RESUMO
BACKGROUND AND OBJECTIVE: Endometriosis and adenomyosis are two common diseases that impair women's health, and dienogest is one of the pharmacologic treatments which is the first-line therapeutic option for patients with pelvic pain and individuals who have no desire for immediate pregnancy. The goal of this study was to summarize the current evidence of adverse events associated with dienogest as well as the prevalence of these adverse events during treatment with dienogest. METHODS: Several databases (PubMed, Embase, Cochrane Central and Clinicaltrials.gov, etc.) and the US FDA Adverse Event Reporting System (FAERS) Public Dashboard were searched on May 31, 2023, using the topic words alongside free words of dienogest and "adverse reaction". Studies were incorporated into this research if they reported or assessed safety issues or adverse reactions of dienogest during the period of endometriosis treatment or adenomyosis therapy. The extracted information comprised trial design, dienogest and control group demographics, as well as reported side effects. RESULTS: This systematic review comprehended 39 publications in total. The mean age of patients in the included studies was 34.43 years. The follow-up duration varied from 3 to 60 months. Most adverse reactions were common and not serious, and the most common adverse reactions during dienogest medication were abnormal uterine bleeding (55%, 95% CI 37-73%), amenorrhea (17%, 95% CI 2-42%) and swelling (13%, 95% CI 3-28%). Uncommon adverse reactions included dysmenorrhea (0.2%, n = 1), dyspepsia (0.4%, n = 1), and (lower) abdominal pain (1%, 95% CI 0-3%), urticaria (1%, 95% CI 0-3%) and peritonitis (1%, n = 1). Serious adverse reactions including decreased lumbar spine Bone Mineral Density (BMD), depression, peritonitis and so on have been reported. Heterogeneity assessment revealed that patient number and study design are influencing factors to adverse reaction prevalence. Moreover, abdominal pain, diarrhea, nausea and vomiting, back pain and anemia are side effects reported both in the FAERS database and in the systematic review. CONCLUSIONS: Dienogest's most frequent side effects were not severe. Dienogest is generally safe for treating endometriosis and adenomyosis. Nevertheless, people should be aware of serious adverse reactions, such as decreased lumbar spine BMD and hemorrhagic shock.
Assuntos
Teorema de Bayes , Endometriose , Nandrolona , Humanos , Nandrolona/análogos & derivados , Nandrolona/efeitos adversos , Nandrolona/uso terapêutico , Feminino , Endometriose/tratamento farmacológico , Adenomiose/tratamento farmacológico , Antagonistas de Hormônios/efeitos adversos , Antagonistas de Hormônios/uso terapêuticoRESUMO
Objective: This study aims to determine whether the live birth rates were similar between GnRH antagonist original reference product Cetrotide® and generic Ferpront®, in gonadotropin-releasing hormone (GnRH) antagonist protocol for controlled ovarian stimulation (COS). Methods: This retrospective cohort study investigates COS cycles utilizing GnRH antagonist protocols. The research was conducted at a specialized reproductive medicine center within a tertiary care hospital, spanning the period from October 2019 to October 2021. Within this timeframe, a total of 924 cycles were administered utilizing the GnRH antagonist originator, Cetrotide® (Group A), whereas 1984 cycles were undertaken using the generic, Ferpront® (Group B). Results: Ovarian reserve markers, including anti-Mullerian hormone, antral follicle number, and basal follicular stimulating hormone, were lower in Group A compared to Group B. Propensity score matching (PSM) was performed to balance these markers between the groups. After PSM, baseline clinical features were similar, except for a slightly longer infertile duration in Group A versus Group B (4.43 ± 2.92 years vs. 4.14 ± 2.84 years, P = 0.029). The duration of GnRH antagonist usage was slightly longer in Group B than in Group A (6.02 ± 1.41 vs. 5.71 ± 1.48 days, P < 0.001). Group B had a slightly lower number of retrieved oocytes compared to Group A (14.17 ± 7.30 vs. 14.96 ± 7.75, P = 0.024). However, comparable numbers of usable embryos on day 3 and good-quality embryos were found between the groups. Reproductive outcomes, including biochemical pregnancy loss, clinical pregnancy, miscarriage, and live birth rate, did not differ significantly between the groups. Multivariate logistic regression analyses suggested that the type of GnRH antagonist did not independently impact the number of oocytes retrieved, usable embryos, good-quality embryos, moderate to severe OHSS rate, clinical pregnancy, miscarriage, or live birth rate. Conclusion: The retrospective analysis revealed no clinically significant differences in reproductive outcomes between Cetrotide® and Ferpront® when used in women undergoing their first and second COS cycles utilizing the GnRH antagonist protocol.
