RESUMO
Common marmosets are small New World monkeys. Since many of their biological mechanisms are similar to those of humans, marmosets are potentially useful for medical and human biology research across a range of fields, such as neuroscience, regenerative medicine, and development. However, there is a lack of literature describing methods for many basic experiments and procedures. Here, detailed methods for determining the levels of sex hormones (progesterone, estradiol, and chorionic gonadotropin) in marmosets are described. The measurement of these hormones enables the prediction of the stage in the ovarian cycle, which is typically 26-30 days in marmosets; accurate determination is essential for the harvesting of oocytes/zygotes at the correct time point and for the preparation of host females for the generation of genetically modified marmosets. Additionally, the measurement of sex hormone levels is useful for endocrinology, ethology, early development, and reproductive biology studies. This protocol provides a detailed description of the methods for blood sampling from the femoral vein, separation of plasma for hormone measurement, measuring chorionic gonadotropin levels using urine and plasma, resetting the ovarian cycle using injections of a prostaglandin F2α analog to shorten and synchronize the cycle, and promoting follicular growth and ovulation by injecting follicle-stimulating hormone and chorionic gonadotropin. Using these protocols, the stages in the ovarian cycle can be determined for the timely collection of oocytes/zygotes.
Assuntos
Callithrix , Gonadotropina Coriônica , Estradiol , Progesterona , Animais , Callithrix/sangue , Callithrix/fisiologia , Feminino , Gonadotropina Coriônica/sangue , Estradiol/sangue , Progesterona/sangue , Coleta de Amostras Sanguíneas/métodos , Ciclo Menstrual/sangue , Ciclo Menstrual/fisiologia , Ovário/fisiologiaRESUMO
BACKGROUND: Endogeneous and exogeneous sex hormones can impact the frequency and severity of migraine attacks, but the underlying mechanisms are poorly understood. In this study, we investigate the relationship between female sex hormones and Pituitary Adenylate Cyclase-Activating Polypeptide-38 (PACAP-38) concentrations in plasma of women with migraine and healthy controls, aiming to elucidate potential hormonal influences on PACAP dynamics and their relevance to migraine pathophysiology. METHODS: This analysis is part of a cross-sectional, matched-cohort study. We recruited two groups of women with episodic migraine: one with a regular menstrual cycle (M-RMC) and another undergoing combined oral contraceptive treatment (M-COC). Additionally, we included corresponding age-matched control groups without migraine for both categories (C-RMC and C-COC). For participants with a RMC, the study visits were scheduled during the perimenstrual period (menstrual cycle day 2 ± 2) and periovulatory period (day 13 ± 2). Participants using COC were examined at day 4 ± 2 of the hormone-free interval and between day 7-14 of the hormone intake phase. During these visits, PACAP-38 concentrations in plasma were measured using a commercial Enzyme-linked-immunosorbent assay (ELISA) kit. RESULTS: The study included 120 women, with 30 participants in each group. Women with migraine and a RMC had significantly higher PACAP-38 plasma concentrations compared to healthy controls at both study visits [day 2 ± 2: M-RMC: 2547.41 pg/ml (IQR 814.27 - 4473.48) vs. C-RMC: 1129.49 pg/ml (IQR 257.34 - 2684.88), p = 0.025; day 13 ± 2: M-RMC: 3098.89 pg/ml (IQR 1186.29 - 4379.47) vs. C-RMC: 1626.89 (IQR 383.83 - 3038.36), p = 0.028]. In contrast, PACAP-38 levels were comparable between migraine and control groups receiving COC. Women with migraine and a RMC exhibited higher PACAP-38 concentrations during menstruation compared to those using COC during the hormone-free interval. CONCLUSION: Systemic PACAP-38 concentrations in women vary based on the presence of migraine diagnosis and their hormonal status.
Assuntos
Transtornos de Enxaqueca , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Humanos , Feminino , Transtornos de Enxaqueca/sangue , Estudos Transversais , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/sangue , Adulto , Estudos de Coortes , Ciclo Menstrual/sangue , Ciclo Menstrual/fisiologia , Adulto Jovem , Hormônios Esteroides Gonadais/sangue , Anticoncepcionais Orais Combinados/sangue , Estradiol/sangue , Progesterona/sangueRESUMO
Oral contraceptive pills, of all types, are used by approximately 151 million women worldwide; however, a clear understanding of the concentrations of endogenous and exogenous hormones across a 28-day combination monophasic oral contraceptive pill pack is not well described. In our study of 14 female participants taking various combination monophasic oral contraceptive pills, we found significant fluctuations in endogenous and exogenous hormone levels throughout the pill cycle. Our analysis revealed significantly greater levels of ethinyl estradiol on the 20th and 21st days of active pill ingestion, compared with days 1-2 (active) and days 27-28 (inactive pill ingestion). Conversely, estradiol concentrations decreased during active pill consumption, while progestin and progesterone levels remained stable. During the 7 days of inactive pill ingestion, estradiol levels rose sharply and were significantly higher at days 27-28 compared with the mid and late active phase time points, while ethinyl estradiol declined and progestin did not change. These findings challenge the previous assumption that endogenous and exogenous hormones are stable throughout the 28-day pill cycle.NEW & NOTEWORTHY The results from this study have wide-ranging implications for research and treatment in women's health including considerations in research design and interpretation for studies including women taking oral contraceptives, the potential for more precise and personalized methods of dosing to reduce unwanted side effects and adverse events, and the potential treatment of a variety of disorders ranging from musculoskeletal to neurological with exogenous hormones.
