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[PMID]: 29522931
[Au] Autor:Mezzullo M; Fanelli F; Di Dalmazi G; Fazzini A; Ibarra-Gasparini D; Mastroroberto M; Guidi J; Morselli-Labate AM; Pasquali R; Pagotto U; Gambineri A
[Ad] Address:Endocrinology Unit, Department of Medical and Surgical Sciences, Centre for Applied Biomedical Research (C.R.B.A.), S. Orsola-Malpighi Hospital, Alma Mater University of Bologna, Bologna, Italy.
[Ti] Title:Salivary cortisol and cortisone responses to short-term psychological stress challenge in late adolescent and young women with different hyperandrogenic states.
[So] Source:Psychoneuroendocrinology;91:31-40, 2018 Feb 24.
[Is] ISSN:1873-3360
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Hyperandrogenic disorders have been associated with psychological distress, reduced quality of life, anxiety and depression. The hypothalamic-pituitary-adrenal (HPA) axis plays a pivotal role in the adaptive response to stressor events. Salivary cortisol (SalF) and cortisone (SalE) testing have been proven to be useful in the evaluation of HPA-axis activity. This study investigated whether SalF and SalE responses to two putative stressor levels differed between the hyperandrogenic states in late adolescent and young women, thus measuring the HPA-axis adaptive response to acute stress events. We selected 161 drug-free females aged 16-19 years from a large population previously enrolled in a cross-sectional epidemiological study. Saliva was collected in the morning before and after two putative stressor events consisting in a self-filled questionnaire (weaker stressor) and in a structured interview plus physical examination by an endocrinologist (stronger stressor). SalF and SalE, as well as blood steroids, were assessed by liquid chromatography-tandem mass spectrometry. Subjects were subdivided into different groups according to the presence of: isolated menstrual irregularities (MI, oligo-amenorrhea; n = 22), isolated hirsutism (HIR, modified Ferriman-Gallwey score ≥ 8; n = 26), isolated hyperandrogenaemia (HT, testosterone >0.438 ng/mL; n = 14), and polycystic ovary syndrome (PCOS, MI with HIR and/or HT, n = 16). The remaining 83 apparently healthy subjects were used as controls. SalF and SalE significantly decreased after the weaker stressor, following the physiologic diurnal loss, in all the groups except for isolated HIR, where they remained unchanged (P = 0.091 and P = 0.118, respectively). In contrast, SalF and SalE remained unchanged after the stronger stressor in isolated MI, isolated HT and controls, whereas SalF increased significantly in isolated HIR (P = 0.011), and SalE increased significantly both in isolated HIR (P = 0.005) and in PCOS (P = 0.011) groups. SalF percentage variation in response to the stronger stressor was positively associated with systolic blood pressure in PCOS (P = 0.018), and both SalF and SalE percentage variations were positively associated with diastolic blood pressure in the isolated HIR group (P = 0.010 and P = 0.006, respectively). In addition, in the isolated HIR group, the SalF percentage variation was negatively associated with HDL cholesterol levels (P = 0.005). Finally, SalF and SalE percentage variations were positively associated with circulating androstenedione (P = 0.031 and P = 0.011, respectively) and DHEA (P = 0.020 and P = 0.003, respectively) in the isolated HIR group. In conclusion, this study demonstrates that hirsute and PCOS adolescent and young women are characterized by HPA-axis overactivity in response to stressful stimuli, as detectable by salivary glucocorticoid measurements. These data also indicate that the higher the HPA-axis activity, the higher the adrenal androgen output and the worse the metabolic profile.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher

  2 / 13406 MEDLINE  
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[PMID]: 29509596
[Au] Autor:Schnall R; Jia H; Olender S; Gradilla M; Reame N
[Ad] Address:Columbia University School of Nursing, New York, NY.
[Ti] Title:In people living with HIV (PLWH), menopause (natural or surgical) contributes to the greater symptom burden in women: results from an online US survey.
[So] Source:Menopause;, 2018 Mar 05.
