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1.
J Pediatr Adolesc Gynecol ; 33(4): 432-434, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32113877

RESUMO

BACKGROUND: Catamenial precipitation of attacks of acute intermittent porphyria (AIP) is commonly treated with gonadotropin-releasing hormone analogues (GnRHas). However, this leads to various adverse effects that might necessitate "add-back" therapy with estrogen. The literature on the efficacy and safety of such therapy is scarce. CASE: A 15-year-old girl presented to us with recurrent catamenial attacks of AIP. GnRHa therapy led to near-complete amelioration of the episodes but her bone density worsened as an adverse effect. To circumvent this, low-dose estrogen was added to her regimen as an "add-back" therapy, which was later coupled with cyclical progesterone. She continues to do well using this regimen, with no new episodes. SUMMARY AND CONCLUSION: GnRHa therapy with estrogen "add-back" is an attractive option for treating catamenial AIP episodes.


Assuntos
Densidade Óssea/efeitos dos fármacos , Estrogênios/uso terapêutico , Hormônio Liberador de Gonadotropina/efeitos adversos , Porfiria Aguda Intermitente/tratamento farmacológico , Progesterona/uso terapêutico , Adolescente , Quimioterapia Combinada , Feminino , Hormônio Liberador de Gonadotropina/administração & dosagem , Humanos , Menstruação
2.
Rev. Hosp. Ital. B. Aires (2004) ; 40(1): 34-38, mar. 2020. tab
Artigo em Espanhol | LILACS | ID: biblio-1102292

RESUMO

Las mujeres han sido tratadas por décadas con testosterona intentando aliviar una gran variedad de síntomas con riesgos y beneficios inciertos. En la mayoría de los países, la testosterona se prescribe "off-label", de modo que las mujeres están utilizando compuestos y dosis ideadas para tratamientos en hombres. En este sentido, varias sociedades médicas de distintos continentes adoptaron recientemente por consenso una toma de posición sobre los beneficios y potenciales riesgos de la terapia con testosterona en la mujer, explorar las áreas de incertidumbre e identificar prácticas de prescripción con potencial de causar daño. Las recomendaciones con respecto a los beneficios y riesgos de la terapia con testosterona se basan en los resultados de ensayos clínicos controlados con placebo de al menos 12 semanas de duración. A continuación se comentan las recomendaciones. (AU)


There are currently no clear established indications for testosterone replacement therapy for women. Nonetheless, clinicians have been treating women with testosterone to alleviate a variety of symptoms for decades with uncertainty regarding its benefits and risks. In most countries, testosterone therapy is prescribed off-label, which means that women are using testosterone formulations or compounds approved for men with a modified dose for women. Due to these issues, there was a need for a global Consensus Position Statement on testosterone therapy for women based on the available evidence from placebo randomized controlled trials (RCTs). This Position Statement was developed to inform health care professionals about the benefits and potential risks of testosterone therapy intended for women. The aim of the Consensus was to provide clear guidance as to which women might benefit from testosterone therapy; to identify symptoms, signs, and certain conditions for which the evidence does not support the prescription of testosterone; to explore areas of uncertainty, and to identify any prescribing practices that have the potential to cause harm. (AU)


Assuntos
Humanos , Feminino , Idoso , Testosterona/uso terapêutico , Pós-Menopausa/efeitos dos fármacos , Depressores do Apetite/efeitos adversos , Fenitoína/efeitos adversos , Placebos/administração & dosagem , Psicotrópicos/efeitos adversos , Tamoxifeno/efeitos adversos , Testosterona/administração & dosagem , Testosterona/análise , Testosterona/efeitos adversos , Testosterona/farmacologia , Fármacos Cardiovasculares/efeitos adversos , Indometacina/efeitos adversos , Hormônio Liberador de Gonadotropina/efeitos adversos , Pós-Menopausa/fisiologia , Ensaios Clínicos Controlados como Assunto , Antagonistas Colinérgicos/efeitos adversos , Anticoncepcionais Orais/efeitos adversos , Disfunções Sexuais Psicogênicas/etiologia , Disfunções Sexuais Psicogênicas/terapia , Danazol/efeitos adversos , Consenso , Inibidores da Aromatase/efeitos adversos , Uso Off-Label , Inibidores do Fator Xa/efeitos adversos , Anfetaminas/efeitos adversos , Antagonistas dos Receptores Histamínicos/efeitos adversos , Antagonistas de Androgênios/efeitos adversos , Androgênios/fisiologia , Cetoconazol/efeitos adversos , Entorpecentes/efeitos adversos
3.
Int J Clin Pract ; 74(3): e13449, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31755635

