => "C. Márquez-Vega" 2 => "Á Rodríguez-Lescure" 3 => "Á. Rovirosa" 4 => "L. Vázquez" 5 => "I. Zeberio-Etxetxipia" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s12094-021-02699-2" "Revista" => array:6 [ "tituloSerie" => "Clin Transl Oncol" "fecha" => "2022" "volumen" => "24" "paginaInicial" => "227" "paginaFinal" => "243" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34635959" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recommendations for gonadotoxicity surveillance in male childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "R. Skinner" 1 => "R.L. Mulder" 2 => "L.C. Kremer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S1470-2045(17)30026-8" "Revista" => array:6 [ "tituloSerie" => "Lancet Oncol" "fecha" => "2017" "volumen" => "18" "paginaInicial" => "e75" "paginaFinal" => "e90" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28214419" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Molecular Mechanism and Prevention Strategy of Chemotherapy- and Radiotherapy-Induced Ovarian Damage" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "S. Kim" 1 => "S.W. Kim" 2 => "S.J. Han" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3390/ijms22147484" "Revista" => array:5 [ "tituloSerie" => "IJMS" "fecha" => "2021" "volumen" => "22" "paginaInicial" => "7484" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34299104" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The PanCareFollowUp Care Intervention: A European harmonised approach to person-centred guideline-based survivorship care after childhood, adolescent and young adult cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "R.J. van Kalsbeek" 1 => "R.L. Mulder" 2 => "R. Haupt" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ejca.2021.10.035" "Revista" => array:6 [ "tituloSerie" => "Eur J Cancer" "fecha" => "2022" "volumen" => "162" "paginaInicial" => "34" "paginaFinal" => "44" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34953441" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "European PanCareFollowUp Recommendations for surveillance of late effects of childhood, adolescent, and young adult cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "R.J. van Kalsbeek" 1 => "H.J.H. van der Pal" 2 => "L.C.M. Kremer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ejca.2021.06.004" "Revista" => array:5 [ "tituloSerie" => "Eur J Cancer" "fecha" => "2021" "volumen" => "154" "paginaInicial" => "316" "paginaFinal" => "328" ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Assessment of ovarian function in adolescents and young adults after childhood cancer treatment—How accurate are young adult/parent proxy‐reported outcomes?" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.A. George" 1 => "R. Williamson Lewis" 2 => "L. McKenzie" 3 => "B. Cherven" 4 => "B.C. Patterson" 5 => "K.E. Effinger" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/pbc.27981" "Revista" => array:3 [ "tituloSerie" => "Pediatr Blood Cancer" "fecha" => "2019" "volumen" => "66" ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Standardizing Risk Assessment for Treatment-Related Gonadal Insufficiency and Infertility in Childhood Adolescent and Young Adult Cancer: The Pediatric Initiative Network Risk Stratification System" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "L.R. Meacham" 1 => "K. Burns" 2 => "K.E. Orwig" 3 => "J. Levine" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1089/jayao.2020.0012" "Revista" => array:6 [ "tituloSerie" => "J Adolesc Young Adult Oncol" "fecha" => "2020" "volumen" => "9" "paginaInicial" => "662" "paginaFinal" => "666" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32456570" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Premature ovarian insufficiency – aetiopathology, epidemiology, and diagnostic evaluation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Rudnicka" 1 => "J. Kruszewska" 2 => "K. Klicka" 3 => "J. Kowalczyk" 4 => "M. Grymowicz" 5 => "J. Skórska" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5114/pm.2018.78550" "Revista" => array:6 [ "tituloSerie" => "Prz Menopauzalny" "fecha" => "2018" "volumen" => "17" "paginaInicial" => "105" "paginaFinal" => "108" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30357004" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cancer statistics, 2017" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "R.L. Siegel" 1 => "K.D. Miller" 2 => "A. Jemal" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3322/caac.21387" "Revista" => array:6 [ "tituloSerie" => "CA Cancer J Clin" "fecha" => "2017" "volumen" => "67" "paginaInicial" => "7" "paginaFinal" => "30" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28055103" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reproductive Complications in Childhood Cancer Survivors" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "H.M. van Santen" 1 => "M.D. van de Wetering" 2 => "A.M.E. Bos" 3 => "M.M. vd Heuvel-Eibrink" 4 => "H.J. van der Pal" 5 => "W.H. Wallace" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.pcl.2020.08.003" "Revista" => array:6 [ "tituloSerie" => "Pediatr Clin North Am" "fecha" => "2020" "volumen" => "67" "paginaInicial" => "1187" "paginaFinal" => "1202" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33131541" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Quality of life among female childhood cancer survivors with and without premature ovarian insufficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. Ida" 1 => "G.K. Alicia" 2 => "F. Anna" 3 => "I. Leijonhufvud" 4 => "A. Nyström" 5 => "M Helenaet" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s11764-021-00987-y" "Revista" => array:5 [ "tituloSerie" => "J Cancer Surviv" "fecha" => "2023" "volumen" => "17" "paginaInicial" => "101" "paginaFinal" => "109" ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chronic Health Conditions in Adult Survivors of Childhood Cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "K.C. Oeffinger" 1 => "A.C. Mertens" 2 => "C.A. Sklar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMsa060185" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2006" "volumen" => "355" "paginaInicial" => "1572" "paginaFinal" => "1582" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17035650" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Premature ovarian insufficiency in female adolescent and young adult survivors of non-gynecological cancers: a population-based cohort study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S.B. Flatt" 1 => "A. Baillargeon" 2 => "C. McClintock" 3 => "J. Pudwell" 4 => "M.P. Velez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s12978-022-01559-8" "Revista" => array:5 [ "tituloSerie" => "Reprod Health" "fecha" => "2023" "volumen" => "20" "paginaInicial" => "4" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/36593491" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fertility of Female Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.M. Green" 1 => "T. Kawashima" 2 => "M. Stovall" 3 => "W. Leisenring" 4 => "C.A. Sklar" 5 => "A.C. Mertens" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2008.20.1541" "Revista" => array:5 [ "tituloSerie" => "JCO" "fecha" => "2009" "volumen" => "27" "paginaInicial" => "2677" "paginaFinal" => "2685" ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ovarian function after autologous bone marrow transplantation in childhood: High-dose busulfan is a major cause of ovarian failure" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "C. Teinturier" 1 => "O. Hartmann" 2 => "D. Valteau-Couanet" 3 => "E. Benhamou" 4 => "P. Bougneres" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/sj.bmt.1701483" "Revista" => array:5 [ "tituloSerie" => "Bone Marrow Transplant" "fecha" => "1998" "volumen" => "22" "paginaInicial" => "989" "paginaFinal" => "994" ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nonsurgical premature menopause and reproductive implications in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study: NSPM and Reproductive Implications" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.M. Levine" 1 => "J.A. Whitton" 2 => "J.P. Ginsberg" 3 => "D.M. Green" 4 => "W. Leisenring" 5 => "M. Stovall" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/cncr.31121" "Revista" => array:5 [ "tituloSerie" => "Cancer" "fecha" => "2018" "volumen" => "124" "paginaInicial" => "1044" "paginaFinal" => "1052" ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fertility Considerations in Pediatric and Adolescent Patients Undergoing Cancer Therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "T.B. Lautz" 1 => "K. Burns" 2 => "E.E. Rowell" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.soc.2020.11.009" "Revista" => array:5 [ "tituloSerie" => "Surg Oncol Clin North Am" "fecha" => "2021" "volumen" => "30" "paginaInicial" => "401" "paginaFinal" => "415" ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fertility Preservation in Female Pediatric Patients With Cancer: A Clinical and Regulatory Issue" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S. Brancati" 1 => "L. Gozzo" 2 => "L. Longo" 3 => "D.C. Vitale" 4 => "G. Russo" 5 => "F. Drago" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3389/fonc.2021.641450" "Revista" => array:3 [ "tituloSerie" => "Front Oncol" "fecha" => "2021" "volumen" => "11" ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Predicting acute ovarian failure in female survivors of childhood cancer: A cohort study in the Childhood Cancer Survivor Study (CCSS) and the St Jude Lifetime Cohort (SJLIFE)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "R.A. Clark" 1 => "S. Mostoufi-Moab" 2 => "Y. Yasui" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S1470-2045(19)30818-6" "Revista" => array:6 [ "tituloSerie" => "Lancet Oncol" "fecha" => "2020" "volumen" => "21" "paginaInicial" => "436" "paginaFinal" => "445" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32066539" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Changes