[Is] ISSN:1530-0374
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:OBJECTIVE: The majority of people living with HIV in the United States are now over the age of 50, but symptom burden research has seldom included older women or the potential role of menopause. The aim of the study was to examine the influence of menopause as part of sex differences in HIV symptom burden. METHODS: A cross-sectional study was conducted that included both a sex-based analysis of previously reported HIV symptom characteristics of 1,342 respondents to an online survey (males, n = 957; female, n = 385) and a follow-up online survey of menstrual bleeding patterns (inferred menopause) in eligible females (n = 242) from the respondent pool. Using linear mixed models, we identified predictors of symptom burden scores in female respondents. RESULTS: For the most troublesome symptoms assessed in the sex-based analysis, depression scores were similar (P > 0.05), but higher (worse) burden scores for fatigue (P = 0.013) and muscle aches/pains (P = 0.004) were exclusively observed in females after adjusting for covariates. Respondents to the female survey (n = 222) were predominantly Black, heterosexual, nonsmokers, and obese, with an HIV diagnosis of approximately 16 years and at least one comorbid condition. Burden scores were higher in women reporting amenorrhea due to natural menopause or hysterectomy (n = 104) versus the menstruating group (n = 118) for muscle aches/pains (P = 0.05), fatigue (P = 0.03), and difficulty falling asleep (P = 0.04), independent of age, HIV duration, and number of HIV-associated non-AIDS conditions. CONCLUSIONS: Two of the most common symptoms in people living with HIV-fatigue and muscle aches/joint pains-invoke additional burden in women. Independent of aging, symptom burden may be exacerbated after menopause, supporting a shifting paradigm for HIV care management.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher
[do] DOI:10.1097/GME.0000000000001083

  3 / 13406 MEDLINE  
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[PMID]: 29517358
[Au] Autor:Pentz I; Nakic Rados S
[Ad] Address:a Polyclinic Fleur , Zagreb , Croatia.
[Ti] Title:Functional hypothalamic amenorrhea and its psychological correlates: a controlled comparison.
[So] Source:J Reprod Infant Psychol;35(2):137-149, 2017 Apr.
[Is] ISSN:0264-6838
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:OBJECTIVE: The goal of the study was to examine differences between adolescents and young women with functional hypothalamic amenorrhea (FHA) and control groups in personality traits, eating attitudes and behaviours, and perception of parental behaviour. BACKGROUND: The FHA is stress-induced anovulation, both related to metabolic challenges, such as excessive exercise and malnutrition, and psychogenic challenges, such as perfectionism and poor coping strategies. METHODS: Three groups of adolescents and young women participated in the study: the FHA group (N=25), the organic anovulation group (N=21) and the eumenorrheic group with regular menstrual cycle (N=20). Questionnaires on multidimensional perfectionism, self-control methods, eating attitudes and behaviours and perception of parental behaviour were administered. A clinical interview (SCID) was conducted with each participant. RESULTS: The FHA group had higher levels of perfectionism traits, i.e. higher levels of concerns over mistakes and personal standards, compared to control groups. The FHA group did not engage in disordered eating behaviours more often in comparison with control groups, but reported more prevalent history of anorexia nervosa. The FHA group did not differ from controls in perception of parental rejection, emotional warmth or overprotection. CONCLUSION: The findings suggest that FHA can be characterised by the subtle psychological differences in personality traits, so the patients need to be diagnosed carefully.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:In-Data-Review
[do] DOI:10.1080/02646838.2016.1278201

  4 / 13406 MEDLINE  
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[PMID]: 29415121
[Au] Autor:Nguyen BT; Dengler KL; Saunders RD
[Ad] Address:Department of Obstetrics and Gynecology, San Antonio Military Medical Center 3551 Roger Brooke Drive, Fort Sam Houston, San Antonio, TX 78234.
[Ti] Title:Mayer-Rokitansky-Kuster-Hauser Syndrome: A Unique Case Presentation.
[So] Source:Mil Med;, 2018 Feb 05.
