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BACKGROUND: Neurokinin 3 receptor antagonists are potential non-hormonal therapies for the treatment of vasomotor symptoms in menopausal women as options are scarce for those who cannot or do not want to take hormone therapy. Fezolinetant is one of the first non-hormonal neurokinin 3 receptor antagonists in development for the treatment of vasomotor symptoms due to menopause. This study investigated the safety and efficacy of fezolinetant for the treatment of moderate-to-severe vasomotor symptoms associated with menopause. METHODS: SKYLIGHT 1 is a randomised, double-blind, placebo-controlled, 12-week, phase 3 trial with a 40-week active treatment extension. This trial was done at 97 facilities across the USA, Canada, Czech Republic, Hungary, Poland, Spain, and the UK. Women aged 40-65 years with an average of seven or more moderate-to-severe hot flashes per day were randomly assigned (1:1:1) to once-daily exact-matched placebo, fezolinetant 30 mg, or fezolinetant 45 mg. Randomisation was done using a web-based interactive response system and investigators, project team members, clinical staff, and participants were masked to treatment assignment. Coprimary endpoints were mean change in frequency and severity of vasomotor symptoms from baseline to weeks 4 and 12. The efficacy and safety analyses comprised all randomly assigned participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov (NCT04003155) and is completed. FINDINGS: Between July 11, 2019, and Aug 11, 2021, 2205 women were recruited of whom 175 were assigned to placebo, 176 to fezolinetant 30 mg, and 176 to fezolinetant 45 mg (175 in the placebo group, 174 in the fezolinetant 30 mg group, and 173 in the fezolinetant 45 mg received at least one dose [safety analysis set]). One participant randomly assigned to fezolinetant 45 mg received fezolinetant 30 mg in error, so the efficacy analysis set (full analysis set) consisted of 173 in the fezolinetant 30 mg group and 174 in the fezolinetant 45 mg group. 23 participants in the placebo group, 31 in the fezolinetant 30 mg group, and 13 in the fezolinetant 45 mg group discontinued treatment before week 12, mostly due to adverse events or participant withdrawal. Compared with placebo, fezolinetant 30 mg and fezolinetant 45 mg significantly reduced the frequency of vasomotor symptoms at week 4 (difference in change in least squares mean -1·87 [SE 0·42; p<0·001], -2·07 [SE 0·42; p<0·001]) and week 12 (-2·39 [SE 0·44; p<0·001], -2·55 [SE 0·43; p<0·001]). Compared with placebo, fezolinetant 30 mg and 45 mg significantly reduced the severity of vasomotor symptoms at week 4 (-0·15 [0·06; p=0·012], -0·19 [0·06; p=0·002]) and week 12 (-0·24 [0·08; p=0·002], -0·20 [0·08; p=0·007]). Improvements in frequency and severity of vasomotor symptoms were observed after 1 week and maintained over 52 weeks. During the first 12 weeks, treatment-emergent adverse events occurred in 65 (37%) of 174 women in the fezolinetant 30 mg group, 75 (43%) of 173 in the fezolinetant 45 mg group, and 78 (45%) of 175 in the placebo group. The incidence of liver enzyme elevations was low (placebo n=1; fezolinetant 30 mg n=2; fezolinetant 45 mg n=0) and these events were generally asymptomatic, transient, and resolved while on treatment or after treatment discontinuation. INTERPRETATION: Data support the clinical use of fezolinetant as a non-hormonal treatment for vasomotor symptoms associated with menopause. The study was placebo-controlled for 12 weeks followed by a 40-week blinded extension to assess the maintenance of effect. Furthermore, the population studied was diverse and representative of the potential target population for fezolinetant therapy. Further characterisation of the benefit of fezolinetant on quality of life, including on symptoms of mood and sexual wellbeing, merits investigation. FUNDING: Astellas Pharma.
