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1.
Menopause ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34636354

RESUMO

OBJECTIVE: Longer menstrual cycles have been associated with greater risk of cardiovascular disease, supporting a contribution of abnormal ovarian function. We aimed to characterize trajectories of menstrual cycle length over the menopause transition (MT) and test whether these trajectories are associated with postmenopausal markers of subclinical atherosclerosis. METHODS: Women from the Study of Women's Health Across the Nation Daily Hormone Study were included if they had an observed date of the final menstrual period (FMP), recorded cycle lengths from ≥2 annual menstrual cycles (mean±SD: 4.22 ± 1.91 cycles), and had measurements of postmenopausal carotid intima-media thickness (cIMT) and/or brachial-ankle pulse wave velocity (baPWV). Trajectories of cycle length over the MT were identified using group-based trajectory modeling and linked with cIMT and baPWV using linear regression. RESULTS: We studied 428 women who had 1,808 cycles over the MT (45.1 ± 2.3 y old at baseline visit), and of whom 263 had cIMT, and 213 had baPWV measured postmenopausally (after 13.88 ±â€Š0.42 and 15.25 ±â€Š0.70 y since baseline visit, respectively). Three distinct trajectories of cycle length were identified: stable (no changes in cycle length over the MT among 62.1% of women), late increase (a late increase 2 y before the FMP among 21.8%), and early-increase (an early increase 5 y before the FMP among 16.2%). Women with the late-increase pattern had significantly lower postmenopausal cIMT (0.72 mm) and baPWV (1392 cm/s) levels than the stable group (0.77 mm and 1508 cm/s, respectively) adjusting for race, concurrent age, socioeconomic status, physical activity level, and premenopausal cardiovascular risk profile. CONCLUSIONS: Patterns of cycle length over the MT seem to be a marker of future vascular health that may help identify groups at greater or lesser risk of atherosclerosis after menopause.

2.
F S Rep ; 2(3): 282-288, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34553152

RESUMO

Objective: To examine the factors associated with increased deoxyribonucleic acid fragmentation index (DFI), evaluate the pregnancy outcomes of men with increased DFI, and compare three independent DFI assays. Design: Secondary analysis. Setting: Nine US-based fertility centers. Patients: Infertile men (N = 147) with sperm concentration ≤15 × 106/mL, motility ≤40%, or normal morphology ≤4% were enrolled. The female partners were ovulatory, ≤40 years old, and had documented tubal patency. Interventions: At a baseline visit, the men provided a semen sample. The couples attempted conception without assistance for 3 months and with ovarian stimulation and intrauterine insemination in the subsequent 3 months. Main Outcome Measures: The DFI was analyzed using the sperm chromatin structure assay (SCSA) with increased DFI defined as >30%. The predictors of increased DFI were determined by a multivariable linear regression model. The pregnancy outcomes were compared using the χ2 test. The independent DFI assays (SCSA, deoxynucleotidyl transferase-mediated dUTP nick end labeling, and Comet) were compared with Pearson and Spearman correlations. Results: The 19% of men with increased DFI were older (36.0 vs. 33.0 years) and had lower total sperm motility (38.2% ± 20.5% vs. 45.2% ± 15.6%). Increased male age was found to be a significant predictor of DFI (0.75, 95% confidence interval [0.06, 1.45]). Increased DFI was not associated with conception or live birth. There was a modest correlation of the deoxynucleotidyl transferase-mediated dUTP nick end labeling assay with the SCSA (r = 0.34) and Comet assay (r = 0.19). Conclusions: Older age was associated with increased DFI among infertile men. The DFI assays were only weakly correlated, indicating a standard definition of DFI is needed to truly interrogate how sperm deoxyribonucleic acid fragmentation impacts male fertility.

3.
Menopause ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34547004
4.
Clin Obstet Gynecol ; 64(4): 793-802, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34482337

RESUMO

The spectacular success of compounded bioidentical hormone therapy is a product of the unanticipated negative-to-neutral findings of the Women's Health Initiative hormone trial and the peculiarities of their regulatory status. By not having to provide scientific evidence of safety and efficacy, a requirement for all Food and Drug Administration (FDA)-approved hormone therapy products, the industry's relatively unfettered marketing now accounts for about one third of menopausal hormone therapy prescriptions. Clinicians are often caught in the middle between patient beliefs and a desire to practice evidence-based medicine. Strategies are needed to redirect patients towards truly safe and effective treatment for their menopausal symptoms.


