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1.
Hum Reprod ; 36(2): 405-414, 2021 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-33279981

RESUMO

STUDY QUESTION: Is psychosocial stress associated with ovarian function in reproductive-aged survivors of cancer diagnosed as adolescents and young adults (AYA survivors)? SUMMARY ANSWER: We observed no association between self-reported and biomarkers of psychosocial stress and ovarian function in AYA survivors. WHAT IS KNOWN ALREADY: Psychosocial stress suppresses hypothalamic-pituitary-ovarian axis, resulting in ovulatory dysfunction, decreased sex steroidogenesis and lower fertility in reproductive-aged women. Many cancer survivors experience high psychosocial stress and hypothalamic-pituitary-adrenal axis dysregulation. The menstrual pattern disturbances and infertility they experience have been attributed to ovarian follicle destruction, but the contribution of psychosocial stress to these phenotypes is unknown. STUDY DESIGN, SIZE, DURATION: A cross-sectional study was conducted estimating the association between perceived stress, measured by self-report and saliva cortisol, and ovarian function, measured by bleeding pattern, dried blood spot (DBS) FSH and LH, and saliva estradiol. We included 377 AYA survivor participants. PARTICIPANTS/MATERIALS, SETTING, METHODS: AYA survivor participants were ages 15-35 at cancer diagnosis and ages 18-40 at study enrollment, had completed primary cancer treatment, had a uterus and at least one ovary, did not have uncontrolled endocrinopathy and were not on hormone therapy. Recruited from cancer registries, physician referrals and cancer advocacy groups, participants provided self-reported information on psychosocial stress (Perceived Stress Scale-10 (PSS-10)) and on cancer and reproductive (fertility, contraception, menstrual pattern) characteristics. DBS samples were collected timed to the early follicular phase (cycle Days 3-7) for menstruating individuals and on a random day for amenorrheic individuals; saliva samples were collected three time points within 1 day. FSH and LH were measured by DBS ELISAs, cortisol was measured by ELISA and estradiol was measured by liquid chromatography tandem mass spectrometry. MAIN RESULTS AND THE ROLE OF CHANCE: The median age of participants was 34.0 years (range 19-41) at a median of 6.0 years since cancer diagnosis. The most common cancer was breast (32.1%). Median PSS-10 score was 15 (range 0-36), with 5.3% scoring ≥26, the cut point suggestive of severe stress. Cortisol levels followed a diurnal pattern and cortisol AUC was negatively correlated with PSS-10 scores (P = 0.03). Neither PSS-10 scores nor cortisol AUC were associated with FSH, LH, estradiol levels or menstrual pattern. Waking and evening cortisol and the cortisol awakening response also were not related to ovarian function measures. LIMITATIONS, REASONS FOR CAUTION: Our analysis is limited by its cross-sectional nature, heterogeneity of cancer diagnosis and treatments and low prevalence of severe stress. WIDER IMPLICATIONS OF THE FINDINGS: The lack of association between psychosocial stress and a variety of ovarian function measures in female AYA cancer survivors suggests that psychosocial stress does not have a significant impact on the reproductive axis of AYA survivors. This finding is important in counseling this population on their menstrual pattern and family building plans. STUDY FUNDING/COMPETING INTEREST(S): NIH HD080952, South Korea Health Industry Development Institute HI18C1837 (JK). Dr A.D. works for Bluebird Bio, Inc., Dr D.Z. works for ZRT Labs and Dr P.M.S. works for Ansh Labs, which did not sponsor, support or have oversight of this research. Other authors report no competing interests. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Sobreviventes de Câncer , Neoplasias , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Sistema Hipotálamo-Hipofisário , Neoplasias/complicações , Sistema Hipófise-Suprarrenal , República da Coreia , Estresse Psicológico , Adulto Jovem
2.
J Sports Sci ; 38(23): 2688-2697, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32705936

RESUMO

Aldosterone and cortisone are released in response to physical and psychological stress. However, aldosterone and cortisone responses in children engaged in physical competition have not been described. We examined salivary aldosterone and salivary cortisone responses among Hong Kongese boys, aged 8-11 years, during (1) a soccer match against unknown competitors (N = 84, high psychological stress condition) and (2) an intrasquad soccer scrimmage against teammates (N = 81, low psychological stress condition). Aldosterone levels increased during the soccer match and intrasquad soccer scrimmage conditions, consistent with the view that aldosterone responds to physical stress. During the soccer match, winning competitors experienced larger increases in aldosterone compared to losing competitors, indicating that the degree of aldosterone increase was attenuated by match outcome. Cortisone increased during the soccer match and decreased during the intrasquad soccer scrimmage. Competitors on teams that resulted in a tie had larger cortisone increases compared to winners or losers. These findings highlight that the degree of cortisone change is related to boy's cognitive appraisal of the competitor type (i.e., teammates vs. unknown competitors) and the competitive nature of the game (e.g., tie). These results shed new light on adrenal hormone mediators of stress and competition during middle childhood.