RESUMO

BACKGROUND: From the primary care perspective, many urologists and oncologists appear to be ignoring an FDA warning to assess patients' cardiovascular (CV) risk before instituting androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists. A growing body of data suggest an association between ADT and CV/cardiometabolic risk, particularly for GnRH agonists. METHODOLOGY: The author examined available evidence regarding CV side effects with GnRH agonists and antagonists to determine what urologists, medical oncologists, primary care physicians (PCPs) and patients need to know about these risks. RESULTS: Data are inconclusive and somewhat conflicting-for example, both low testosterone and testosterone replacement have been associated with elevated CV risk. But the distinction between GnRH agonists and antagonists is becoming clearer, as agonists appear to be more strongly linked with CV risk, perhaps due to the transient testosterone surge they cause upon administration. Moreover, adverse CV events associated with GnRH agonists can emerge relatively quickly, within weeks to months. Conversely, two studies show that GnRH antagonists may significantly reduce CV risk compared to GnRH agonists. CONCLUSIONS: Both GnRH agonists and antagonists carry some degree of CV risk. Although the risk appears to be lower with GnRH antagonists, urologists and oncologists should communicate with PCPs to determine patients' baseline CV risk levels before implementing ADT with either type of agent.


Assuntos
Antagonistas de Androgênios/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Hormônio Liberador de Gonadotropina/efeitos adversos , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Terapia de Reposição Hormonal/efeitos adversos , Antagonistas de Androgênios/uso terapêutico , Medicina Baseada em Evidências , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Medição de Risco , Fatores de Risco
4.
Fertil Steril ; 112(5): 799-803, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31731934

RESUMO

Gonadotropin-releasing hormone analogues (GnRH-a) are commonly utilized in moderate to severe endometriosis to induce atrophy of endometriotic lesions. Unfortunately, cessation of therapy can lead to recurrence of symptoms. Therefore, long term therapy is sometimes necessary. GnRH analogues cause an immediate decrease in bone mineral density which usually recovers after cessation of its use. However, this recovery in bone mineral density may not always occur after long term use. In order to prevent the deleterious effects on bone, add-back therapy is used frequently. This review will explore the impact of GnRH analogues on both bone loss and fracture risk as well as describe different add-back regimens.


Assuntos
Densidade Óssea/efeitos dos fármacos , Endometriose/tratamento farmacológico , Fraturas Ósseas/induzido quimicamente , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/administração & dosagem , Densidade Óssea/fisiologia , Endometriose/diagnóstico , Endometriose/epidemiologia , Feminino , Fraturas Ósseas/diagnóstico , Fraturas Ósseas/epidemiologia , Hormônio Liberador de Gonadotropina/efeitos adversos , Humanos , Fatores de Tempo , Resultado do Tratamento
6.
Acta Biomed ; 90(3): 345-359, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31580327

RESUMO

Central precocious puberty (CPP) is defined as an early pubertal development that occurs before the age of 9 years in boys and 8 years in girls. It results from premature activation of the hypothalamic-pituitary-gonadal axis. Gonadotropin-releasing hormone agonists (GnRHa) have been the gold standard therapy for CPP for more than 30 years. These compounds have a high affinity for the pituitary LHRH receptor and are resistant to enzymatic degradation. Through continuous stimulation, GnRHa inhibit the pulsatile secretion of gonadotropin, resulting in hormonal suppression, cessation of pubertal development, and normalization of growth and skeletal maturation rates. The goal of therapy is to halt pubertal progression and delay epiphyseal maturation that leads to improvement of final adult height. There are no widely accepted guidelines for how long to continue treatment with a GnRHa for CPP, and individual practice varies widely. Furthermore, conflicting results have been published on the long-term effects of GnRHa therapy in patients with CPP. Therefore, we reviewed the current literature focusing our attention on the long-term effects and the significant adverse drug reactions (ADRs) observed during treatment with GnRHa in patients with CPP. Our review may provide the necessary data to enable clinicians to administer GnRHa in the safest and most appropriate way. Further studies are necessary to identify the mechanisms of development of potential adverse drug reactions related to GnRHa therapy in CPP.


Assuntos
Hormônio Liberador de Gonadotropina/análogos & derivados , Puberdade Precoce/tratamento farmacológico , Estatura/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Hormônio Liberador de Gonadotropina/efeitos adversos , Hormônio Liberador de Gonadotropina/farmacologia , Humanos , Síndrome do Ovário Policístico/epidemiologia , Puberdade Precoce/metabolismo
7.
Reprod Biol ; 19(2): 145-148, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31133458

RESUMO

Vascular endothelial growth factor (VEGF) is the most important angiogenic mediator in ovarian hyperstimulation syndrome OHSS. Studies proved that cabergoline administration blocks the increase in vascular permeability via dephosphorylation of VEGF receptors and hence can be used as prophylactic agent against OHSS. This study aimed at evaluating the effectiveness of early administration of cabergoline in the prevention of OHSS in high risk cases prepared for ICSI. This case series study was conducted on 126 high risk patients prepared for ICSI using the fixed antagonist protocol. High risk patients were defined as having more than 20 follicles >12 mm in diameter, and/or E2 more than 3000 pg/ml when the size of the leading follicle is more than 15 mm. When the size of the leading follicle reached 15 mm, cabergoline was administered (0.5 mg/day) for 8 days. Patients were followed up clinically, ultrasonographically and hematologically. The final E2 was 6099.5 ±â€¯2730 and the mean number of retrieved oocytes was 19.7 ±â€¯7.8. The clinical pregnancy rate was 62/126 (49.2%). There were no significant changes (p > 0.05) comparing hematological parameters, renal function tests and liver function tests between the day of HCG and the day of blastocyst transfer. The incidence of severe OHSS in this group was 1/126 (0.9%), while moderate OHSS was 12 (9.5%) and there were no cases of critical OHSS. We concluded that early administration of cabergoline is a safe and potentially more effective approach for prophylaxis against OHSS in high risk cases.