[Is] ISSN:1930-613X
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Background: Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is a congenital condition characterized by aplasia of the vagina with or without concurrent uterine and/or cervical aplasia. Type II (MURCS) is a rare form involving MUllerian agenesis, Renal agenesis, and Cervicothoracic Somite anomalies. Case: A 17-yr-old virginal female presented for evaluation of primary amenorrhea and pelvic pain. Her medical history was significant for a bicuspid aortic valve and right radial dysplasia. She demonstrated normal secondary sexual development and a normal karyotype. Pelvic magnetic resonance imaging revealed an aplastic vaginal, no identifiable cervix or uterus, and normal ovaries. A laparoscopy was performed for the evaluation of pain and findings were significant for bilateral uterine horn and fallopian tube remnants noted along the pelvic sidewalls. This patient evaluation suggests a unique presentation of MURCS association. Conclusion: To our knowledge, this is the first case of MRKH presenting with a bicuspid aortic valve and radial dysplasia. A review of the literature reveals no other cases of MRKH with these unique anomalies.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:Publisher
[do] DOI:10.1093/milmed/usx066

  5 / 13406 MEDLINE  
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[PMID]: 29332135
[Au] Autor:Zhang Y; Ji Y; Li J; Lei L; Wu S; Zuo W; Jia X; Wang Y; Mo M; Zhang N; Shen Z; Wu J; Shao Z; Liu G
[Ad] Address:Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dongan Road, Xuhui, 200032, Shanghai, People's Republic of China.
[Ti] Title:Sequential versus simultaneous use of chemotherapy and gonadotropin-releasing hormone agonist (GnRHa) among estrogen receptor (ER)-positive premenopausal breast cancer patients: effects on ovarian function, disease-free survival, and overall survival.
[So] Source:Breast Cancer Res Treat;168(3):679-686, 2018 Apr.
[Is] ISSN:1573-7217
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:OBJECTIVE: To investigate ovarian function and therapeutic efficacy among estrogen receptor (ER)-positive, premenopausal breast cancer patients treated with gonadotropin-releasing hormone agonist (GnRHa) and chemotherapy simultaneously or sequentially. METHOD: This study was a phase 3, open-label, parallel, randomized controlled trial (NCT01712893). Two hundred sixteen premenopausal patients (under 45years) diagnosed with invasive ER-positive breast cancer were enrolled from July 2009 to May 2013 and randomized at a 1:1 ratio to receive (neo)adjuvant chemotherapy combined with sequential or simultaneous GnRHa treatment. All patients were advised to receive GnRHa for at least 2years. The primary outcome was the incidence of early menopause, defined as amenorrhea lasting longer than 12months after the last chemotherapy or GnRHa dose, with postmenopausal or unknown follicle-stimulating hormone and estradiol levels. The menstrual resumption period and survivals were the secondary endpoints. RESULT: The median follow-up time was 56.9months (IQR 49.5-72.4months). One hundred and eight patients were enrolled in each group. Among them, 92 and 78 patients had complete primary endpoint data in the sequential and simultaneous groups, respectively. The rates of early menopause were 22.8% (21/92) in the sequential group and 23.1% (18/78) in the simultaneous group [simultaneous vs. sequential: OR 1.01 (95% CI 0.50-2.08); p=0.969; age-adjusted OR 1.13; (95% CI 0.54-2.37); p=0.737]. The median menstruation resumption period was 12.0 (95% CI 9.3-14.7) months and 10.3 (95% CI 8.2-12.4) months for the sequential and simultaneous groups, respectively [HR 0.83 (95% CI 0.59-1.16); p=0.274; age-adjusted HR 0.90 (95%CI 0.64-1.27); p=0.567]. No significant differences were evident for disease-free survival (p=0.290) or overall survival (p=0.514) between the two groups. CONCLUSION: For ER-positive premenopausal patients, the sequential use of GnRHa and chemotherapy showed ovarian preservation and survival outcomes that were no worse than simultaneous use. The application of GnRHa can probably be delayed until menstruation resumption after chemotherapy.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:In-Data-Review
[do] DOI:10.1007/s10549-018-4660-y

  6 / 13406 MEDLINE  
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[PMID]: 29240891
[Au] Autor:Al-Agha AE; Ahmed IA; Nuebel E; Moriwaki M; Moore B; Peacock KA; Mosbruger T; Neklason DW; Jorde LB; Yandell M; Welt CK
[Ad] Address:Pediatric Department, King Abdulaziz University Hospital, Jeddah, Saudi Arabia.