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Qualidade de Vida , Receptores da Neurocinina-3 , Humanos , Feminino , Resultado do Tratamento , Menopausa , Método Duplo-CegoRESUMO
RESEARCH QUESTION: Does ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), delay ovulation? DESIGN: Two-stage, proof-of-concept, controlled study, assessing the percentage of non-ovulated follicles 42 h after HCG injection in patients taking ibuprofen. The intervention group consisted of women undergoing natural cycle IVF treatment taking ibuprofen 3â¯×â¯400 mg per day. The control group consisted of women undergoing timed sexual intercourse or intrauterine insemination. The proportion of patients with non-ovulated follicles in the ibuprofen group was first compared against a reference of 50% using a one-sample binomial test, and second against the proportion observed in the control group using an adjusted logistic regression. RESULTS: A total of 26 women were recruited in the ibuprofen intervention group. Twenty-five patients were recruited in the control group. The proportion of patients with delayed ovulation observed (22/26 [84.6%]; 95% CI 65.1% to 95.6%) was significantly higher than the reference of 50% (P < 0.001). In the control group, the proportion of patients with delayed ovulation was 20.0% ([5/25], 95% CI 6.8% to 40.7%). Compared with the ibuprofen group, a significantly increased probability of a delayed ovulation was found in the ibuprofen intervention group (adjusted OR 22.72, 95% CI 5.77 to 115; P < 0.001). Of the 22 women with delayed ovulation, oocytes were retrieved in 20 women (90.9%) and all oocytes were mature (metaphase II). CONCLUSIONS: Women trying to conceive should avoid non-selective NSAIDs around the time of ovulation. Ibuprofen or other NSAID can be used to delay ovulation for several hours in assisted reproductive technology and other infertility treatments if required.
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OBJECTIVE: To assess the effect of fezolinetant treatment on health-related quality of life using pooled data from SKYLIGHT 1 and 2 studies. DESIGN: Prespecified pooled analysis. SETTING: USA, Canada, Europe; 2019-2021. POPULATION: 1022 women aged ≥40 to ≤65 years with moderate-to-severe vasomotor symptoms (VMS; minimum average seven hot flushes/day), seeking treatment for VMS. METHODS: Women were randomised to 12-week double-blind treatment with once-daily placebo or fezolinetant 30 or 45 mg. Completers entered a 40-week, active extension (those receiving fezolinetant continued that dose; those receiving placebo re-randomised to fezolinetant received 30 or 45 mg). MAIN OUTCOME MEASURES: Mean changes from baseline to weeks 4 and 12 on Menopause-Specific Quality of Life (MENQoL) total and domain scores, Work Productivity and Activity Impairment questionnaire specific to VMS (WPAI-VMS) domain scores, Patient Global Impression of Change in VMS (PGI-C VMS); percentages achieving PGI-C VMS of 'much better' (PGI-C VMS responders). Mean reduction was estimated using mixed model repeated measures analysis of covariance. RESULTS: Fezolinetant 45 mg mean reduction over placebo in MENQoL total score was -0.57 (95% confidence interval [CI] -0.75 to -0.39) at week 4 and -0.47 (95% CI -0.66 to -0.28) at week 12. Reductions were similar for 30 mg. MENQoL domain scores were also reduced and WPAI-VMS scores improved. Twice as many women receiving fezolinetant reported VMS were 'much better' than placebo based on PGI-C VMS assessment. CONCLUSIONS: Fezolinetant treatment was associated with improvement in overall QoL, measured by MENQoL, and work productivity, measured by WPAI-VMS. A high proportion receiving fezolinetant felt VMS were 'much better' based on PGI-C VMS responder analysis.
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Fogachos , Menopausa , Qualidade de Vida , Humanos , Feminino , Pessoa de Meia-Idade , Fogachos/tratamento farmacológico , Menopausa/fisiologia , Menopausa/efeitos dos fármacos , Menopausa/psicologia , Método Duplo-Cego , Adulto , Idoso , Resultado do TratamentoRESUMO
OBJECTIVE: The purpose of this scoping review was to highlight the current scientific evidence on eHealth-based information tools for menopause in terms of quality, requirements and previous intervention outcomes. METHODS: We systematically searched electronic databases (Embase, CINAHL, Cochrane Library, Global Health Database [Ovid], Web of Science, ClinicalTrials.gov [NLM], LIVIVO Search Portal [ZB MED] and Google Scholar) from 1974 to March 2022 for relevant records. RESULTS: Our search yielded 1773 records, of which 28 met our inclusion criteria. Thirteen of 28 selected studies were cross-sectional with qualitative content analysis of websites about menopause; 9 studies were cohort studies examining the impact of an eHealth intervention; two studies were randomized controlled trials comparing eHealth tools with conventional ones; and four studies were non-systematic literature reviews. CONCLUSION: This scoping review highlights the potential of eHealth-based information tools for the management of menopause and shows that most eHealth-based information tools are inadequate in terms of readability and the balanced view on information. Providers of eHealth-based information tools should pay attention to a participatory design, readability, balance of content and the use of multimedia tools for information delivery to improve understanding.