Assuntos
Anticoncepcionais Orais Combinados , Estradiol , Etinilestradiol , Ciclo Menstrual , Progesterona , Espectrometria de Massas em Tandem , Humanos , Feminino , Adulto , Anticoncepcionais Orais Combinados/administração & dosagem , Espectrometria de Massas em Tandem/métodos , Etinilestradiol/administração & dosagem , Etinilestradiol/sangue , Progesterona/sangue , Ciclo Menstrual/efeitos dos fármacos , Ciclo Menstrual/sangue , Adulto Jovem , Estradiol/sangue , Cromatografia Líquida/métodos , Progestinas/sangue , Progestinas/administração & dosagem , Anticoncepcionais Orais Hormonais/administração & dosagemRESUMO
OBJECTIVE: Alcohol use disorder (AUD) constitutes a critical public health issue and has sex-specific characteristics. Initial evidence suggests that progesterone and estradiol might reduce or increase alcohol intake, respectively. However, there is a need for a better understanding of how the menstrual cycle in females and the ratio of progesterone to estradiol in females and males influence alcohol use patterns in individuals with AUD. METHODS: In this sex-separated multicenter longitudinal study, the authors analyzed 12-month data on real-life alcohol use (from 21,460 smartphone entries), menstrual cycle, and serum progesterone-to-estradiol ratios (from 667 blood samples at four individual study visits) in 74 naturally cycling females and 278 males with AUD between 2020 and 2022, using generalized and general linear mixed modeling. RESULTS: Menstrual cycle phases were significantly associated with binge drinking and progesterone-to-estradiol ratio. During the late luteal phase, females showed a lower predicted binge drinking probability of 13% and a higher predicted marginal mean of progesterone-to-estradiol ratio of 95 compared with during the menstrual, follicular, and ovulatory phases (binge drinking probability and odds ratios vs. late luteal phase, respectively: 17%, odds ratio=1.340, 95% CI=1.031, 1.742; 19%, odds ratio=1.523, 95% CI=1.190, 1.949; and 20%, odds ratio=1.683, 95% CI=1.285, 2.206; difference in progesterone-to-estradiol ratios, respectively: -61, 95% CI=-105.492, -16.095; -78, 95% CI=-119.322, -37.039; and -71, 95% CI=-114.568, -27.534). In males, a higher progesterone-to-estradiol ratio was related to lower probabilities of binge drinking and of any alcohol use, with a 10-unit increase in the hormone ratio resulting in odds ratios of 0.918 (95% CI=0.843, 0.999) and 0.914 (95% CI=0.845, 0.988), respectively. CONCLUSIONS: These ecologically valid findings suggest that high progesterone-to-estradiol ratios can have a protective effect against problematic alcohol use in females and males with AUD, highlighting the progesterone-to-estradiol ratio as a promising treatment target. Moreover, the results indicate that females with AUD may benefit from menstrual cycle phase-tailored treatments.
Assuntos
Consumo de Bebidas Alcoólicas , Alcoolismo , Estradiol , Ciclo Menstrual , Progesterona , Humanos , Feminino , Estradiol/sangue , Progesterona/sangue , Masculino , Adulto , Ciclo Menstrual/sangue , Estudos Longitudinais , Alcoolismo/sangue , Alcoolismo/epidemiologia , Consumo de Bebidas Alcoólicas/sangue , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo Excessivo de Bebidas Alcoólicas/sangue , Consumo Excessivo de Bebidas Alcoólicas/epidemiologia , Fatores Sexuais , Pessoa de Meia-Idade , Adulto JovemRESUMO
Abstract Developing objective measures to diagnose sport-related concussion (SRC) is a top priority, particularly in the pediatric context, given the vulnerability of the developing brain. While advances in SRC blood biomarkers are being made in adult populations, less data are available for adolescents. Clinical validation of blood biomarkers post-SRC will first require investigation in a healthy uninjured state. Further, rapid pubertal changes during adolescence may implicate possible interactions with circulating sex hormones and the menstrual cycle for females. This cross-sectional study aimed to characterize pre-injury plasma levels of glial fibrillary acidic protein (GFAP), neurofilament light (NF-L), ubiquitin C-terminal hydrolase-L1 (UCH-L1), total tau (T-tau), and phosphorylated tau-181 (P-tau-181), considering previous concussion, age, and sex in healthy adolescent sport participants. Possible associations with menstrual cycle phase and