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Compelling body of evidence exists to use bevacizumab, a humanized monoclonal anti-VEGF antibody, in selected paediatric patients with low-grade CNS tumours. Common toxicities of bevacizumab, hypertension, proteinuria, epistaxis, mucosal perforation, decreased wound healing are well reported. However, the effect of bevacizumab on female ovarian function and long-term fertility is still being documented. Current evidence for bevacizumab-associated decline in ovarian function is largely from breast and colon cancer cohorts where exposure to multimodal chemotherapy confounds causative relationships. Fertility counseling and oocyte cryopreservation is currently offered as standard of care to post-pubertal females at high risk of infertility due to high-dose radiation and chemotherapy. Adolescent females with low-grade CNS tumours on bevacizumab represent a unique population which could potentially be at high risk for infertility. We report 2 cases of adolescent girls treated with bevacizumab as a single agent and in combination with vinblastine for NF2-associated vestibular schwannomas and brainstem glioma respectively. Both patients were postpubertal with established menstrual cycles and normal baseline FSH/LH/ oestradiol/AMH values prior to commencement of therapy. They became amenorrhoeic shortly after starting of therapy with levels of FSH/LH/oestradiol suggestive of premature ovarian failure. One patient has remained asymptomatic, whereas the other has developed profound post-menopausal symptoms interfering with quality of life which necessitated commencement of hormone-replacement therapy. Appropriate pretreatment fertility investigation and consultation should be offered to all post-pubertal females starting on bevacizumab. Further research into the long-term effects of gonadal toxicity in both females and males with drugs inhibiting angiogenesis is needed.

Compelling body of evidence exists to use bevacizumab, a humanized monoclonal anti-VEGF antibody, in selected paediatric patients with low-grade CNS tumours. Common toxicities of bevacizumab, hypertension, proteinuria, epistaxis, mucosal perforation, decreased wound healing are well reported. However, the effect of bevacizumab on female ovarian function and long-term fertility is still being documented. Current evidence for bevacizumab-associated decline in ovarian function is largely from breast and colon cancer cohorts where exposure to multimodal chemotherapy confounds causative relationships. Fertility counseling and oocyte cryopreservation is currently offered as standard of care to post-pubertal females at high risk of infertility due to high-dose radiation and chemotherapy. Adolescent females with low-grade CNS tumours on bevacizumab represent a unique population which could potentially be at high risk for infertility. We report 2 cases of adolescent girls treated with bevacizumab as a single agent and in combination with vinblastine for NF2-associated vestibular schwannomas and brainstem glioma respectively. Both patients were postpubertal with established menstrual cycles and normal baseline FSH/LH/ oestradiol/AMH values prior to commencement of therapy. They became amenorrhoeic shortly after starting of therapy with levels of FSH/LH/oestradiol suggestive of premature ovarian failure. One patient has remained asymptomatic, whereas the other has developed profound post-menopausal symptoms interfering with quality of life which necessitated commencement of hormone-replacement therapy. Appropriate pretreatment fertility investigation and consultation should be offered to all post-pubertal females starting on bevacizumab. Further research into the long-term effects of gonadal toxicity in both females and males with drugs inhibiting angiogenesis is needed.

