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1.
Taiwan J Obstet Gynecol ; 58(4): 471-476, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31307735

RESUMO

OBJECTIVE: To study the impact of stimulation duration on intracytoplasmic sperm injection (ICSI) - embryo transfer (ET) outcome in poor and normal responders during controlled ovarian stimulation using gonadotropin-releasing hormone (GnRH) antagonist protocol. MATERIALS AND METHODS: This is a retrospective cohort study. There were 1481 women undergoing ICSI-ET cycles. Women with ovum pick-up number ≤3 were defined as poor responders (n = 235), and those with a number ≥4 were normal responders (n = 1246). RESULTS: The mean stimulation duration was shorter in poor responders with pregnancy group as compared with normal responders with pregnancy group (7.8 ± 2.2 vs. 9.2 ± 1.6 days, p < 0.01). Poor responders with a shortest stimulation duration (≤6 days) appeared a higher live birth rate (≤6 days: 33.3%, 7-8 days: 20.0%, 9-10 days: 15.9%, and ≥11 days: 11.1%, p = 0.18). Normal responders with a shortest stimulation duration (≤6 days) appeared a lowest live birth rate (≤6 days: 28.6%, 7-8 days: 35.8%, 9-10 days: 33.6%, and ≥11 days: 29.3%, p = 0.61). Oocyte maturation rate was significantly lower at stimulation durations ≤6 days group (≤6 days: 67%, 7-8 days: 80%, 9-10 days: 85%, and ≥11 days: 87%, p = 0.02) in normal responders. CONCLUSION: In ICSI-ET cycles, stimulation duration appears to have different impact on oocyte maturation, clinical pregnancy rates and live birth rates in both poor and normal responders.


Assuntos
Transferência Embrionária/métodos , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Ciclo Menstrual/efeitos dos fármacos , Indução da Ovulação/métodos , Taxa de Gravidez , Adulto , Estudos de Coortes , Transferência Embrionária/efeitos adversos , Feminino , Fertilização In Vitro/efeitos adversos , Fertilização In Vitro/métodos , Seguimentos , Hormônio Liberador de Gonadotropina/administração & dosagem , Hospitais Universitários , Humanos , Ciclo Menstrual/fisiologia , Recuperação de Oócitos/métodos , Oócitos/efeitos dos fármacos , Gravidez , Valores de Referência , Estudos Retrospectivos , Medição de Risco , Taiwan , Fatores de Tempo
2.
Mol Med Rep ; 20(2): 1306-1312, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173216

RESUMO

17ß­estradiol (E2) and aquaporin 2 (AQP2) are associated with endometrial receptivity, and E2 directly regulates AQP2 expression in endometrial cancer cells. The present study aimed to investigate the role of AQP2 in embryo implantation. Normal endometrial samples were collected at the Women's Hospital (Hangzhou, China) from women seeking in vitro fertilization and embryo transfer; women with endometrial abnormalities were excluded from the study. Samples were categorized into early­mid proliferative, late proliferative, early secretory, mid­secretory and late secretory phase groups, according to the menstrual cycle. The mRNA and protein expression levels of AQP2 were assessed in normal human endometrium in response to E2 via reverse transcription­quantitative polymerase chain reaction and western blotting, respectively. The effects of AQP2 on spheroid attachment were assessed using an in vitro co­culture assay with small interfering (si)RNA against AQP2. The highest expression levels of AQP2 were observed in the late proliferative and mid­secretory phases, with the lowest levels detected in the early proliferative and late secretory phases. In addition, treatment with 10­9 or 10­7 M E2 for 24 h upregulated AQP2 in the cultured endometrium. Knockdown of AQP2 by siRNA significantly decreased JAr spheroid attachment; however, this effect was significantly reversed when AQP2 siRNA­transfected cells were treated with 10­7 M E2. The results of the present study suggested that AQP2 expression levels in human endometrium may be mediated by estrogen, and low AQP2 expression levels may be a potential cause of impaired uterine receptivity.


Assuntos
Aquaporina 2/genética , Endométrio/metabolismo , Estradiol/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Esferoides Celulares/metabolismo , Adulto , Aquaporina 2/metabolismo , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Humanos , Ciclo Menstrual/efeitos dos fármacos
3.
Fertil Steril ; 112(2): 258-265, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31103285

RESUMO

OBJECTIVE: To evaluate differences in euploidy rates between IVF cycles triggered with either GnRH agonist (GnRHa) or hCG. DESIGN: Retrospective cohort study. SETTING: University-affiliated fertility center. PATIENT(S): A total of 366 patients performing 539 IVF cycles utilizing preimplantation genetic testing for aneuploidy (PGT-A). INTERVENTION(S): Gonadotropin-releasing hormone agonist or hCG trigger of oocyte maturation during IVF cycles. MAIN OUTCOME MEASURE(S): Rate of euploid embryos. RESULT(S): Patients in the GnRHa trigger arm were younger, with a lower body mass index and higher antimüllerian hormone level, and they had a higher number of oocytes retrieved and embryos biopsied. Euploid rate per embryo biopsied was higher after GnRHa trigger than after hCG trigger (37.8% ± 2.1% vs. 30.3% ± 1.8%), but multivariate regression analysis controlling for potential confounding factors did not show any differences between the two groups. Moreover, the euploid rate per oocyte retrieved was not significantly different overall (GnRHa vs. hCG: 33.9% ± 2.2% vs. 28.0% ± 1.9%). The anticipated decline in the rate of euploid embryos per oocyte retrieved went from 15.8% ± 1.2% for age <35 years to 4.3% ± 0.9% for patients aged ≥41 years. There were no significant differences between the two groups after stratifying by age and controlling for PGT-A testing modality. CONCLUSION(S): Both GnRHa and hCG trigger result in comparable euploid rates. Trigger with GnRHa should therefore be considered a valid option for trigger modality in freeze-all PGT-A cycles, in view of its demonstrated effectiveness and known safety enhancement.