circulating sex hormone levels (i.e., progesterone, estradiol, testosterone) were also explored. Pre-injury blood samples were obtained from 149 healthy adolescents (48% female, ages 11-18) participating in a larger Surveillance in High Schools and Community Sports to Reduce Concussions and their Consequences (SHRed Concussions) multi-site longitudinal cohort study. Main outcomes were natural log (ln) transformed plasma GFAP, NF-L, UCH-L1, T-tau, and P-tau-181 concentrations, quantified on the Quanterix Simoa HD-X platform. Mixed-effects multi-variable linear regression was used to assess associations between biomarkers and self-reported previous concussion (yes/no), age (years), sex (male/female), objectively determined menstrual cycle phase (follicular/luteal), plasma progesterone, estradiol, and testosterone. Males had 19.8% lower UCH-L1 (ß = -0.221, 95% confidence interval [CI; -0.396, -0.046]), 18.9% lower GFAP (ß = -0.210, 95% CI [-0.352, -0.068]), and 21.8% higher P-tau-181 (ß = 0.197, 95% CI [0.048, 0.346]) compared with females, adjusting for age and previous concussion. GFAP decreased 9.5% with each 1-year increase in age, adjusting for previous concussion and sex (ß = -0.100, 95% CI [-0.152, -0.049]). No biomarkers were associated with a history of previous concussion. Exploratory investigations found no associations between biomarkers and menstrual cycle phase. Females displayed an age-adjusted negative association between T-tau and progesterone (ß = -0.010, 95% CI [-0.018, -0.002]), whereas males had a negative age-adjusted association between UCH-L1 and testosterone (ß = -0.020, 95% CI [-0.037, -0.002]). As such, age- and sex-specific reference intervals may be warranted for pediatric athlete populations prior to clinical validation of blood biomarkers for SRC. Additionally, hormonal associations highlight the need to consider puberty and development in adolescent studies. Overall, findings suggest these biomarkers are resilient to a history of previous concussion and menstrual cycle phase, supporting continued investigation in adolescent SRC.
Assuntos
Traumatismos em Atletas , Biomarcadores , Concussão Encefálica , Adolescente , Feminino , Humanos , Masculino , Traumatismos em Atletas/sangue , Biomarcadores/sangue , Concussão Encefálica/sangue , Estudos Transversais , Estradiol/sangue , Proteína Glial Fibrilar Ácida , Estudos Longitudinais , Progesterona/sangue , Testosterona/sangue , Criança , Ciclo Menstrual/sangue , PuberdadeRESUMO
Animal experiments have consistently shown that estrogen receptor ß (ERß)-selective ligands have antidepressant and anxiolytic effects. In humans, endogenous ligands for ERß include 5α-androstane-3ß, 17ß-diol (3ßAdiol) and androstenediol (Δ5-diol). We determined, for the first time, the exact serum levels of 3ßAdiol and Δ5-diol in young healthy volunteers using liquid chromatography-tandem mass spectrometry (LC-MS/MS). We investigated the effect of the menstrual cycle on the levels of these steroids in women; then, we performed a gender comparison. Blood samples were collected from 48 subjects: 23 women (mean age = 28.4±7.8 years) and 25 men (mean age = 31.4±7.8 years). We collected the blood samples of women at three time-points in the menstrual cycle: the early follicular phase, ovulatory or mid-cycle phase, and mid-luteal phase. A total of 92 blood samples were analyzed using LC-MS/MS. The levels of two well-studied steroids, namely dehydroepiandrosterone (DHEA) and 17ß-estradiol (E2), were simultaneously measured. Depression rating scale (Hamilton Rating Scale for Depression, Beck Depression Inventory-II and Quick Inventory of Depressive Symptomatology) scores were also recorded at the time of blood sampling. Significant differences in the levels of 3ßAdiol and E2 and in the depression rating scale scores were observed over the duration of the menstrual cycle of the women. The levels of 3ßAdiol and Δ5-diol were significantly lower in women than in men. E2 levels were higher in women than in men, and DHEA levels did not differ significantly between men and women. Further, women had higher scores than men on the Hamilton Rating Scale for Depression. Sex differences in depressive symptoms can be explained by 3ßAdiol and Δ5-diol levels, and the effect of the menstrual cycle on mood can be explained by 3ßAdiol and E2 levels, not by Δ5-diol level.