Functional hypothalamic amenorrhea, FHA, is the clinical diagnosis for a woman in whommenstrual periods have been absent for three months or longer and where no other organic ormedical explanation is found. The aim was to explore characteristics and life experiencesamong women showing signs of FHA and to investigate what diagnoses and treatment/advicethey received when seeking medical help. Self-reported data were collected via an onlinesurvey. Descriptive data were presented regarding global representation, education levels,characteristics, life experiences, diagnoses, treatment/advice, treatment satisfaction, recoverysuccess and congruence between undertaken lifestyle changes and treatment/advice.Respondents consisted of 1,035 women from 71 different countries. The results showedcommon characteristics among respondents: the majority reported body appearancedissatisfaction, drive for thinness, high expectations of oneself, anxiety, obsessive behavioursand perfectionism. Life experiences were childhood bullying, loneliness and having a closerelative with mental health issues. Less than half of the participants received the diagnosisFHA and roughly a third did not receive any diagnosis/were told nothing was wrong. One infive were not given any treatment/advice that would help them regain their menstrual period.Ninety-three percent of those who recovered stated that they had gained weight, engaged lessin physical activity and/or undertaken cognitive behavioural therapy. Seventy-two percentwere dissatisfied with the treatment/advice they were given. In conclusion, the results fromthis study point to FHA as an underdiagnosed/misdiagnosed, neglected and mistreatedmedical condition and public health issue affecting women globally., SAMMANFATTNING Funktionell hypotalamisk amenorré, FHA, är den kliniska diagnosen för en kvinna som varitutan menstruation i tre månader eller längre, där ingen annan organisk eller medicinskförklaring hittats. Syftet var att utforska förekomsten av personlighetsdrag ochlivserfarenheter bland kvinnor med kliniska tecken på FHA och att undersöka vilka diagnoseroch behandling/råd de fått när de sökt vård. Självrapporterad data inhämtades viainternetbaserade frågeformulär. Deskriptiv data presenterades avseende global representation,utbildningsnivå, personlighetsdrag, livserfarenheter, erhållna diagnoser, erhållnaråd/behandling, tillfredsställelse med behandling, behandlingsframgång och samstämmighetmellan livsstilsförändringar och erhållna råd/behandling. Svarspersonerna bestod av 1 035kvinnor från 71 olika länder. Resultaten visade gemensamma personlighetsdrag blandsvarspersonerna: majoriteten rapporterade kroppsmissnöje (utseendemässigt), strävan eftersmal kropp, höga förväntningar på sig själv, ångest/oro, tvångsmässiga beteenden ochperfektionism. Livserfarenheter var mobbning under barndomen, ensamhet och att ha ensläkting med psykisk ohälsa. Mindre än hälften fick diagnosen FHA och ungefär en tredjedelfick ingen diagnos/fick höra att ingenting var fel. En av fem fick ingen behandling/råd somhade kunnat hjälpa dem att återfå sin menstruation. Sjuttiotre procent var missnöjda medbehandlingen/råden de fick av sin läkare. Nittiotre procent av de som återfick sinmenstruation uppgav att de hade gått upp i vikt, ägnat sig mindre åt fysisk aktivitet och/ellergenomgått kognitiv beteendeterapi. Sjuttiotvå procent var missnöjda med den behandling/rådde gavs. Sammanfattningsvis pekar resultaten från denna studie mot att FHA är ettunderdiagnostiserat/feldiagnostiserat, negligerat och felbehandlat medicinskt tillstånd ochfolkhälsoproblem som drabbar kvinnor över hela världen.

Functional hypothalamic amenorrhea, FHA, is the clinical diagnosis for a woman in whommenstrual periods have been absent for three months or longer and where no other organic ormedical explanation is found. The aim was to explore characteristics and life experiencesamong women showing signs of FHA and to investigate what diagnoses and treatment/advicethey received when seeking medical help. Self-reported data were collected via an onlinesurvey. Descriptive data were presented regarding global representation, education levels,characteristics, life experiences, diagnoses, treatment/advice, treatment satisfaction, recoverysuccess and congruence between undertaken lifestyle changes and treatment/advice.Respondents consisted of 1,035 women from 71 different countries. The results showedcommon characteristics among respondents: the majority reported body appearancedissatisfaction, drive for thinness, high expectations of oneself, anxiety, obsessive behavioursand perfectionism. Life experiences were childhood bullying, loneliness and having a closerelative with mental health issues. Less than half of the participants received the diagnosisFHA and roughly a third did not receive any diagnosis/were told nothing was wrong. One infive were not given any treatment/advice that would help them regain their menstrual period.Ninety-three percent of those who recovered stated that they had gained weight, engaged lessin physical activity and/or undertaken cognitive behavioural therapy. Seventy-two percentwere dissatisfied with the treatment/advice they were given. In conclusion, the results fromthis study point to FHA as an underdiagnosed/misdiagnosed, neglected and mistreatedmedical condition and public health issue affecting women globally., SAMMANFATTNING Funktionell hypotalamisk amenorré, FHA, är den kliniska diagnosen för en kvinna som varitutan menstruation i tre månader eller längre, där ingen annan organisk eller medicinskförklaring hittats. Syftet var att utforska förekomsten av personlighetsdrag ochlivserfarenheter bland kvinnor med kliniska tecken på FHA och att undersöka vilka diagnoseroch behandling/råd de fått när de sökt vård. Självrapporterad data inhämtades viainternetbaserade frågeformulär. Deskriptiv data presenterades avseende global representation,utbildningsnivå, personlighetsdrag, livserfarenheter, erhållna diagnoser, erhållnaråd/behandling, tillfredsställelse med behandling, behandlingsframgång och samstämmighetmellan livsstilsförändringar och erhållna råd/behandling. Svarspersonerna bestod av 1 035kvinnor från 71 olika länder. Resultaten visade gemensamma personlighetsdrag blandsvarspersonerna: majoriteten rapporterade kroppsmissnöje (utseendemässigt), strävan eftersmal kropp, höga förväntningar på sig själv, ångest/oro, tvångsmässiga beteenden ochperfektionism. Livserfarenheter var mobbning under barndomen, ensamhet och att ha ensläkting med psykisk ohälsa. Mindre än hälften fick diagnosen FHA och ungefär en tredjedelfick ingen diagnos/fick höra att ingenting var fel. En av fem fick ingen behandling/råd somhade kunnat hjälpa dem att återfå sin menstruation. Sjuttiotre procent var missnöjda medbehandlingen/råden de fick av sin läkare. Nittiotre procent av de som återfick sinmenstruation uppgav att de hade gått upp i vikt, ägnat sig mindre åt fysisk aktivitet och/ellergenomgått kognitiv beteendeterapi. Sjuttiotvå procent var missnöjda med den behandling/rådde gavs. Sammanfattningsvis pekar resultaten från denna studie mot att FHA är ettunderdiagnostiserat/feldiagnostiserat, negligerat och felbehandlat medicinskt tillstånd ochfolkhälsoproblem som drabbar kvinnor över hela världen.