[Ti] Title:Primary Ovarian Insufficiency and Azoospermia in Carriers of a Homozygous PSMC3IP Stop Gain Mutation.
[So] Source:J Clin Endocrinol Metab;103(2):555-563, 2018 Feb 01.
[Is] ISSN:1945-7197
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Context: The etiology of primary ovarian insufficiency (POI) remains unknown in most cases. Objective: We sought to identify the genes causing POI. Design: The study was a familial genetic study. Setting: The study was performed at two academic institutions. Patients: We identified a consanguineous Yemeni family in which four daughters had POI. A brother had azoospermia. Intervention: DNA was subjected to whole genome sequencing. Shared regions of homozygosity were identified using Truploidy and prioritized using the Variant Annotation, Analysis, and Search Tool with control data from 387 healthy subjects. Imaging and quantification of protein localization and mitochondrial function were examined in cell lines. Main Outcome: Homozygous recessive gene variants shared by the four sisters. Results: The sisters shared a homozygous stop gain mutation in exon 6 of PSMC3IP (c.489 C>G, p.Tyr163Ter) and a missense variant in exon 1 of CLPP (c.100C>T, p.Pro34Ser). The affected brother also carried the homozygous PSMC3IP mutation. Functional studies demonstrated mitochondrial fragmentation in cells infected with the CLPP mutation. However, no abnormality was found in mitochondrial targeting or respiration. Conclusions: The PSMC3IP mutation provides additional evidence that mutations in meiotic homologous recombination and DNA repair genes result in distinct female and male reproductive phenotypes, including delayed puberty and primary amenorrhea caused by POI (XX gonadal dysgenesis) in females but isolated azoospermia with normal pubertal development in males. The findings also suggest that the N-terminal missense mutation in CLPP does not cause substantial mitochondrial dysfunction or contribute to ovarian insufficiency in an oligogenic manner.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1712
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:In-Data-Review
[do] DOI:10.1210/jc.2017-01966

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[PMID]: 29216361
[Au] Autor:Pohl O; Marchand L; Fawkes N; Gotteland JP; Loumaye E
[Ad] Address:ObsEva, Geneva, Switzerland.
[Ti] Title:Gonadotropin-Releasing Hormone Receptor Antagonist Mono- and Combination Therapy With Estradiol/Norethindrone Acetate Add-Back: Pharmacodynamics and Safety of OBE2109.
[So] Source:J Clin Endocrinol Metab;103(2):497-504, 2018 Feb 01.
[Is] ISSN:1945-7197
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Context: OBE2109 is a potent, oral gonadotropin-releasing hormone receptor antagonist being developed for the treatment of sex-hormone-dependent diseases in women. Objective: We assessed the pharmacodynamics and safety of OBE2109 alone and combined with estradiol (E2)/norethindrone acetate (NETA) add-back therapy on E2 levels and vaginal bleeding. Design, Setting, and Participants: This was a single-center, open-label, randomized, parallel-group study in 76 healthy premenopausal women. Interventions: Women were randomly assigned to take the following doses (in milligrams) once daily for 6 weeks: OBE2109, 100 or 200; or OBE2109/E2/NETA, 100/0.5/0.1, or 100/1.0/0.5, or 200/1.0/0.5. Main Outcome Measures: E2 concentrations, bleeding pattern, exploratory bone metabolism biomarkers, and adverse events. Results: OBE2109 100 mg and 200 mg alone reduced E2 levels to reach median levels of 19.5 and 3.2 pg/mL, respectively, at week 4. Median E2 levels after combined OBE2109/add-back therapy ranged between 25 and 40 pg/mL. OBE2109 100 mg or 200 mg alone induced amenorrhea. By day 15, >85% of women had no vaginal bleeding during the last 4 weeks of treatment. Add-back therapy partially impaired bleeding control: The highest amenorrhea rate (53%) was observed with OBE2109 100 mg/1.0 mg/0.5 mg. The addition of E2/NETA, particularly at 1 mg/0.5 mg, mitigated the increase of two bone markers induced by OBE2109 200 mg. Conclusion: OBE2109 promptly lowered E2 levels. Add-back therapy may be required to prevent adverse effects on bone in women treated with the 200-mg dose (at 100 mg in some women). These results provide a basis for OBE2109 regimen selection to treat sex-hormone-dependent diseases.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1712
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:In-Data-Review
[do] DOI:10.1210/jc.2017-01875

  8 / 13406 MEDLINE  
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[PMID]: 29389968
[Au] Autor:Matcho A; Ryan P; Fife D; Gifkins D; Knoll C; Friedman A
[Ad] Address:Epidemiology Analytics, Janssen Research and Development, LLC, Raritan, New Jersey, United States of America.