Assuntos
Androstenodiol/sangue , Desidroepiandrosterona/sangue , Estradiol/sangue , Caracteres Sexuais , Adulto , Cromatografia Líquida , Feminino , Humanos , Masculino , Ciclo Menstrual/sangue , Espectrometria de Massas em Tandem , Adulto JovemRESUMO
PURPOSE: To examine the temporal changes in blood oxidative stress biomarkers in recreationally-trained women that were naturally-cycling (WomenNC) or using oral contraceptives (WomenOC) across one month. METHODS: Blood samples were acquired at three timepoints of the menstrual cycle (1: early-follicular, 2: late-follicular and 3: mid-luteal) and oral contraceptive packet (1: InactiveOC, 2: Mid-activeOC and 3: Late-activeOC) for determination of estradiol, progesterone, oxidative stress, C-reactive protein (CRP) and other cardiometabolic biomarkers in plasma and serum. RESULTS: There was a Group by Time effect on estradiol (p < 0.001, partial η2 = 0.64) and progesterone (p < 0.001, partial η2 = 0.77). Malondialdehyde, lipid hydroperoxides and CRP concentrations were higher in WomenOC during Late-activeOC compared to InactiveOC (+ 96%, + 23% and + 104%, respectively, p < 0.05). However, there were no changes in these biomarkers across the menstrual cycle in WomenNC (p > 0.05). At all timepoints (i.e., 1, 2 and 3), WomenOC had elevated lipid hydroperoxides (+ 28, + 48% and + 50%) and CRP (+ 71%, + 117% and + 130%) compared to WomenNC (p < 0.05, partial η2 > 0.25). There was no Group by Time effect on non-enzymatic antioxidants or glutathione peroxidase; however, glutathione peroxidase was lower in WomenOC, i.e., main effect of group (p < 0.05, partial η2 > 0.20). CONCLUSION: These findings demonstrate that WomenOC not only have higher oxidative stress and CRP than WomenNC, but also a transient increase across one month of habitual oral contraceptive use. Since changes in oxidative stress and CRP often relate to training stress and recovery, these outcomes may have implications to workload monitoring practices in female athletes.
Assuntos
Anticoncepcionais Orais/farmacologia , Ciclo Menstrual/sangue , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Adulto , Biomarcadores/sangue , Feminino , Humanos , Ciclo Menstrual/fisiologia , Fatores de Tempo , Adulto JovemRESUMO
Capsule: Oligo/amenorrhea is an independent risk factor of low ovarian response but not high ovarian response, particularly in women with low AMH levels. Objective: To investigate the association of menstrual cycle length (MCL) with anti-Müllerian hormone (AMH) and ovarian response. Methods: This was a retrospective cohort study. A total of 7471 women who underwent ovarian stimulation and oocyte retrieval were enrolled. The main outcome was the number of oocytes retrieved. Main Results: A total of 5734 patients were eligible for analysis. In women without polycystic ovary syndrome (PCOS), serum AMH levels and antral follicle count were significantly lower in women with short cycles and higher in women with oligo/amenorrhea than those with a normal menstrual cycle. In women with PCOS, compared to women with a normal menstrual cycle, women with short cycles and women with oligo/amenorrhea showed higher antral follicle count and higher serum AMH levels. Compared with the 0-25th range group of AMH levels, 75-100th percentile groups showed a significantly increased rate of oligo/amenorrhea in women with and without PCOS [adjusted odds ratio (OR) =1.9 (1.04, 3.46), 2.4 (1.70, 3.35)]. In women without PCOS, the low ovarian response was more common in women with short cycles and less common in women with oligo/amenorrhea compared to women with normal cycles [OR=3.0 (2.38, 3.78), 0.7 (0.55, 0.96), respectively]. When adjusted for AMH levels, both short cycles and oligo/amenorrhea were associated with an increased risk of low response [adjusted OR=1.3 (1.02, 1.75), 1.3 (0.93, 1.86), respectively]. In women without PCOS and with low AMH levels, the low ovarian response was more common in women with short cycles as well as in women with oligo/amenorrhea [OR=1.5 (1.08, 1.98), 1.7 (1.08, 2.69), adjusted OR=1.2 (0.86, 1.74), 2.2 (1.31, 3.82), respectively]. Conclusion: AMH levels are significantly associated with increased risk of oligo/amenorrhea in women with and without PCOS. AMH is an indispensable confounder in the association between MCL and ovarian response in women without PCOS. Oligo/amenorrhea is an independent risk factor associated with a low ovarian response in women without PCOS, particularly those with low AMH levels.
Assuntos
Amenorreia/sangue , Hormônio Antimülleriano/sangue , Ciclo Menstrual/sangue , Recuperação de Oócitos/métodos , Indução da Ovulação/métodos , Síndrome do Ovário Policístico/sangue , Adulto , Feminino , Humanos , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
The menstrual cycle (MC) is a sex hormone-related phenomenon that repeats itself cyclically during the woman's reproductive life. In this explorative study, we hypothesized that coordinated variations of multiple sex hormones may affect the large-scale organization of the brain functional network and that, in turn, such changes might have psychological correlates, even in the absence of overt clinical signs of anxiety and/or depression. To test our hypothesis, we investigated longitudinally, across the MC, the relationship between the sex hormones and both brain network and psychological changes. We enrolled 24 naturally cycling women and, at the early-follicular, peri-ovulatory, and mid-luteal phases of the MC, we performed: (a) sex hormone dosage, (b) magnetoencephalography recording to study the brain network topology, and (c) psychological questionnaires to quantify anxiety, depression, self-esteem, and well-being. We showed that during the peri-ovulatory phase, in the alpha band, the leaf fraction and the tree hierarchy of the brain network were reduced, while the betweenness centrality (BC) of the right posterior cingulate gyrus (rPCG) was increased. Furthermore, the increase in BC was predicted by estradiol levels. Moreover, during the luteal phase, the variation of estradiol correlated positively with the variations of both the topological change and environmental mastery dimension of the well-being test, which, in turn, was related to the increase in the BC of rPCG. Our results highlight the effects of sex hormones on the large-scale brain network organization as well as on their possible relationship with the psychological state across the MC. Moreover, the fact that physiological changes in the brain topology occur throughout the MC has widespread implications for neuroimaging studies.