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Menopausa , Autogestão , Telemedicina , Humanos , Telemedicina/métodos , Feminino , Autogestão/métodosRESUMO
Menopausal transition in women involves complex neurobiochemical changes linked to ovarian dysfunction, resulting in symptoms like vasomotor symptoms (VMS), sleep disturbances, anxiety, and cognitive impairments. Hormone replacement therapy is the first-line treatment. However, many women are reluctant to use HRT or have contraindications toward HRT and seek for alternatives. Non-hormonal therapies with extracts of Cimicifuga racemosa rhizomes like the isopropanolic extract (iCR, black cohosh) offer a promising alternative. A preclinical pilot study exploring iCR's effects on gene expression in the hippocampus and hypothalamus of ovarectomized (OVX) rats mimicking menopausal conditions identified important signaling pathways and CNS-based contributions to the multitargeted modes of action of iCR. Especially in the hippocampus, iCR compensated effects of OVX on gene expression profiles. These changes are reflected by the genes AVPR1A, GAL, CALCA, HCRT, PNOC, ESR1, ESR2 and TAC3 contributing to the formation of hot flushes or thermoregulation as well as to secondary effects such as blood pressure, metabolism, hormonal regulation, homeostasis, mood regulation, neuroendocrine modulation, regulation of sleep and arousal, and in learning, memory and cognition. To understand the mechanisms in the brain of estrogen-depressed animals (OVX) and subsequent iCR treatment we combined the results of the pilot study with those of up-to-date literature and tried to transfer the current knowledge to humans during menopausal transition and adaptation. Focus was laid on changes in the hippocampal function, that is disturbed by hormonal fluctuations, but can also be brought back into balance by iCR.
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Cimicifuga , Hipocampo , Menopausa , Extratos Vegetais , Cimicifuga/química , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Feminino , Animais , Menopausa/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ratos , Projetos Piloto , Humanos , OvariectomiaRESUMO
PURPOSE: The immune system is influenced by many factors, including female sex hormones. The extent of this influence, however, is not completely understood so far. This systematic literature review aims at giving an overview of the existing concepts on how endogenous progesterone influences the female immune system along the menstrual cycle. METHODS: The inclusion criteria were healthy female subjects in their reproductive age with a regular menstrual cycle. The exclusion criteria were exogenous progesterone, animal models, nonhealthy study populations and pregnancy. This led to 18 papers covered in this review. The search was performed using the databases EMBASE, Ovid MEDLINE and Epub, and the last search was conducted on September 18, 2020. Our findings were analyzed in four categories: cellular immune defense, humoral immune defense, objective and subjective clinical parameters. RESULTS: We demonstrated that progesterone acts in an immunosuppressive way, favoring a Th-2-like cytokine profile. Further, we showed that progesterone inhibits mast cell degranulation and relaxes smooth muscle cells. Furthermore, we found supporting evidence for a so-called window of vulnerability after ovulation, where immune functions are lowered and mediated through progesterone. CONCLUSION: The clinical relevance of these findings is not completely understood yet. As the sample sizes of included studies were rather small and the content of them was broad, further investigations are needed to define to which extent the described changes actually clinically meaningful, whether they are capable of influencing the female health and how these findings can be used to increase well-being.
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Sistema Imunitário , Ciclo Menstrual , Progesterona , Feminino , Humanos , Sistema Imunitário/metabolismo , Ciclo Menstrual/metabolismo , Ovulação , Progesterona/metabolismo , ReproduçãoRESUMO
PURPOSE: Short-acting progestin-only injectables containing depot medroxyprogesterone acetate (DMPA) are a safe method of contraception. Although DMPA has been available for several decades, there is little data on its influence on the risk of breast cancer. Hence, the aim of this paper was to provide an overview of the existing studies and create clarity regarding a possible association with breast cancer. METHODS: Literature searches were executed in MEDLINE, Embase, the Cochrane Library, ClinicalTrials.gov and ICTRP. Search terms were related to DMPA and breast cancer. After elimination of duplicates, 3'850 studies were identified and assessed according to inclusion and exclusion criteria. Finally, ten studies were selected and included in this review. RESULTS: All the selected papers were case-control-studies, except for one pooled analysis and one study comparing observed and expected number of cancer cases. Most of the included studies found no overall elevated breast cancer incidence in DMPA users, only one study found a slightly increased risk and two studies concluded with a significant increase for the overall breast cancer risk. CONCLUSION: There is little evidence that DMPA may increase the overall risk for breast cancer. However, the incidence of breast cancer is possibly increased in current and more recent users, especially in women younger than 35 years. Long-term use did not result in any risk increase. Nevertheless, further studies will be necessary to confirm these findings and weigh up the individual risks and benefits of this contraceptive method.