Assuntos
Cabergolina/administração & dosagem , Cabergolina/uso terapêutico , Hormônio Liberador de Gonadotropina/análogos & derivados , Gonadotropinas/efeitos adversos , Síndrome de Hiperestimulação Ovariana/tratamento farmacológico , Adulto , Agonistas de Dopamina/administração & dosagem , Agonistas de Dopamina/uso terapêutico , Esquema de Medicação , Feminino , Fármacos para a Fertilidade Feminina/efeitos adversos , Fármacos para a Fertilidade Feminina/uso terapêutico , Hormônio Liberador de Gonadotropina/administração & dosagem , Hormônio Liberador de Gonadotropina/efeitos adversos , Hormônio Liberador de Gonadotropina/uso terapêutico , Gonadotropinas/administração & dosagem , Gonadotropinas/uso terapêutico , Humanos , Síndrome do Ovário Policístico/tratamento farmacológico , Fatores de Risco , Injeções de Esperma Intracitoplásmicas , Adulto Jovem
8.
J Ethnopharmacol ; 238: 111840, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-30935866

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Cimicifuga racemose is previously proved effective on nature menopausal syndrome (MPS). However, its clinical value in treating with MPS induced by luteinizing-hormone releasing hormone analogue (LHRH-a) therapy of pre-/peri-menopausal breast cancer patients is still unknown. AIM OF STUDY: This perspective randomised-design study is to investigate the effect and safety of cimicifuga racemosa on MPS induced by LHRH-a in breast cancer (clinical trial registered: NCT03339882). MATERIALS AND METHODS: Breast cancer patients planning for LHRH-a treatment were randomly divided into 2 groups. The control group which was being treated with the standard treatment of LHRH-a. The other group was being treated with Remifemin, the commercialized product of cimicifuga racemose extract, combined with LHRH-a, called Remifemin group. Our main endpoint was Kupperman menopause index (KMI). Hormone levels in peripheral blood and gynecological complications were also evaluated. RESULTS: Totally, 85 patients (42 in Remifemin group and 43 in control group) were enrolled in Zhejiang Cancer Hospital. At the 4th, 8th and 12th week after using LHRH-a, the KMI were all significantly lower in Remifemin group than in control group (P < 0.01), while the hormone levels, including estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were similar in the two groups. In addition, the incidence of cervical cyst in Remifemin group was higher than that in control group (P = 0.02), and there was no significant difference in the other gynecological complications, including endometrial thickening, ovarian cyst or uterine fibroid (P > 0.05). CONCLUSIONS: Cimicifuga racemose is effective, oncological safe and reliable for treatment of MPS caused by LHRH-a in breast cancer.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Hormônio Liberador de Gonadotropina/efeitos adversos , Menopausa Precoce/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Adulto , Cimicifuga , Feminino , Humanos , Fitoterapia , Síndrome
9.
Endocrinol Metab Clin North Am ; 48(2): 341-355, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31027544

RESUMO

Transgender women often seek hormone therapy to attain feminine physical features congruent with their gender identity. The aim of feminizing hormone therapy (FHT) is to provide suppression of endogenous testosterone and to maintain estradiol levels within the normal female range. Overall, FHT is safe if provided under supervision of an experienced health care provider and has been shown to improve quality of life. Data on care of transgender women are scarce and high-quality evidence-based recommendations are lacking. This article aims to review the published literature on FHT and provide guidance to clinicians caring for transgender women.


Assuntos
Antagonistas de Androgênios , Terapia de Reposição de Estrogênios , Disforia de Gênero , Hormônio Liberador de Gonadotropina , Transexualidade , Antagonistas de Androgênios/efeitos adversos , Antagonistas de Androgênios/uso terapêutico , Terapia de Reposição de Estrogênios/efeitos adversos , Disforia de Gênero/tratamento farmacológico , Disforia de Gênero/metabolismo , Hormônio Liberador de Gonadotropina/efeitos adversos , Hormônio Liberador de Gonadotropina/análise , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , Transexualidade/tratamento farmacológico , Transexualidade/metabolismo
10.
Taiwan J Obstet Gynecol ; 58(2): 255-260, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30910149