Hyperprolactinemia in premenopausal women often presents with amenorrhea, symptoms of estrogen deficiency and sub-fertility. After exclusion of other common causes and in the context of a normal pituitary MRI scan, hyperprolactinemia is typically deemed "idiopathic." Here we present a case where excess prolactin secretion was attributed to a uterine fibroid and following myomectomy the hyperprolactinemia and its clinical sequelae resolved. Following 6 years of secondary infertility, a 41-year-old woman presented with secondary amenorrhea, expressible galactorrhea, and symptoms of estrogen deficiency. Prolactin levels were consistently raised (1300 mU/L to 2100 mU/L, reference interval < 600 mU/L), and repeated pituitary imaging demonstrated no pituitary abnormality. Prolactin levels demonstrated a paradoxical rise in response to dopamine agonist therapy (2000 mU/L to 5900 mU/L). Imaging demonstrated a uterine fibroid and the patient underwent myomectomy. Following myomectomy, prolactin levels became undetectable, galactorrhea and symptoms of estrogen deficiency resolved, menses returned, and a planned unassisted pregnancy followed. Ectopic prolactin secretion from uterine fibroids is a rare cause of hyperprolactinemia and can result in the same clinical sequelae as pituitary causes. As ectopic prolactin secretion is not under inhibitory control of dopamine, it is usually resistant to, or may rise in response to, dopamine agonist therapy. Prior to a diagnosis of "idiopathic" hyperprolactinemia, ectopic sources of prolactin should be considered.Copyright © 2020, Springer Nature Switzerland AG.

Hyperprolactinemia in premenopausal women often presents with amenorrhea, symptoms of estrogen deficiency and sub-fertility. After exclusion of other common causes and in the context of a normal pituitary MRI scan, hyperprolactinemia is typically deemed "idiopathic." Here we present a case where excess prolactin secretion was attributed to a uterine fibroid and following myomectomy the hyperprolactinemia and its clinical sequelae resolved. Following 6 years of secondary infertility, a 41-year-old woman presented with secondary amenorrhea, expressible galactorrhea, and symptoms of estrogen deficiency. Prolactin levels were consistently raised (1300 mU/L to 2100 mU/L, reference interval < 600 mU/L), and repeated pituitary imaging demonstrated no pituitary abnormality. Prolactin levels demonstrated a paradoxical rise in response to dopamine agonist therapy (2000 mU/L to 5900 mU/L). Imaging demonstrated a uterine fibroid and the patient underwent myomectomy. Following myomectomy, prolactin levels became undetectable, galactorrhea and symptoms of estrogen deficiency resolved, menses returned, and a planned unassisted pregnancy followed. Ectopic prolactin secretion from uterine fibroids is a rare cause of hyperprolactinemia and can result in the same clinical sequelae as pituitary causes. As ectopic prolactin secretion is not under inhibitory control of dopamine, it is usually resistant to, or may rise in response to, dopamine agonist therapy. Prior to a diagnosis of "idiopathic" hyperprolactinemia, ectopic sources of prolactin should be considered.Copyright © 2020, Springer Nature Switzerland AG.