in Anti-Müllerian Hormone and Inhibin B in Children Treated for Cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A.L.L.F. van der Kooi" 1 => "M.M. van den Heuvel-Eibrink" 2 => "S.A.A. van den Berg" 3 => "W. van Dorp" 4 => "S.M.F. Pluijm" 5 => "J.S.E. Laven" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1089/jayao.2018.0130" "Revista" => array:5 [ "tituloSerie" => "J AdolescYoung Adult Oncol" "fecha" => "2019" "volumen" => "8" "paginaInicial" => "281" "paginaFinal" => "290" ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anti-Müllerian hormone as a marker of ovarian reserve and premature ovarian insufficiency in children and women with cancer: A systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "R.A. Anderson" 1 => "D. Cameron" 2 => "F. Clatot" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/humupd/dmac004" "Revista" => array:6 [ "tituloSerie" => "Hum Reprod Update" "fecha" => "2022" "volumen" => "28" "paginaInicial" => "417" "paginaFinal" => "434" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/35199161" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0145" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Uses of anti-Müllerian hormone (AMH) measurement before and after cancer treatment in women" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C.E. Dunlop" 1 => "R.A. Anderson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.maturitas.2014.12.005" "Revista" => array:6 [ "tituloSerie" => "Maturitas" "fecha" => "2015" "volumen" => "80" "paginaInicial" => "245" "paginaFinal" => "250" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25596814" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0150" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Global oncofertility index—data gap slows progress†" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "S.F. de Roo" 1 => "A.S. Rashedi" 2 => "C.C.M. Beerendonk" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/biolre/iox051" "Revista" => array:6 [ "tituloSerie" => "Biol Reprod" "fecha" => "2017" "volumen" => "96" "paginaInicial" => "1124" "paginaFinal" => "1128" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28575176" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0155" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Doxorubicin Has Dose-Dependent Toxicity on Mouse Ovarian Follicle Development, Hormone Secretion, and Oocyte Maturation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S. Xiao" 1 => "J. Zhang" 2 => "M. Liu" 3 => "H. Iwahata" 4 => "H.B. Rogers" 5 => "T.K. Woodruff" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/toxsci/kfx047" "Revista" => array:6 [ "tituloSerie" => "Toxicol Sci" "fecha" => "2017" "volumen" => "157" "paginaInicial" => "320" "paginaFinal" => "329" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28329872" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0160" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Will Imatinib Compromise Reproductive Capacity?" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "A.M. Zamah" 1 => "M.J. Mauro" 2 => "B.J. Druker" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1634/theoncologist.2011-0137" "Revista" => array:6 [ "tituloSerie" => "Oncologist" "fecha" => "2011" "volumen" => "16" "paginaInicial" => "1422" "paginaFinal" => "1427" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21948652" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0165" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sexual function of women with premature ovarian failure" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "D.M. Bueno de Almeida" 1 => "C.L. Benetti-Pinto" 2 => "M.Y. Makuch" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/gme.0b013e3181f4318d" "Revista" => array:6 [ "tituloSerie" => "Menopause" "fecha" => "2011" "volumen" => "18" "paginaInicial" => "262" "paginaFinal" => "266" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21127440" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23412879/0000009900000006/v1_202312211250/S2341287923002612/v1_202312211250/en/main.assets" "Apartado" => array:4 [ "identificador" => "26005" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original Articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23412879/0000009900000006/v1_202312211250/S2341287923002612/v1_202312211250/en/main.pdf?idApp=UINPBA00005H&text.app=https://analesdepediatria.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287923002612?idApp=UINPBA00005H" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 77 | 46 | 123 |
| 2024 September | 65 | 39 | 104 |
| 2024 August | 109 | 65 | 174 |
| 2024 July | 85 | 25 | 110 |
| 2024 June | 61 | 24 | 85 |
| 2024 May | 86 | 53 | 139 |
| 2024 April | 79 | 29 | 108 |
| 2024 March | 89 | 32 | 121 |
| 2024 February | 136 | 27 | 163 |
| 2024 January | 146 | 34 | 180 |
| 2023 December | 123 | 50 | 173 |
| 2023 November | 47 | 44 | 91 |