Assuntos
Terapia de Reposição de Estrogênios , Menopausa , Composição de Medicamentos , Feminino , Terapia de Reposição Hormonal , Hormônios , Humanos
5.
Clin Obstet Gynecol ; 64(4): 784-792, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34560765

RESUMO

Biopotent androgens such as testosterone circulate in low levels in women. However, androgen precursors, such as dehyroepiandrosterone, are among the most abundant hormones produced in both men and women. While testosterone exerts obvious phenotypic effects in men and is essential for male sexual function, considerable debate and controversy abounds over the role of androgens in women and whether androgens exert an analogous role in women as they do in men. This piece reviews androgen economy in women and the clinical case for and against androgen treatment for women for specific indications.


Assuntos
Androgênios , Ciclismo , Animais , Feminino , Humanos , Masculino , Testosterona
6.
Clin Obstet Gynecol ; 64(4): 719-720, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34446651
7.
JAMA ; 326(5): 390-400, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34342619

RESUMO

Importance: Women with an early nonviable pregnancy of unknown location are at high risk of ectopic pregnancy and its inherent morbidity and mortality. Successful and timely resolution of the gestation, while minimizing unscheduled interventions, are important priorities. Objective: To determine if active management is more effective in achieving pregnancy resolution than expectant management and whether the use of empirical methotrexate is noninferior to uterine evacuation followed by methotrexate if needed. Design, Setting, and Participants: This multicenter randomized clinical trial recruited 255 hemodynamically stable women with a diagnosed persisting pregnancy of unknown location between July 25, 2014, and June 4, 2019, in 12 medical centers in the United States (final follow up, August 19, 2019). Interventions: Eligible patients were randomized in a 1:1:1 ratio to expectant management (n = 86), active management with uterine evacuation followed by methotrexate if needed (n = 87), or active management with empirical methotrexate using a 2-dose protocol (n = 82). Main Outcomes and Measures: The primary outcome was successful resolution of the pregnancy without change from initial strategy. The primary hypothesis tested for superiority of the active groups combined vs expectant management, and a secondary hypothesis tested for noninferiority of empirical methotrexate compared with uterine evacuation with methotrexate as needed using a noninferiority margin of -12%. Results: Among 255 patients who were randomized (median age, 31 years; interquartile range, 27-36 years), 253 (99.2%) completed the trial. Ninety-nine patients (39%) declined their randomized allocation (26.7% declined expectant management, 48.3% declined uterine evacuation, and 41.5% declined empirical methotrexate) and crossed over to a different group. Compared with patients randomized to receive expectant management (n = 86), women randomized to receive active management (n = 169) were significantly more likely to experience successful pregnancy resolution without change in their initial management strategy (51.5% vs 36.0%; difference, 15.4% [95% CI, 2.8% to 28.1%]; rate ratio, 1.43 [95% CI, 1.04 to 1.96]). Among active management strategies, empirical methotrexate was noninferior to uterine evacuation followed by methotrexate if needed with regard to successful pregnancy resolution without change in management strategy (54.9% vs 48.3%; difference, 6.6% [1-sided 97.5% CI, -8.4% to ∞]). The most common adverse event was vaginal bleeding for all of the 3 management groups (44.2%-52.9%). Conclusions and Relevance: Among patients with a persisting pregnancy of unknown location, patients randomized to receive active management, compared with those randomized to receive expectant management, more frequently achieved successful pregnancy resolution without change from the initial management strategy. The substantial crossover between groups should be considered when interpreting the results. Trial Registration: ClinicalTrials.gov Identifier: NCT02152696.