RESUMO

OBJECTIVE: Ovarian hyperstimulation syndrome (OHSS) is a major complication of assisted reproductive technologies (ART). Polycystic ovary syndrome (PCOS) is a risk factor for OHSS. The aim of this randomized clinical trial (RCT) was to study the effect of low-dose aspirin (LDA) on the development of OHSS and ART outcomes in PCOS during ART. MATERIALS AND METHODS: This double-blinded placebo controlled RCT was performed on 232 PCOS infertile women in their first ART cycles during 2010-2016. LDA and placebo capsules were prepared, packed and specified by code numbers in similar shapes. One package was given to every woman and asked to take one capsule/day since the 21st day of her cycle prior to the gonadotropin stimulation. Gonadotropin releasing hormone agonist long protocol and triggering by human chorionic gonadotropin were used. Development of moderate to severe OHSS and their ART outcomes were documented then the codes were broken and data analyzed. Chi-square and Mann-Whitney U tests were used for the statistical analyses. RESULTS: Eighteen cases that did not follow the study design were excluded. 214 cycles remained for the final analyses with 109 cases in LDA and 105 in the placebo group. Rate of the moderate to severe OHSS in LDA group was 34.9% compared to 30.5% in placebo group (P = 0.494). Fertilization rate was 71.8% vs 65.1% (P = <0.001) and the mean number of grade III embryos were 3.28 ± 3.53 vs 1.46 ± 1.42 (P = 0.014) in LDA and placebo groups, respectively. The mean number of the oocytes in different grades, total and frozen embryos also implantation and clinical pregnancy rates were not different between the groups. CONCLUSION: Moderate to Severe OHSS was not decreased but fertilization rate and the mean number of poor quality embryos were increased in LDA arm. REGISTRATION NUMBER: IRCT 201105216541N1.


Assuntos
Aspirina/administração & dosagem , Hormônio Liberador de Gonadotropina/uso terapêutico , Oócitos/efeitos dos fármacos , Síndrome de Hiperestimulação Ovariana/prevenção & controle , Indução da Ovulação/efeitos adversos , Adulto , Aspirina/efeitos adversos , Método Duplo-Cego , Feminino , Fertilização In Vitro/efeitos adversos , Fertilização In Vitro/métodos , Hormônio Liberador de Gonadotropina/efeitos adversos , Hormônio Liberador de Gonadotropina/agonistas , Humanos , Infertilidade Feminina/etiologia , Recuperação de Oócitos/estatística & dados numéricos , Síndrome de Hiperestimulação Ovariana/diagnóstico , Síndrome do Ovário Policístico/complicações , Gravidez , Resultado do Tratamento , Adulto Jovem
11.
Hum Reprod ; 34(5): 872-880, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30927417

RESUMO

STUDY QUESTION: Is oral medroxiprogesterone acetate (MPA) non-inferior compared to ganirelix with respect to the number of mature oocytes (MII) retrieved at ovum pick-up (OPU) in oocyte donation cycles? SUMMARY ANSWER: MPA is comparable to ganirelix in terms of number of MII retrieved at OPU in oocyte donation cycles. WHAT IS KNOWN ALREADY: Oral treatment with MPA inhibits the pituitary LH surge during ovarian stimulation in infertile patients. Because of its negative effect on the endometrium, MPA suppression is combined with freeze-all. Published reports indicate that both the number of MII retrieved and pregnancy rates from these oocytes are comparable to short protocol of GnRH agonists during IVF cycles with freeze-all. MPA might allow for more comfortable and cost-effective ovarian stimulation. STUDY DESIGN, SIZE, DURATION: Randomized clinical trial, open-label, single center, to assess the non-inferiority of MPA (10 mg/day) versus ganirelix (0.25 mg/day) from Day 7, in ovarian stimulation cycles triggered with triptoreline acetate. Trigger criterion was ≥3 follicles of diameter >18 mm. PARTICIPANTS/MATERIALS, SETTING, METHODS: Overall, 252 oocyte donors were selected (eligible), 216 were randomized and 173 reached OPU: 86 under MPA and 87 under ganirelix. The main outcome was the number of MII retrieved at OPU. Secondary outcomes were embryological laboratory outcomes and reproductive outcomes in recipients. The study was powered to test that the lower limit of the 95% confidence interval of the difference in retrieved MII between groups will be above the non-inferiority limit of -3. Differences were tested using a two-sided Student's t-test or a Pearson's Chi2 test, as appropriate. MAIN RESULTS AND THE ROLE OF CHANCE: All participants were in their first cycle of oocyte donation. On average, donors were 24 (SD 4.5) years old and with a BMI of 23 (SD 2.9) kg/m2. Duration of stimulation was similar in both groups (11.2 days), as well as the total gonadotropin dose up to trigger (2162 IU in MPA and 2163 IU in ganirelix). The number of MII retrieved was no different: 15.1 (SD 8.3) with MPA and 14.6 (SD 7.0), 95% CI of the difference -2.78, -1.83 excluding the pre-defined non-inferiority limit (-3). Recipients and embryo transfer (ET) characteristics were also similar between groups. The average age of recipients was 42 (SD 4.8) years and the BMI was 24 (SD 4.4) kg/m2. The mean number of MII assigned to each recipients was 6.7 (SD 1.2) in MPA and 6.6 (SD 1.2) in ganirelix (P = 0.58). MII were fertilized with partner sperm in 84% cycles overall and fertilization rate was 76% in MPA versus 74% in ganirelix (P = 0.34). Overall, there was 54% of double ET and 46% of single ET, with 40% of ETs were performed in D5. In spite of similar recipients and cycle characteristics, reproductive outcomes were unexpectedly lower with MPA. Biochemical pregnancy rate was 44 versus 57% (P = 0.023); clinical pregnancy rate 31 versus 46% (P = 0.006); ongoing pregnancy rate 27 versus 40%, (P = 0.015) and live birth rate 22 versus 31%, (P = 0.10). LIMITATIONS, REASONS FOR CAUTION: Although oocyte recipient and ET characteristics are similar among groups, this RCT has been designed under a hypothesis of non-inferiority in the number of MII obtained and recipients were not randomized; therefore, the reproductive outcomes in recipients should be evaluated with extreme caution. WIDER IMPLICATION OF THE FINDINGS: Ovarian stimulation using MPA for prevention of LH surge yields comparable number of MII oocytes compared to ganirelix in oocyte donation cycles. The unexpected finding in reproductive outcomes should be further investigated. STUDY FUNDING/COMPETING INTEREST(S): None to report. TRIAL REGISTRATION NUMBER: EudraCT number: 2015-004328-73; ClinicalTrials.gov Identifier: NCT02796105. TRIAL REGISTRATION DATE: 29 September 2015 (EudraCT); 9 June 2016 (ClinicalTrials.gov). DATE OF FIRST PATIENT'S ENROLLMENT: The date of enrollment of the first participant was 07 July 2016, and the last participant last visit in the study was on 10 July 2017.