Assuntos
Gonadotropina Coriônica/uso terapêutico , Fármacos para a Fertilidade Feminina/uso terapêutico , Testes Genéticos/estatística & dados numéricos , Hormônio Liberador de Gonadotropina/uso terapêutico , Indução da Ovulação/métodos , Ploidias , Diagnóstico Pré-Implantação/estatística & dados numéricos , Adulto , Aneuploidia , Feminino , Fertilização In Vitro/estatística & dados numéricos , Humanos , Infertilidade Feminina/epidemiologia , Infertilidade Feminina/genética , Infertilidade Feminina/terapia , Ciclo Menstrual/efeitos dos fármacos , Oogênese/efeitos dos fármacos , Oogênese/genética , Indução da Ovulação/efeitos adversos , Indução da Ovulação/estatística & dados numéricos , Gravidez , Estudos Retrospectivos
4.
Biomed Res Int ; 2019: 2513067, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31080813

RESUMO

Introduction: Many patients who were diagnosed as polycystic ovary syndrome- (PCOS-) related acne were not capable of sustaining or beginning oral contraceptive pills (OCPs) due to pill scaring, contraindications of OCP use, migraine, or smoking. In this situation, oral isotretinoin treatment may become an important option for PCOS-related acne. The aim of the study was to determine the effects of isotretinoin treatment on PCOS patients who were complicated with severe cystic acne. Materials and Methods: This study consisted of 40 female patients diagnosed as PCOS complicated with severe cystic acne. These patients were not eligible candidates for OCP use due to migraine, thrombophilia, heavy smoking, or pill scare. To establish baseline values of hormone levels, on days 2-5 of the menstrual cycle, venous blood samples were obtained. Moreover Modified Ferriman-Gallwey (mFG) score, acne score (AS), follicle count, and bilateral ovarian volumes were evaluated both before and after isotretinoin treatment. Results: Isotretinoin treatment significantly decreased Ferriman-Gallwey score, free testosterone, insulin level, hemoglobin level, acne score, and ovarian volume. Increased triglyceride and cholesterol levels were detected after treatment. Conclusion: Isotretinoin treatment may have beneficial effects on free testosterone, insulin, acne score, and Ferriman-Gallwey score. Solely isotretinoin administration may supply adequate healing in PCOS patients' symptoms complicated with severe cystic acne who is not eligible candidates for OCP use. This trial is registered with Clinicaltrials.gov NCT02855138.


Assuntos
Acne Vulgar/tratamento farmacológico , Isotretinoína/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Acne Vulgar/metabolismo , Adolescente , Adulto , Anticoncepcionais Orais Combinados/uso terapêutico , Feminino , Humanos , Hiperandrogenismo/tratamento farmacológico , Hiperandrogenismo/metabolismo , Insulina/metabolismo , Ciclo Menstrual/efeitos dos fármacos , Ciclo Menstrual/metabolismo , Síndrome do Ovário Policístico/metabolismo , Estudos Prospectivos , Testosterona/metabolismo , Adulto Jovem
5.
Gynecol Endocrinol ; 35(5): 422-426, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30668208

RESUMO

It is not clear whether oral contraceptive (OC) treatment affects premenstrual symptoms in women. The aim of the present study was to evaluate changes in premenstrual symptoms (PMS) in women starting to use or discontinuing the use of OCs. Twenty-four healthy women with no previous diagnosis of premenstrual dysphoric disorder were included in this study with a prospective crossover design. Nineteen women completed daily ratings of somatic and mood symptoms during two hormonally different cycles, during a normal menstrual cycle and while using OCs. The menstrual cycle phases were hormonally verified and the low-dose, monophasic OCs were used in a 21/7 regimen. The onset of OC use significantly decreased premenstrual somatic symptoms, but it did not affect mood symptoms. In the women who discontinued OC use, no significant changes in neither somatic nor mood symptoms appeared in the premenstrual phase.


Assuntos
Afeto/efeitos dos fármacos , Anticoncepcionais Orais Hormonais/administração & dosagem , Ciclo Menstrual/efeitos dos fármacos , Adulto , Estudos Cross-Over , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Ciclo Menstrual/sangue , Progesterona/sangue , Estudos Prospectivos , Adulto Jovem
6.
J Clin Endocrinol Metab ; 104(4): 1181-1186, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30608551