Assuntos
Abortivos não Esteroides/administração & dosagem , Metotrexato/administração & dosagem , Gravidez Ectópica/tratamento farmacológico , Gravidez Ectópica/cirurgia , Conduta Expectante , Aborto Espontâneo , Adulto , Gonadotropina Coriônica/sangue , Terapia Combinada , Dilatação e Curetagem , Feminino , Humanos , Satisfação do Paciente , Gravidez , Ultrassonografia Pré-Natal , Hemorragia Uterina
8.
J Assist Reprod Genet ; 38(11): 3005-3013, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34455507

RESUMO

PURPOSE: The understanding of the role of plasma antioxidant levels in male fertility in the USA is limited. In a secondary analysis of the Males, Antioxidants, and Infertility (MOXI) randomized clinical trial, we sought to determine whether serum levels of vitamin E (α-tocopherol), zinc, and selenium were correlated with semen parameters and couple fertility outcomes. METHODS: This study is a secondary analysis of the MOXI clinical trial. The primary endpoints in this secondary analysis include semen parameters, and DNA fragmentation and clinical outcomes including pregnancy and live birth. Analyses were completed using Wilcoxon's rank-sum test and linear regression models. RESULTS: At baseline, the analysis included plasma labs for vitamin E (n = 131), selenium (n = 124), and zinc (n = 128). All baseline plasma values were in the normal ranges. There was no association between selenium, zinc, or vitamin E levels and semen parameters or DNA fragmentation. Baseline antioxidant levels in the male partners did not predict pregnancy or live birth among all couples. Among those randomized to placebo, baseline male antioxidant levels did not differ between those couples with live birth and those that did not conceive or have a live birth. CONCLUSIONS: Among men attending fertility centers in the USA, who have sufficient plasma antioxidant levels of zinc, selenium, or vitamin E, no association was observed between vitamins and semen parameters or clinical outcomes in couples with male infertility. Higher levels of antioxidants among men with circulating antioxidants in the normal range do not appear to confer benefit on semen parameters or male fertility.

9.
Reprod Sci ; 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34363198

RESUMO

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.

10.
Fertil Steril ; 116(4): 973-979, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34289935

RESUMO

OBJECTIVE: To determine the association between vitamin D levels in the male partner and fertility outcomes in couples with mild male factor infertility. DESIGN: Secondary analysis of a randomized, controlled trial. SETTING: Nine fertility centers in the United States. PATIENT(S): Men (n = 154) with sperm concentration between 5 and 15 million/mL, motility ≤40%, or normal morphology ≤4% were eligible. Female partners were ovulatory, ≤40 years old, and had documented tubal patency. INTERVENTION(S): Men provided semen and blood at baseline for semen analysis and 25-hydroxyvitamin D (25(OH)D) levels. They were randomly assigned to receive a vitamin formulation including vitamin D 2,000 IU daily or placebo for up to 6 months. Couples attempted to conceive naturally during the first 3 months and with clomiphene citrate with intrauterine insemination of the female partner in months 4 through 6. MAIN OUTCOME MEASURE(S): Primary: sperm concentration, motility, morphology, and DNA fragmentation at baseline. Secondary: cumulative pregnancy, miscarriage, and live birth rates. RESULT(S): Semen parameters and sperm DNA fragmentation were not statistically significantly different between men with vitamin D deficiency and men with 25(OH)D levels ≥20 ng/mL. In addition, clinical pregnancy and live birth rates were similar. Male 25(OH)D level <20 ng/mL was associated with a higher rate of pregnancy loss (adjusted odds ratio 9.0; 95% confidence interval 1.3 to 61.3). CONCLUSION(S): Vitamin D deficiency in the male partner did not significantly impact semen parameters or treatment outcomes. Further study is warranted to better characterize the rate of miscarriage in couples with male vitamin D deficiency.


Assuntos
Clomifeno/uso terapêutico , Fármacos para a Fertilidade Feminina/uso terapêutico , Fertilidade , Infertilidade Masculina/terapia , Inseminação Artificial Homóloga , Deficiência de Vitamina D/sangue , Vitamina D/análogos & derivados , Aborto Espontâneo/etiologia , Adulto , Biomarcadores/sangue , Clomifeno/efeitos adversos , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Fertilidade/efeitos dos fármacos , Fármacos para a Fertilidade Feminina/efeitos adversos , Humanos , Infertilidade Masculina/sangue , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/fisiopatologia , Inseminação Artificial Homóloga/efeitos adversos , Nascido Vivo , Masculino , Gravidez , Taxa de Gravidez , Estudos Prospectivos , Fatores de Risco , Sêmen/metabolismo , Análise do Sêmen , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Vitamina D/sangue , Vitamina D/uso terapêutico , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/tratamento farmacológico
11.
Mol Hum Reprod ; 27(8)2021 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-34314477