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Neoplasias da Mama , Anticoncepcionais Femininos , Feminino , Humanos , Acetato de Medroxiprogesterona/efeitos adversos , Preparações de Ação Retardada/efeitos adversos , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/epidemiologia , Anticoncepcionais Femininos/efeitos adversos , ProgestinasRESUMO
PURPOSE: Polycystic ovary syndrome (PCOS) management has hardly been standardized until recent years. Despite the existence of a detailed, evidence-based guideline published by the European Society of Human Reproduction and Embryology (ESHRE), it remains unclear to what extent healthcare providers adhere to this guideline. Our aim is to evaluate the gynaecological medical care provided in women with PCOS, particularly in terms of mental health, from the patients' perspective. METHODS: For this cross-sectional online cohort study in women with PCOS, we designed a standardized, non-validated questionnaire covering aesthetic aspects, metabolism, menstrual cycle, reproduction, mental health, and prevention of chronic non-communicable diseases. RESULTS: Among 1879 participants, various mental health aspects were reported: body image (n = 1879), eating patterns/habits (n = 1878), and emotional well-being (n = 1874). Although nearly all women (99.7%) reported complaints on at least one session of mental health, consultation rates were low (body image 9.7%, eating patterns/habits 16.6%, emotional well-being 4.4%). Mean satisfaction with counselling on the different domains varied from moderate to fairly satisfying, with scores of 56.0 points (SD 31.7), 53.5 points (SD 32.0), and 63.7 points (SD 30.2), respectively. More complaints were associated with lower satisfaction. The overall satisfaction with the management provided by the healthcare practitioner (HCP) was low, averaging 36.5 points (SD 29.7). Consequently, most women wished for more counselling (58.9%). CONCLUSION: Women affected by PCOS are not properly managed according to ESHRE guideline in regard to mental health issues. Overall consultation rates and corresponding satisfaction with management were poor, highlighting the need for significant improvements in healthcare provision.
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Síndrome do Ovário Policístico , Humanos , Feminino , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/terapia , Síndrome do Ovário Policístico/psicologia , Estudos Transversais , Saúde Mental , Estudos de Coortes , Ciclo MenstrualRESUMO
PURPOSE: Little is known about the reasoning behind the desire to have children in non-heterosexual individuals. This study compares the motives of different sexual-romantic orientations and their preferred ways of fulfilling this desire. METHODS: This was a monocentric cross-sectional study. Subjects were recruited via social media, personal contacts and queer organisations in Switzerland. An anonymous questionnaire comprised general questions about the participant's background, a validated survey about the desire to have children and additional non-validated questions addressing the impact of sexual-romantic orientation on the desire to have children. The inclusion criteria were adults without children and a completed questionnaire. RESULTS: Of 837 participants, 642 were included in the study. Four groups of sexual-romantic orientations consisted of more than 35 participants: bisexual-biromantic (n = 38), heterosexual-heteroromantic (n = 230), homosexual-homoromantic (n = 159) and pansexual-panromantic (n = 55). Subgroups with a positive wish for a child rated all motives in the same order and with minimal numeric difference. The most important aspect seemed to be emotional involvement. Non-heterosexual-heteroromantic showed concerns about adverse reactions regarding their wish for a child. All orientations hoped for a biological child. CONCLUSION: Our findings about bi-, hetero-, homo- and pansexual people and their motives for a desire to have children agree with the existing literature about hetero, homo and bisexual. The impact of the fear of adverse reaction and discrimination has been discussed before and is supported by our data. We suggest better support before and during the realization of the wish for a child as well as support for non-traditional aspiring parents.
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Identidade de Gênero , Comportamento Sexual , Adulto , Criança , Humanos , Estudos Transversais , Comportamento Sexual/psicologia , Motivação , Inquéritos e QuestionáriosRESUMO
PURPOSE: Menopause is associated with a decrease in smell discrimination ability. This study assessed the impact of black cohosh on hippocampal (HC) and hypothalamic (HT) gene expression profiles in rats, to understand, if herbal treatment has an impact on neurologic changes due to menopause and whether this could address a decrease in smell discrimination. METHODS: HC and HT tissues from female Sprague Dawley rats (total n = 19) were analyzed at three different life stages: intact tissues of the HC (n = 4) and the HT (n = 4), oophorectomized tissues 3 months after oophorectomy (OVX) of the HC (n = 4) and the HT (n = 3), and tissues after treatment with an isopropanolic extract (iCR) from the rhizomes of black cohosh (60 mg/kg) for 3 months after OVX of the HC (n = 2) and the HT (n = 2). MAIN OUTCOME MEASURES: To reveal underlying biological processes a gene set enrichment analysis (GSEA) was performed. RESULTS: The GSEA revealed gene ontology terms that were significantly enriched, including several genes associated with the olfactory system, indicating biological processes regulated by treatment with iCR. Six olfactory receptor genes were further analyzed by another GSEA, demonstrating the possibility of iCR treatment to compensate for oophorectomy-induced changes. CONCLUSION: Findings suggest that herbal treatment, such as iCR, has an esteeming impact on HC and HT genes that are changed through menopause. Further studies are needed to suggest black cohosh as a treatment option for decreased smell discrimination.