Assuntos
Hormônio Liberador de Gonadotropina/análogos & derivados , Infertilidade Feminina/terapia , Acetato de Medroxiprogesterona/administração & dosagem , Doação de Oócitos/métodos , Indução da Ovulação/métodos , Administração Oral , Adolescente , Adulto , Coeficiente de Natalidade , Transferência Embrionária/métodos , Transferência Embrionária/estatística & dados numéricos , Endométrio/efeitos dos fármacos , Feminino , Hormônio Liberador de Gonadotropina/administração & dosagem , Hormônio Liberador de Gonadotropina/efeitos adversos , Humanos , Masculino , Acetato de Medroxiprogesterona/efeitos adversos , Pessoa de Meia-Idade , Gravidez , Taxa de Gravidez , Injeções de Esperma Intracitoplásmicas/métodos , Injeções de Esperma Intracitoplásmicas/estatística & dados numéricos , Resultado do Tratamento , Pamoato de Triptorrelina/administração & dosagem , Adulto Jovem
13.
J Obstet Gynaecol ; 39(2): 212-217, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30230393

RESUMO

Ovarian torsion (OT) in IVF is rare, however, the consequences are significant, which include ovariotomy. In the present study, it was aimed for the first time to compare the incidence of OT between hCG triggered cycles with ICSI and fresh transfer and GnRH-agonist triggered cycles with the ICSI-freeze-all and frozen embryo transfer (FET). In total, 15,577 ICSI cycles performed between 2001 and 2016 were categorised into two groups (Group 1, n: 9978): cycles with controlled ovarian stimulation (COS) and hCG-triggered (Group 2, n: 5599) and COS, with GnRH-agonist only triggered and freeze-all. Thirteen patients (0.13%) were diagnosed with OT and corrected by laparoscopy (12) and laparotomy (1) in Group 1. One patient (0.018%) was diagnosed with OT and corrected by laparotomy in Group 2 (Group 1 vs. Group 2, p = .049). The incidence of severe ovarian hyperstimulation syndrome (OHSS) was 2.4% in Group 1 and 0.05% in Group 2 (p < .001). The use of freeze-all with GnRH agonist trigger in ART significantly reduced the incidence of OT and concomitantly OHSS, with no effect on the reproductive outcome. Impact Statement What is already known on this subject? Adnexal ovarian torsion (OT) is a well-known gynaecological event that constitutes a surgical emergency. Assisted reproduction technologies (ART) may result in ovarian conditions that predispose patients to ovarian hyperstimulation syndrome (OHSS) and torsion. What the results of this study add? The combined use of GnRH agonist trigger for final oocyte maturation after OS with freeze-all and frozen embryo transfer (FET) significantly reduces the incidence of OT, as well as OHSS. What the implications are of these findings for clinical practice and/or further research? The treatment strategy of GnRH agonist trigger with freeze-all significantly reduces the risks of adverse complications.