Assuntos
Encéfalo/diagnóstico por imagem , Emoções , Estradiol/sangue , Ciclo Menstrual/sangue , Ciclo Menstrual/psicologia , Rede Nervosa/diagnóstico por imagem , Adulto , Encéfalo/metabolismo , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética/métodos , Magnetoencefalografia/métodos , Rede Nervosa/metabolismo , Ultrassonografia de Intervenção/métodosRESUMO
OBJECTIVE: Migraine, endometriosis, and the comorbidity of both are frequent pain disorders of special relevance for women. The neuropeptide calcitonin gene-related peptide (CGRP) is critically involved in migraine, and circumstantial evidence suggests a role in endometriosis. We assessed CGRP levels at different times of menstrual cycle in four groups: healthy women, women with migraine or endometriosis and with the comorbidity of both. METHODS: Women with episodic migraine and women with a histologically confirmed endometriosis were recruited from specialized centers. For CGRP determination with a commercial enzyme immunoassay kit, cubital vein blood samples were collected on menstrual cycle day 2 ± 2 (during menstruation) and on day 15 ± 2 (periovulatory period). The primary endpoint of the study was the absolute difference of CGRP plasma levels between the menstrual and the periovulatory phase of all study groups. Groups were compared using nonparametric test procedures. RESULTS: A total of 124 women were included in the study. The change of CGRP plasma levels between menstruation and the periovulatory period was different between groups (p = 0.007). Women with comorbid migraine and endometriosis showed an increase of CGRP in the menstrual phase of +6.32 (interquartile range, IQR -3.64-13.60) compared to the periovulatory time, while healthy controls had a decrease of -10.14 (-22.54-0.91, p = 0.004). CGRP levels were different in the periovulatory phase among groups (p = 0.008), with highest values in healthy controls. INTERPRETATION: CGRP levels change significantly during the menstrual cycle. Different patterns in women with the comorbidity point to a deviant regulation of CGRP release.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina/sangue , Endometriose/sangue , Ciclo Menstrual/sangue , Transtornos de Enxaqueca/sangue , Fragmentos de Peptídeos/sangue , Adulto , Comorbidade , Endometriose/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Transtornos de Enxaqueca/epidemiologiaRESUMO
RESEARCH QUESTION: Is natural cycle IVF treatment beneficial to middle-aged women with poor ovarian response? DESIGN: Retrospective investigation of outcomes in women aged 45 years and older, who underwent natural cycle IVF treatment between 2009 and 2018 in a single assisted reproduction clinic with the aim of reporting several successful outcomes. RESULTS: In total, 2408 IVF retrievals in women aged 45 years and older were included in this study. Mean serum FSH level on day 3 was 21.4 ± 12.5 (range: 0.3-93.7) IU/ml. One fresh cleavage-stage embryo was transferred in 37.4% (900/2408) of the initiated cycles. The overall clinical pregnancy rate and live birth rate per fresh embryo transfer were 2.8% (25/900) and 0.8% (7/900), respectively. Natural cycle IVF treatment led to seven successful deliveries during the period. All seven women who successfully delivered were poor ovarian responders who met the diagnostic Bologna criteria and, among them, three had elevated serum FSH levels on day 3 (range: 39.0-47.1 mIU/ml). All seven had full-term delivery, and no congenital abnormalities were observed in their infants. No significant difference was found in serum FSH level on day 3 between those with and without positive beta-HCG test results. CONCLUSIONS: These findings suggest that natural cycle IVF treatment could be an option for older poor responders in countries that do not permit egg donation. Careful counselling is required, however, because of the low probability of live births after IVF in middle-aged women.