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PURPOSE: To evaluate clinical characteristics, quality of life (QoL) and effectiveness in patients with menstrual cycle disorders (MCDs) including abnormal uterine bleeding, dysmenorrhea and mastodynia/mastalgia related to premenstrual syndrome taking the Vitex agnus-castus (VAC) products Cyclodynon® or Mastodynon® in a real-world setting. METHODS: A single-center retrospective longitudinal cohort study (3 ± 1 months), using data obtained from healthcare data archive and telephone interviews. The main study variables were changes in bleeding, menstrual pain, breast tenderness and patients' QoL. RESULTS: Data from 1700 women with a mean age of 30.2 years (± 6.3) were analyzed. The most common MCDs were dysmenorrhea (43.8%) and mastodynia/mastalgia (21.1%). Three-month treatment with VAC extract substantially decreased the percentage of patients with irregular cycle (from 9.1% to 0.1%) and breast tenderness (from 39.9% to 0.8%). Improvement in bleeding intensity, frequency and menstrual pain was experienced by 83.4%, 79.2%, and 85.2% of the patients, respectively. When analyzed by disease category, these parameters improved in almost all dysmenorrhea patients, while they improved to a lesser extent in mastodynia/mastalgia patients. QoL improved in all aspects, but was reported by a higher proportion of dysmenorrhea patients compared to mastodynia/mastalgia patients. Treatment was overall well tolerated with a favorable safety profile. CONCLUSION: These real-world data demonstrate the effectiveness of the VAC-containing products Cyclodynon® and Mastodynon® in the three-month treatment of MCDs, with a pronounced improvement in key disease symptoms and QoL. Intriguingly, while QoL was generally greatly improved, the response to VAC therapy varied depending on the type of underlying MCD.
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Mastodinia , Vitex , Humanos , Feminino , Adulto , Mastodinia/tratamento farmacológico , Dismenorreia/tratamento farmacológico , Qualidade de Vida , Estudos Longitudinais , Estudos Retrospectivos , Distúrbios Menstruais/tratamento farmacológico , Ciclo MenstrualRESUMO
RESEARCH QUESTION: Does high-dose gonadotrophin stimulation have an effect on oocyte and early-stage embryo development? DESIGN: This was a retrospective study including 616 natural cycle IVF (NC-IVF) and 167 conventional IVF (cIVF) cycles. In total, 2110 oocytes were retrieved and analysed in fresh cycles. In NC-IVF, only human chorionic gonadotrophin was applied to trigger ovulation. In cIVF, antagonist protocols with daily 150-300 IU of human menopausal gonadotrophins were performed. The effect of gonadotrophins on oocyte and early-stage embryo development was analysed. Primary outcomes were the occurrence of mature (metaphase II) oocytes, zygotes and embryos with good morphology at the cleavage stage 2 days after oocyte retrieval. RESULTS: The mature oocyte rate (number of mature oocytes/number of retrieved oocytes) was higher in NC-IVF than cIVF cycles (89% versus 82%, adjusted odds ratio [aOR] 1.79, Pâ¯=â¯0.001), as was the zygote rate per oocyte retrieved (70% versus 58%, aOR 1.76, Pâ¯=â¯0.001) and the zygote rate per mature oocyte (79% versus 71%, aOR 1.62, Pâ¯=â¯0.001). The percentage of zygotes that developed into cleavage-stage embryos was no different. For the transferred embryos, the probability of having a good embryo morphology with four blastomeres and a fragmentation of <10% (score 0) in cleavage-stage embryos was found to be higher in NC-IVF (proportional aOR for four blastomeres 2.00, P < 0.001; aOR 1.87 for a fragmentation score of 0, Pâ¯=â¯0.003). CONCLUSIONS: Oocyte maturity, oocyte fertilization and morphology of the cleavage-stage embryo are affected by high-dose gonadotrophin stimulation in fresh IVF cycles.