Assuntos
Aldosterona/metabolismo , Comportamento Competitivo/fisiologia , Cortisona/metabolismo , Saliva/metabolismo , Futebol/fisiologia , Estresse Psicológico/metabolismo , Biomarcadores/metabolismo , Criança , Humanos , Sistema Hipotálamo-Hipofisário/fisiologia , Masculino
3.
Proc Biol Sci ; 286(1910): 20191062, 2019 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-31480979

RESUMO

The capacity to infer others' mental states (known as 'mind reading' and 'cognitive empathy') is essential for social interactions across species, and its impairment characterizes psychopathological conditions such as autism spectrum disorder and schizophrenia. Previous studies reported that testosterone administration impaired cognitive empathy in healthy humans, and that a putative biomarker of prenatal testosterone exposure (finger digit ratios) moderated the effect. However, empirical support for the relationship has relied on small sample studies with mixed evidence. We investigate the reliability and generalizability of the relationship in two large-scale double-blind placebo-controlled experiments in young men (n = 243 and n = 400), using two different testosterone administration protocols. We find no evidence that cognitive empathy is impaired by testosterone administration or associated with digit ratios. With an unprecedented combined sample size, these results counter current theories and previous high-profile reports, and demonstrate that previous investigations of this topic have been statistically underpowered.


Assuntos
Empatia/fisiologia , Testosterona/metabolismo , Adulto , Cognição , Método Duplo-Cego , Emoções , Expressão Facial , Humanos , Relações Interpessoais , Masculino , Caracteres Sexuais
4.
Am J Hum Biol ; 30(6): e23190, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30387532

RESUMO

OBJECTIVES: Little is known about salivary steroid hormone responses to dyadic competition among prepubescent boys. The current study explored pre-match and post-match testosterone, dehydroepiandrosterone (DHEA), androstenedione, and cortisol among 22 ethnically Chinese, Hong Kongese table tennis athletes, aged 8-11 years, during dyadic competition against peers. These data provide novel comparative insight into boys' hormone responses when participating in similar forms of competition to that of adults. METHODS: Measures of salivary steroid hormones, age, outcome, and participant's self-reported perceived performance were obtained. Pre-match salivary steroid hormones and competition-induced steroid hormone changes were explored to further assess overall hypothalamic-pituitary-adrenal axis activity. RESULTS: Cortisol decreased for most participants, whereas testosterone measures were below the sensitivity of the assay. DHEA and androstenedione did not significantly change during the table tennis exhibitions and were unrelated to independent performance variables. Correlational analyses indicated that competition-induced androstenedione and cortisol change were positively related. CONCLUSIONS: Findings show that juvenile boys' steroid hormone responses during dyadic athletic competition differ in comparison to adult males, in whom cortisol and testosterone tend to rise. Lack of significant DHEA and androstenedione change during the table tennis competition differs from our previous work that showed DHEA and androstenedione were sensitive to more physically taxing forms of athletic competition (eg, soccer). These results are discussed in light of potential factors that may have contributed to these differences.


Assuntos
Atletas , Comportamento Competitivo/fisiologia , Hormônios Esteroides Gonadais/metabolismo , Tênis/fisiologia , Androstenodiona/metabolismo , Criança , Desidroepiandrosterona/metabolismo , Hong Kong , Humanos , Hidrocortisona/metabolismo , Masculino , Saliva/química , Testosterona/metabolismo
5.
Psychol Sci ; 28(10): 1398-1407, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28771393

RESUMO

In nonhumans, the sex steroid testosterone regulates reproductive behaviors such as fighting between males and mating. In humans, correlational studies have linked testosterone with aggression and disorders associated with poor impulse control, but the neuropsychological processes at work are poorly understood. Building on a dual-process framework, we propose a mechanism underlying testosterone's behavioral effects in humans: reduction in cognitive reflection. In the largest study of behavioral effects of testosterone administration to date, 243 men received either testosterone or placebo and took the Cognitive Reflection Test (CRT), which estimates the capacity to override incorrect intuitive judgments with deliberate correct responses. Testosterone administration reduced CRT scores. The effect remained after we controlled for age, mood, math skills, whether participants believed they had received the placebo or testosterone, and the effects of 14 additional hormones, and it held for each of the CRT questions in isolation. Our findings suggest a mechanism underlying testosterone's diverse effects on humans' judgments and decision making and provide novel, clear, and testable predictions.


