Influence of the number and severity of comorbidities in the course of acute non-specific low back pain in older adults: longitudinal results from the Back Complaints in the Elders (BACE-Brazil).

BACKGROUND: The presence of comorbidities is quite common in older adults. However, the effects of comorbidities on the course of acute low back pain (LBP) are not fully understood. OBJECTIVE: To investigate the effects of the number and severity of comorbidities on the severity of pain and disability 3 months from baseline in people with an acute episode of non-specific LBP. METHODS: Data from the Back Complaints in the Elders study, a cohort that enrolled 602 community-dwelling older adults with acute LBP at baseline, were used in these analyses. Comorbidities, pain intensity and disability were assessed using the Self-Administered Comorbidities Questionnaire (SCQ), the Numeric Rating Scale (NRS) and the Roland-Morris Disability Questionnaire (RMDQ), respectively. Age, sex, marital status, education, income and body mass index were covariates. RESULTS: The mean age of participants was 67.6 ± 7.0 years. Both pain and disability scores decreased from 7.2 (95% confidence interval [95% CI] 7.0-7.4) to 5.8 (95% CI 5.5-6.1) in NRS and from 13.5 (95% CI 13.0-14.1) to 12.0 (95% CI 11.4-12.7) in RMDQ 3 months from baseline. The linear regression analysis showed a significant association between SCQ scores at baseline and pain (coefficient = 0.16, 95% CI 0.08-0.24; P < 0.001) or disability (coefficient = 0.29, 95% CI 0.16-0.41; P < 0.001) scores at the 3-month follow-up, after adjusting for confounders. Participants with highest SCQ scores were less likely to report improvement of at least 30% in pain (OR: 0.41, 95% CI 0.22-0.79; P = 0.008) and disability (OR: 0.42, 95% CI 0.28-0.85; P = 0.015). CONCLUSION: The presence and severity of comorbidities were independently associated with the prognosis of acute non-specific LBP in older adults.

Correction: Management of vertebral compression fracture in general practice: BEACH program.

[This corrects the article DOI: 10.1371/journal.pone.0176351.].

Association between pain and the frailty phenotype in older men: longitudinal results from the Concord Health and Ageing in Men Project (CHAMP).

Objectives: to determine whether pain increases the risk of developing the frailty phenotype and whether frailty increases the risk of developing chronic or intrusive pain, using longitudinal data. Design/Setting: longitudinal data from the Concord Health and Ageing in Men Project (CHAMP), a prospective population based cohort study. Participants: a total of 1,705 men aged 70 years or older, living in an urban area of New South Wales, Australia. Measurements: data on the presence of chronic pain (daily pain for at least 3 months), intrusive pain (pain causing moderate to severe interference with activities) and the criteria for the Cardiovascular Health Study (CHS) frailty phenotype were collected in three waves, from January 2005 to October 2013. Data on age, living arrangements, education, smoking status, alcohol consumption, body mass index, comorbidities, cognitive function, depressive symptoms and history of vertebral or hip fracture were also collected and included as covariates in the analyses. Results: a total of 1,705 participants were included at baseline, of whom 1,332 provided data at the 2-year follow-up and 940 at the 5-year follow-up. Non-frail (robust and pre-frail) men who reported chronic pain were 1.60 (95% confidence interval (CI): 1.02-2.51, P = 0.039) times more likely to develop frailty at follow-up, compared to those with no pain. Intrusive pain did not significantly increase the risk of future frailty. Likewise, the frailty status was not associated with future chronic or intrusive pain in the adjusted analysis. Conclusions: the presence of chronic pain increases the risk of developing the frailty phenotype in community-dwelling older men.

Efficacy and Safety of Oral and Transdermal Opioid Analgesics for Musculoskeletal Pain in Older Adults: A Systematic Review of Randomized, Placebo-Controlled Trials.