RESUMO

Mechanisms that directly control mammalian ovarian primordial follicle (PF) growth activation and the selection of individual follicles for survival are largely unknown. Follicle cells produce factors that can act as potent inducers of cellular stress during normal function. Consistent with this, we show here that normal, untreated ovarian cells, including pre-granulosa cells of dormant PFs, express phenotype and protein markers of the activated integrated stress response (ISR), including stress-specific protein translation (phospho-Serine 51 eukaryotic initiation factor 2α; P-EIF2α), active DNA damage checkpoints, and cell-cycle arrest. We further demonstrate that mRNAs upregulated in primary (growing) follicles versus arrested PFs mostly include stress-responsive upstream open reading frames (uORFs). Treatment of a granulosa cell (GC) line with the PF growth trigger tumor necrosis factor alpha results in the upregulation of a 'stress-dependent' translation profile. This includes further elevated P-eIF2α and a shift of uORF-containing mRNAs to polysomes. Because the active ISR corresponds to slow follicle growth and PF arrest, we propose that repair and abrogation of ISR checkpoints (e.g. checkpoint recovery) drives the GC cell cycle and PF growth activation (PFGA). If cellular stress is elevated beyond a threshold(s) or, if damage occurs that cannot be repaired, cell and follicle death ensue, consistent with physiological atresia. These data suggest an intrinsic quality control mechanism for immature and growing follicles, where PFGA and subsequent follicle growth and survival depend causally upon ISR resolution, including DNA repair and thus the proof of genomic integrity.

12.
J Clin Endocrinol Metab ; 106(11): e4414-e4426, 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34180998

RESUMO

CONTEXT: Sleep plays important roles in metabolic and reproductive function, and polycystic ovary syndrome (PCOS) is associated with sleep disturbances, including increased prevalence of obstructive sleep apnea. OBJECTIVE: We sought to evaluate sleep parameters in infertile women with PCOS compared with women with unexplained infertility (UI) and identify risk factors for disturbed sleep. METHODS: At private and academic ambulatory gynecology and infertility practices, we evaluated a prospective cohort of women diagnosed with PCOS or UI from 2 randomized clinical trials. We included 1603 infertile women enrolled in 2 concurrent randomized clinical trials. The main outcome measures were self-reported sleep measures. RESULTS: Sleep duration <6 hours (6.1% vs 2.7%; P < .001), habitual snoring (37.8% vs 19.0%; P < .001), and clinical sleepiness (12.0% vs 8.6%; P < .026) were more common in women with PCOS than those with UI. After adjusting for covariates, PCOS and elevated fasting insulin were associated (P = .010) with clinical symptoms of obstructive sleep apnea (OSA) diagnosis, whereas PCOS, elevated insulin (P = .003), WC >88 cm (P = .003), and current smoking (P = .012) were associated with habitual snoring. Clinical depression score (P < .001) and PCOS diagnosis (P = .002) were associated with perceived daytime sleepiness. Short sleep duration and clinical symptoms of OSA were not associated with conception and live birth rates. CONCLUSION: Infertile women with PCOS more commonly report sleep disturbances than those with UI. Markers of insulin resistance are associated with previous diagnosis of OSA, habitual snoring, and short sleep duration. The presence of clinical symptoms of OSA or short sleep duration does not affect fertility treatment response.