Assuntos
Hormônio Liberador de Gonadotropina , Antagonistas de Hormônios , Indução da Ovulação , Humanos , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hormônio Liberador de Gonadotropina/análogos & derivados , Feminino , Estudos Retrospectivos , Indução da Ovulação/métodos , Gravidez , Adulto , Antagonistas de Hormônios/uso terapêutico , Antagonistas de Hormônios/administração & dosagem , Antagonistas de Hormônios/efeitos adversos , Taxa de Gravidez , Coeficiente de Natalidade , Medicamentos Genéricos/uso terapêutico , Reserva Ovariana/efeitos dos fármacosRESUMO
BACKGROUND: Oral gonadotropin-releasing hormone (GnRH) antagonists are promising agents in the treatment of endometriosis-related pain. Here we assessed the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of SHR7280, an oral non-peptide GnRH antagonist in premenopausal women with endometriosis. METHODS: In the Phase 1 part of the randomized, double-blinded, placebo-controlled, dose-ascending, Phase 1/2 trial, premenopausal women with endometriosis were randomized (4:1) to receive SHR7280 or placebo treatment for 21 consecutive days. The treatment dose started from 200 mg QD, and then increased to 300 mg QD and 200 mg BID. Safety, PK, and PD parameters were assessed. RESULTS: In total, 30 patients received assigned treatment, 24 with SHR7280 and 6 with placebo. SHR7280 was well tolerated. Adverse events (AEs) were reported in 19 (79.2%, 19/24) patients in the SHR7280 group and 5 (83.3%, 5/6) patients in the placebo group. Most AEs were mild and no severe AEs occurred. SHR7280 showed a rapid absorption, with a time to maximum plasma concentration (Tmax) of 1.0 h, 1.0 h, and 0.8 h for the 200 mg QD, 300 mg QD, and 200 mg BID regimens, respectively. Plasma concentration of SHR7280 was dose dependent. The mean half-life (t1/2) at steady state was 6.9 h, 7.4 h, and 2.8 h, respectively, and little or no accumulation was observed. Pharmacodynamic analysis showed that SHR7280 could effectively suppress estradiol and luteinizing hormone concentrations and prevent progesterone increase in a dose-dependent manner. SHR7280 at doses of 300 mg QD and 200 mg BID could suppress estradiol levels within the desired therapeutic window of 20-50 pg/mL throughout the treatment period. CONCLUSIONS: SHR7280 showed favorable safety, PK, and PD profiles in the doses of 200 mg QD, 300 mg QD, and 200 mg BID. The results of this study provide evidence to support the further development of SHR7280 as a GnRH antagonist for the treatment of endometriosis-related pain in the subsequent Phase 2 trial. TRIAL REGISTRY: Trial registration number: Clinicaltrials.gov, identifier: NCT04417972. Trial registration date: 5 June 2020.
Assuntos
Endometriose , Humanos , Feminino , Endometriose/tratamento farmacológico , Antagonistas de Hormônios/efeitos adversos , Estradiol/uso terapêutico , Dor , Método Duplo-Cego , Hormônio Liberador de Gonadotropina , Relação Dose-Resposta a DrogaRESUMO
Pegvisomant, the first and currently only clinically available growth hormone receptor antagonist, is an effective therapeutic option for the medical treatment of acromegaly, a rare disorder characterized by excessive growth hormone secretion. With now over 20 years of real world experience, its safety and efficacy is well-established. However, several aspects of its clinical use are still controversially discussed. The high cost of pegvisomant has limited its use in several countries, and recent studies have reported a lower efficacy than the initial clinical trials. A reported increase in tumor volume under therapy varies between studies and has been attributed to either actual growth or re-expansion after cessation of somatostatin receptor ligand therapy. Furthermore, different combinations of pegvisomant and other therapeutic agents aiming at reduction of acromegaly disease activity have been proposed to increase or retain effectiveness while lowering side effects and cost. This review aims to assess current clinical data on the safety and efficacy of pegvisomant while also addressing controversies surrounding its use.