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Fertilização in vitro , Indução da Ovulação , Feminino , Humanos , Fertilização in vitro/métodos , Estudos Retrospectivos , Indução da Ovulação/métodos , Gonadotropinas , Oócitos , FertilizaçãoRESUMO
7-Keto-DHEA has been commercially advertised as a dietary supplement to support weight loss. The objective of the present systematic review it to summarize the evidence supporting the use of 7-keto-DHEA in overweight and obese population. The systematic search was conducted in Medline, Embase, Cochrane Library, CINAHL, Web of Science, Scopus, ICTRP, and ClinicalTrials.gov. Additionally, reference lists of eligible studies were considered, and authors of relevant studies were contacted. Two authors independently screened the studies against the inclusion criteria and assessed their risk of bias. In total, 4 out of 686 studies were included in the review. They all held a low risk of bias. Half of them showed a significant reduction in body weight. One study found a decrease in body fat percentage and another one reported a decrease in BMI. Two studies stated an increase in resting metabolic rate. No serious adverse effects were reported. Various possible mechanisms in favor of weight loss are discussed; however, with the evidence currently available, no clear answer can be given regarding 7-keto-DHEA and weight loss. Further studies need to be conducted to clarify the efficacy and safety of this drug before it can be recommended for therapeutic use.
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Obesidade , Sobrepeso , Humanos , Peso Corporal , Obesidade/tratamento farmacológico , Redução de PesoRESUMO
PURPOSE: The intention of this systematic review was to analyze the literature on breast cancer (BC) and the use of the levonorgestrel-releasing intrauterine system (LNG-IUS). METHODS: The literature was searched in Medline, Embase, Cochrane Library, CINAHL, Web of Science and ClinicalTrials.com and included search terms related to breast cancer and LNG-IUS. After elimination of duplicates, 326 studies could be identified and were assessed according to inclusion and exclusion criteria. In the end, 10 studies met the defined criteria and were included in the systematic review. RESULTS: 6 out of the 10 selected studies were cohort studies, three were case-control studies and one a systematic review/meta-analysis. 6 found a positive association between BC and the use of LNG-IUS. One study only found an increased risk for invasive BC in the subgroup of women aged 40-45 years. In contrast, three studies showed no indication of a higher BC risk. CONCLUSION: The results imply an increased BC risk in LNG-IUS users, especially in postmenopausal women and with longer duration of use. Positive effects of the LNG-IUS such as reduced risks for other hormonal cancers have been observed, were, however, not focus of this systematic review. The heterogeneity of the analyzed studies and vast number of confounding factors call for further investigations in this issue. Patients should be advised according to their individual risk profile and hormone-free alternatives may be considered for women with a history of BC.
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Neoplasias da Mama , Anticoncepcionais Femininos , Dispositivos Intrauterinos Medicados , Humanos , Feminino , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/epidemiologia , Levanogestrel/efeitos adversos , Dispositivos Intrauterinos Medicados/efeitos adversos , Anticoncepcionais Femininos/efeitos adversos , Fatores de TempoRESUMO
OBJECTIVES: We aimed to assess prevalence and age at menopause, identify factors associated with early menopause and explore the provision and utilization of healthcare in women living with HIV in Switzerland. METHODS: This was a retrospective Swiss HIV Cohort Study analysis from January 2010 to December 2018. Descriptive statistics to characterise the population and menopause onset. Logistic regression analysis to identify risk factors for early menopause. RESULTS: Of all women in the SHCS, the proportion of postmenopausal women tripled from 11.5% (n = 274) in 2010 to 36.1% (n = 961) in 2018. The median age at menopause was 50 years. Early menopause (< 45 years) occurred in 115 (10.2%) women and premature ovarian insufficiency (POI) (< 40 years) in 23 (2%) women. Early menopause was associated with black ethnicity (52.2% vs. 21.6%, p < 0.001), but not with HIV acquisition mode, CDC stage, viral suppression, CD4 cell count, hepatitis C, smoking or active drug use. While 92% of the postmenopausal women underwent a gynaecological examination during the 36 months before menopause documentation, only 27% received a bone mineral density measurement within 36 months after the last bleed and 11% were on hormone replacement therapy at the time of menopause documentation. CONCLUSIONS: The median age of women living with HIV at menopause is around 2 years lower than that reported for HIV-negative women in Switzerland. HIV care providers need to adapt their services to the requirements of the increasing number of women living with HIV transitioning through menopause. They should be able to recognize menopause-associated symptoms and improve access to bone mineral density measurement as well as hormone replacement therapy.
