Made available in DSpace on 2016-06-02T20:18:23Z (GMT). No. of bitstreams: 1 6236.pdf: 2944020 bytes, checksum: dcbf2b2eaca77c3425524a77887f4d6b (MD5) Previous issue date: 2014-06-06 / Universidade Federal de Minas Gerais / The aging process affects many systems of the human body, including: autonomic nervous system, which can be assessed by heart rate variability (HRV); cellular structures, such as telomere length; and mechanisms of regulation of the inflammatory process, which can be evaluated by inflammatory markers such as high-sensitivity C-reactive protein (hsCRP). The combined analysis of these variables enables the study of the aging process in a multidimensional way. Additionally, the effects of hormone replacement therapy (HRT) on HRV are contradictory. In this way, we conducted the study I, which aimed to investigate the effects of HRT on HRV in healthy postmenopausal women. Two groups were evaluated: Group 1 (G1): 20 women who did not use HRT (60 ± 5.89 years) and group 2 (G2): 20 women undergoing HRT (59 ± 5.70 years). The electrocardiogram was recorded in supine position for 10 min. Spectral analysis included low and high frequency in absolute (LF and HF) and normalized (LFnu and HFnu) units. LF/HF ratio was also calculated. Symbolic analysis (0V%, 1V%, 2LV% e 2UV%), Shannon and conditional entropy were calculated. LF, LFnu and LF/HF ratio were higher, whereas HFnu was lower in G2 than in G1. Correlations between complexity indices and HFnu were significant and positive only in G1. We conclude that women undergoing HRT had higher cardiac sympathetic modulation and reduced cardiac vagal modulation compared to women not using HRT. Moreover, the expected positive relationship between cardiac vagal modulation and HRV complexity was found only in the group not undergoing HRT, indicating that vagal modulation in women under therapy drop below a minimum value necessary to the association to become apparent, suggesting an unfavorable cardiac autonomic modulation in spite of HRT. Considering the findings of the study I, we chose to adopt the use of the therapy as an exclusion criterion for the study II. Thus, the study II aimed to examine the aging effect on heart rate variability in supine and standing, on serum hsCRP and leukocyte telomere length, as well as to verify the age at which the changes caused by aging process are accentuated. One hundred and ten volunteers were divided into five groups according to age: G21-30 years, G31-40 years, G41-50 years, G51-60 years, and G61-70 years. Venous blood samples were collected for measurements of serum hsCRP and telomere length. ECG signals were recorded in rest supine and standing (15 min in each posture). HRV was assessed by spectral analysis in low and high frequencies in absolute (LF e HF) and normalized (LFnu e HFnu) units; symbolic analysis (0V%, 1V%, 2LV% e 2UV%); Shannon entropy; and complexity index (CI) and normalized CI (NCI) from conditional entropy. The main results were: 1) HF and 2UV% reduction (vagal modulation) in G51-60, and 0V% increase (sympathetic modulation) and NCI reduction (complexity) in G61-70, in supine; 2) less efficient response to postural change from supine to standing with advancing age; 3) hsCRP increase in G51-60; 4) telomere shortening in G61-70; 5) in supine, HRV indices showed stronger relationship with the principal component of most relevance from the multivariate principal component analysis, compared to hsCRP and telomere length. Considering that HRV indices in supine had a stronger association with the aging process, we can conclude that the decrease in cardiac vagal modulation may have influenced the increase in serum hsCRP (although normal values), in G51-60, since this effect is described by the cholinergic anti-inflammatory pathway. Decreased cardiac vagal modulation and increased hsCRP may have contributed to the telomere shortening identified in the following decade (G61-70). In this way, we must consider the importance of preventive actions prior to the onset of aging effects, particularly in the 41-50 age range, in an attempt to attenuate the natural effects of senescence. / O envelhecimento exerce influência sobre vários sistemas do corpo humano, dentre eles: sistema nervoso autonômico, que pode ser avaliado pela variabilidade