13.
J Infect Dis ; 2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34174074

RESUMO

BACKGROUND: Persistent immune activation due to gut barrier dysfunction is a suspected cause of morbidity in HIV, but the impact of menopause on this pathway is unknown. METHODS: In 350 women with HIV from the Women's Interagency HIV Study, plasma biomarkers of gut barrier dysfunction (intestinal fatty acid binding protein; IFAB), innate immune activation (soluble CD14 and CD163; sCD14, sCD163), and systemic inflammation (interleukin-6 and tumor necrosis factor receptor 1; IL-6, TNFR1), were measured at 674 person-visits spanning ≤2 years. RESULTS: Menopause (post- vs. pre-menopausal status) was associated with higher plasma sCD14 and sCD163 in linear mixed-effects regression adjusting for age and other covariates (B [95% CI]=161.89ng/mL [18.37, 305.41] and 65.48 ng/mL [6.64, 124.33], respectively); but not with plasma IFAB, IL-6, or TNFR1. In piece-wise linear mixed-effects regression of biomarkers on years before/after the final menstrual period, sCD14 increased during the menopausal transition by 250.71 ng/mL per year (95% CI: 16.63, 484.79; p=0.04), but not in the pre-menopausal or post-menopausal periods. CONCLUSIONS: In women with HIV, menopause may increase innate immune activation, but data did not support an influence on the gut barrier or inflammation. Clinical implications of immune activation during the menopausal transition warrants further investigation.

15.
Fertil Steril ; 116(2): 566-574, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33838870

RESUMO

OBJECTIVE: To study the reprometabolic syndrome in normal-weight, eumenorrheic women by infusing a combination of insulin and lipid. Women with obesity have been shown to have reduced gonadotropins and impaired luteinizing hormone (LH) and follicle-stimulating hormone (FSH) response to gonadotropin-releasing hormone (GnRH). DESIGN: Randomized crossover. SETTING: Academic medical center. PARTICIPANT(S): Fifteen women, median age 32 (interquartile ranged [IQR] 26, 36) years and body mass index 21.9 (IQR 20.2, 22.9) kg/m2 were recruited. INTERVENTION(S): Early follicular phase, 6-hour infusions of insulin (20-40 mU/m2 per minute) and lipid (Intralipid)-insulin/lipid infusion; or saline infusion (controls). The first 4 hours of each study assessed endogenous gonadotropins; at 4 hours, GnRH (75 ng/kg) bolus was administered and sampling continued until 6 hours. MAIN OUTCOME MEASURE(S): Linear mixed model analysis was used to determine differences between insulin/lipid and saline influence on endogenous LH pulse amplitude (primary outcome), mean FSH, and area under the curve (AUC) response to GnRH (secondary outcomes). RESULT(S): Twelve women completed both intended studies and an additional 3 women completed only 1 of the 2 studies. LH pulse amplitude, mean FSH, and both AUC responses to GnRH were reduced by insulin/lipid, mean FSH and AUC for LH were at or near statistical significance. LH response to GnRH was significantly reduced when 1 participant with very high LH and antimullerian hormone levels was excluded. CONCLUSION(S): Acute infusion of insulin/lipid to eumenorrheic, normal-weight women recapitulated the reprometabolic syndrome of obesity. These findings imply that specific circulating factors in obese women contribute to their subfertility and thus may be amenable to discovery and treatment. CLINICAL TRIAL REGISTRATION NUMBER: NCT02653092.


Assuntos
Hormônio Foliculoestimulante/sangue , Insulina/farmacologia , Hormônio Luteinizante/sangue , Síndrome Metabólica/etiologia , Obesidade/complicações , Fosfolipídeos/farmacologia , Óleo de Soja/farmacologia , Adulto , Estudos Cross-Over , Emulsões/farmacologia , Feminino , Humanos , Magreza
16.
PLoS One ; 16(3): e0247638, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33764994