This systematic review with meta-analysis was performed to evaluate the efficacy and safety of using opioid analgesics in older adults with musculoskeletal pain. We searched Cochrane Library, MEDLINE, EMBASE, Web of Science, AMED, CINAHL, and LILACS for randomized controlled trials with mean population age of 60 years or older, comparing the efficacy and safety of opioid analgesics with placebo for musculoskeletal pain conditions. Reviewers extracted data, assessed risk of bias, and evaluated the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. Random effects models were used to calculate standardized mean differences (when different scales were used across trials), mean differences and odds ratios with respective 95% confidence intervals (CIs). Meta-regressions were carried out to assess the influence of opioid analgesic daily dose and treatment duration on our main outcomes. We included 23 randomized placebo-controlled trials in the meta-analysis. Opioid analgesics had a small effect on decreasing pain intensity (standardized mean difference = -.27; 95% CI = -.33 to -.20) and improving function (standardized mean difference = -.27, 95% CI = -.36 to -.18), which was not associated with daily dose or treatment duration. The odds of adverse events were 3 times higher (odds ratio = 2.94; 95% CI = 2.33-3.72) and the odds of treatment discontinuation due to adverse events 4 times higher (odds ratio = 4.04; 95% CI = 3.10-5.25) in patients treated with opioid analgesics. The results show that in older adults suffering from musculoskeletal pain, using opioid analgesics had only a small effect on pain and function at the cost of a higher odds of adverse events and treatment discontinuation. For this specific population, the opioid-related risks may outweigh the benefits. PERSPECTIVE: The systematic review shows that, in older adults suffering from musculoskeletal conditions, opioid analgesics have only a small effect on pain and disability. Conversely, this population is at higher risk of adverse events. The results may reflect age-related physiological changes in pain processing, pharmacokinetics, and pharmacodynamics.

An overview of clinical guidelines for the management of vertebral compression fracture: a systematic review.

BACKGROUND CONTEXT: Vertebral compression fractures (VCFs) are the most common type of osteoporotic fracture comprising approximately 1.4 million cases worldwide. Clinical practice guidelines can be powerful tools for promoting evidence-based practice as they integrate research findings to support decision making. However, currently available clinical guidelines and recommendations, established by different medical societies, are sometimes contradictory. PURPOSE: The aim of this study was to appraise the recommendations and the methodological quality of international clinical guidelines for the management of VCFs. STUDY DESIGN: This is a systematic review of clinical guidelines for the management of VCF. METHODS: Guidelines were selected by searching MEDLINE and PubMed, PEDro, CINAHL, and EMBASE electronic databases between 2010 and 2016. We also searched clinical practice guideline databases, including the National Guideline Clearinghouse and the Canadian Medical Association InfoBase. The methodological quality of the guidelines was assessed by two authors independently using the Appraisal of Guidelines, Research and Evaluation (AGREE) II Instrument. We also classified the strength of each recommendation as either strong (ie, based on high-quality studies with consistent findings for recommending for or against the intervention), weak (ie, based on a lack of compelling evidence resulting in uncertainty for benefit or potential harm), or expert consensus (ie, based on expert opinion of the working group rather than on scientific evidence). Guideline recommendations were grouped into diagnostic, conservative care, interventional care, and osteoporosis treatment and prevention of future fractures. Our study was prospectively registered on PROSPERO. RESULTS: Four guidelines from three countries, published in the period 2010-2013, were included. In general, the quality was not satisfactory (50% or less of the maximum possible score). The domains scoring 50% or less of the maximum possible score were rigor of development, clarity of presentation, and applicability. The use of plain radiography or dual-energy X-ray absorptiometry for diagnosis was recommended in two of the four guidelines. Vertebroplasty or kyphoplasty was recommended in three of the four guidelines. The recommendation for bed rest, trunk orthoses, electrical stimulation, and supervised or unsupervised exercise was inconsistent across the included guidelines. CONCLUSIONS: The comparison of clinical guidelines for the management of VCF showed that diagnostic and therapeutic recommendations were generally inconsistent. The evidence available to guideline developers was limited in quantity and quality. Greater efforts are needed to improve the quality of the majority of guidelines.