Assuntos
Fertilização in vitro/estatística & dados numéricos , Ciclo Menstrual/sangue , Taxa de Gravidez , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Estudos RetrospectivosRESUMO
Objective: To investigate the hormonal interrelationships during the menstrual cycle in women of late reproductive age with suppressed serum AMH and antral follicle count (AFC). Methods: Serum hormones (AMH, FSH, LH, estradiol, progesterone, inhibin A, inhibin B), AFC (2-10 mm) and AMH/AFC ratio (an estimate of AMH/follicle) were assessed every 2-3 days across the menstrual cycle in 26 healthy ovulatory women aged 18-50 years. Results: An 11-fold fall in AMH/AFC was observed in women aged ≥45 years compared to those 18-45 years (P < .001). Although women ≥45 years exhibited normal menstrual cycle patterns of serum estradiol, progesterone, LH and inhibin A, FSH was elevated (P < .001) and inhibin B suppressed (P < .001) compared to the younger group. Overall FSH was inversely correlated (r = .55, P < .05) and AMH directly correlated (r = .88, P < .01) with AFC; however, these relationships were curvilinear and more pronounced when AFC was low. Inhibin B was directly linearly correlated (r = .70, P < .01) with AFC across both high and low AMH/follicle groups. Conclusions: It is hypothesized that the marked fall in AMH/follicle in late reproductive age is attributed to the change in the hormonal interplay between the pituitary and ovary. The fall in AFC leads to a decrease in inhibin B and a concomitant increase in FSH by a recognized feedback mechanism. It is postulated the elevated FSH suppresses AMH either directly or indirectly through oocyte-specific growth factors leading to a marked fall in AMH/follicle. We propose that pituitary-ovarian and intra-ovarian regulatory systems underpin the accelerated fall in AMH/follicle during the transition to menopause.
Assuntos
Envelhecimento/sangue , Envelhecimento/patologia , Hormônio Antimülleriano/sangue , Contagem de Células , Hormônio Foliculoestimulante/sangue , Inibinas/sangue , Menopausa/sangue , Ciclo Menstrual/sangue , Folículo Ovariano/citologia , Folículo Ovariano/patologia , Adolescente , Adulto , Feminino , Voluntários Saudáveis , Humanos , Pessoa de Meia-Idade , Adulto JovemRESUMO
To investigate whether there is an association between androgens and ovarian reserve, expressed through anti-Mullerian hormone. This is a retrospective cross-sectional analysis of all consecutive women attending a tertiary fertility center, who presented with regular menstrual cycles. Patients had their AMH values measured with the same AMH assay (Immunotech (IOT) Beckmann Coulter assay), the same day in which androgens sampling was performed. Women with PCOS or other forms of androgen excess or untreated endocrine or metabolic disorders were excluded. A total of 942 women were included. Significant correlation was observed between total testosterone/free androgens index (FAI)/DHEAS and AMH (Spearman's r = 0.20/0.14/0.13, P value < 0.001, P value < 0.001, and P value < 0.001, respectively). After multiple linear regression analysis adjusting for confounders (age, BMI, cause of infertility, day of the menstrual cycle when the blood sample was performed), the regression slope in all participants for total testosterone predicting logAMH was 0.20 (P value < 0.001). Similarly, FAI was significantly associated with logAMH (regression coefficient = 0.04, P value = 0.04). In contrast, DHEAS was not significantly associated with logAMH. There was a significant, but weak relation between testosterone and AMH, while no significant association was observed between DHEAS and AMH. Future research is needed to elucidate whether testosterone supplementation may have any effect on ovarian function.
Assuntos
Androgênios/sangue , Hormônio Antimülleriano/sangue , Infertilidade Feminina/sangue , Infertilidade Feminina/diagnóstico , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/diagnóstico , Adulto , Estudos Transversais , Feminino , Humanos , Ciclo Menstrual/sangue , Testosterona/sangueRESUMO
OBJECTIVE: To characterize and evaluate the variation in serum concentrations of oocyte-secreted growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) throughout the menstrual cycle in women from young to advanced reproductive ages. DESIGN: Cross-sectional, observational, and exploratory study. SETTING: Multicenter university-based clinical practices and laboratories. PATIENT(S): Serum was collected every 1-3 days throughout the menstrual cycle from 3 cohorts of healthy, ovulatory women: menses to late luteal phase (21-29 years of age; n = 16; University of Otago) and across one interovulatory interval (18-35 years of age; n = 10; and 45-50 years of age; n = 15; University of Saskatchewan). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): To detect the changes in serum GDF9 and BMP15 across the cycle, mean concentration and variance were statistically modeled using a generalized additive model of location, shape and scale (GAMLSS). Follicle-stimulating hormone, luteinizing hormone, estradiol, progesterone, and anti-Müllerian hormone were also assessed. RESULT(S): GDF9 and BMP15 were detectable in 54% and 73% of women and varied 236-fold and 52-fold between women, respectively. Across the menstrual cycle, there were minimal changes in GDF9 or BMP15 within a woman for all cohorts, with no significant differences detected in the modeled mean concentrations. However, modeled variances were highest in the luteal phases of all women for BMP15 immediately after ovulation, regardless of age. CONCLUSION(S): Serial changes in GDF9 or BMP15 concentrations across the cycle were not statistically detected and are likewise similar across the reproductive lifespan. Further research is required to fully elucidate the utility of these oocyte biomarkers at diagnosing fertility potential and/or disease.