In the study group of 92 girls aged 13 to 17 years with secondary amenorrhea (SA), and the control group of 54 age-matched girls with regular menstrual cycle, the levels of testosterone and sex hormone-binding globulin (SHBG) have been estimated; free androgen index (FAI) has been calculated. Not only normal or increased FAI values, but also low FAI levels have been found. The FAI value was connected to the intensity of hirsutism syndrome, the duration of amenorrhea, the values of the body weight index and the menarche date., У 92 девочек 13-17 лет с вторичной аменореей и 54 девочек того же возраста с регулярным менструальным циклом определены уровни тестостерона, сексстероидсвязывающего глобулина (ССГ), рассчитан индекс свободных андрогенов. Показано, что у девочек-подростков с вторичной аменореей обнаруживается не только нормальный и повышенный, но и сниженный индекс свободных андрогенов. Величина индекса свободных андрогенов связана с выраженностью гирсутного синдрома, длительностью аменореи, показателями индекса массы тела и временем появления первой менструации., У 92 дівчаток 13-17 років із вторинною аменореєю і 54 дівчаток того ж віку з регулярним менструальним циклом визначені рівні тестостерону, сексстероїдзв’язуючого глобуліну (ССГ), розрахований індекс вільних андрогенів. Показано, що в дівчаток-підлітків із вторинною аменореєю виявляється не тільки нормальний і підвищений, але і знижений індекс вільних андрогенів. Величина індексу вільних андрогенів пов'язана з вираженістю гірсутного синдрому, тривалістю аменореї, показниками індексу маси тіла і часом появи першої менструації.

Since 1960 combined hormonal contraceptives are studied given the increased associated risk of venous and arterial thromboembolism. It was possible to observe how those containing drospirenone or cyproterone in their composition increase the risk of venous thromboembolism compared with second generation hormonal contraceptives. In this article, the case of a patient with malnutrition and secondary amenorrhea due to her nutritional status, and with hormonal contraceptives by prescription from your gynecologist will be explain., Desde 1960 los anticonceptivos hormonales combinados son objeto de estudio dado el aumento del riesgo asociado de tromboembolia venosa y arterial. Se ha podido observar cómo aquéllos que contienen drospirenona o ciproterona en su composición aumentan el riesgo de tromboembolia venosa en comparación con las píldoras de segunda generación. En este caso, se tratará el caso de una paciente con desnutrición que, presentando amenorrea secundaria por su estado nutricional, inició la toma de anticonceptivos hormonales por prescripción de su ginecólogo.

Since 1960 combined hormonal contraceptives are studied given the increased associated risk of venous and arterial thromboembolism. It was possible to observe how those containing drospirenone or cyproterone in their composition increase the risk of venous thromboembolism compared with second generation hormonal contraceptives. In this article, the case of a patient with malnutrition and secondary amenorrhea due to her nutritional status, and with hormonal contraceptives by prescription from your gynecologist will be explain., Desde 1960 los anticonceptivos hormonales combinados son objeto de estudio dado el aumento del riesgo asociado de tromboembolia venosa y arterial. Se ha podido observar cómo aquéllos que contienen drospirenona o ciproterona en su composición aumentan el riesgo de tromboembolia venosa en comparación con las píldoras de segunda generación. En este caso, se tratará el caso de una paciente con desnutrición que, presentando amenorrea secundaria por su estado nutricional, inició la toma de anticonceptivos hormonales por prescripción de su ginecólogo.

A 31-year-old woman with oligomenorrhea and primary infertility consulted for evaluation. A clinical investigation, sonographic imaging of the reproductive organs, and an assessment of endogenous hormone production were performed. During the initial visit, the ultrasound identified a "pseudogestational sac" (i.e. fluid [blood or secretions] in the uterine cavity Pregnancy was excluded by serum beta-HCG assessment, and after 3 weeks, spontaneous menstruation occurred. Serum follicle-stimulating hormone, AMH, and inhibin B levels confirmed premature ovarian insufficiency (POI). High-resolution chromosomal evaluation identified normal 46XX karyotype with double satellites on chromosome 15 (46XX, 15 pss). Two months later, our patient presented with typical symptoms of hypoestrogenism: hot flushes, night sweats, and dyspareunia. Chromosome 15 with double satellites was not considered to be clinically significant. No cases of POI in women with karyotype 46XX 15pss have been reported. By reporting a case of POI in an infertile woman with double satellites on the short arm of chromosome 15 (15pss), we consider that autosomal chromosomes polymorphism may have clinical significance, and we recommend that the genetic cause of POI be investigated more seriously. © 2015 © 2015 Taylor & Francis.