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Etnicidade , Infecções por HIV , Densidade Óssea , Pré-Escolar , Estudos de Coortes , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Menopausa , Estudos Retrospectivos , Suíça/epidemiologiaRESUMO
RESEARCH QUESTION: Do follicular fluid hormone concentrations and the mRNA expression of LHCG, FSH and androgen receptors, aromatase and anti-Müllerian hormone (AMH) in cumulus granulosa cells differ in naturally matured and stimulated follicles? DESIGN: Cross-sectional study involving 57 natural cycle IVF (NC-IVF) and 36 conventional gonadotrophin-stimulated IVF (cIVF) cycles performed between 2014 and 2016. cIVF was performed by ovarian stimulation with human menopausal gonadotrophin and gonadotrophin-releasing hormone antagonists. Hormone concentrations were determined in the follicular fluid of the leading follicle, and mRNA concentrations were quantified by reverse transcription polymerase chain reaction in RNA extracted from granulosa cells of the cumulus oophorus complex obtained from these fluids. RESULTS: Follicular fluid hormone concentrations were significantly lower in cIVF compared with NC-IVF follicles. Median concentrations were 0.50 and 14.5 mIU/ml for LH (P < 0.001), 16.1 and 46.5 nmol/l for testosterone (P < 0.001), 1270 and 2675 nmol/l for oestradiol (P < 0.001), and 12.3 and 28.9 pmol/l for AMH (P < 0.001), respectively. In cumulus granulosa cells, mRNA concentrations for LH receptor, FSH receptor, androgen receptor, aromatase and AMH did not differ between cIVF and NC-IVF follicles. Several hormone and mRNA concentrations were quantitatively associated in natural cycles such as follicular fluid AMH and cumulus granulosa cells AMH RNA (r2â¯=â¯0.107, Pâ¯=â¯0.013), follicular fluid testosterone and cumulus granulosa cell AMH RNA (r2â¯=â¯0.158, Pâ¯=â¯0.002), follicular fluid oestradiol and cumulus granulosa cell AMH RNA (r2â¯=â¯0.105, Pâ¯=â¯0.014) and follicular fluid oestradiol and aromatase (r2â¯=â¯0.113, Pâ¯=â¯0.011). In contrast, these associations were not observed in stimulated cycles. CONCLUSION: These findings indicate some effects of gonadotrophin stimulation on follicular physiology, which could be a cause for the previously suggested lower oocyte quality in cIVF compared with NC-IVF.
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Células do Cúmulo , Líquido Folicular , Hormônio Antimülleriano/metabolismo , Aromatase/genética , Estudos Transversais , Células do Cúmulo/metabolismo , Estradiol/metabolismo , Estrona , Feminino , Hormônio Foliculoestimulante/metabolismo , Líquido Folicular/metabolismo , Gonadotropinas/metabolismo , Células da Granulosa/metabolismo , Humanos , RNA Mensageiro/metabolismo , Testosterona/metabolismoRESUMO
Chronic non-communicable diseases (NCD) are the major reason for death, morbidity, loss of independency and public health cost. NCD prevalence could be significantly reduced by adopting a healthy lifestyle. This cross-sectional cohort study (online survey) in 221 women aimed to assess NCD awareness, knowledge about NCD prevention and willingness to adopt a healthier lifestyle in women. Overall, NCD awareness level was quite high with, however, information mainly originating from lay media, probably being one reason for false estimations of age groups mainly affected by NCD, impact of NCD on quality of life, NCD mortalities, and the extent of NCD prevention by lifestyle interventions, respectively. Furthermore, also due to mainly lay media, half of women knew online NCD risk calculators, most of them would like to know their NCD risk, but only few had been offered NCD risk calculation by their physician. The mean threshold for willing to adopt a healthier lifestyle was a roughly calculated 37% 5-10 years risk to develop a certain NCD. Acceptance of non-pharmacological interventions for NCD prevention was high, however, major barriers for not implementing a healthier lifestyle were lack of expert information and lack of time. In conclusion, future public health strategies should focus on distributing better understandable and correct information about NCD as well as meeting the individuals' request for personalized NCD risk calculation. Furthermore, physicians should be better trained for personalized NCD prevention counseling.