Assuntos
Acromegalia , Hormônio do Crescimento Humano , Humanos , Acromegalia/tratamento farmacológico , Acromegalia/induzido quimicamente , Acromegalia/patologia , Receptores da Somatotropina/uso terapêutico , Hormônio do Crescimento Humano/efeitos adversos , Antagonistas de Hormônios/efeitos adversos , Fator de Crescimento Insulin-Like IRESUMO
OBJECTIVE: To review the use of oral gonadotropin-releasing hormone (GnRH) antagonists and synthesize their efficacy and safety parameters for the treatment of endometriosis-associated pain. DESIGN: Systematic review and network meta-analysis. SETTING: Not applicable. PATIENT(S): Premenopausal women with endometriosis who had experienced moderate or severe pain. INTERVENTION(S): The Web of Science, Embase, Scopus, and MEDLINE were searched until April 10, 2022. Only randomized controlled trials were included. The risk of bias in the included studies was assessed using the Cochrane Risk of Bias tool 2. A Bayesian random-effects network meta-analysis was used to perform indirect comparisons. I2 was used to assess the global heterogeneity. Relative treatment estimates were performed. Treatment ranking was performed through the surface under the cumulative ranking curve. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation framework. MAIN OUTCOME MEASURE(S): Endometriosis-associated pain, dysmenorrhea, dyspareunia, and noncyclic pelvic pain reduction. RESULT: (s): Five studies and 6 randomized controlled trials, including a total of 2,796 women and 10 different doses of oral GnRH antagonist treatments, were eligible for inclusion. All studies were considered to have a low risk of bias. Almost all efficacy- and safety-related outcomes showed a dose-response relationship. Regarding endometriosis-associated pain, the top 3 treatments were elagolix 400 mg, linzagolix 75 mg, and linzagolix 200 mg, with mean differences of -1.26 (95% credible interval [CrI], -1.70 to -0.79), -0.98 (95% CrI, -1.84 to -0.15), and -0.98 (95% CrI, -1.90 to -0.064), respectively. The top 3 treatments to decrease dysmenorrhea were relugolix 40 mg, elagolix 400 mg, and relugolix 20 mg, with mean differences of -1.60 (95% CrI, -2.07 to -1.14), -1.25 (95% CrI, -1.56 to -0.95), and -1.10 (95% CrI, -1.59 to -0.62), respectively. However, only high-dose treatments were significantly associated with most quality of life- and adverse effect-related outcomes. Relugolix 40 and 20 mg and elagolix 400 mg, with odds ratios of 6.88 (95% CrI, 2.18-24.58), 1.60 (95% CrI, 0.62-4.13), and 1.85 (95% CrI, 1.05-3.30), had a significantly increased incidence of adverse events. CONCLUSION: (s): Oral GnRH antagonists are effective for endometriosis-associated pain and dysmenorrhea and the patient global impression. The incidence of ovarian hypoestrogenic effects in a short-term duration was significant in a dose-effect response, particularly the highest dose. CLINICAL TRIAL REGISTRATION NUMBER: International Prospective Register of Systematic Reviews registration number CRD42022332904.
Assuntos
Endometriose , Qualidade de Vida , Feminino , Humanos , Teorema de Bayes , Dismenorreia/diagnóstico , Dismenorreia/tratamento farmacológico , Dismenorreia/etiologia , Endometriose/complicações , Endometriose/diagnóstico , Endometriose/tratamento farmacológico , Hormônio Liberador de Gonadotropina , Antagonistas de Hormônios/efeitos adversos , Metanálise em Rede , Dor Pélvica/diagnóstico , Dor Pélvica/tratamento farmacológico , Dor Pélvica/etiologiaRESUMO
Endometriosis is a chronic pain condition affecting 1 in 10 women. There is an unmet need for better medical treatments for endometriosis. We spotlight trials of a single preparation combined HRT-GnRH antagonist (Relugolix) by Giudice et al.,1 for endometriosis-associated pain.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Endometriose , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Endometriose/tratamento farmacológico , Feminino , Hormônio Liberador de Gonadotropina/uso terapêutico , Antagonistas de Hormônios/efeitos adversos , Humanos , Dor/induzido quimicamenteRESUMO
INTRODUCTION: Endometriosis is a chronic, estrogen-dependent, inflammatory disease associated with pelvic pain, infertility, impaired sexual function, and psychological suffering. Therefore, tailored patient management appears of primary importance to address specific issues and identify the appropriate treatment for each woman. Over the years, abundant research has been carried out with the objective to find new therapeutic approaches for this multifaceted disease. AREAS COVERED: This narrative review aims to present the latest advances in the pharmacological management of endometriosis. In particular, the potential role of GnRH antagonists, selective progesterone receptor modulators (SPRMs), and selective estrogen receptors modulators (SERMs) will be discussed. We performed a literature search in PubMed and Embase, and selected the best quality evidence, giving preference to the most recent and definitive original articles and reviews. EXPERT OPINION: Medical therapy represents the cornerstone of endometriosis management, although few advances have been made in the last decade. Most studies have focused on the evaluation of the efficacy and safety of GnRH antagonists (plus add-back therapy in cases of prolonged treatment), which should be used as second-line treatment options in selected cases (i.e. non-responders to first-line treatments). Further studies are needed to identify the ideal treatment for women with endometriosis.