Management of vertebral compression fracture in general practice: BEACH program.

IMPORTANCE: The pain associated with vertebral compression fractures can cause significant loss of function and quality of life for older adults. Despite this, there is little consensus on how best to manage this condition. OBJECTIVE: To describe usual care provided by general practitioners (GPs) in Australia for the management of vertebral compression fractures. DESIGN, SETTING AND PARTICIPANTS: Data from the Bettering the Evaluation And Care of Health (BEACH) program collected between April 2005 and March 2015 was used for this study. Each year, a random sample of approximately 1,000 GPs each recorded information on 100 consecutive encounters. We selected those encounters at which vertebral compression fracture was managed. Analyses of management options were limited to encounters with patients aged 50 years or over. MAIN OUTCOME(S) AND MEASURE(S): i) patient demographics; ii) diagnoses/problems managed; iii) the management provided for vertebral compression fracture during the encounter. Robust 95% confidence intervals, adjusted for the cluster survey design, were used to assess significant differences between group means. RESULTS: Vertebral compression fractures were managed in 211 (0.022%; 95% CI: 0.018-0.025) of the 977,300 BEACH encounters recorded April 2005- March 2015. That provides a national annual estimate of 26,000 (95% CI: 22,000-29,000) encounters at which vertebral fractures were managed. At encounters with patients aged 50 years or over (those at higher risk of primary osteoporosis), prescription of analgesics was the most common management action, particularly opioids analgesics (47.1 per 100 vertebral fractures; 95% CI: 38.4-55.7). Prescriptions of paracetamol (8.2; 95% CI: 4-12.4) or non-steroidal anti-inflammatory drugs (4.1; 95% CI: 1.1-7.1) were less frequent. Non-pharmacological treatment was provided at a rate of 22.4 per 100 vertebral fractures (95% CI: 14.6-30.1). At least one referral (to hospital, specialist, allied health care or other) was given for 12.3 per 100 vertebral fractures (95% CI: 7.8-16.8). CONCLUSIONS AND RELEVANCE: The prescription of oral opioid analgesics remains the common general practice approach for vertebral compression fractures management, despite the lack of evidence to support this. Clinical trials addressing management of these fractures are urgently needed to improve the quality of care patients receive.

Apolipoprotein E polymorphism and functional disability in Brazilian elders: the Bambuí Health and Aging Study.

Numerous studies have associated the apolipoprotein E (apoE) ε4 allele with worse health status, but few have assessed the existence of genotype-dependent variations in functional performance. Among participants in the Bambuí Health and Aging Study, Minas Gerais State, Brazil, 1,408 elderly underwent apoE genotyping. Functionality was assessed with a questionnaire, and individuals were classified as dependent in basic activities of daily living (BADLs), instrumental activities of daily living (IADLs), and mobility. The association between apoE genotype and functional status was assessed by logistic regression, taking confounding factors into account. Presence of ε4 allele was associated with lower odds of mobility deficit (OR = 0.65; 95%CI: 0.47-0.92) in the adjusted analysis. There were no significant differences in relation to presence of dependency in BADLs and IADLs. The reasons are not entirely understood, but they may involve the role of ε4 allele as a "thrifty gene" in a sample exposed to high risk of infectious and nutritional diseases in the past.

Apolipoprotein E polymorphism and functional disability in Brazilian elders: the Bambuí Health and Aging Study / Polimorfismo da apolipoproteína E e incapacidade funcional em idosos brasileiros: Projeto Bambuí / Polimorfismo de la apolipoproteína E e incapacidad funcional en los ancianos brasileños: Proyecto Bambuí