Assuntos
Gonadotropina Coriônica/efeitos adversos , Hormônio Liberador de Gonadotropina/análogos & derivados , Doenças Ovarianas/etiologia , Indução da Ovulação/efeitos adversos , Anormalidade Torcional/etiologia , Adulto , Coeficiente de Natalidade , Gonadotropina Coriônica/administração & dosagem , Transferência Embrionária , Feminino , Hormônio Liberador de Gonadotropina/administração & dosagem , Hormônio Liberador de Gonadotropina/efeitos adversos , Humanos , Estudos Retrospectivos
14.
Reprod Sci ; 26(7): 939-953, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30270741

RESUMO

OBJECTIVE: A systematic review and meta-analysis was conducted to investigate whether gonadotropin-releasing hormone analogs (GnRHa) have a protective role in women treated with alkylating agents. DATA SOURCES: Major databases (PubMED, EMBASE, Cochrane Central Register of Controlled Trials), systematic snowballing, and trial registries were screened from the inception dates until September 2017. METHODS AND STUDY SELECTION: Comparative studies involving reproductive-aged women undergoing chemotherapy with or without coadministration of GnRHa were included. Spontaneous menstrual resumption was assessed as a main outcome. Statistical analyses were performed with STATA 14.2 statistical software. Effect estimates were presented as risk ratios (RR) with 95% confidence intervals (CIs). RESULTS: The literature search yielded 25 436 citations and 84 papers were assessed in full text. Eighteen studies (11 randomized controlled trials [RCTs] and 7 cohort studies) published between 1987 and 2015 were included in the analysis, revealing a significant protective effect of GnRHa (n = 1043; RR:1.38; 95% CI: 1.18-1.63) although with high heterogeneity (I2 = 83.3%). Subgroup analyses revealed a significant benefit of GnRHa cotreatment both in RCTs and in cohort studies. Statistical significance was found in all subgroups by the underlying disease, that is, hematological malignancies, autoimmune diseases, and breast cancer. Sensitivity analyses in GnRH agonist-treated patients, in patients younger than 40 years old, and in patients without supradiaphragmatic radiotherapy also revealed a significant benefit of GnRHa cotreatment. CONCLUSION: Our results indicate that concurrent GnRHa administration is an effective method to decrease gonadotoxicity of alkylating agents. The presence of low-quality evidence favoring gonadoprotective effect requires a strong recommendation for offering GnRHa coadministration to young women who are to undergo gonadotoxic chemotherapy. CAPSULE: The present systematic review and meta-analysis shows a significant gonadoprotective effect of gonadotropin-releasing hormone analogs in women treated with alkylating agents.


Assuntos
Antineoplásicos Alquilantes/efeitos adversos , Sobreviventes de Câncer , Fármacos para a Fertilidade Feminina/uso terapêutico , Preservação da Fertilidade/métodos , Fertilidade/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/uso terapêutico , Infertilidade Feminina/prevenção & controle , Neoplasias/tratamento farmacológico , Adolescente , Adulto , Feminino , Fármacos para a Fertilidade Feminina/efeitos adversos , Hormônio Liberador de Gonadotropina/efeitos adversos , Hormônio Liberador de Gonadotropina/análogos & derivados , Humanos , Infertilidade Feminina/induzido quimicamente , Infertilidade Feminina/fisiopatologia , Pessoa de Meia-Idade , Fatores de Proteção , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
15.
Mol Reprod Dev ; 85(12): 921-933, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30307666

RESUMO

Human secondary hypogonadism is associated with impaired testicular function, however, little is known about its impact on sperm epididymal maturation. Endocrine disruption in the epididymis could impair the secretion of key proteins, such as ß-defensins, responsible for spermatozoa maturation during epididymal transit. This study evaluated the sequence and structural similarities between porcine epididymal ß-defensins porcine ß-defensins (pBD3), pBD4, pBD125, and pEP2C and their human homologs using bioinformatics integrated with information derived from protein databanks. We then verified whether the expression of pBD3, pBD4, pBD125, and pEP2C genes in the testis and epididymis are influenced by disruption of the hypothalamic-pituitary-testicular (HPT) axis in a pig model for male human secondary hypogonadism. Upon modeling porcine ß-defensins, structural and functional analysis confirmed the presence of motifs associated with ß-defensin function, validating the models generated in silico. pBD3 and pBD4 showed acceptable structural alignments with human ß-defensins BDEF103 and BDEF110, respectively. In addition, evaluation of hormonal regulation of ß-defensins was assessed by analyzing the expression of these four ß-defensins in adult boars immunized against gonadotropin-releasing hormone (GnRH). Our results indicate that HPT axis disruption modifies the expression of pBD3, pBD4, pBD125, and pEP2C in boar testis and epididymis, suggesting an endocrine-dependent regulation of ß-defensins in swine epididymis. In conclusion, sequence and structural homology between pBD3 and pBD4 and their human homologs provide a basis for using the pig as a model for the study of human secondary hypogonadism. Further investigation of the human homologs in hypogonadal men could elucidate the connections between fertility and epididymal expression of ß-defensins.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Hormônio Liberador de Gonadotropina , Hipogonadismo/metabolismo , RNA Mensageiro/metabolismo , Testículo , beta-Defensinas/metabolismo , Animais , Modelos Animais de Doenças , Epididimo/metabolismo , Epididimo/patologia , Hormônio Liberador de Gonadotropina/efeitos adversos , Hormônio Liberador de Gonadotropina/farmacologia , Humanos , Hipogonadismo/induzido quimicamente , Hipogonadismo/patologia , Imunização , Masculino , Suínos , Testículo/metabolismo , Testículo/patologia
16.
J Clin Endocrinol Metab ; 103(11): 3931-3938, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30137415