Assuntos
Endometriose , Endometriose/complicações , Endometriose/tratamento farmacológico , Estrogênios , Feminino , Hormônio Liberador de Gonadotropina , Antagonistas de Hormônios/efeitos adversos , Humanos , Receptores de Estrogênio/uso terapêutico , Receptores de Progesterona/uso terapêutico , Moduladores Seletivos de Receptor Estrogênico/uso terapêuticoRESUMO
BACKGROUND: The gonadotropin-releasing hormone (GnRH) antagonist protocol is advantageous given that it can avoid severe ovarian hyperstimulation syndrome (OHSS), especially for patients with polycystic ovary syndrome (PCOS). Basic and clinical evidence has shown that a threshold of luteinizing hormone (LH) stimulation is required for adequate follicular development and oocyte maturation. Ultra-low or high levels of LH are detrimental to pregnancy outcomes. We previously demonstrated that LH could be an indicator for the timing and dosage of antagonist administration in a retrospective study. METHODS/DESIGN: In this randomized, single-center, non-inferiority trial, we aim to test the hypothesis that there is no significant difference in cumulative ongoing pregnancy rates between PCOS patients stimulated with LH-based flexible protocol versus traditional flexible GnRH antagonist protocol. The primary efficacy endpoint will be the cumulative ongoing pregnancy rate per cycle. The secondary outcomes will be clinical pregnancy rate, cancelation rate, serious OHSS rate, and cost-efficiency. The cumulative ongoing pregnancy rate per cycle in PCOS women was 80%. Considering that a non-inferiority threshold should retain 80% of the clinical effect of a control treatment, a minimal clinical difference of 16% (two-sided: α, 2.5%; ß, 20%) and a total of 196 patients were needed. Anticipating a 10% dropout rate, the total number of patients required was 216. DISCUSSION: The results of this study will provide evidence for the efficacy and safety of the LH-based flexible GnRH antagonist protocol in PCOS patients. Moreover, it evaluates the cost-efficiency of both protocols. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800018129. Date assigned: 31 August 2018. PROTOCOL VERSION: 1.0 (18 July 2017).
Assuntos
Síndrome de Hiperestimulação Ovariana , Síndrome do Ovário Policístico , Estudos de Equivalência como Asunto , Feminino , Fertilização in vitro/métodos , Hormônio Liberador de Gonadotropina , Antagonistas de Hormônios/efeitos adversos , Humanos , Hormônio Luteinizante , Indução da Ovulação/métodos , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/tratamento farmacológico , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos RetrospectivosRESUMO
Objective: To evaluate the clinical outcomes and maternal-neonatal safety of gonadotropin releasing hormone antagonist (GnRH-ant) and gonadotropin releasing hormone agonist (GnRH-a) protocols. Methods: A total of 2505 women undergoing their first in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) were retrospectively analyzed. Patients were divided into GnRH-ant group (n = 1514) and GnRH-a group (n = 991) according their stimulation protocol. Propensity Score Matching (PSM) was used for balancing the baseline of two groups. The pregnancy outcomes were analyzed in fresh transfer cycles, and the obstetric and perinatal outcomes were calculated in singleton live births of fresh cycles. The primary outcome was the live birth rate. The secondary outcome measures were maternal complications, preterm birth rate, low birthweight rate, multiple pregnancy rate, and moderate-severe OHSS rate. Results: After 1:1 PSM, baseline characteristics of the GnRH-ant group and GnRH-a group were matched and assigned 991 cycles in each group. Before PSM, there were 700 fresh cycles including 237 singleton live births in the GnRH-ant group and 588 fresh cycles including 187 singleton live births in the GnRH-a group. After PSM, there were 471 fresh cycles including 166 singleton live births in the GnRH-ant group and 588 fresh cycles including 187 singleton live births in the GnRH-a group. No significant differences were observed in the live birth rate (44.6% vs 48.8%), maternal complications, preterm birth rate (9.0% vs 6.4%), and low birthweight rate (17.5% vs 24.1%) between two groups after PSM (P > 0.05). The moderate-severe OHSS rate (2.9% vs 6.0%, P = 0.002) and multiple pregnancy rate (24.5% vs 33.1%, P = 0.025) was significantly lower in the GnRH-ant group than that in the GnRH-a group after PSM. Conclusion: GnRH-ant protocol was comparable with GnRH-a protocol in clinical outcomes, obstetric and perinatal outcomes, and with a lower risk of OHSS. For those who want to get an effective and safe outcome, and a shorter treatment period, GnRH-ant is a suitable choice.