Assuntos
Proteína Morfogenética Óssea 15/sangue , Fator 9 de Diferenciação de Crescimento/sangue , Ciclo Menstrual/sangue , Adulto , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
CONTEXT: While age-related changes in menstrual cycle length are well known, it is unclear whether anti-Müllerian (AMH) or other ovarian reserve biomarkers have a direct association with cycle length. OBJECTIVE: To determine the association between biomarkers of ovarian reserve and menstrual cycle length. METHODS: Secondary analysis using data from time to conceive (TTC), a prospective time to pregnancy cohort study. The age-independent association between cycle length and biomarkers of ovarian reserve was analyzed using linear mixed and marginal models. Study participants were TTC-enrolled women aged 30-44 years with no history of infertility who were attempting to conceive for <3 months were enrolled. Serum AMH, follicle-stimulating hormone, and inhibin B levels were measured on cycle day 2, 3, or 4. Participants recorded daily menstrual cycle data for ≤4 months. The primary outcome was menstrual cycle length; follicular and luteal phase lengths were secondary outcomes. RESULTS: Multivariable analysis included 1880 cycles from 632 women. Compared with AMH levels of 1.6 to 3.4 ng/mL, women with AMH <1.6 ng/mL had cycles and follicular phases that were 0.98 (95% CI -1.46, -0.50) and 1.58 days shorter (95% CI -2.53, -0.63), respectively, while women with AMH >8 ng/mL had cycles that were 2.15 days longer (95% CI 1.46, 2.83), follicular phases that were 2 days longer (95% CI 0.77, 3.24), and luteal phases that were 1.80 days longer (95% CI 0.71, 2.88). CONCLUSION: Increasing AMH levels are associated with longer menstrual cycles due to both a lengthening of the follicular and the luteal phase independent of age.
Assuntos
Hormônio Antimülleriano/sangue , Ciclo Menstrual/fisiologia , Reserva Ovariana/fisiologia , Adulto , Biomarcadores , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Inibinas/sangue , Ciclo Menstrual/sangue , Estudos ProspectivosRESUMO
OBJECTIVE: Multiple sclerosis (MS) is a demyelinating, chronic, and progressive autoimmune disease of the central nervous system that causes the loss of axons and grey matter, and has a high prevalence in young female patients. Fingolimod is an oral treatment agent that acts by blocking the passage of the T lymphocytes responsible for the pathogenesis of MS from lymphoid tissue into the peripheral blood. We aimed to research the effects of menstrual cycles on leukocytes and lymphocyte levels in RRMS (relapsing-remitting MS) patients who received fingolimod treatment. PATIENTS AND METHODS: This study was performed to determine the most suitable phase of the menstrual cycle in patients with RRMS for follow-up assessment of lymphopaenia levels after fingolimod treatment. The study population consisted of 41 RRMS patients receiving fingolimod therapy and 33 healthy women of reproductive age. Complete blood counts were performed in three different phases of the menstrual cycle, and the two groups were compared. Variability in the total leukocyte, lymphocyte, and neutrophil immune cell numbers between cycles was examined. RESULTS: The results indicated that total leukocyte, neutrophil, and lymphocyte levels were decreased in RRMS patients receiving fingolimod treatment, but these changes were not related to the phase of the menstrual cycle. In our study, leukocyte levels in healthy individuals were significantly lower in the proliferative phase than in other phases. CONCLUSIONS: The results indicated that lymphocyte monitoring in RRMS patients receiving fingolimod treatment can be performed at any stage of the menstrual cycle.
Assuntos
Cloridrato de Fingolimode/farmacologia , Linfopenia/tratamento farmacológico , Ciclo Menstrual/efeitos dos fármacos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adolescente , Adulto , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Leucócitos/efeitos dos fármacos , Contagem de Linfócitos , Linfócitos/efeitos dos fármacos , Linfopenia/sangue , Linfopenia/patologia , Ciclo Menstrual/sangue , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/sangue , Esclerose Múltipla Recidivante-Remitente/patologia , Neutrófilos/efeitos dos fármacos , Adulto JovemRESUMO
OBJECTIVE: To examine the association between plasma glycemia in women attempting to conceive and fecundability, as measured by time to pregnancy. DESIGN: Prospective preconception population-based study. SETTING: Hospital. PATIENT(S): Asian preconception women, 18-45 years old, attempting conception for ≤12 cycles at study entry. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): We ascertained time to pregnancy within a year of glycemic assessment in menstrual cycles. We estimated fecundability ratios (FRs) and 95% confidence intervals using discrete-time proportional hazards models, adjusting for age, ethnicity, education, body mass index, and cycle regularity and accounting for left truncation and right censoring. RESULT(S): We studied a population sample of 766 women from the Singapore Preconception Study of Long-Term Maternal and Child Outcomes prospective cohort. Compared with women with normoglycemia, women with dysglycemia (prediabetes and diabetes, defined by the American Diabetes Association) had a lower FR (0.56). Compared with the respective lowest quintiles, women in the highest quintile of fasting glucose (≥5.1 mmol/L) had an FR of 0.60, while women in the highest 2-hour postload glucose quintile (≥6.9 mmol/L) had an FR of 0.66. Overall, the FRs decreased generally across the range of fasting and 2-hour plasma glucose. Glycated hemoglobin was not associated with fecundability. CONCLUSION(S): Increasing preconception plasma glucose is associated with reduced fecundability, even within the normal range of glucose concentrations. CLINICAL TRIAL REGISTRATION NUMBER: NCT03531658.