RESUMO

BACKGROUND: Although the 2017 Endocrine Society Guidelines for gender dysphoria stipulated that cross-sex hormone therapy (CHT) achieve gonadal steroid levels equivalent to those of a cisperson of the chosen sex, for transgender women (male-to-female gender dysphoria), current gonadal therapy is usually estradiol. Accumulated evidence indicates that normally ovulatory menstrual cycles are necessary for ciswomen's current fertility, as well as for later-life bone and cardiovascular health and the prevention of breast and endometrial cancers. EVIDENCE ACQUISITION: Extensive past clinical experience with transgender women's CHT using estradiol/estrogen combined with progesterone/medroxyprogesterone and pioneering the addition of spironolactone. Comprehensive progesterone physiology research plus a brief review of transgender women's literature to assess current therapy and clinical outcomes, including morbidity and mortality. PURPOSE: To emphasize that both ovarian hormones, progesterone as well as estradiol, are theoretically and clinically important for optimal transgender women's CHT. EVIDENCE SYNTHESIS: It is important to add progesterone to estradiol and an antiandrogen in transgender women's CHT. Progesterone may add the following: (i) more rapid feminization, (ii) decreased endogenous testosterone production, (iii) optimal breast maturation to Tanner stages 4/5, (iv) increased bone formation, (v) improved sleep and vasomotor symptom control, and (vi) cardiovascular health benefits. CONCLUSIONS: Evidence has accrued that normal progesterone (and ovulation), as well as physiological estradiol levels, is necessary during ciswomen's premenopausal menstrual cycles for current fertility and long-term health; transgender women deserve progesterone therapy and similar potential physiological benefits.


Assuntos
Estradiol/administração & dosagem , Disforia de Gênero/tratamento farmacológico , Terapia de Reposição Hormonal/métodos , Progesterona/administração & dosagem , Pessoas Transgênero , Administração Oral , Relação Dose-Resposta a Droga , Quimioterapia Combinada/métodos , Estradiol/efeitos adversos , Estradiol/fisiologia , Medicina Baseada em Evidências/métodos , Feminino , Disforia de Gênero/fisiopatologia , Humanos , Masculino , Ciclo Menstrual/efeitos dos fármacos , Ciclo Menstrual/fisiologia , Ovulação/efeitos dos fármacos , Ovulação/fisiologia , Pré-Menopausa/efeitos dos fármacos , Pré-Menopausa/fisiologia , Progesterona/fisiologia , Embolia Pulmonar/induzido quimicamente , Embolia Pulmonar/epidemiologia , Adesivo Transdérmico/efeitos adversos , Tromboembolia Venosa/induzido quimicamente , Tromboembolia Venosa/epidemiologia
7.
Gynecol Endocrinol ; 35(6): 506-510, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30612488

RESUMO

To evaluate the effects of the combination of d-chiro inositol and alpha lipoic acid on menstrual cycles and insulin sensitivity in women with polycystic ovary syndrome (PCOS). Forty-one women with PCOS and 31 controls have been enrolled in the study. The menstrual cycle, BMI, homeostasis model assessment index (HOMA-I), and insulin secretion in response to an OGTT were evaluated before and after 6 months of treatment. During the observation period, the patients have been asked to not modify their diet and physical activity. The menstrual cycle length improved in 76.7% of the women. Ovulation was restored in 40%. During treatment, BMI significantly decreased (p<.002). The HOMA-I and insulin secretion were unchanged by treatment. However, when women were divided according to the presence of insulin resistance (IR; HOMA-I > 2.5), in those with IR the HOMA-I and the insulin secretion significantly decreased (p<.05 and p<.006). The association of d-chiro-inositol and alpha lipoic acid improves menstrual cycle length, restoring ovulation in the majority of women. Insulin sensitivity improved in women with IR only, confirming that in presence of IR the d-chiro-inositol has a role in restoring the insulin action overcoming the inactivity of epimerase in transforming myo-inositol to d-chiro inositol.


Assuntos
Peso Corporal/efeitos dos fármacos , Inositol/uso terapêutico , Ciclo Menstrual/efeitos dos fármacos , Síndrome do Ovário Policístico/tratamento farmacológico , Ácido Tióctico/uso terapêutico , Adolescente , Adulto , Índice de Massa Corporal , Quimioterapia Combinada , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Inositol/farmacologia , Resistência à Insulina/fisiologia , Hormônio Luteinizante/sangue , Ciclo Menstrual/sangue , Síndrome do Ovário Policístico/sangue , Ácido Tióctico/farmacologia , Resultado do Tratamento , Adulto Jovem
8.
J Acquir Immune Defic Syndr ; 80(1): 79-88, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30212395

RESUMO

OBJECTIVE: Endogenous and exogenous contraceptive hormones may affect mucosal pharmacokinetics (PKs) of topical antiretrovirals such as tenofovir. We present PK data from healthy women using tenofovir vaginal gel, at baseline (follicular and luteal phases) and after oral contraceptive pill (OCP) or depot medroxyprogesterone acetate (DMPA) use. METHODS: CONRAD A10-114 was a prospective, interventional, open-label, parallel study. We enrolled 74 women and 60 completed the study (32 and 28 who selected OCPs or DMPA, respectively). Participants used 2 doses of tenofovir gel separated by 2 hours, without intercourse, and were examined 3 or 11 hours after the last dose. We assessed pharmacokinetics in plasma, cervicovaginal (CV) aspirate, and vaginal tissue. RESULTS: In general, there were no significant differences in mucosal tenofovir and tenofovir diphosphate concentrations (P > 0.23) in the follicular and luteal phases, except for lower mean tenofovir tissue concentrations (P < 0.01) in the follicular phase. Tenofovir concentrations significantly decreased in CV aspirate (P < 0.01) after contraceptive use, but overall remained very high (>10 ng/mL). Mean tissue tenofovir diphosphate increased to 6229 fmol/mg after DMPA use compared with 3693 and 1460 fmol/mg in the follicular and luteal phases, respectively (P < 0.01). The molecular conversion of tenofovir into tenofovir diphosphate was more effective in DMPA users (molecular ratio of 2.02 versus 0.65 luteal phase, P < 0.01). CONCLUSIONS: Both menstrual cycle phase and exogenous hormones affect topical tenofovir mucosal and systemic PKs. However, high levels of tenofovir and tenofovir diphosphate were observed in the CV mucosa in the presence or absence of OCPs and DMPA, with tissue levels exceeding benchmarks of predicted mucosal anti-HIV efficacy (tenofovir >1.00 ng/mL in CV aspirate and tenofovir diphosphate >1000 fmol/mg).