Abstract Numerous studies have associated the apolipoprotein E (apoE) ε4 allele with worse health status, but few have assessed the existence of genotype-dependent variations in functional performance. Among participants in the Bambuí Health and Aging Study, Minas Gerais State, Brazil, 1,408 elderly underwent apoE genotyping. Functionality was assessed with a questionnaire, and individuals were classified as dependent in basic activities of daily living (BADLs), instrumental activities of daily living (IADLs), and mobility. The association between apoE genotype and functional status was assessed by logistic regression, taking confounding factors into account. Presence of ε4 allele was associated with lower odds of mobility deficit (OR = 0.65; 95%CI: 0.47-0.92) in the adjusted analysis. There were no significant differences in relation to presence of dependency in BADLs and IADLs. The reasons are not entirely understood, but they may involve the role of ε4 allele as a "thrifty gene" in a sample exposed to high risk of infectious and nutritional diseases in the past.

Resumo Inúmeros estudos têm associado o alelo ε4 da apolipoproteína E (apoE) com pior condição de saúde, mas poucos avaliaram a existência de variações genótipo-dependentes no desempenho funcional. Entre os participantes da coorte de Bambuí, Minas Gerais, Brasil, 1.408 idosos foram submetidos à genotipagem da apoE. A funcionalidade foi avaliada por questionário, sendo os indivíduos classificados em dependentes para atividades básicas da vida diária (ABVDs), atividades instrumentais da vida diária (AIVDs) e mobilidade. A associação entre o genótipo da apoE e o estado funcional foi avaliada pela regressão logística, considerando variáveis de confusão. A presença do alelo ε4 foi associada a uma menor chance de déficit na mobilidade (OR = 0,65; IC95%: 0,47-0,92), na análise ajustada. Não houve diferenças significativas em relação à presença de incapacidades em ABVDs e AIVDs. Os motivos não estão completamente compreendidos, mas podem envolver o seu papel como um "thrifty gene" em uma amostra exposta a um risco elevado de doenças infecciosas e nutricionais no passado.

Resumen Innumerables estudios han asociado el alelo ε4 de la apolipoproteína E (apoE) con una peor condición de salud, pero pocos evaluaron la existencia de variaciones genotipo-dependientes en el desempeño funcional. Entre los participantes de la cohorte de Bambuí, Minas Gerais, Brasil, 1.408 ancianos fueron sometidos a una determinación del genotipo de la apoE. La funcionalidad fue evaluada por cuestionario, siendo los individuos clasificados en: dependientes para actividades básicas de la vida diaria (ABVDs), actividades instrumentales de la vida diaria (AIVDs) y movilidad. La asociación entre el genotipo de la apoE y el estado funcional fue evaluada por regresión logística, considerando variables de confusión. La presencia del alelo ε4 fue asociada a una menor probabilidad de déficit en la movilidad (OR = 0,65; IC95%: 0,47-0,92) en el análisis ajustado. No hubo diferencias significativas en relación con la presencia de incapacidades en ABVDs y AIVDs. Los motivos no están completamente claros, pero pueden están involucrados por su papel como un "thrifty gene" en una muestra expuesta a un riesgo elevado de enfermedades infecciosas y nutricionales en el pasado.

Polimorfismo da apolipoproteína E e sua associação com incapacidade funcional em idosos: Projeto Bambuí

Vários estudos tem demonstrado o papel da genética no envelhecimento mas ainda não se sabe como os genes influenciam esse processo, sendo possível o envolvimento de vários genes, cada um deles com apenas um modesto efeito. Entre os genes potencialmente relacionados ao envelhecimento mais estudados, destaca-se o gene da apolipoproteína E. Além de participar do transporte de lipídeos, essa apolipoproteína tem papel importante na aterosclerose, no reparo e manutenção de células do sistema nervoso central e na inflamação. Inúmeros estudos tem associado o alelo ε4 da apoE a doenças comuns em idosos como a doença arterial coronariana, o acidente vascular encefálico e a doença de Alzheimer. Mais recentemente, o gene da apolipoproteína E também tem sido considerado um gene da vulnerabilidade já que portadores de ε4 apresentam um pior prognóstico em várias outras condições clínicas como traumatismo craniano, doença arterial periférica e diabetes. Idosos mais vulneráveis tendem a acumular mais incapacidades com o envelhecimento e, se o gene da apolipoproteína E for realmente um gene ligado a vulnerabilidade, é possível imaginar que existam variações genótipo-dependentes no desempenho funcional dos idosos. Para avaliar a associação do genótipo da apolipoproteína E com incapacidade funcional e com um fenótipo de “envelhecimento bem sucedido” 1408 idosos incluídos na linha de base do Projeto Bambuí foram submetidos a genotipagem da apolipoproteína E e constituíram a amostra desse estudo.