[Ti] Title:Inferring pregnancy episodes and outcomes within a network of observational databases.
[So] Source:PLoS One;13(2):e0192033, 2018.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Administrative claims and electronic health records are valuable resources for evaluating pharmaceutical effects during pregnancy. However, direct measures of gestational age are generally not available. Establishing a reliable approach to infer the duration and outcome of a pregnancy could improve pharmacovigilance activities. We developed and applied an algorithm to define pregnancy episodes in four observational databases: three US-based claims databases: Truven MarketScan Commercial Claims and Encounters (CCAE), Truven MarketScan Multi-state Medicaid (MDCD), and the Optum ClinFormatics (Optum) database and one non-US database, the United Kingdom (UK) based Clinical Practice Research Datalink (CPRD). Pregnancy outcomes were classified as live births, stillbirths, abortions and ectopic pregnancies. Start dates were estimated using a derived hierarchy of available pregnancy markers, including records such as last menstrual period and nuchal ultrasound dates. Validation included clinical adjudication of 700 electronic Optum and CPRD pregnancy episode profiles to assess the operating characteristics of the algorithm, and a comparison of the algorithm's Optum pregnancy start estimates to starts based on dates of assisted conception procedures. Distributions of pregnancy outcome types were similar across all four data sources and pregnancy episode lengths found were as expected for all outcomes, excepting term lengths in episodes that used amenorrhea and urine pregnancy tests for start estimation. Validation survey results found highest agreement between reviewer chosen and algorithm operating characteristics for questions assessing pregnancy status and accuracy of outcome category with 99-100% agreement for Optum and CPRD. Outcome date agreement within seven days in either direction ranged from 95-100%, while start date agreement within seven days in either direction ranged from 90-97%. In Optum validation sensitivity analysis, a total of 73% of algorithm estimated starts for live births were in agreement with fertility procedure estimated starts within two weeks in either direction; ectopic pregnancy 77%, stillbirth 47%, and abortion 36%. An algorithm to infer live birth and ectopic pregnancy episodes and outcomes can be applied to multiple observational databases with acceptable accuracy for further epidemiologic research. Less accuracy was found for start date estimations in stillbirth and abortion outcomes in our sensitivity analysis, which may be expected given the nature of the outcomes.
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Entry month:1802
[Cu] Class update date: 180305
[Lr] Last revision date:180305
[St] Status:In-Process
[do] DOI:10.1371/journal.pone.0192033

  9 / 13406 MEDLINE  
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[PMID]: 29420395
[Au] Autor:Simon JA; Catherino W; Segars JH; Blakesley RE; Chan A; Sniukiene V; Al-Hendy A
[Ad] Address:George Washington University School of Medicine, Women's Health & Research Consultants, Washington, DC; Uniformed Services University of the Health Sciences, Bethesda, Maryland; Johns Hopkins University School of Medicine, Baltimore, Maryland; Allergan plc, Madison, New Jersey; and Augusta University, Augusta, Georgia.
[Ti] Title:Ulipristal Acetate for Treatment of Symptomatic Uterine Leiomyomas: A Randomized Controlled Trial.
[So] Source:Obstet Gynecol;131(3):431-439, 2018 Mar.