Assuntos
Testosterona/farmacologia , Pensamento/efeitos dos fármacos , Adulto , Humanos , Masculino , Testosterona/administração & dosagem , Testosterona/efeitos adversos , Adulto Jovem
6.
Med Sci Monit ; 23: 5041-5048, 2017 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-29056745

RESUMO

BACKGROUND The aim of this study was to evaluate changes in sex hormone metabolism in patients with threatened miscarriage. MATERIAL AND METHODS We recruited 73 women in early pregnancy (6-8 weeks of gestation) and divided them into the following 2 groups based on whether they had vaginal bleeding: group A (n=34), the threatened abortion group; and group B (n=39), the normal pregnancy group. Human chorionic gonadotrophin (hCG), estradiol (E2), progesterone (P4), and testosterone (T) serum levels were tested and sex hormone metabolites in the urine were detected using gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS). As the control, data for sex hormones and their metabolites were obtained in normal women of childbearing age without pregnancy (group C: n=23). RESULTS E2 and T serum levels were lower in women with threatened miscarriage (group A). Estrone (E1), E2, estriol (E3), 16α-hydroxyestrone (16α-OHE1), 4-methoxyestrone (4-MeOE1), 2-hydroxyestradiol (2-OHE2), and 4-methoxyestradiol (4-MeOE2) levels were significantly lower in group A (P=0.001, 0.003, 0.009, 0.001, 0.012, 0.032, and 0.047, respectively.). Urine levels of dehydroepiandrosterone (DHEA), androstenedione (A2), and the metabolite of (A2) were also significantly lower in group A (P=0.007, 0.009, and 0.011, respectively). The 2-OHE1/E1, 4-OHE1/E1, 2-MeOE1/E1, and 2-MeOE2/E2 ratios were lower in group B, whereas the 2-OHE2/E2, 4-OHE2/E2, and 4-MeOE2/E2 ratios were dramatically lower in all pregnant women (groups A and B) than in group C. CONCLUSIONS Deficiency in DHEA and abnormal levels of sex hormone metabolites may cause a reduction in the activity of estrogens in women with threatened abortion. These alterations may result in bleeding during the first trimester of pregnancy.


Assuntos
Ameaça de Aborto/metabolismo , Hormônios Esteroides Gonadais/análise , Hormônios Esteroides Gonadais/metabolismo , Ameaça de Aborto/fisiopatologia , Adulto , Gonadotropina Coriônica/análise , Gonadotropina Coriônica/sangue , Estradiol/análise , Estradiol/sangue , Estrogênios/análogos & derivados , Estrogênios/análise , Feminino , Hormônios Esteroides Gonadais/urina , Humanos , Hidroxiestronas/análise , Hidroxiestronas/sangue , Gravidez , Progesterona/análise , Progesterona/sangue , Espectrometria de Massas em Tandem/métodos , Testosterona/análise , Testosterona/sangue
8.
BMC Complement Med Ther ; 22(1): 127, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35513823

RESUMO

BACKGROUND: The International Cohort on Lifestyle Determinants of Health (INCLD Health) is an ongoing, prospective cohort study assessing the health behaviours and lifestyles of higher education students, including their use of specialty diets and complementary and integrative health (CIH) practices. PURPOSE: This cross-sectional analysis of the INCLD Health cohort aims to (1) evaluate the associations between perceived stress, sleep disturbance, and meditative practices with diurnal salivary free cortisol and (2) evaluate the associations of meditative practices as well as mind-body practices with perceived stress and sleep disturbance. METHODS: Serial multivariable linear regression models, adjusting for sociodemographic and lifestyle behaviours, were used to assess associations of (1) perceived stress, sleep disturbance, and meditative practices with salivary cortisol, and (2) meditative practices as well as mind-body practices with perceived stress and sleep disturbance. Meditative and mind-body practices were evaluated using a stress-management and self-care survey; perceived stress and sleep disturbance were evaluated using the 10-item Perceived Stress Scale (PSS), and the patient reported outcome measures information system-29 (PROMIS-29) sleep sub-score respectively. Salivary cortisol was collected at 4 time points over a 24-hour period and area under the curve (AUC) calculations conducted. RESULTS: 82.5% (n = 80) of participants utilized at least monthly meditative practices. Greater disturbed sleep, but not perceived-stress, meditative, nor mind-body practices was independently associated with increased AUC cortisol (b = 0.02, 95% CI: 0.002-0.05, p = 0.03) after adjusting for age, sex, race, ethnicity, and BMI. Neither meditative nor mind-body practices were associated with perceived stress or disturbed sleep. CONCLUSIONS: Among INCLD Health participants, greater sleep disturbance, but not perceived stress or meditative practices were associated with daytime cortisol.