Assuntos
Indução da Ovulação , Nascimento Prematuro , Peso ao Nascer , Feminino , Hormônio Liberador de Gonadotropina , Antagonistas de Hormônios/efeitos adversos , Humanos , Recém-Nascido , Masculino , Indução da Ovulação/métodos , Gravidez , Nascimento Prematuro/epidemiologia , Estudos Retrospectivos , SêmenRESUMO
PURPOSE OF REVIEW: This review is intended to provide perspective on the history of selective progesterone receptor modulators (SPRMs) and progesterone antagonists, their current availability, therapeutic promise and safety concerns. RECENT FINDINGS: Despite keen interest in synthesis of these compounds, only a handful have had clinical test results allowing for commercialization. Mifepristone is well tolerated and effective for single dose first trimester at-home pregnancy termination and is available in much of the world. Ulipristal acetate, at single doses, is well tolerated and effective for emergency contraception, with less availability. Chronic use of these agents has been associated with abnormal liver enzymes, and rarely, with hepatic failure; causality is not understood. SUMMARY: SPRMs and progesterone antagonists have great therapeutic promise for use in other reproductive disorders, including breast cancer, endometriosis, adenomyosis, estrogen-free contraception and cervical ripening but require additional study. Alternative formulations, whether local (topical breast or intrauterine) or extended-release may reduce the incidence of liver function abnormalities and should be explored.
Assuntos
Progesterona , Receptores de Progesterona , Feminino , Antagonistas de Hormônios/efeitos adversos , Humanos , Mifepristona/efeitos adversos , Gravidez , Saúde ReprodutivaRESUMO
RESEARCH QUESTION: Does a once-daily regimen of linzagolix, a new oral gonadotrophin-releasing hormone (GnRH) antagonist, given at a fully suppressive dose (200 mg) for 12 weeks, followed by a partially suppressive dose (100 mg) for a further 12 weeks, reduce adenomyotic uterine size and associated symptoms? DESIGN: Eight women (aged 37-45 years) with adenomyosis confirmed by magnetic resonance imaging (MRI) were enrolled in a single-centre, open-label pilot study. The primary efficacy end-point was the change in uterine volume on MRI at 24 weeks. Secondary efficacy end-points included serum oestradiol, overall pelvic pain, dysmenorrhoea, non-menstrual pelvic pain, dyspareunia, dyschezia and quality of life (QoL). Bone mineral density (BMD) was assessed at baseline and 24 weeks. RESULTS: At baseline, uterine volume (mean ± SD) was 333 ± 250 cm3. After 24 weeks, it was 204 ± 126 cm3, a reduction of 32% from baseline (Pâ¯=â¯0.0057). After 12 weeks, it was 159 ± 95 cm3, a reduction of 55% (Pâ¯<â¯0.0001). Median serum oestradiol was suppressed below 20 pg/ml during the 12 weeks on 200 mg linzagolix, and maintained below 60 pg/ml on 100 mg linzagolix. Improvements in overall pelvic pain, dysmenorrhoea, non-menstrual pelvic pain, dyspareunia, dyschezia and QoL were observed. Mean percentage change in BMD loss at 24 weeks was -2.4%, -1.3% and -4.1% for the spine, femoral neck and total hip, respectively. The most common adverse events were hot flushes. CONCLUSIONS: A once-daily regimen of 200 mg linzagolix for 12 weeks and then 100 mg for another 12 weeks decreased adenomyotic uterine volume and improved associated symptoms.
Assuntos
Adenomiose , Ácidos Carboxílicos , Antagonistas de Hormônios , Pirimidinas , Adenomiose/diagnóstico por imagem , Adenomiose/tratamento farmacológico , Adulto , Ácidos Carboxílicos/efeitos adversos , Constipação Intestinal/epidemiologia , Dismenorreia/epidemiologia , Dispareunia/epidemiologia , Estradiol/sangue , Feminino , Hormônio Liberador de Gonadotropina , Antagonistas de Hormônios/efeitos adversos , Humanos , Pessoa de Meia-Idade , Dor Pélvica/epidemiologia , Projetos Piloto , Pirimidinas/efeitos adversos , Qualidade de VidaRESUMO
The Pre-IVF Treatment with a GnRH Antagonist in Women with Endometriosis (PREGnant) Trial (clinicaltrials.gov no. NCT04173169) was designed to test the hypothesis that 60-day pre-treatment with an oral GnRH antagonist in women with documented endometriosis and planning an IVF cycle will result in a superior live birth rate to placebo. Eight hundred fourteen women are required from 4 national sites. To determine the feasibility of using an electronic medical record (EMR)-based strategy to recruit 204 participants at the Colorado site, we conducted a survey of women within the UCHealth system. Eligible women, identified using relevant ICD-10 codes, were invited to complete a 6-question survey to assess planned utilization of IVF, potential interest in participation, and whether delays in treatment due to COVID-19 would influence their decision to participate. Of 6354 age-eligible women with an endometriosis diagnosis, 421 had a concurrent infertility diagnosis. After eliminating duplicates, 212 were emailed a survey; 76 (36%) responded, 6 of whom reported no endometriosis diagnosis. Of the remaining 70, 29 (41%) were planning fertility treatment; only 19 planned IVF. All 19 expressed interest in participation. COVID-19 delays in treatment were not considered as a factor affecting participation by 8/19; the remaining 11 felt that it would "somewhat" affect their decision. None reported that they would not consider participation because of COVID-19. EMR-based recruitment for an endometriosis clinical trial is feasible although the overall yield of participants is low. Delays in treatment due to COVID-19 did not appear to overly influence potential recruitment.