Os participantes responderam a um questionário para avaliação da funcionalidade e foram classificados de acordo com a presença ou ausência de incapacidades em atividades relacionadas à AVDs, AIVDs e mobilidade. Um subgrupo de idosos que não apresentavam nenhuma dificuldade nas tarefas avaliadas foram considerados idosos com “envelhecimento bem sucedido”. A associação do genótipo da apolipoproteína E e os fenótipos descritos foi avaliada pela regressão logística múltipla, considerando as possíveis variáveis de confusão.Não houve diferenças significativas em relação a presença de incapacidades em AVDs e AIVDs e o genótipo da apoE mas a presença do alelo ε4 foi associado a uma menor frequência de comprometimento na mobilidade, tanto quando comparado ao grupo ε3ε3 (OR=0,71; IC95%=0,50-1,00), quando comparado aos idosos sem a presença do alelo ε4 (OR=0,69; IC95%=0,49-0,97). A presença do alelo ε4 também foi associada ao envelhecimento bem sucedido, aumentando a chance de um envelhecimento livre de incapacidades em cerca de 40% (OR=1,41; IC95%=1,02-1,94).Em Bambuí a presença do alelo ε4 esteve relacionada a um melhor desempenho funcional em idosos em relação às tarefas de mobilidade, ressaltando a importância de estudos sobre a associação desse genótipo com a funcionalidade de idosos em diferentes populações.

Polimorfismo da apolipoproteína E e sua associação com incapacidade funcional em idosos: Projeto Bambuí / Apolipoprotein E and its association with functional disability in the elderly: the Bambuí Project

Vários estudos tem demonstrado o papel da genética no envelhecimento mas ainda não se sabe como os genes influenciam esse processo, sendo possível o envolvimento de vários genes, cada um deles com apenas um modesto efeito. Entre os genes potencialmente relacionados ao envelhecimento mais estudados, destaca-se o gene da apolipoproteína E. Além de participar do transporte de lipídeos, essa apolipoproteína tem papel importante na aterosclerose, no reparo e manutenção de células do sistema nervoso central e na inflamação. Inúmeros estudos tem associado o alelo ε4 da apoE a doenças comuns em idosos como a doença arterial coronariana, o acidente vascular encefálico e a doença de Alzheimer. Mais recentemente, o gene da apolipoproteína E também tem sido considerado um gene da vulnerabilidade já que portadores de ε4 apresentam um pior prognóstico em várias outras condições clínicas como traumatismo craniano, doença arterial periférica e diabetes. Idosos mais vulneráveis tendem a acumular mais incapacidades com o envelhecimento e, se o gene da apolipoproteína E for realmente um gene ligado a vulnerabilidade, é possível imaginar que existam variações genótipo-dependentes no desempenho funcional dos idosos. Para avaliar a associação do genótipo da apolipoproteína E com incapacidade funcional e com um fenótipo de “envelhecimento bem sucedido” 1408 idosos incluídos na linha de base do Projeto Bambuí foram submetidos a genotipagem da apolipoproteína E e constituíram a amostra desse estudo...