Assuntos
Fármacos Anti-HIV/farmacocinética , Anticoncepcionais Femininos/farmacocinética , Infecções por HIV/prevenção & controle , Acetato de Medroxiprogesterona/farmacocinética , Tenofovir/farmacocinética , Cremes, Espumas e Géis Vaginais/farmacocinética , Administração Intravaginal , Adulto , Fármacos Anti-HIV/administração & dosagem , Anticoncepcionais Femininos/administração & dosagem , Interações Medicamentosas , Feminino , Voluntários Saudáveis , Humanos , Acetato de Medroxiprogesterona/administração & dosagem , Ciclo Menstrual/efeitos dos fármacos , Pessoa de Meia-Idade , Estudos Prospectivos , Tenofovir/administração & dosagem , Resultado do Tratamento , Cremes, Espumas e Géis Vaginais/administração & dosagem , Adulto Jovem
9.
J Pharmacol Exp Ther ; 368(2): 262-271, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30591530

RESUMO

The purpose of the study was to determine whether the in vivo activities of drug-metabolizing enzymes CYP1A2 and CYP2A6, xanthine oxidase (XO), and N-acetyltransferase-2 (NAT2) vary across the menstrual cycle. Forty-two healthy women were studied at early follicular phase (EFP: 2nd to 4th days), late follicular phase (LFP: 10th to 12th days), and luteal phase (LP: 19th to 25th days) of a single menstrual cycle, and blood and urine samples were collected at each phase. Spot urine samples obtained 6 hours following 200-mg caffeine administration were used to determine caffeine metabolite ratios (CMRs); blood samples were used to determine CYP1A2*1F (rs762551) and CYP1A2*1C (rs2069514) polymorphisms and the hormonal profile (estradiol, progesterone, and luteinizing and follicle-stimulating hormones) at EFP, LFP, and LP. CMR and hormone variations were analyzed at three levels (EFP, LFP, LP) using one-way repeated-measures analysis of variance. CYP1A2 activity was lower and that of CYP2A6 and NAT2 were higher at LFP compared with EFP and LP. Enzyme alterations were significant in volunteers (n = 21) whose hormonal profiles at EFP, LFP, and LP corresponded to expected levels, but not in volunteers (n = 15) with presumed early or late sampling around LFP. No significant difference was detected in any enzyme activity in presumed anovulatory volunteers (n = 6). The reduction of CYP1A2 activity at LFP was not associated with smoking or CYP1A2*1F polymorphism. XO and NAT2 (fast acetylators) activities remained unaltered. It is suggested that drug-metabolizing enzyme activities are altered across the menstrual cycle. Selection of appropriate sampling periods verified by hormonal assessment and identification of anovulatory cycles are decisive factors in disclosing altered enzyme activity across the menstrual cycle.


Assuntos
Arilamina N-Acetiltransferase/metabolismo , Citocromo P-450 CYP1A2/metabolismo , Citocromo P-450 CYP2A6/metabolismo , Ciclo Menstrual/metabolismo , Xantina Oxidase/metabolismo , Xenobióticos/metabolismo , Adolescente , Adulto , Feminino , Voluntários Saudáveis , Humanos , Ciclo Menstrual/efeitos dos fármacos , Pessoa de Meia-Idade , Xenobióticos/farmacologia , Adulto Jovem
10.
Eur J Contracept Reprod Health Care ; 23(6): 393-399, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30465698

RESUMO

OBJECTIVE: The aim of the study was to examine treatment continuation and satisfaction over 1 year among women receiving nomegestrol acetate (NOMAC)/oestradiol (E2) combined oral contraception (COC) in real-world clinical practice. METHODS: The 17ß-Estradiol and Nomegestrol Acetate (BOLERO) Study is an observational, non-interventional, prospective, multicentre cohort study of premenopausal women (aged 18-50 years) who received prescription NOMAC/E2 (2.5 mg/1.5 mg) for contraception during routine clinical practice. Assessments were carried out at enrolment and at 3, 6 and 12 months. Probability of treatment continuation through 12 months (primary outcome) was examined using Kaplan-Meier survival analysis. Secondary outcomes included treatment satisfaction, menstrual cycle-related symptoms, libido and adverse events (AEs). RESULTS: Of 298 enrolled women, 292 were evaluable. The probability of NOMAC/E2 continuation through 12 months was 73.7% (95% confidence interval [CI] 68.0%, 78.5%). Satisfaction with NOMAC/E2 increased from 56.9% (37/65) of women at initial evaluation to 89.2% (58/65) of women at 12 months. Physician ratings at 12 months showed satisfactory to very satisfactory in 84.0% (168/200) of women. Libido was not affected. Menstrual cycle-related symptoms significantly declined from enrolment (6.04 ± 4.32) to 3 months (3.25 ± 3.05) and 12 months (2.62 ± 2.74; p < .0001). Treatment-related AEs were reported by 38.7% (113/292) of women. CONCLUSION: The real-world experience of women receiving NOMAC/E2 indicated very good treatment continuation, high satisfaction and significantly improved menstrual cycle-related symptoms.