RESUMO

CONTEXT: Obesity, is a state of chronic inflammation, characterized by elevated lipids, insulin resistance and relative hypogonadotropic hypogonadism. We have defined the accompanying decreased Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), ovarian steroids and reduced pituitary response to Gonadotropin-releasing Hormone (GnRH) as Reprometabolic syndrome, a phenotype that can be induced in healthy normal weight women (NWW) by acute infusion of free fatty acids and insulin. OBJECTIVE: To identify potential mediators of insulin and lipid-related reproductive endocrine dysfunction. DESIGN, SETTING, PARTICIPANTS: Secondary analysis of crossover study of eumenorrheic reproductive aged women of normal Body Mass Index (BMI) (<25 kg/m2) at an academic medical center. INTERVENTION: Participants underwent 6-hour infusions of either saline/heparin or insulin plus fatty acids (Intralipid plus heparin), in the early follicular phase of sequential menstrual cycles, in random order. Euglycemia was maintained by glucose infusion. Frequent blood samples were obtained. MAIN OUTCOME MEASURES: Pooled serum from each woman was analyzed for cytokines, interleukins, chemokines, adipokines, Fibroblast Growth Factor-21 (FGF-21) and markers of endoplasmic reticulum (ER) stress (CHOP and GRP78). Wilcoxon signed-rank tests were used to compare results across experimental conditions. RESULTS: Except for Macrophage Inflammatory Protein-1ß (MIP-1ß), no significant differences were observed in serum levels of any of the inflammatory signaling or ER stress markers tested. CONCLUSION: Acute infusion of lipid and insulin, to mimic the metabolic syndrome of obesity, was not associated with an increase in inflammatory markers. These results imply that the endocrine disruption and adverse reproductive outcomes of obesity are not a consequence of the ambient inflammatory environment but may be mediated by direct lipotoxic effects on the hypothalamic-pituitary-ovarian (HPO) axis.


Assuntos
Ácidos Graxos não Esterificados/administração & dosagem , Hiperinsulinismo/metabolismo , Hiperlipidemias/metabolismo , Insulina/administração & dosagem , Síndrome Metabólica/metabolismo , Transdução de Sinais , Centros Médicos Acadêmicos , Adolescente , Adulto , Índice de Massa Corporal , Estudos Cross-Over , Citocinas/genética , Citocinas/metabolismo , Estresse do Retículo Endoplasmático , Emulsões Gordurosas Intravenosas/administração & dosagem , Feminino , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Hormônio Foliculoestimulante/genética , Hormônio Foliculoestimulante/metabolismo , Expressão Gênica , Aptidão Genética/efeitos dos fármacos , Aptidão Genética/genética , Técnica Clamp de Glucose , Hormônio Liberador de Gonadotropina/genética , Hormônio Liberador de Gonadotropina/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Hiperinsulinismo/induzido quimicamente , Hiperinsulinismo/genética , Hiperinsulinismo/patologia , Hiperlipidemias/induzido quimicamente , Hiperlipidemias/genética , Hiperlipidemias/patologia , Hormônio Luteinizante/genética , Hormônio Luteinizante/metabolismo , Síndrome Metabólica/induzido quimicamente , Síndrome Metabólica/genética , Síndrome Metabólica/patologia , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Fator de Transcrição CHOP/genética , Fator de Transcrição CHOP/metabolismo
17.
Endocrinol Metab Clin North Am ; 50(1): 43-55, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33518185

RESUMO

The triad of hirsutism, amenorrhea, and enlarged polycystic ovaries first was described in 1935 and later become known as polycystic ovarian syndrome (PCOS). Women with PCOS are more likely to have cardiometabolic challenges that also have an indirect relationship to their fertility and fertility outcomes. Despite these challenges, their fertile life span appears to be longer. Ovulation induction is considered first-line management of infertility in women with PCOS, with letrozole superior to clomiphene. Women with PCOS undergoing in vitro fertilization are high risk for ovarian hyperstimulation syndrome but also have a higher live birth rate compared with controls.


Assuntos
Infertilidade Feminina , Síndrome do Ovário Policístico , Clomifeno , Feminino , Fertilidade , Fármacos para a Fertilidade Feminina , Humanos , Infertilidade Feminina/etiologia , Síndrome do Ovário Policístico/complicações
18.
Reprod Sci ; 28(4): 933-935, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33638133

RESUMO

Human fetal tissue (HFT) has been used in biomedical research for nearly a century and has led to extraordinarily valuable discoveries that have benefitted humankind. Politicization of the use of HFT over recent years has led to the creation of numerous obstacles to scientific progress in this field. In July 2019, the imposition of redundant ethics policies was supplemented with the creation of the Human Fetal Tissue Ethics Advisory Board, which withheld funding of 13 out of 14 NIH grants that were favorably peer reviewed in the Summer of 2020. We believe that these new sets of restrictions are harmful to the goals of scientific progress and call upon the new administration of our government to allow peer review, not politics, to determine scientific merit and to reinstitute the previously existing ethics policies that were more than adequate to assure the appropriateness of human fetal tissue research.