Assuntos
Glicemia/análise , Fertilidade/fisiologia , Adolescente , Adulto , Glicemia/metabolismo , Estudos de Coortes , Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Feminino , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Humanos , Infertilidade Feminina/sangue , Infertilidade Feminina/epidemiologia , Ciclo Menstrual/sangue , Pessoa de Meia-Idade , Estado Pré-Diabético/sangue , Estado Pré-Diabético/epidemiologia , Estudos Prospectivos , Singapura/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Sex hormones influence lipoprotein metabolism; whether the hormonal fluctuation during normal menstrual cycle has impact on non-fasting lipids remains unclear. OBJECTIVE: To examine the differences in postprandial triglyceride, apolipoprotein B (ApoB) and nonhigh density lipoprotein cholesterol (non-HDL-C) concentrations using a standardized fat tolerance test during the 2 menstrual cycle phases. METHODS: We enrolled 25 healthy, menstruating women. Each of them underwent a fat tolerance test during the 2 phases of the menstrual cycle. Blood samples were collected at baseline and up to 6 h postprandially. Differences in serum triglycerides, ApoB and non-HDL-C between the 2 phases were assessed. The incremental area under the curve (iAUC) was calculated. Reproducibility of the measurements was tested using the intraclass correlation coefficient (ICC) and coefficient of variation (CV). RESULTS: Serum triglyceride concentrations increased postprandially in both phases and the values were higher during the follicular compared with the luteal phase; however, the overall triglyceride response expressed as iAUC [median value (interquartile range)] did not differ between the follicular and the luteal phase [54.0 (-26.5, 107.0) and 48.0 (6.0, 114.5) mg x h/dl, respectively, p=0.64]. Serum ApoB concentrations did not increase postprandially and the overall ApoB response was not different between the 2 phases. Non-HDL-C concentrations changed postprandially, but the overall response was not different between the 2 phases of the menstrual cycle. Reproducibility of the measurements was moderate: ICC 0.689-0.848 for triglycerides, 0.721-0.771 for ApoB, 0.457-0.867 for non-HDL-C, and %CV >8 for all parameters. CONCLUSION: Serum triglyceride levels were higher during the follicular compared with the luteal phase after standardized meal consumption, but the overall postprandial triglyceride response did not differ between the 2 phases. Postprandial ApoB and non-HDL-C serum concentrations were not affected by the menstrual cycle.
Assuntos
Apolipoproteínas B , Ciclo Menstrual , Período Pós-Prandial , Triglicerídeos , Apolipoproteínas B/sangue , Feminino , Humanos , Ciclo Menstrual/sangue , Reprodutibilidade dos Testes , Triglicerídeos/sangueRESUMO
This study aimed to elucidate the effects of change in estrogen during the menstrual cycle and menopause on shear-mediated dilation of the internal carotid artery (ICA), a potential index of cerebrovascular endothelial function. Shear-mediated dilation of the ICA and serum estradiol were measured in 11 premenopausal (Pre-M, 21 ± 1 yr), 13 perimenopausal (Peri-M, 49 ± 2 yr), and 10 postmenopausal (Post-M, 65 ± 7 yr) women. Measurements were made twice within the Pre-M group at their early follicular (EF, lower estradiol) and late follicular (LF, higher estradiol) phases. Shear-mediated dilation was induced by 3 min of hypercapnia (target PETCO2 + 10 mmHg from individual baseline) and was calculated as the percent rise in peak diameter relative to baseline diameter. ICA diameter and blood velocity were simultaneously measured by Doppler ultrasound. In Pre-M, shear-mediated dilation was higher during the LF phase than during the EF phase (P < 0.01). Comparing all groups, shear-mediated dilation was reduced across the menopausal transition (P < 0.01), and Pre-M during the LF phase showed the highest value (8.9 ± 1.4%) compared with other groups (Pre-M in EF, 6.4 ± 1.1%; Peri-M, 5.5 ± 1.3%; Post-M, 5.2 ± 1.9%, P < 0.05 for all). Shear-mediated dilation was positively correlated with serum estradiol even after adjustment of age (P < 0.01, r = 0.55, age-adjusted; P = 0.02, r = 0.35). Collectively, these data indicate that controlling the menstrual cycle phase is necessary for the cross-sectional assessments of shear-mediated dilation of the ICA in premenopausal women. Moreover, current findings suggest that a decline in cerebrovascular endothelial function may be partly related to the reduced circulating estrogen levels in peri- and postmenopausal women.NEW & NOTEWORTHY The present study evaluated the effects of the menstrual cycle and menopause stages on the shear-mediated dilation of the ICA, a potential index of cerebrovascular endothelial function, in pre-, peri-, and postmenopausal women. Shear-mediated dilation of the ICA was increased from the low- to high-estradiol phases in naturally cycling premenopausal women and was reduced with advancing menopause stages. Furthermore, lower estradiol was associated with reduced shear-mediated dilation of the ICA, independent of age.