Assuntos
Comportamento Contraceptivo/estatística & dados numéricos , Anticoncepcionais Orais Combinados/administração & dosagem , Estradiol/administração & dosagem , Megestrol/administração & dosagem , Norpregnadienos/administração & dosagem , Cooperação e Adesão ao Tratamento/estatística & dados numéricos , Adolescente , Adulto , Feminino , Humanos , Ciclo Menstrual/efeitos dos fármacos , Ciclo Menstrual/psicologia , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Prospectivos , Adulto Jovem
11.
Psychopharmacology (Berl) ; 235(12): 3465-3477, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30306229

RESUMO

17-Beta-estradiol (E2) stimulates neural plasticity and dopaminergic transmission in the prefrontal cortex, which is critically involved in attentional control, working memory, and other executive functions. Studies investigating E2's actions on prefrontally mediated behavior in the course of the menstrual cycle or during hormone replacement therapy are inconclusive, with numerous null findings as well as beneficial and detrimental effects. The current study focused on the effect of E2 on attentional performance, as animal studies indicate that supraphysiological doses (i.e., above estrous cycle levels) of E2 have beneficial effects on measures of attention in female rodents. To translate these findings to humans, we administered 12 mg E2-valerate or placebo orally to 34 naturally cycling women in the low-hormone early follicular phase using a randomized, double-blinded, pre-post design. Behavioral performance was tested twice during baseline and E2 peak, where E2 levels reached mildly supraphysiological levels in the E2 group. Aside from mainly prefrontally mediated tasks of attention, working memory, and other executive functions, we employed tasks of affectively modulated attention, emotion recognition, and verbal memory. E2 administration had a significant, but subtle negative impact on general processing speed and working memory performance. These effects could be related to an overstimulation of dopaminergic transmission. The negative effect of supraphysiological E2 on working memory connects well to animal literature. There were no effects on attentional performance or any other measure. This could be explained by different E2 levels being optimal for changing behavioral performance in specific tasks, which likely depends on the brain regions involved.


Assuntos
Estradiol/administração & dosagem , Estrogênios/administração & dosagem , Memória de Curto Prazo/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Desempenho Psicomotor/efeitos dos fármacos , Administração Oral , Adulto , Animais , Método Duplo-Cego , Emoções/efeitos dos fármacos , Emoções/fisiologia , Ciclo Estral/efeitos dos fármacos , Ciclo Estral/fisiologia , Função Executiva/efeitos dos fármacos , Função Executiva/fisiologia , Feminino , Humanos , Memória de Curto Prazo/fisiologia , Ciclo Menstrual/efeitos dos fármacos , Ciclo Menstrual/fisiologia , Ciclo Menstrual/psicologia , Córtex Pré-Frontal/fisiologia , Desempenho Psicomotor/fisiologia , Adulto Jovem
12.
Eur J Contracept Reprod Health Care ; 23(4): 260-264, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30203678

RESUMO

OBJECTIVE: Oral combined hormonal contraceptives (CHCs) are available that limit the number of menses when used in a flexible extended regimen. Our aim was to investigate the decision-making processes of women presented with a flexible extended CHC option. METHODS: The FLEXO study is an epidemiological, cross-sectional, multicentre study conducted under typical clinical practice conditions to determine women's acceptance of a flexible continuous CHC regimen versus a cyclical 21/7 day regimen, after receiving standardised information during contraceptive counselling. RESULTS: A total of 1350 women were invited to participate, of whom 1156 were enrolled. Of these, 47.2% chose the flexible extended CHC regimen. Their main reason for choosing this regimen was to reduce the number of menses (25.7%), followed by the desire to avoid symptoms related to menstruation (21.6%). The reasons given for rejecting this regimen were the desire to have monthly menstrual cycles (24.9%) and the fear of becoming pregnant and not being aware of it due to the absence of menstruation (18.1%). CONCLUSION: Many women chose the extended flexible regimen when they received information about this option. Women primarily chose this pattern to relieve or eliminate discomfort related to menstruation.


Assuntos
Anticoncepção , Anticoncepcionais Orais Combinados/uso terapêutico , Anticoncepcionais Orais Hormonais/uso terapêutico , Tomada de Decisões , Serviços de Planejamento Familiar , Menstruação/psicologia , Adulto , Comportamento de Escolha , Anticoncepção/métodos , Anticoncepção/psicologia , Aconselhamento , Estudos Transversais , Serviços de Planejamento Familiar/métodos , Serviços de Planejamento Familiar/estatística & dados numéricos , Feminino , Humanos , Ciclo Menstrual/efeitos dos fármacos , Espanha
13.
Eur J Contracept Reprod Health Care ; 23(4): 245-254, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30203681