Assuntos
COVID-19 , Endometriose/terapia , Fármacos para a Fertilidade Feminina/uso terapêutico , Fertilização in vitro , Conhecimentos, Atitudes e Prática em Saúde , Antagonistas de Hormônios/uso terapêutico , Infertilidade Feminina/terapia , Seleção de Pacientes , Sujeitos da Pesquisa/psicologia , Adolescente , Adulto , Comportamento de Escolha , Método Duplo-Cego , Registros Eletrônicos de Saúde , Endometriose/diagnóstico , Endometriose/fisiopatologia , Feminino , Fármacos para a Fertilidade Feminina/efeitos adversos , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Antagonistas de Hormônios/efeitos adversos , Humanos , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/fisiopatologia , Nascido Vivo , Gravidez , Taxa de Gravidez , Resultado do Tratamento , Estados Unidos , Adulto JovemRESUMO
Teverelix trifluoroacetate is a decapeptide, gonadotropin-releasing hormone antagonist that binds competitively and reversibly to gonadotropin-releasing hormone receptors in the pituitary gland, resulting in immediate suppression of luteinizing hormone and follicle-stimulating hormone, which in turn causes a very rapid decrease in testosterone production in the Leydig cells of the testes in men and in estradiol in the ovaries in women. This phase 1 clinical study was an open-label, parallel-design, single-center, single-dose study in older, healthy male subjects. Following injection, teverelix is released into the systemic circulation in a biphasic manner. An initial rapid phase is followed by a slow-release phase thought to be due to the formation of a depot, which limits the diffusion of teverelix into the blood. The release characteristics differ significantly for the subcutaneous (SC) and intramuscular (IM) routes. Teverelix maximum concentration and exposure increased in an approximately dose-proportional manner across the 60 to 120 mg SC doses. All 3 pharmacodynamic end points (luteinizing hormone, follicle-stimulating hormone, and total testosterone) showed reductions that were more prolonged following the 90 mg IM administration compared to 90 mg SC administration.
Assuntos
Antagonistas de Hormônios , Oligopeptídeos , Idoso , Hormônio Liberador de Gonadotropina , Antagonistas de Hormônios/efeitos adversos , Humanos , Masculino , Oligopeptídeos/efeitos adversos , Ácido TrifluoracéticoRESUMO
Ovarian Hyperstimulation Syndrome (OHSS) remains a risk to women undergoing assisted conception despite available preventative measures, which are usually applied on the basis of ovarian response. We performed a retrospective cohort study with robust ascertainment of OHSS cases in women undergoing treatment using GnRH antagonist. FSH dose was based on Anti-Mullerian Hormone concentration. A total of 1492 cycles were carried out over 18 months. Moderate/severe OHSS occurred in 24 cycles (1.6%). AMH of 35 pmol/L and/or AFC of 20 or more identified 18/24 (76%) OHSS cases. The optimal thresholds for predicting OHSS were 22.5 pmol/L for AMH (sensitivity 87.5%, specificity 60.6%), 19.5 for AFC (sensitivity 70.8%, specificity 67%), and 9.5 for egg numbers (sensitivity 83.5%, specificity 62.7%). Peak oestradiol levels had no predictive value. The utility of egg number is limited as it is only known after the ovulatory trigger has been administered. Thus, ovarian reserve parameters are better than ovarian response at predicting the risk of significant OHSS in GnRH antagonist cycles in modern clinical practice. Patients with a high ovarian reserve are at risk of OHSS even if their ovarian response is not excessive. Decisions about preventative measures should be based on ovarian reserve rather than ovarian response.