da frequência cardíaca (VFC); estruturas celulares, como o comprimento de telômeros; e mecanismos reguladores de processos inflamatórios, que podem ser avaliados por marcadores inflamatórios, como a proteína C-reativa ultra sensível (PCRus). A análise conjunta dessas variáveis permitiria o estudo do processo de envelhecimento de forma multidimensional. Adicionalmente, são controversos os efeitos da terapia de reposição hormonal (TRH) sobre a VFC. Assim, foi realizado o estudo I, o qual teve por objetivo investigar os efeitos da TRH na VFC em mulheres pós-menopáusicas saudáveis. Foram avaliados dois grupos: grupo 1 (G1): 20 mulheres que não faziam uso de TRH (60 ± 5,89 anos) e grupo 2 (G2): 20 mulheres submetidas à TRH (59 ± 5,70 anos). O eletrocardiograma foi registrado na posição supina por 10 min. A análise espectral incluiu a baixa e a alta frequência em unidades absolutas (BF e AF) e normalizadas (BFun e AFun). A relação BF/AF também foi calculada. A análise simbólica (0V%, 1V%, 2LV% e 2UV%), e entropias de Shannon e condicional também foram calculadas. BF, BFun e a razão BF/AF foram maiores, enquanto AFun foi menor no G2 do que no G1. As correlações entre índices de complexidade e AFun foram significativos e positivos apenas no G1. Concluímos que mulheres submetidas à TRH apresentaram maior modulação cardíaca simpática e menor modulação cardíaca vagal em comparação às que não faziam a terapia. Além disso, a relação positiva esperada entre modulação cardíaca vagal e a complexidade da VFC foi encontrada apenas no grupo não submetido à TRH, indicando que a modulação vagal em mulheres sob a terapia não atinge um valor mínimo necessário para a associação se tornar aparente, sugerindo uma modulação autonômica cardíaca desfavorável, apesar da TRH. A partir dos achados do estudo I, optou-se por adotar, como critério de exclusão para o estudo II, o uso da terapia. Assim, o estudo II teve por objetivo analisar o efeito do envelhecimento sobre a VFC nas posições supina e ortostática, os níveis séricos da PCRus e o comprimento de telômeros leucocitários, além de verificar em qual faixa etária se acentuam as alterações provocadas pelo processo de envelhecimento. Foram avaliados 110 voluntários, divididos em cinco grupos, de acordo com a idade: G21-30 anos, G31-40 anos, G41-50 anos, G51-60 anos e G61-70 anos. Amostras de sangue venoso foram coletadas para medidas de PCRus e comprimento de telômeros. Os sinais eletrocardiográficos foram registrados em repouso nas posições supina e ortostática (15 min em cada postura). A VFC foi avaliada por índices de baixa e alta frequências em unidades absolutas (BF e AF) e normalizadas (BFun e AFun) da análise espectral; índices 0V%, 1V%, 2LV% e 2UV% da análise simbólica; entropia de Shannon; e índice de complexidade (IC) e IC normalizado (ICN) da entropia condicional. Os principais resultados foram: 1) redução de AF e 2UV% (modulação vagal) em G51-60, além de aumento de 0V% (modulação simpática) e diminuição de ICN (complexidade) em G61-70 na posição supina; 2) resposta menos eficiente à manobra de mudança postural de supino para ortostatismo com o avanço da idade; 3) aumento da PCRus em G51-60; 4) encurtamento do comprimento de telômeros em G61-70; 5) na posição supina, os índices da VFC apresentaram relação mais alta com o componente principal de maior relevância, proveniente da análise multivariada por componentes principais, em comparação à PCRus e ao comprimento de telômeros. Considerando-se que os índices da VFC na posição supina apresentaram uma associação mais forte com o envelhecimento, podemos concluir que a diminuição da modulação cardíaca vagal possa ter contribuído para o aumento dos níveis séricos de PCRus (apesar dos valores estarem dentro de faixa de normalidade), na faixa etária de 51 a 60 anos, uma vez que este efeito é descrito pela via anti-inflamatória colinérgica. A diminuição da modulação cardíaca vagal e o aumento da PCRus podem ter contribuído para o encurtamento de telômeros, identificado na década seguinte, de 61 a 70 anos. Dessa maneira, torna-se importante a proposição de ações preventivas em faixas etárias anteriores ao início das alterações provocadas pelo envelhecimento, especialmente na década de 41 a 50 anos, na tentativa de atenuar os efeitos naturais da senescência.