RESUMO

PURPOSE: To identify at least one contraceptive vaginal ring that effectively inhibits ovulation and demonstrates cycle control that is non-inferior to NuvaRing® (Merck Sharp & Dohme B.V., The Netherlands) in terms of an unscheduled bleeding incidence, with a non-inferiority margin of 10%. METHODS: This was a randomised, active controlled, parallel group, multicentre, partially blinded trial in healthy women 18-35 years of age. Subjects received one of six contraceptive vaginal rings with an average daily release rate of 300 µg 17ß-estradiol (E2) and various rates of either etonogestrel (ENG; 75, 100, or 125 µg/day) or nomegestrol acetate (NOMAC; 500, 700, or 900 µg/day), or the active control NuvaRing® (ENG/ethinylestradiol 120/15 µg), for three 28-day cycles. RESULTS: Ovulation inhibition was observed in all groups as confirmed by absence of progesterone concentrations compatible with ovulation (>16 nmol/L) and absence of ultrasound evidence of ovulation. All investigational rings provided good cycle control, with the ENG-E2 125/300 µg/day group being associated with the best cycle control based on the numerically lowest incidence of unscheduled bleeding and absence of scheduled bleeding. Non-inferiority to NuvaRing® with respect to the incidence of unscheduled bleeding could not be concluded for any of the investigational ring groups. The safety profile was consistent with the known safety profile of combined estrogen/progestin contraceptives and similar across all groups. CONCLUSIONS: Contraceptive rings releasing 300 µg E2 and 75-125 µg/day of ENG or 500-900 µg/day of NOMAC provided adequate ovulation inhibition and cycle control and are generally well-tolerated. While non-inferiority to NuvaRing® was not met, among the investigational rings, the ENG-E2 125/300 ring provided the best cycle control.


Assuntos
Desogestrel/análogos & derivados , Estradiol , Etinilestradiol , Ciclo Menstrual/efeitos dos fármacos , Inibição da Ovulação/efeitos dos fármacos , Adulto , Anticoncepcionais Femininos/administração & dosagem , Anticoncepcionais Femininos/efeitos adversos , Dispositivos Anticoncepcionais Femininos , Desogestrel/administração & dosagem , Desogestrel/efeitos adversos , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Monitoramento de Medicamentos/métodos , Estradiol/administração & dosagem , Estradiol/efeitos adversos , Estrogênios Conjugados (USP)/administração & dosagem , Estrogênios Conjugados (USP)/efeitos adversos , Etinilestradiol/administração & dosagem , Etinilestradiol/efeitos adversos , Feminino , Humanos
14.
Viral Immunol ; 31(7): 486-491, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30133352

RESUMO

Epstein-Barr virus (EBV) is a gamma-herpesvirus persisting mainly in human B lymphocytes. EBV reactivation induces host cells to differentiate into plasma cells and is related to autoimmune diseases. Graves' disease, an autoimmune hyperthyroidism, is caused by the thyrotropin receptor antibody (TRAb), which overstimulates thyroid stimulating hormone receptor. The disease occurs predominantly in women, which suggests involvement with estrogen. Graves' disease patients and healthy controls have EBV-infected lymphocytes with TRAb on the surface (TRAb(+)EBV(+) cells) in peripheral blood mononuclear cells (PBMCs). TRAb can be produced by reactivation of EBV in vitro, which is an alternative system of antibody production. In this study, we cultured PBMCs from Graves' disease patients and healthy controls with 0, 1, and 100 nM estradiol, corresponding to control, midluteal, and pregnancy levels, respectively, and analyzed the levels of TRAb, total-IgG, and total-IgM during EBV reactivation. We found that 1 nM estradiol increased TRAb levels and 100 nM estradiol slightly lowered them in both patients and controls. In patients, IgM production at 100 nM estradiol was significantly lower than that at 0 nM estradiol (p = 0.028). Estradiol increased the ratio of IgG production to immunoglobulin G (IgG) and immunoglobulin M (IgM) production (IgG/IgG + IgM), which suggested an increase in class switch recombination in the process of EBV reactivation-induced Ig production. Moreover, TRAb production was stimulated by a midluteal level of estradiol and was suppressed by a pregnancy level of estradiol in controls and patients. These results were consistent with premenstrual worsening and maternity improving of autoimmune diseases, including Graves' disease.


Assuntos
Formação de Anticorpos/efeitos dos fármacos , Estradiol/administração & dosagem , Doença de Graves/virologia , Herpesvirus Humano 4/imunologia , Receptores da Tireotropina/imunologia , Adulto , Autoanticorpos/sangue , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Ciclo Menstrual/efeitos dos fármacos , Pessoa de Meia-Idade , Gravidez , Estatísticas não Paramétricas
15.
Zhonghua Fu Chan Ke Za Zhi ; 53(6): 377-383, 2018 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-29961279