Assuntos
Síndrome de Hiperestimulação Ovariana , Reserva Ovariana , Hormônio Antimülleriano , Feminino , Fertilização in vitro , Hormônio Liberador de Gonadotropina , Antagonistas de Hormônios/efeitos adversos , Humanos , Síndrome de Hiperestimulação Ovariana/prevenção & controle , Indução da Ovulação/efeitos adversos , Estudos RetrospectivosRESUMO
RATIONALE: Dienogest is a type of progestin used for the treatment of endometriosis (EM). However, a significant adverse effect of dienogest is depression; therefore, assessing for a history of mood disorders is recommended before prescribing the drug. Herein, we present the case of a patient with no history of psychiatric disorders who was diagnosed with dienogest-induced major depressive disorder. This case emphasizes the importance of close monitoring for negative mood changes in patients taking dienogest. PATIENT CONCERNS: A 41-year-old woman underwent surgery for EM. Postoperatively, her gynecologist prescribed dienogest (2 mg/d) to control EM symptoms. Two months after the initiation of dienogest, she manifested insomnia almost daily, gradually became depressed, lost interest in all activities, had incessant cries, and repeatedly thought of death. She had no history of major physical or psychiatric disorders. DIAGNOSIS: Major depressive disorder, single episode, severe. INTERVENTIONS: A psychiatric consultation was recommended, an antidepressant was prescribed, and dienogest was discontinued. OUTCOMES: Two weeks later, there was significant improvement in the symptoms, and after 4 weeks, she remained in a stable mood with no suicidal thoughts. She was followed up for 13 months with a maintenance dose of escitalopram (5 -10mg/d), until the psychiatrist recommended treatment discontinuation, with a confirmed state of remission. LESSONS: This was a case of dienogest-induced depression in a patient with no history of mood disorders. Clinicians should be aware of the possibility of the occurrence of severe depression in progestin users regardless of their previous history.
Assuntos
Transtorno Depressivo Maior/etiologia , Endometriose/tratamento farmacológico , Antagonistas de Hormônios/efeitos adversos , Nandrolona/análogos & derivados , Ideação Suicida , Adulto , Endometriose/cirurgia , Feminino , Antagonistas de Hormônios/uso terapêutico , Humanos , Nandrolona/efeitos adversos , Nandrolona/uso terapêuticoRESUMO
BACKGROUND: Uterine fibroids are benign. They belong to the category of "abdominal mass" in traditional Chinese medicine, and pathogenesis is mainly caused by weakness of the body, qi stagnation, and blood stasis. Drug therapy is the preferred treatment of uterine fibroids in clinical practice, and mifepristone is the most commonly used drug. In the past decade, a large number of clinical randomized controlled trials have proven that Chinese patent medicine combined with mifepristone in the treatment of uterine fibroids has a better curative effect, fewer adverse reactions, and higher safety than mifepristone alone. However, there is a lack of evidence-based research. This study aims to integrate clinical data through network meta-analysis to provide more evidence-based medical evidence for clinical medication. METHODS: The comprehensive search included Chinese and other-language databases, such as MEDLINE (PubMed), Web of Science, The Cochrane Library, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China Scientific Journal Database, and China Biomedical Literature Database. Clinical randomized controlled trials of 6 Chinese patent medicines combined with mifepristone for the treatment of uterine fibroids, including Guizhi Fuling Capsule, Gongliuxiao Capsule, Gongliuqing Capsule, Danbie Capsule, Gongliuning Capsule, and Xiaojiean Capsule were retrieved. The search period was from January 2010 to April 2021. Two researchers screened the literature through EndNote and used Excel to extract data. RevMan 5.3 was used to evaluate the quality of the literature. Treatment measures were analyzed in R language, and a forest map and probability ranking map of various interventions were drawn. The network evidence map and correction comparison funnel map of various interventions were drawn by STATA 14.0 software. RESULTS: This study provides the clinical efficacy and safety of network meta-analysis of 6 kinds of Chinese patent medicines combined with mifepristone in the treatment of uterine fibroids will be systematically evaluated or descriptively analyzed. CONCLUSION: This study's purpose is to provide a reference for the clinical treatment of uterine fibroids to choose more effective intervention therapies.
Assuntos
Antagonistas de Hormônios/uso terapêutico , Leiomioma/tratamento farmacológico , Medicina Tradicional Chinesa/métodos , Mifepristona/uso terapêutico , Quimioterapia Combinada , Antagonistas de Hormônios/administração & dosagem , Antagonistas de Hormônios/efeitos adversos , Humanos , Leiomioma/patologia , Medicina Tradicional Chinesa/efeitos adversos , Mifepristona/administração & dosagem , Mifepristona/efeitos adversos , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Metanálise como AssuntoRESUMO
Cancer- and treatment-related cognitive dysfunction (CRCD) is a common challenge faced by patients diagnosed with non-central nervous system (CNS) cancer. It has become increasingly recognized that multiple factors likely play a role in these symptoms, including the cancer disease process, systemic treatments (e.g., chemotherapy and endocrine therapies), and risk factors that may predispose an individual to both cancer and cognitive dysfunction. As the field has evolved, advanced neuroimaging techniques have been applied to better understand the neural correlates of CRCD. This review focuses on structural neuroimaging findings related to CRCD in adult non-CNS cancer populations, including examination of gray matter volume/density and white matter integrity differences between cancer patients and comparison groups, as well as emerging findings regarding structural network abnormalities. Overall, this literature has demonstrated consistent findings of reduced gray matter volume/density and white matter integrity in cancer patients relative to comparison groups. These are most prominent in individuals treated with chemotherapy, though alterations have also been noted in those treated with anti-estrogen and androgen-deprivation therapies. Alterations in gray and white matter structural network connectivity have also been identified. These structural abnormalities have been observed most prominently in frontal and temporal brain regions, and have been shown to correlate with subjective and objective cognitive function, as well as with physiological and clinical variables, helping to inform understanding of CRCD mechanisms. To date, however, structural neuroimaging techniques have not been utilized in systematic studies of potential CRCD treatments, suggesting a potentially fruitful avenue for future research.