Os participantes responderam a um questionário para avaliação da funcionalidade e foram classificados de acordo com a presença ou ausência de incapacidades em atividades relacionadas à AVDs, AIVDs e mobilidade. Um subgrupo de idosos que não apresentavam nenhuma dificuldade nas tarefas avaliadas foram considerados idosos com “envelhecimento bem sucedido”. A associação do genótipo da apolipoproteína E e os fenótipos descritos foi avaliada pela regressão logística múltipla, considerando as possíveis variáveis de confusão.Não houve diferenças significativas em relação a presença de incapacidades em AVDs e AIVDs e o genótipo da apoE mas a presença do alelo ε4 foi associado a uma menor frequência de comprometimento na mobilidade, tanto quando comparado ao grupo ε3ε3 (OR=0,71; IC95%=0,50-1,00), quando comparado aos idosos sem a presença do alelo ε4 (OR=0,69; IC95%=0,49-0,97). A presença do alelo ε4 também foi associada ao envelhecimento bem sucedido, aumentando a chance de um envelhecimento livre de incapacidades em cerca de 40% (OR=1,41; IC95%=1,02-1,94).Em Bambuí a presença do alelo ε4 esteve relacionada a um melhor desempenho funcional em idosos em relação às tarefas de mobilidade, ressaltando a importância de estudos sobre a associação desse genótipo com a funcionalidade de idosos em diferentes populações...

Variation in ovarian follicle density during human fetal development.

PURPOSE: To obtain a precise estimate of ovarian follicle density and variation in the number of follicles at several gestational ages during human fetal development. METHODS: Twelve necropsied ovaries from 9 fetuses (gestational age: 24 to 36 weeks) and 3 neonates (who died within the first hours of life) were studied. Ovaries were fixed with 4 % formaldehyde and embedded in paraffin. Serial, 7 mm thick sections of the ovaries were cut and evaluated at every 50 cuts. Follicles were counted in 10 regions (each measuring 625 µm(2)) of the ovarian cortex and the number of follicles per mm³ was calculated. RESULTS: The number of follicles per 0.25 mm² ranged from 10.9 (± 4.8) in a neonate to 34.7 (± 10.6) also in a neonate. Among fetuses, follicle density was lowest at 36 weeks of gestation (11.1 ± 6.2) and highest at 26 weeks (32 ± 8.9). The total number of follicles ranged from 500,000 at the age of 22 weeks to > 1,000,000 at the age of 39 weeks. CONCLUSION: Our results show a peak in the number of follicles during intrauterine life at approximately 26 weeks, followed by a rapid reduction in this number before birth, providing a step forward towards the understanding of primordial follicular assembly in humans and, ultimately, the identification of the determinants of reproductive capacity.

Avaliação da densidade folicular em ovários de fetos humanos / Follicular density evaluation in ovaries of human fetuses

OBJETIVO: avaliar a variação da população de folículos ovarianos ao longo do desenvolvimento fetal e acrescentar dados aos escassos, incompletos e, algumas vezes, divergentes dados descritos na literatura. MÉTODOS: doze ovários de fetos necropsiados foram estudados, sendo nove de fetos e três de neonatos. As idades dos fetos foram determinadas pela cronologia e por ultra-sonografia, enquanto os neonatos nascidos na 39ª semana de gravidez faleceram nas primeiras horas de vida. As peças foram fixadas com formaldeído e incluídas em parafina. Foram realizados cortes seriados com espessura de 7 mm e a cada 50 cortes, o material foi corado com HE e analisado com microscópio com aumento de 400 vezes. Foram contados os folículos em dez diferentes regiões do córtex ovariano, cada região com uma área de 625 mm². O número total de folículos em 1 mm³ foi calculado usando-se a fórmula: Nt=(No x St x t)/do, onde Nt é o número de folículos, No é a média de folículos observados em 1 mm², St é o total de cortes em 1 mm³ do ovário, t é a espessura do corte e do é o diâmetro médio do núcleo. RESULTADOS: a idade dos fetos variou de 24 a 39 semanas. O número de folículos por 0,25 mm² variou de 10,9 ± 4,8 em um neonato até 34,7 ± 10,6 também em um neonato. Entre os fetos, tivemos o menor valor com 36 semanas (11,1 ± 6,2) e o maior valor com 28 semanas (25,3 ± 9,6). O número de cortes observados por ovário variou de seis a 13, correspondendo à contagem de folículos em áreas que variaram de 15 a 32,5 mm². O total de folículos estimado variou de 500.000, na idade de 22 semanas, a mais de 1.000.000, na idade de 39 semanas. CONCLUSÕES: nossos resultados demonstram as diferentes densidades de folículos ovarianos durante o período gestacional, contribuindo para o escasso conhecimento existente na literatura até o momento.