Assuntos
Hidrocortisona , Transtornos do Sono-Vigília , Estudos Transversais , Humanos , Estudos Prospectivos , Sono , Estudantes
9.
J Pediatr Adolesc Gynecol ; 35(4): 420-425, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35031446

RESUMO

Limited data exist on the reproductive hormone dynamics that govern the transition from menarche to the establishment of the mature ovulatory cycles of a fertile young woman. It is also unclear how environmental and lifestyle factors could modulate this transition in contemporary girls. Here, we introduce A Girl's First Period Study, an ambitious longitudinal study aimed at charting the early post-menarchal course of a cohort of healthy girls in the Triangle region of North Carolina.


Assuntos
Ciclo Menstrual , Ovulação , Adolescente , Feminino , Humanos , Estudos Longitudinais , Hormônio Luteinizante , Menarca , Distúrbios Menstruais
10.
Bioanalysis ; 13(1): 13-28, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33319585

RESUMO

Aim: Coronavirus disease 2019 antibody testing often relies on venous blood collection, which is labor-intensive, inconvenient and expensive compared with finger-stick capillary dried blood spot (DBS) collection. The purpose of our work was to determine if two commercially available anti-severe acute respiratory syndrome coronavirus 2 enzyme-linked immunosorbent assays for IgG antibodies against spike S1 subunit and nucleocapsid proteins could be validated for use with DBS. Materials & methods: Kit supplied reagents were used to extract DBS, and in-house DBS calibrators were included on every run. Results: Positive/negative concordance between DBS and serum was 100/99.3% for the spike S1 subunit assay and 100/98% for the nucleocapsid assay. Conclusion: Validation of the DBS Coronavirus disease 2019 IgG antibody assays demonstrated that serum and DBS can produce equivalent results with minimal kit modifications.


Assuntos
Teste para COVID-19/normas , COVID-19/diagnóstico , Teste em Amostras de Sangue Seco/normas , Ensaio de Imunoadsorção Enzimática/normas , SARS-CoV-2/imunologia , Anticorpos Antivirais/química , Antígenos Virais/sangue , Antígenos Virais/imunologia , COVID-19/sangue , COVID-19/imunologia , COVID-19/virologia , Proteínas do Nucleocapsídeo de Coronavírus/sangue , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Feminino , Humanos , Imunoglobulina G/química , Masculino , Pessoa de Meia-Idade , Fosfoproteínas/sangue , Fosfoproteínas/imunologia , Kit de Reagentes para Diagnóstico/normas , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Glicoproteína da Espícula de Coronavírus/sangue , Glicoproteína da Espícula de Coronavírus/imunologia
11.
Brain Res ; 1752: 147203, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33482998

RESUMO

Existing theories suggest that moderate arousal improves selective attention, as would be expected in the context of competitive sports or sensation-seeking activities. Here we investigated how riding a motorcycle, an attention-demanding physical activity, affects sensory processing. To do so, we implemented the passive auditory oddball paradigm and measured the EEG response of participants as they rode a motorcycle, drove a car, and sat at rest. Specifically, we measured the N1 and mismatch negativity to auditory tones, as well as alpha power during periods of no tones. We investigated whether riding and driving modulated non-CNS metrics including heart rate and concentrations of the hormones epinephrine, cortisol, DHEA-S, and testosterone. While participants were riding, we found a decrease in N1 amplitude, increase in mismatch negativity, and decrease in relative alpha power, together suggesting enhancement of sensory processing and visual attention. Riding increased epinephrine levels, increased heart rate, and decreased the ratio of cortisol to DHEA-S. Together, these results suggest that riding increases focus, heightens the brain's passive monitoring of changes in the sensory environment, and alters HPA axis response. More generally, our findings suggest that selective attention and sensory monitoring seem to be separable neural processes.