Assuntos
Doenças não Transmissíveis , Estudos Transversais , Feminino , Humanos , Doenças não Transmissíveis/epidemiologia , Doenças não Transmissíveis/prevenção & controle , Doenças não Transmissíveis/psicologia , Prevalência , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
PURPOSE: This study aims to verify that the mental-cognitive domain of the validated generic bio-functional status (BFS)/bio-functional age (BFA) assessment tool, incorporating the concept of Active and Healthy Ageing (AHA), reflects cognitive performance. In addition, the effects of chronic stress exposure on the mental-cognitive BFS/BFA should be investigated. METHODS: The study was carried out as a monocenter, cross-sectional, observational, non-interventional trial (Bern Cohort Study 2014, BeCS-14) with the participation of 147 non-pediatric, non-geriatric subjects. All participants followed a standardized battery of biopsychosocial assessments consisting of BFS/BFA, a validated cognitive performance test battery (Inventar zur Gedächtnisdiagnostik; IGD) and a validated questionnaire for the assessment of chronic stress (Trier Inventory for the assessment of Chronic Stress; TICS), respectively. RESULTS: Mean cognitive performance was average and higher in younger or better educated individuals. The BFA of the participants was 7.8 ± 7.8 year-equivalents below their chronological age. The mental-cognitive BFS/BFA assessment correlated well with the validated questionnaire for cognition assessment, the IGD. Further, three TICS subdomains (work overload (r = - 0.246, p = 0.003), work discontent (r = - 0.299, p = 0.006) and pressure to succeed (r = - 0.274, p < 0.001)), reflecting mainly work-related stress, showed a significant negative correlation with the mental-cognitive BFS/BFA. CONCLUSIONS: Our study shows that the BFS/BFA assessment tool follows European Innovation Partnership on Active and Healthy Ageing (EIP-AHA) requirements. Further, we could demonstrate that higher levels of chronic work-related stress may be associated with poorer mental-cognitive performance and a pro-aging state indicating that cognitive impairments can be reduced by stress management interventions.
Assuntos
Envelhecimento Saudável , Idoso , Cognição , Estudos de Coortes , Estudos Transversais , Humanos , Inquéritos e QuestionáriosRESUMO
PURPOSE: This study aimed at assessing gene expression profiles in hippocampus and hypothalamus of ovariectomized (OVX) rats with or without treatment with an isopropanolic extract of Cimicifuga racemosa rhizomes (iCR) in comparison to intact rats. METHODS: Exploration of hippocampal (Hi) and hypothalamic (Hy) tissue from Sprague Dawley rats: without OVX (NHi = NHy = 4), tissues 3 months after OVX (NHi = 4, NHy = 3), or tissues of rats after their treatment with iCR for 3 months after OVX (NHi = NHy = 2). Gene expression profiles in these tissues were investigated by RNA-microarray-analysis and subsequent verification by qPCR. RESULTS: 4812 genes were differentially regulated when comparing the three groups in hippocampus and hypothalamus. iCR compensated the effects of OVX in 518 genes. This compensatory effect was most prominent in hippocampal signalling pathways, thereof genes (GAL, CALCA, HCRT, AVPR1A, PNOC, etc.) involved in thermoregulation, regulation of sleep and arousal, blood pressure regulation, metabolism, nociception, hormonal regulation, homeostasis, learning and cognition, mood regulation, neuroendocrine modulation, etc.. In the hypothalamus, iCR compensated OVX-effects at TAC3 and OPRM1 but not at KISS1. These genes are involved in the pathophysiology of hot flashes. CONCLUSIONS: Our pilot study findings support a multifaceted mode of action of iCR in menopausal complaints on a tissue-specific brain gene expression level.
Assuntos
Cimicifuga , Hipocampo/metabolismo , Hipotálamo/metabolismo , Extratos Vegetais , Transcriptoma , Animais , Cimicifuga/química , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Menopausa , Ovariectomia , Fitoterapia , Projetos Piloto , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
PURPOSE: The transition from the fertile phase of life to menopause is associated with numerous physical changes. Hormone replacement therapy (HRT), as the most effective and efficient form of drug treatment, involves the use of oestrogens and progestins with the aim of increasing health-related quality of life through symptom reduction, sleep improvement and affect enhancement. METHODS: The medical care situation and disease burden of menopausal women was investigated by means of a survey of 1000 women aged 45-60 years on the topics of quality of life, menopause and HRT and a quantitative, longitudinal healthcare study based on an anonymised and age- and sex-adjusted Statutory Health Insurance (SHI) routine data set with approximately four million anonymous insured persons per year. RESULTS: Out of more than half a million women aged 35-70 years, and with statutory health insurance, (n = 613,104), 14% (n = 82,785) had climacteric disorder documented as a first diagnosis in 2014. The proportion of women with the climacteric disorder, who were prescribed HRT on an outpatient basis, was 21%; according to the forsa survey, 50% of the women surveyed felt moderate to poorly/very poorly informed about treatment options. CONCLUSION: Findings from the health insurance research conducted with different data sources (survey and SHI claims data) indicate the need for increasing awareness and providing an early and informative education on HRT and its risks and benefits.