PURPOSE: to determine the variation of the number of ovarian follicles during fetal life. METHODS: twelve ovaries donated for research were included in our study, nine from fetuses and three from newborn babies who died in the first hour after being delivered with 39 weeks of pregnancy. Fetal age was confirmed both by the last menstrual period of the woman and by ultrasonography. Ovaries were fixed in formaldehyde, included in paraffin and serially sliced at 7 mm. At every 50 cuts, the obtained material was haematoxilin-eosin stained and evaluated with an optical microscope (400 X). The follicles were counted in ten different regions of the ovarian cortex, each region with an area of 625 mm². The presence of a nucleus was considered the parameter for counting. Follicular density, per 1 mm³ was calculated using the formula Nt=(No x St x t)/do, where Nt is the number of follicles; No is the mean number of follicles in 1 mm²; St is the total number of slices in 1 mm³; t is the slice thickness and do is the nuclei mean diameter. RESULTS: the gestational age of fetuses ranged from 24 to 39 weeks. The number of follicles per 0.25 mm² ranged from 10.9 ± 4.8 in a newborn to 34.7 ± 10.6 in another newborn. Among the fetuses, the least value was obtained in a 36 week-old fetus (11.1 ± 6.2) and the highest in a 28 week-old fetus (25.3 ± 9.6). The total number of slices per ovary ranged from six to 13, corresponding to follicles counted in areas from 15 to 32.5 mm². The total number of follicles ranged from 500,000 at the age of 22 weeks to > 1,000,000 at the age of 39 weeks. CONCLUSIONS: our results demonstrate different (increasing) densities of ovarian follicles along the gestational period, providing more knowledge about this still not well-known subject.

Dinâmica folicular dos ovários humanos / Follicular development in human ovaries

Apesar de todo conhecimento adquirido a respeito da fisiologia ovariana, existem ainda questões que precisam ser esclarecidas. Sabemos que um número máximo de folículos ovarianos é atingido durante a vida intra-uterina e que a partir de então ocorre queda inexorável desse número até que o ovário entre em exaustão. Não compreendemos, entretanto, como o ovário controla suas reservas. A razão para isso está na dificuldade de se realizar estudos quantitativos para estimar a queda na população folicular ao longo da vida reprodutiva. Muitos autores fizeram tentativas heroicas nesse sentido, contando folículos em ovários de diferentes idades, mas, até o momento, não existe método ideal para se realizar essa contagem, e erros estão presentes em todos os estudos realizados. A partir da análise dos poucos estudos realizados, alguns autores concluíram que a taxa de depleção folicular não é constante como se acreditava, e que uma queda acentuada ocorre na última década de vida reprodutiva. Maior número de estudos mais detalhados é necessário para aumentar o conhecimento a respeito da dinâmica folicular e dos fatores que regulam o recrutamento dos folículos.

Although our knowledge concerning ovarian physiology has increased in the last 20 years, many questions are still answered. It is well established that the maximumnumber of ovarian follicles is reached during intra-uterine life and after birth in starts to decrease until menopause, when they reach complete exhaustion. It is not known, however, how the ovaries control their follicular reserve, being very difficult to perform quantitative studies in human ovaries. Several authors have tried to count ovarian follicles among different populations of ovaries from patients at different ages. Many differences were found o these studies. The initial results have demonstrated that the rate of follicular depletion is not constant and that an important decrease is found only in the last decade of the reproductive life. Therefore, more studies are needed to improve our knowledge on follicular development and recruitment.