19.
Menopause ; 28(5): 491-501, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33438892

RESUMO

OBJECTIVE: Gut microbiota respond to host physiological phenomena, yet little is known regarding shifts in the gut microbiome due to menopausal hormonal and metabolic changes in women. HIV infection impacts menopause and may also cause gut dysbiosis. We therefore sought to determine the association between menopausal status and gut microbiome composition in women with and without HIV. METHODS: Gut microbiome composition was assessed in stool from 432 women (99 premenopausal HIV+, 71 premenopausal HIV-, 182 postmenopausal HIV+, 80 postmenopausal HIV-) via 16S rRNA gene sequencing. We examined cross-sectional associations of menopause with gut microbiota overall diversity and composition, and taxon and inferred metagenomic pathway abundance. Models were stratified by HIV serostatus and adjusted for age, HIV-related variables, and other potential confounders. RESULTS: Menopause, ie post- versus premenopausal status, was associated with overall microbial composition only in women with HIV (permutational MANOVA of Jensen Shannon Divergence: P = 0.01). In women with HIV, menopause was associated with enrichment of gram-negative order Enterobacteriales, depletion of highly abundant taxa within Prevotella copri, and alterations in other low-abundance taxa. Additionally, menopause in women with HIV was associated with enrichment of metagenomic pathways related to Enterobacteriales, including degradation of amino acids and phenolic compounds, biosynthesis of enterobactin, and energy metabolism pathways. Menopause-related differences in some low-abundance taxa were also observed in women without HIV. CONCLUSIONS: A changing gut microbiome may be an overlooked phenomenon of reproductive aging in women with HIV. Longitudinal assessments across all reproductive stages are necessary to confirm these findings and identify health implications.


Assuntos
Microbioma Gastrointestinal , Infecções por HIV , Estudos Transversais , Feminino , Humanos , Menopausa , Prevotella , RNA Ribossômico 16S/genética
20.
J Clin Endocrinol Metab ; 106(1): 1-15, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33095879

RESUMO

CONTEXT: Menopause, the permanent cessation of menses, reflects oocyte depletion and loss of gonadal steroids. It is preceded by a transition state, the perimenopause, which is characterized by the gradual loss of oocytes, altered responsiveness to gonadal steroid feedback, wide hormonal fluctuations, and irregular menstrual patterns. The goal of this mini-review is to discuss the basic pathophysiology of the menopausal transition and the hormonal and nonhormonal management of clinicopathology attributed to it. EVIDENCE ACQUISITION: A Medline search of epidemiologic, population-based studies, and studies of reproductive physiology was conducted. A total of 758 publications were screened. EVIDENCE SYNTHESIS: The reproductive hormonal milieu of the menopausal transition precipitates bothersome vasomotor symptoms, mood disruption, temporary cognitive dysfunction, genitourinary symptoms, and other disease processes that reduce the quality of life of affected women. The endocrine tumult of the menopause transition also exposes racial and socioeconomic disparities in the onset, severity, and frequency of symptoms. Hormone therapy (HT) treatment can be effective for perimenopausal symptoms but its use has been stymied by concerns about health risks observed in postmenopausal HT users who are older than 60 and/or women who have been postmenopausal for greater than 10 years. CONCLUSIONS: The menopause transition is a disruptive process that can last for over a decade and causes symptoms in a majority of women. It is important for clinicians to recognize early signs and symptoms of the transition and be prepared to offer treatment to mitigate these symptoms. Many safe and effective options, including HT, are available.


Assuntos
Terapia de Reposição de Estrogênios , Menopausa/fisiologia , Avaliação de Sintomas , Terapia de Reposição de Estrogênios/métodos , Terapia de Reposição de Estrogênios/estatística & dados numéricos , Feminino , Hormônios Esteroides Gonadais/sangue , Hormônios Esteroides Gonadais/fisiologia , Hormônios Esteroides Gonadais/uso terapêutico , Fogachos/diagnóstico , Fogachos/epidemiologia , Fogachos/etiologia , Fogachos/terapia , Humanos , Perimenopausa/fisiologia , Qualidade de Vida , Avaliação de Sintomas/métodos , Sistema Vasomotor/fisiopatologia
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