RESUMO

Background: Children born small for gestational age (SGA) with a poor adult height (AH) expectation benefit from treatment with GH and additional gonadotropin-releasing hormone analog (GnRHa). Because both SGA birth and GnRHa treatment might negatively influence cognition, health-related quality of life (HRQoL), and psychosocial functioning, we assessed these outcomes at AH. Methods: A randomized, dose-response GH study until AH involving 99 adolescents born SGA, of whom 61 children received 2 additional years of GnRHa treatment. At AH, the Wechsler Adult Intelligence Scale and TNO-AZL Adults Quality of Life questionnaire were administered to the study group. Additionally, the study group and 67 adolescents born SGA (19 GnRHa) from a second study group completed the Self-Perception Profile of Adolescents and Child/Adolescent Behavior Checklist at AH. Scores in GH-treated young adults with GnRHa treatment (GH/GnRHa group) were compared with GH-treated adolescents without GnRHa treatment (GH group) and a reference population. Results: Mean age (SD) at AH was 17.5 (1.2) and 17.4 (1.4) years in the GH/GnRHa and GH group, respectively. Intelligence quotient scores were similar in GH/GnRHa and GH groups (96.33 vs 92.47). HRQoL was similar between both groups and also when compared with the reference population, but the GH/GnRHa group had a significantly lower perception of cognitive functioning. Self-perception and problem behavior were similar in the GH/GnRHa and GH groups. AH did not correlate with HRQoL, self-perception, or problem behavior. Conclusion: Combined GH/GnRHa treatment has no long-term negative effects on cognition, HRQoL, self-perception, and behavior in early adulthood, compared with GH treatment only.


Assuntos
Comportamento do Adolescente/efeitos dos fármacos , Desenvolvimento do Adolescente/efeitos dos fármacos , Cognição/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/efeitos adversos , Hormônio do Crescimento Humano/efeitos adversos , Recém-Nascido Pequeno para a Idade Gestacional/fisiologia , Adolescente , Comportamento do Adolescente/fisiologia , Desenvolvimento do Adolescente/fisiologia , Adulto , Estatura/efeitos dos fármacos , Criança , Relação Dose-Resposta a Droga , Feminino , Hormônio Liberador de Gonadotropina/administração & dosagem , Hormônio do Crescimento Humano/administração & dosagem , Humanos , Recém-Nascido , Masculino , Países Baixos , Gravidez , Comportamento Problema , Qualidade de Vida , Autoimagem , Maturidade Sexual/efeitos dos fármacos , Maturidade Sexual/fisiologia , Inquéritos e Questionários , Adulto Jovem
17.
Pharmazie ; 73(4): 187-190, 2018 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-29609683

RESUMO

In the physiological view the human cardiomyocytes express receptors of gonadotropin-releasing hormone and follicle-stimulating hormone. The local effects of these hormones in the heart are related also to some interstitial cells, such as endothelial cells with follicle-stimulating hormone receptors and immune cells with gonadotropin-releasing hormone receptors. The administration of androgen deprivation therapy in patients with prostate cancer is associated with increased incidence of cardiovascular complications. It is suggested that negative action of this therapy on cardiovascular system is due to the loss of testosterone but also levels of gonadotropin-releasing hormone and follicle-stimulating hormone are changed by therapy. In this article we review the literature to date with an emphasis on recent investigation focused on potential role of abnormal gonadotropin-releasing hormone and follicle-stimulating hormone levels induced by gonadotropin-releasing hormone agonists on the cardiovascular risk. These facts exacerbate the complexity of specific hormone and cell relationships within heart and vessels. Androgen deprivation therapy reveals the physiological relationships between hormones and specific tissues that are not part of the endocrine system.


Assuntos
Doenças Cardiovasculares/etiologia , Hormônio Foliculoestimulante/efeitos adversos , Hormônio Liberador de Gonadotropina/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Feminino , Hormônio Liberador de Gonadotropina/agonistas , Humanos , Masculino
18.
Fertil Steril ; 109(4): 708-719.e8, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29605411

RESUMO

OBJECTIVE: To systematically review and appraise the existing evidence in relation to the efficacy and safety of pulsatile gonadotropin-releasing hormone (pGnRH) for the treatment of women with hypothalamic amenorrhea (HA). DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): A total of 35 studies (three randomized and 32 observational) encompassing 1,002 women with HA. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Primary outcomes: ovulation rate (OvR), pregnancy per ovulatory cycle rate (POR), and live birth per ovulatory cycle rate (LBOR). SECONDARY OUTCOMES: multiple gestation (MG), ovarian hyperstimulation syndrome (OHSS), and superficial thrombophlebitis (ST) rates. The summary measures were expressed as proportions and 95% confidence intervals (CI). RESULT(S): Pulsatile GnRH treatment appears to achieve high OvRs. A trend toward high PORs and LBORs among women with HA is demonstrated. SC pGnRH achieves comparable OvR compared with IV pGnRH. The incidence of OHSS is low and of mild severity. Treatment with pGnRH is associated with low but slightly higher MG rates compared with the general population. IV administered pGnRH is rarely associated with ST. CONCLUSION(S): The high OvRs leading to a high rate of singleton pregnancies and the low likelihood of OHSS render the pGnRH treatment modality both effective and safe for the treatment of women with HA of either primary or secondary origin.