Assuntos
Nível de Alerta/fisiologia , Atenção/fisiologia , Encéfalo/fisiologia , Desempenho Psicomotor , Estresse Psicológico , Adulto , Eletroencefalografia , Potenciais Evocados Auditivos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Motocicletas
12.
BMC Cancer ; 10: 547, 2010 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-20937135

RESUMO

BACKGROUND: Correlation between circulating sex steroid levels and breast cancer has been controversial, with measurement of free, or bioavailable hormone rarely available. Salivary hormone levels represent the bioavailable fraction. To further elucidate the role of endogenous hormones in breast cancer, we aimed to assess correlation between salivary sex steroid levels and breast cancer prevalence. METHODS: Salivary hormone levels of testosterone (T), Estradiol (E2), Progesterone (P), Estriol (E3), Estrone (E1), DHEAS and Cortisol (C) were measured by Enzyme Immunoassay (EIA) in 357 women with histologically verified breast cancer and 184 age-matched control women. RESULTS: Salivary T and DHEAS levels were significantly lower in breast cancer cases vs. controls (27.2+13.9 vs. 32.2+17.5 pg/ml, p < 0.001 for T and 5.3+4.3 vs. 6.4+4.5 ng/ml, p = 0.007 for DHEAS). E2 and E1 levels were elevated and E3 levels were lowered in cases vs. controls. CONCLUSIONS: Salivary T levels, representing the bioavailable hormone, are significantly lower in women with breast cancer compared to age-matched control women. These findings support the protective role of bioavailable testosterone in counteracting the proliferative effects of estrogens on mammary tissue.


Assuntos
Neoplasias da Mama/metabolismo , Regulação Neoplásica da Expressão Gênica , Saliva/metabolismo , Testosterona/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Desidroepiandrosterona/metabolismo , Estradiol/metabolismo , Estriol/metabolismo , Estrona/metabolismo , Feminino , Humanos , Hidrocortisona/metabolismo , Técnicas Imunoenzimáticas/métodos , Pessoa de Meia-Idade , Progesterona/metabolismo
13.
BMC Womens Health ; 10: 19, 2010 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-20507626

RESUMO

BACKGROUND: Although research suggests that socio-sexual behavior changes in conjunction with the menstrual cycle, several potential factors are rarely taken into consideration. We investigated the role of changing hormone concentrations on self-reported physical discomfort, sleep, exercise and socio-sexual interest in young, healthy women. METHODS: Salivary hormones (dehydroepiandrosterone sulfate-DHEAS, progesterone, cortisol, testosterone, estradiol and estriol) and socio-sexual variables were measured in 20 women taking oral contraceptives (OC group) and 20 not using OCs (control group). Outcome measures were adapted from questionnaires of menstrual cycle-related symptoms, physical activity, and interpersonal relations. Testing occurred during menstruation (T1), mid-cycle (T2), and during the luteal phase (T3). Changes in behavior were assessed across time points and between groups. Additionally, correlations between hormones and socio-behavioral characteristics were determined. RESULTS: Physical discomfort and sleep disturbances peaked at T1 for both groups. Exercise levels and overall socio-sexual interest did not change across the menstrual cycle for both groups combined. However, slight mid-cycle increases in general and physical attraction were noted among the control group, whereas the OC group experienced significantly greater socio-sexual interest across all phases compared to the control group. Associations with hormones differed by group and cycle phase. The estrogens were correlated with socio-sexual and physical variables at T1 and T3 in the control group; whereas progesterone, cortisol, and DHEAS were more closely associated with these variables in the OC group across test times. The direction of influence further varies by behavior, group, and time point. Among naturally cycling women, higher concentrations of estradiol and estriol are associated with lower attraction scores at T1 but higher scores at T3. Among OC users, DHEAS and progesterone exhibit opposing relationships with attraction scores at T1 and invert at T3. CONCLUSIONS: Data from this study show no change across the cycle in socio-sexual interest among healthy, reproductive age women but higher social and physical attraction among OC users. Furthermore, a broader range of hormones may be associated with attraction than previously thought. Such relationships differ by use of oral contraceptives, and may either reflect endogenous hormone modulation by OCs and/or self-selection of sexually active women to practice contraceptive techniques.