[Is] ISSN:1873-233X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:OBJECTIVE: To assess efficacy and tolerability of ulipristal acetate, a selective progesterone receptor modulator, for treatment of symptomatic uterine leiomyomas. METHODS: This phase 3, double-blind, placebo-controlled study enrolled premenopausal women (aged 18-50 years) with abnormal uterine bleeding, one or more discrete leiomyomas, and uterine size 20 weeks of gestation or less. Patients were randomized 1:1:1 to 5 mg ulipristal, 10 mg ulipristal, or placebo once daily for 12 weeks followed by 12-week drug-free follow-up. Coprimary endpoints were rate of and time to amenorrhea, defined as no bleeding for the last 35 consecutive days of treatment. Secondary endpoints included rates of amenorrhea from day 11 and change from baseline to endpoint in the Revised Activities subscale of the Uterine Fibroid Symptom and Quality of Life questionnaire, which includes questions pertaining to physical and social activities. Safety assessments included adverse event monitoring and endometrial biopsies. A sample size of 150 was planned to compare separately each dose of ulipristal with placebo. RESULTS: From March 2014 to March 2016, 157 patients were randomized. Demographics were similar across treatment groups. Amenorrhea was achieved by 25 of 53 (47.2% [97.5% CI 31.6-63.2]) and 28 of 48 (58.3% [97.5% CI 41.2-74.1]) patients treated with 5 mg and 10 mg ulipristal, respectively, compared with 1 of 56 (1.8% [97.5% CI 0.0-10.9]) placebo-treated patients (both P<.001). Time to amenorrhea was shorter for both ulipristal doses compared with placebo (P<.001), and both doses of ulipristal resulted in improved quality of life compared with placebo (P<.001). Common adverse events (5% or greater in either ulipristal group during treatment) were hypertension, elevated blood creatinine phosphokinase, and hot flushes. Serious adverse events occurred in four patients, but none was considered related to treatment. Endometrial biopsies were benign. CONCLUSION: Ulipristal at 5 mg and 10 mg were well tolerated and superior to placebo in rate of and time to amenorrhea in women with symptomatic uterine leiomyomas. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov number, NCT02147197.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180301
[Lr] Last revision date:180301
[Cl] Clinical Trial:ClinicalTrial
[St] Status:In-Data-Review
[do] DOI:10.1097/AOG.0000000000002462

  10 / 13406 MEDLINE  
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[PMID]: 29375085
[Au] Autor:Iwasa T; Matsuzaki T; Yano K; Mayila Y; Irahara M
[Ad] Address:Department of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan.
[Ti] Title:The roles of kisspeptin and gonadotropin inhibitory hormone in stress-induced reproductive disorders.
[So] Source:Endocr J;65(2):133-140, 2018 Feb 26.
[Is] ISSN:1348-4540
[Cp] Country of publication:Japan
[La] Language:eng
[Ab] Abstract:Several kinds of stress suppress the hypothalamic-pituitary-gonadal (HPG) axis and reproductive behavior in humans and animals. These changes can eventually cause diseases and disorders, such as amenorrhea and infertility. In previous studies, it has been shown that stress-related factors, e.g., corticotropin-releasing hormone, cortisol, and pro-inflammatory cytokines, promote the stress-induced suppression of the HPG axis. However, these mechanisms are not sufficient to explain how stress suppresses HPG axis activity, and it has been suggested that some other factors might also be involved. In the early 21st century, novel neuroendocrine peptides, kisspeptin and gonadotropin inhibitory hormone (GnIH)/RFamide-related peptide 3 (RFRP-3), which directly regulate GnRH/gonadotropin synthesis and secretion, were newly discovered. Growing evidence indicates that kisspeptin and GnIH/RFRP-3 play pivotal roles in the stress-induced disruption of the HPG axis and reproductive behavior in addition to their physiological functions. This review summarizes what is currently known about the roles of kisspeptin and GnIH/RFRP-3 in stress-induced reproductive disorders.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180226
[Lr] Last revision date:180226
[St] Status:In-Process
[do] DOI:10.1507/endocrj.EJ18-0026


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