RESUMO

Objective: Using a questionnaire to evaluate different regimens of chemotherapy on ovarian function and quality of life of patients with gestational trophoblastic neoplasia (GTN) . Methods: At least 6 months after completion of chemotherapy, 200 patients with GTN treated in Peking Union Medical College Hospital from January 2010 to June 2017 were randomly selected to fill up the questionnaire. The questionnaire items were included the patient's menstrual cycles, sexual life, gestational issues and common health. The patients were divided into 3 groups by chemotherapy regimens: actinomycin D (Act-D) group, floxuridine+Act-D+vincristine (FAV) or floxuridine+Act-D+etoposide+vincristine (FAEV) group (FAV-FAEV group) , and etoposide+methotrexate+Act-D (EMA) /vincristine+cyclophosphamide (CO) or EMA/ etoposide+cisplatin (EP) group (EMA/CO-EMA/EP group) . Chi-square test was used with a significance level of P-value less than 0.05. Results: One hundred and seventy-three (86.5%,173/200) of the patients completed the questionnaire. Forty three point two percent (43.2%, 19/44) in the EMA/CO-EMA/EP group had a normal menstrual cycle, which were significantly lower than those of Act-D group (84.6%,22/26) and FAV-FAEV group (71.2%, 37/52; all P<0.05) . Amenorrhea rate was also significantly higher in EMA/CO-EMA/EP group (25.0%, 11/44) than in Act-D group (0) and FAV-FAEV group (17.3%, 9/52; all P<0.05) . The sexual life parameters were comparable among 3 groups. Ten out of thirty-two patients conceived after chemotherapy, 2 had miscarriages and 8 had full-term delivery of healthy babies. The common health and labor capacity were significantly decreased after chemotherapy (all P<0.05) . Conclusions: EMA/CO or EMA/EP regimen have a worse impact on ovarian function than Act-D and FAV or FAEV regimen. Gynecologic oncologist should be concerned about the ovarian function and quality of life of GTN patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença Trofoblástica Gestacional/tratamento farmacológico , Doença Trofoblástica Gestacional/psicologia , Ciclo Menstrual/efeitos dos fármacos , Ovário/fisiologia , Qualidade de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Dactinomicina/administração & dosagem , Dactinomicina/efeitos adversos , Etoposídeo , Feminino , Floxuridina/administração & dosagem , Floxuridina/efeitos adversos , Doença Trofoblástica Gestacional/patologia , Humanos , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Ovário/efeitos dos fármacos , Gravidez , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversos
16.
Gen Physiol Biophys ; 37(5): 581-588, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30047923

RESUMO

The purpose of the study was to investigate the effect of oral contraceptives on static postural stability in young healthy women during their menstrual cycle. Twenty-three women with the regular menstrual cycle, using or not using oral contraceptives, participated in this study. Salivary progesterone and estradiol levels were measured during one menstrual cycle. Measurements of balance were performed during a quiet stance on a firm and foam surface by the force platform, with eyes either opened or closed, on day 2, 7, 14, 21 and 28 of the cycle. Results of stability on a firm surface with eyes opened showed a significant effect in the amplitude of body sway in the anterior-posterior direction since women using oral contraceptives had a lower amplitude compared to control women on day 28. During stance on a firm surface with eyes closed we showed only impact of the menstrual cycle on postural stability of women. In condition of stance on a foam surface with the eyes opened or closed no significant effects were found. Our results showed that oral contraceptives intake can improve the static postural stability before the onset of menstruation and decrease a risk of injury of young healthy women.


Assuntos
Anticoncepcionais Orais/farmacologia , Voluntários Saudáveis , Ciclo Menstrual/efeitos dos fármacos , Ciclo Menstrual/fisiologia , Equilíbrio Postural/efeitos dos fármacos , Adulto , Relação Dose-Resposta a Droga , Feminino , Humanos , Fatores de Tempo , Adulto Jovem
17.
Exp Physiol ; 103(10): 1309-1317, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30051938

RESUMO

NEW FINDINGS: What is the topic of this review? We review methodological considerations for the inclusion of women in sex and menstrual cycle phase comparison studies. What advances does it highlight? Improving the methodological design for studies exploring sex differences, menstrual cycle phase differences and/or endogenous versus exogenous female sex hormones will help to close the gap in our understanding of the effects of endogenous and exogenous hormones on exercise science and sports medicine outcomes. ABSTRACT: In recent years, the increase in scientific literature exploring sex differences has been beneficial to both clinicians and allied health science professionals, although female athletes are still significantly under-represented in sport and exercise science research. Women have faced exclusion throughout history though the complexities of sociocultural marginalization and biomedical disinterest in women's health. These complexities have contributed to challenges of studying women and examining sex differences. One underlying complexity to methodological design may be hormonal perturbations of the menstrual cycle. The biphasic responses of oestrogen and progesterone across the menstrual cycle significantly influence physiological responses, which contribute to exercise capacity and adaptation in women. Moreover, oral contraceptives add complexity through the introduction of varying concentrations of circulating exogenous oestrogen and progesterone, which may moderate physiological adaptations to exercise in a different manner to endogenous ovarian hormones. Thus, applied sport and exercise science research focusing on women remains limited, in part, by poor methodological design that does not define reproductive status. By highlighting specific differences between phases with regard to hormone perturbations and the systems that are affected, methodological inconsistencies can be reduced, thereby improving scientific design that will enable focused research on female athletes in sports science and evaluation of sex differences in responses to exercise. The aims of this review are to highlight the differences between endogenous and exogenous hormone profiles across a standard 28-32 day menstrual cycle, with the goal to improve methodological design for studies exploring sex differences, menstrual cycle phase differences and/or endogenous versus exogenous female sex hormones.