Assuntos
Hormônios Esteroides Gonadais/metabolismo , Libido/fisiologia , Ciclo Menstrual/fisiologia , Ciclo Menstrual/psicologia , Anticoncepcionais Orais Hormonais/administração & dosagem , Feminino , Humanos , Libido/efeitos dos fármacos , Ciclo Menstrual/efeitos dos fármacos , Dor/etiologia , Saliva/química , Transtornos do Sono-Vigília/etiologia , Adulto Jovem
14.
J Midwifery Womens Health ; 64(4): 443-450, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30887687

RESUMO

INTRODUCTION: Clinical studies conducted in the early to mid-twentieth century, and recent self-reports by some maternal placentophagy practitioners, suggest that human maternal placentophagy improves breast milk quality and quantity, although little research has evaluated this claim. Some placentophagy providers and advocates suggest that increased prolactin levels after placenta ingestion could account for the purported lactation benefits. The current study was conducted to evaluate these claims by comparing plasma prolactin levels of women consuming steamed, dehydrated, and encapsulated placenta with those of women consuming a placebo. Neonatal weight gain was also compared between the 2 groups. METHODS: A randomized, double-blind, placebo-controlled pilot trial was conducted in which postpartum women (N = 27) were given a supplement containing their dehydrated placenta (n = 12) or placebo (n = 15). Plasma prolactin concentrations were measured 4 times across late pregnancy and early postpartum, and neonatal weights were recorded 3 times over the first 3 weeks postpartum. RESULTS: The results showed no statistically significant (P < .05) differences in either plasma prolactin levels or neonatal weight gain between groups. DISCUSSION: Maternal consumption of steamed, dehydrated, and encapsulated placenta postpartum does not appear to affect maternal postpartum prolactin or neonatal weight in the first 3 weeks postpartum. Further research is needed to investigate the possible effects of variation in placenta preparation methods or daily intake on human lactation.


Assuntos
Peso ao Nascer , Placenta , Período Pós-Parto , Prolactina/sangue , Aumento de Peso , Adulto , Cápsulas , Método Duplo-Cego , Feminino , Humanos , Recém-Nascido , Gravidez , Adulto Jovem
15.
Am J Transl Res ; 11(8): 4992-5007, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31497216

RESUMO

Sex hormone metabolism is altered during mammary gland tumorigenesis, and different metabolites may have different effects on mammary epithelial cells. This study aimed to evaluate associations between urinary sexual metabolite levels and breast cancer risk among premenopausal women of Mainland China. The molecular metabolism of the cancer-related metabolites was also explored based on the clinical data. The sex hormone metabolites in the urine samples of patients with breast cancer versus normal healthy women were analyzed comprehensively. Among many alterations of sex hormone metabolisms, 4-hydroxy estrogen (4-OH-E) metabolite was found to be significantly increased in the urine samples of patients with breast cancer compared with the normal healthy controls. This was the most important risk factor for breast cancer. Several experiments were conducted in vitro and in vivo to probe this mechanism. 4-Hydroxyestradiol (4-OH-E2) was found to induce malignant transformation of breast cells and tumorigenesis in nude mice. At the molecular level, 4-OH-E2 compromised the function of spindle-assembly checkpoint and rendered resistance to the anti-microtubule drug. Further, transgenic mice with high expression of CYP1B1, a key enzyme of 4-hydroxy metabolites, were established and stimulated with estrogen. Cancerous tissue was found to appear in the mammary gland of transgenic mice.

16.
J Clin Endocrinol Metab ; 104(6): 2184-2194, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30649404

RESUMO

CONTEXT: During puberty, LH pulse frequency increases during sleep; in women, LH pulse frequency slows during sleep in the early/middle follicular phase (FP) of the menstrual cycle. The origin and significance of this developmental transition are unknown. OBJECTIVE: To determine the relationship between progesterone (P4) exposure, sleep-related slowing of LH pulses in the FP, and the intercycle FSH rise, which promotes folliculogenesis, in early postmenarchal girls. METHODS: 23 girls (gynecologic age 0.4 to 3.5 years) underwent hormone measurements and pelvic ultrasounds during two consecutive cycles and one frequent blood sampling study with concurrent polysomnography during the FP. RESULTS: Subjects demonstrated one of four patterns during cycle 1 that represent a continuum of P4 exposure: ovulatory cycles with normal or short luteal phase lengths or anovulatory cycles ± follicle luteinization. Peak serum P4 and urine pregnanediol (Pd) in cycle 1 were inversely correlated with LH pulse frequency during sleep in the FP of cycle 2 (r = -0.5; P = 0.02 for both). The intercycle FSH rise and folliculogenesis in cycle 2 were maintained after anovulatory cycles without P4 or Pd exposure or nocturnal slowing of LH pulse frequency in the FP. CONCLUSIONS: During late puberty, rising P4 levels from follicle luteinization and ovulation may promote a slower LH pulse frequency during sleep in the FP. However, a normal FSH rise and follicle growth can occur in the absence of P4-associated slowing. These studies therefore suggest that an immature LH secretory pattern during sleep is unlikely to contribute to menstrual irregularity in the early postmenarchal years.