Assuntos
Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/diagnóstico por imagem , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Neuroimagem/métodos , Adulto , Antineoplásicos/efeitos adversos , Encéfalo/efeitos dos fármacos , Disfunção Cognitiva/epidemiologia , Antagonistas de Hormônios/efeitos adversos , Humanos , Neoplasias/epidemiologia , Neuroimagem/tendências , Resultado do TratamentoRESUMO
INTRODUCTION: Uterine myomas and endometriosis are benign hormone-dependent diseases affecting women of reproductive age. Substantial efforts have been made to develop innovative medical options for treating these gynecologic diseases. Elagolix and relugolix have been approved in some countries for treating endometriosis and myomas, respectively; however, linzagolix (OBE 2109, KLH 2109) is a new oral gonadotropin-releasing hormone (GnRH) antagonist in phase II-III trials. Treatment options for women with contraindications for hormonal therapies or who refuse particular options, are the driving force behind the development of new drugs in this area. AREA COVERED: This drug evaluation highlights definitive and preliminary results from previous and ongoing studies of linzagolix for the treatment of endometriosis and myomas. EXPERT OPINION: Linzagolix showed a dose-dependent and rapidly reversible action on the pituitary-gonadal axis. In a recent phase II trial (EDELWEISS), linzagolix significantly reduced pain related to endometriosis and improved quality of life at single daily doses of 75-200 mg. The preliminary results of international, double-blind phase III trials (PRIMROSE 1 and 2) reported its efficacy in treating heavy menstrual bleeding related to myomas with a good safety profile. Further studies will determine the necessity of add-back therapy during long-term use of linzagolix.
Assuntos
Ácidos Carboxílicos/administração & dosagem , Endometriose/tratamento farmacológico , Leiomioma/tratamento farmacológico , Pirimidinas/administração & dosagem , Neoplasias Uterinas/tratamento farmacológico , Ácidos Carboxílicos/efeitos adversos , Ácidos Carboxílicos/farmacologia , Relação Dose-Resposta a Droga , Feminino , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Antagonistas de Hormônios/administração & dosagem , Antagonistas de Hormônios/efeitos adversos , Antagonistas de Hormônios/farmacologia , Humanos , Pirimidinas/efeitos adversos , Pirimidinas/farmacologiaAssuntos
Antagonistas de Hormônios/efeitos adversos , Cirurgia de Readequação Sexual/legislação & jurisprudência , Pessoas Transgênero/legislação & jurisprudência , Populações Vulneráveis/legislação & jurisprudência , Adolescente , Criança , Hormônios/uso terapêutico , Humanos , Transtornos Mentais/epidemiologia , Puberdade/efeitos dos fármacos , Direito à Saúde/ética , Sexismo/psicologia , Estereotipagem , Pessoas Transgênero/psicologia , Pessoas Transgênero/estatística & dados numéricos , Populações Vulneráveis/psicologia , Populações Vulneráveis/estatística & dados numéricosRESUMO
BACKGROUND: Uterine leiomyoma (UL) is a common severe gynecological issue. In China, Xuefu Zhuyu Decoction (XFZYD), combined with Mifepristone, is widely used in the treatment of UL. However, their combined effectiveness and safety for this purpose have not yet been explored. OBJECTIVE: This systematic review aims to evaluate the effectiveness and safety of XFZYD combined with Mifepristone as a method of treatment for UL. METHODS: We searched the following 7 databases: 3 English medical databases (PubMed, EMBASE, Cochrane Library), and 4 Chinese medical databases (Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), and the Wanfang database). The primary outcome was the effect of XFZYD combined with Mifepristone on the effective rate, uterine leiomyoma volume (ULV), and uterine volume (UV) of uterine leiomyoma. Bias risk was assessed using the Cochrane risk of bias tool. The software RevMan5 was used to evaluate the quality of the included studies and process the data. RESULTS: This study will evaluate the efficacy and safety of XFZYD combined with Mifepristone in the treatment of uterine fibroids by evaluating the effective rate, Uterine Leiomyoma volume, and uterine volume, the incidence of estradiol, luteinizing hormone, and other indicators. CONCLUSION: This study will provide reliable evidence-based evidence for Xuefu Zhuyu Decoction Combined with Mifepristone in the treatment of uterine fibroids. ETHICS AND DISSEMINATION: Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval will not be required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/YADN3.