Assuntos
Ciclo Menstrual/fisiologia , Adaptação Fisiológica/fisiologia , Atletas , Anticoncepcionais Orais/farmacologia , Estrogênios/metabolismo , Exercício Físico/fisiologia , Feminino , Humanos , Ciclo Menstrual/efeitos dos fármacos , Ciclo Menstrual/metabolismo , Progesterona/metabolismo , Caracteres Sexuais , Esportes/fisiologia
18.
Reproduction ; 155(6): 493-503, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29764928

RESUMO

Endoplasmic reticulum (ER) stress is a common cellular stress response that enhances apoptosis to trigger cell death. However, recent studies have shown that estrogen suppresses apoptosis by inhibiting ER stress in some cell types, suggesting that ER stress-induced apoptosis is regulated by ovarian steroid hormones. In endometrial cells, ER stress may also be controlled by ovarian steroid hormones and could be involved in apoptosis induction during the menstrual cycle. To test this hypothesis, we elucidate whether ER stress is regulated by ovarian steroid hormones in human endometrial cells and if it is involved in apoptosis induction. Specifically, we sought to determine the effects of estrogen and progesterone on the PERK/eIF2α/ATF4/CHOP pathway, a pro-apoptotic pathway mediated by ER stress. Our results show that ER stress maker GRP78 expression was increased in human endometrial Ishikawa and endometrial stromal cells (ESCs) treated with tunicamycin. Addition of estrogen decreased tunicamycin-induced GRP78 expression. In contrast, progesterone treatment increased GRP78 in estrogen-treated Ishikawa and ESCs, which significantly increased CHOP expression through phosphorylation of eIF2α and upregulation of ATF4. This upregulation was accompanied by an increased apoptosis induction. The progesterone-induced increase in apoptosis was reversed by either mifepristone (progesterone receptor modulator) or salubrinal (ER stress inhibitor). Furthermore, our in vivo results also showed that GRP78, CHOP expression and apoptosis were significantly increased in endometrial cells during the secretory phase as well as by in vitro treatment with progesterone. In conclusion, our results suggest that estrogen inhibits ER stress in human endometrial cells. This inhibition is reversed by progesterone during the secretory phase, and this is directly involved in apoptosis induction.


Assuntos
Apoptose/efeitos dos fármacos , Endométrio/patologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Estrogênios/farmacologia , Ciclo Menstrual/efeitos dos fármacos , Ovário/metabolismo , Progesterona/farmacologia , Adulto , Células Cultivadas , Endométrio/efeitos dos fármacos , Feminino , Humanos , Ovário/patologia , Fosforilação , Transdução de Sinais/efeitos dos fármacos , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo , Células Estromais/patologia
19.
Mol Cell Endocrinol ; 476: 70-78, 2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-29709683

RESUMO

In order to get further information on the effects of ulipristal acetate (UPA) upon the process of decidualization of endometrium, a functional analysis of the differentially expressed genes in endometrium (DEG) from UPA treated-versus control-cycles of normal ovulatory women was performed. A list of 1183 endometrial DEG, from a previously published study by our group, was submitted to gene ontology, gene enrichment and ingenuity pathway analyses (IPA). This functional analysis showed that decidualization was a biological process overrepresented. Gene set enrichment analysis identified LIF, PRL, IL15 and STAT3 among the most down-regulated genes within the JAK STAT canonical pathway. IPA showed that decidualization of uterus was a bio-function predicted as inhibited by UPA. The results demonstrated that this selective progesterone receptor modulator, when administered during the periovulatory phase of the menstrual cycle, may affect the molecular mechanisms leading to endometrial decidualization in response to progesterone during the period of maximum embryo receptivity.


Assuntos
Decídua/fisiologia , Endométrio/fisiologia , Ciclo Menstrual/efeitos dos fármacos , Norpregnadienos/administração & dosagem , Norpregnadienos/farmacologia , Ovulação/efeitos dos fármacos , Adulto , Biomarcadores/metabolismo , Biópsia , Decídua/efeitos dos fármacos , Endométrio/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Acetato de Medroxiprogesterona/farmacologia , Mifepristona/farmacologia , Modelos Biológicos , Transdução de Sinais/efeitos dos fármacos , Transcrição Genética/efeitos dos fármacos
20.
Clin Pharmacol Ther ; 104(6): 1229-1239, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29637542

RESUMO

Current formulations of combined oral contraceptives (COC) containing ethinylestradiol (EE) have ≤35 µg due to increased risks of cardiovascular diseases (CVD) with higher doses of EE. Low-dose formulations however, have resulted in increased incidences of breakthrough bleeding and contraceptive failure, particularly when coadministered with inducers of cytochrome P450 enzymes (CYP). The developed physiologically based pharmacokinetic model quantitatively predicted the effect of CYP3A4 inhibition and induction on the pharmacokinetics of EE. The predicted Cmax and AUC ratios when coadministered with voriconazole, fluconazole, rifampicin, and carbamazepine were within 1.25 of the observed data. Based on published clinical data, an AUCss value of 1,000 pg/ml.h was selected as the threshold for breakthrough bleeding. Prospective application of the model in simulations of different doses of EE (20 µg, 35 µg, and 50 µg) identified percentages of the population at risk of breakthrough bleeding alone and with varying degrees of CYP modulation.


Assuntos
Simulação por Computador , Anticoncepcionais Orais Hormonais/farmacocinética , Etinilestradiol/farmacocinética , Ciclo Menstrual/efeitos dos fármacos , Modelos Biológicos , Biotransformação , Doenças Cardiovasculares/induzido quimicamente , Eficácia de Contraceptivos , Anticoncepcionais Orais Hormonais/administração & dosagem , Anticoncepcionais Orais Hormonais/efeitos adversos , Citocromo P-450 CYP3A/metabolismo , Indutores do Citocromo P-450 CYP3A/administração & dosagem , Inibidores do Citocromo P-450 CYP3A/administração & dosagem , Relação Dose-Resposta a Droga , Interações Medicamentosas , Etinilestradiol/administração & dosagem , Etinilestradiol/efeitos adversos , Feminino , Humanos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Medição de Risco , Fatores de Risco
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