Assuntos
Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Progesterona/sangue , Sono , Adolescente , Criança , Feminino , Hormônio Liberador de Gonadotropina/fisiologia , Humanos , Ciclo Menstrual/fisiologia
17.
J Clin Endocrinol Metab ; 104(2): 613-623, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30289507

RESUMO

Context: Menstrual irregularity after menarche has been attributed to immature estrogen positive feedback activity (E+FB) but data are conflicting. Objective: To determine the hypothalamic-pituitary-ovarian contributions to menstrual irregularity in adolescents. Methods: Twenty-three healthy girls [aged 12.8 to 17.6 years; 0.4 to 3.5 years postmenarche; body mass index (BMI) percentile, 41.0 to 99.3] underwent serial hormone measurements and pelvic ultrasounds during two consecutive menstrual cycles. Hormones and follicle growth were compared with 65 adult historic controls with ovulatory cycles (OVs). Results: Girls had anovulatory cycles (ANOVs; 30%), OVs with a short luteal phase (short OVs; 22%), or OVs with normal luteal phase (normal OVs; 48%) without differences in cycle length, chronologic or gynecologic age, or BMI. Adolescents showed a spectrum of E+FB [midcycle LH adjusted for preovulatory estradiol (E2)]; only normal OV girls were comparable to adults. All OV girls had lower E2, progesterone, and gonadotropins during the luteal phase and luteal-follicular transition compared with adults. Normal OV girls also had lower follicular phase LH and FSH levels, a longer follicular phase, a slower dominant follicle growth rate, and smaller estimated preovulatory follicle size than adults. Follicular phase E2 and inhibin B levels were lower in normal OV girls than in adults even after adjusting for differences in FSH and follicle size. Conclusions: Early postmenarchal girls with normal OVs demonstrate mature E+FB but continue to have lower gonadotropin levels, diminished ovarian responsiveness, and decreased corpus luteum sex steroid synthesis compared with adults, indicating that reproductive axis maturity requires coordinated development of all components of the hypothalamic-pituitary-ovarian axis.


Assuntos
Desenvolvimento do Adolescente/fisiologia , Sistema Hipotálamo-Hipofisário/metabolismo , Menarca/fisiologia , Ciclo Menstrual/fisiologia , Ovário/metabolismo , Adolescente , Adulto , Criança , Estudos de Coortes , Estradiol , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Foliculoestimulante/metabolismo , Humanos , Inibinas/sangue , Inibinas/metabolismo , Hormônio Luteinizante/sangue , Hormônio Luteinizante/metabolismo , Ovulação/fisiologia , Progesterona/sangue , Progesterona/metabolismo
18.
Gynecol Obstet Invest ; 66(2): 111-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18446040

RESUMO

BACKGROUND/AIMS: There is a lack of evidence in the literature supporting vaginal application of a combination hormone-containing cream for local and systemic symptom relief. This pilot study examined the extent of absorption of a single cream containing estriol, estradiol, progesterone, DHEA, and testosterone. METHODS: A combination cream was administered to 12 postmenopausal women in two differing doses over two independent time periods. Following 28 days (arm 1) and an additional 14 days (arm 2), measurement of hormones in saliva and blood and measurements of symptom relief, patient tolerability, and health-related quality of life (HRQoL) were obtained. RESULTS: The dosage and time of evaluation for study arm 1 was not ideal for providing documented increases in hormone levels. HRQoL measurements supported measured improvement in this arm. The second arm did document absorption of the various hormones when given vaginally. CONCLUSION: This study is the first documenting systemic absorption of multiple hormones by both saliva and blood as well as improvement of HRQoL. This therapy was generally well-tolerated with only 2 patients experiencing minor irritation, not necessitating discontinuation. Additional studies in larger numbers of patients will provide better knowledge for clinicians wanting to provide similar therapy at the lowest effective dose.