Assuntos
Amenorreia/tratamento farmacológico , Fármacos para a Fertilidade Feminina/administração & dosagem , Hormônio Liberador de Gonadotropina/administração & dosagem , Hipotálamo/fisiopatologia , Infertilidade Feminina/tratamento farmacológico , Indução da Ovulação/métodos , Ovulação/efeitos dos fármacos , Adolescente , Adulto , Amenorreia/complicações , Amenorreia/diagnóstico , Amenorreia/fisiopatologia , Feminino , Fármacos para a Fertilidade Feminina/efeitos adversos , Hormônio Liberador de Gonadotropina/efeitos adversos , Humanos , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/etiologia , Infertilidade Feminina/fisiopatologia , Nascimento Vivo , Indução da Ovulação/efeitos adversos , Gravidez , Taxa de Gravidez , Pulsoterapia , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
19.
J Pediatr Adolesc Gynecol ; 31(4): 376-381, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29551430

RESUMO

STUDY OBJECTIVE: To explore the potential occurrence of long-term side effects and tolerability of gonadotropin-releasing hormone agonist (GnRHa) plus 2 different add-back regimens in adolescent patients with endometriosis. DESIGN: Follow-up questionnaire sent in 2016 to patients who participated in a drug trial between 2008 and 2012. SETTING: Tertiary care center in Boston, Massachusetts. PARTICIPANTS: Female adolescents with surgically confirmed endometriosis (n = 51) who enrolled in a GnRHa plus add-back trial as adolescents. INTERVENTIONS: Leuprolide depot 11.25 mg intramuscular injection every 3 months, plus oral norethindrone acetate 5 mg daily or oral norethindrone acetate 5 mg daily and oral conjugated equine estrogens 0.625 mg daily. MAIN OUTCOME MEASURES: Side effects during and after treatment, irreversible side effects, changes in pain, overall satisfaction. RESULTS: The response rate was 61% (25 of 41; 10 subjects could not be located). Almost all (24 of 25) reported side effects during treatment; 80% (16 of 21) reported side effects lasting longer than 6 months after stopping treatment. Almost half (9 of 20) reported side effects they considered irreversible, including memory loss, insomnia, and hot flashes. Despite side effects, participants rated GnRHa plus add-back as the most effective hormonal medication for treating endometriosis pain; two-thirds (16 of 25) would recommend it to others. More participants who received a modified 2-drug add-back regimen vs standard 1-drug add-back would recommend GnRHa and believed it was the most effective hormonal medication. CONCLUSION: Subjects believed that GnRHa used with add-back was effective and would recommend it to others, despite significant side effects. Those who received 2-drug add-back reported more success than those who received standard add-back. A subset of patients reported side effects they consider to be irreversible.


Assuntos
Endometriose/tratamento farmacológico , Estrogênios Conjugados (USP)/efeitos adversos , Hormônio Liberador de Gonadotropina/efeitos adversos , Leuprolida/efeitos adversos , Noretindrona/efeitos adversos , Adolescente , Boston , Estrogênios Conjugados (USP)/uso terapêutico , Feminino , Hormônio Liberador de Gonadotropina/agonistas , Humanos , Leuprolida/uso terapêutico , Estudos Longitudinais , Noretindrona/uso terapêutico , Inquéritos e Questionários , Adulto Jovem
20.
BMJ Case Rep ; 20182018 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-29507026

RESUMO

Ovarian hyperstimulation syndrome (OHSS) is a well-recognised iatrogenic complication following controlled ovarian stimulation (COS). Mild to moderate cases are mostly managed conservatively. Severe cases of OHSS can be potentially fatal. For this reason, UK clinics providing licensed fertility treatment are obliged to follow Human Fertilisation and Embryology Authority guidelines for reporting severe incidents. We present an unusually severe complication of OHSS resulting in significant morbidity. A nulligravida woman aged 25, with a 4-year history of subfertility and multiple risk factors for the development of OHSS, underwent COS. Immediately following oocyte retrieval, the patient developed symptoms of early-onset severe OHSS. The subsequent clinical deterioration of the patient precipitated multiple organ failure, including renal and hepatic dysfunction. Despite supportive management in an intensive care unit, the patient required transfer to a tertiary liver centre for specialist treatment. OHSS is a preventable complication; therefore, such an uncommon presentation of the syndrome provides important clinical lessons to be discussed.


Assuntos
Hormônio Liberador de Gonadotropina/efeitos adversos , Insuficiência de Múltiplos Órgãos/etiologia , Síndrome de Hiperestimulação Ovariana/complicações , Indução da Ovulação/efeitos adversos , Doença Aguda , Adulto , Feminino , Hormônio Liberador de Gonadotropina/administração & dosagem , Humanos , Doença Iatrogênica , Fatores de Risco
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