Assuntos
Hormônios Esteroides Gonadais/administração & dosagem , Hormônios Esteroides Gonadais/farmacocinética , Terapia de Reposição Hormonal/métodos , Mucosa/metabolismo , Vagina/metabolismo , Administração Intravaginal , Adsorção , Idoso , Desidroepiandrosterona/administração & dosagem , Desidroepiandrosterona/sangue , Desidroepiandrosterona/farmacocinética , Emolientes/administração & dosagem , Emolientes/farmacocinética , Estradiol/administração & dosagem , Estradiol/sangue , Estradiol/farmacocinética , Estriol/administração & dosagem , Estriol/sangue , Estriol/farmacocinética , Feminino , Hormônios Esteroides Gonadais/sangue , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Qualidade de Vida , Saliva/metabolismo , Testosterona/administração & dosagem , Testosterona/sangue , Testosterona/farmacocinética
19.
Women Birth ; 31(4): e258-e271, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29174273

RESUMO

BACKGROUND: Human maternal placentophagy is gaining popularity among a growing number of women who believe it provides maternal benefits, including prevention of postpartum blues/depression, improved maternal bonding, and reduced fatigue. METHODS: We conducted a randomized, double-blind, placebo-controlled pilot study (N=27) in which participants consumed either their processed, encapsulated placenta (n=12), or similarly prepared placebo (n=15). Maternal mood, bonding, and fatigue were assessed via validated scales across four time points during late pregnancy and early postpartum. Psychometric data were analyzed for changes between and within both groups over time. RESULTS: No significant main effects related to maternal mood, bonding, or fatigue were evident between placenta and placebo group participants. However, examination of individual time points suggested that some measures had specific time-related differences between placenta and placebo groups that may warrant future exploration. Though statistical significance should not be interpreted in these cases, we did find some evidence of a decrease in depressive symptoms within the placenta group but not the placebo group, and reduced fatigue in placenta group participants at the end of the study compared to the placebo group. CONCLUSIONS: No robust differences in postpartum maternal mood, bonding, or fatigue were detected between the placenta and placebo groups. This finding may be especially important for women considering maternal placentophagy as a 'natural' (i.e., non-pharmacological) means of preventing or treating blues/depression. Given the study limitations, these findings should be interpreted as preliminary. Small, time-related improvements in maternal mood and lower fatigue post-supplementation among placenta group participants may warrant further research.


Assuntos
Afeto , Depressão , Ingestão de Alimentos , Mães/psicologia , Apego ao Objeto , Placenta , Período Pós-Parto , Adulto , Depressão Pós-Parto/prevenção & controle , Método Duplo-Cego , Fadiga , Feminino , Humanos , Comportamento Materno , Projetos Piloto , Gravidez , Escalas de Graduação Psiquiátrica
20.
Women Birth ; 31(4): e245-e257, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29174274

RESUMO

BACKGROUND: Recent studies show that human placenta, processed and encapsulated for postpartum consumption, contains a host of trace minerals and hormones that could conceivably affect maternal physiology. Our objective was to investigate whether salivary hormone concentrations of women ingesting their own encapsulated placenta during the early postpartum differed from those of women consuming a placebo. METHODS: Randomly assigned participants (N=27) were given a supplement containing either their dehydrated and homogenized placenta (n=12), or placebo (n=15). Saliva samples were collected during late pregnancy and early postpartum. Samples of participants' processed placenta, and the encapsulated placebo, were also collected. Hormone analyses were conducted on all samples utilizing liquid chromatography-tandem mass spectrometry. RESULTS: There were no significant differences in salivary hormone concentrations between the placenta and placebo groups post-supplementation that did not exist pre-supplementation. There were, however, significant dose-response relationships between the concentration of all 15 detected hormones in the placenta capsules and corresponding salivary hormone measures in placenta group participants not seen in the placebo group. The higher salivary concentrations of these hormones in the placenta group reflects the higher concentrations of these hormones in the placenta supplements, compared to the placebo. CONCLUSIONS: Some hormones in encapsulated placenta lead to small but significant differences in hormonal profiles of women taking placenta capsules compared to those taking a placebo, although these dose-response changes were not sufficient to result in significant hormonal differences between groups. Whether modest hormonal changes due to placenta supplementation are associated with therapeutic postpartum effects, however, awaits further investigation.


Assuntos
Ingestão de Alimentos , Hormônios/análise , Organoterapia , Placenta , Período Pós-Parto , Saliva/química , Adulto , Terapias Complementares , Feminino , Humanos , Organoterapia/efeitos adversos , Organoterapia/métodos , Organoterapia/psicologia , Projetos Piloto , Cuidado Pós-Natal , Gravidez , Adulto Jovem
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