A perimenopausa é a fase da vida reprodutiva feminina caracterizada diversas alterações, inclusive cognitivas devido ao hipoestrogenismo. Através de estudo duplo-cego randomizado com 16 mulheres na perimenopausa deprimidas que receberam estradiol e 16 que receberam placebo analisou-se as alterações cognitivas da atenção, memória e linguagem; o efeito da reposição hormonal com estradiol e a correlação entre os sintomas depressivos e menopausais com as alterações destas funções. Os resultados mostraram: melhora do controle inibitório, memória imediata e tardia (verbal e visual) e da capacidade de nomeação nos dois grupos; melhora dos sintomas depressivos e menopausais para o grupo que recebeu reposição hormonal: e não correlação entre a melhora destes sintomas e a melhora das funções cognitivas / Perimenopause is the female reproductive life period characterized by several changes including cognitive impairments related to hypoestrogenism. In a randomized double-blind study 16 depressive perimenopaused women took estradiol, while another group of 16 depressive perimenopaused women took placebo. Cognitive alterations associated to attention, memory and language, and estradiol hormone replacement therapy effects were evaluated. In addition, correlations among symptoms of depression and menopause, and cognitive alterations were also analyzed. The results had shown, in both groups, an improvement in inhibitory mental control, in immediate and delayed (verbal and visual) memory, and in naming capacity. In the group that received hormone replacement therapy our findings revealed a weakening of depression and menopause symptoms, which had shown no correlation with cognitive functions

Contexte: La maladie de Fabry (MF) se caractérise par l'accumulation de sphingolipides dans de multiples organes dont l'oreillette gauche (OG). La littérature existante ne permet pas d'établir si les fonctions réservoir, conduit et pompe de l'OG étudiées par échocardiographie de suivi des marqueurs acoustiques (speckle-tracking echocardiography, STE) sont affectées dans la MF et si la thérapie de remplacement enzymatique (TRE) permet d'améliorer la fonction de l'OG. Méthodes: Dans cette étude de cohorte rétrospective, la déformation, le taux de déformation et les volumes phasiques de l'OG ont été étudiés chez 50 patients atteints de la MF et comparés à 50 contrôles sains. Résultats: Les trois fonctions phasiques de l'OG étaient altérées. La déformation positive maximale (fonction réservoir) était de 38,9 ± 14,9 % vs. 46,5 ± 10,9 % (p=0,004) et la déformation télédiastolique (fonction pompe) était de 12,6 ± 5,9 % vs. 15,6 ± 5,3 % (p=0,010). Chez 15 patients ayant débuté la TRE pendant l'étude, la majorité des paramètres de fonction de l'OG se sont améliorés après un suivi d'un an (déformation positive maximale de 32,0 ± 13,5 % à 38,0 ± 13,5 %; p=0,006) alors qu'il y a eu une tendance vers une détérioration des paramètres chez 15 patients n'ayant jamais reçu de traitement (déformation positive maximale de 47,3 ± 10,8 % à 41,3 ± 9,3 %; p=0,058). Neuf patients atteints de la MF (21%) ont développé une fibrillation auriculaire ou un accident vasculaire cérébral pendant un suivi de quatre ans. La déformation positive maximale et la déformation protodiastolique étaient plus fortement associés aux événements cliniques que les paramètres cliniques et les paramètres échocardiographiques standards. Conclusions: Les fonctions réservoir, conduit et pompe de l'OG par STE étaient affectées dans la MF. La TRE a permis d'améliorer la fonction de l'OG. Les paramètres de déformation de l'OG étaient associés à la survenue de fibrillation auriculaire et d'accidents vasculaires cérébraux. / Background: Fabry disease (FD) is characterized by the accumulation of sphingolipids in multiple organs including the left atrium (LA). It is uncertain if the LA reservoir, conduit and contractile functions evaluated by speckle-tracking echocardiography are affected in Fabry cardiomyopathy and whether enzyme replacement therapy can improve LA function. Methods: In this retrospective cohort study, LA strain, strain rates and phasic LA volumes were studied in 50 FD patients and compared to 50 healthy controls. Results: All three LA phasic functions were altered. The peak positive strain (reservoir function) was 38.9 ± 14.9 % vs. 46.5 ± 10.9 % (p=0.004) and the late diastolic strain (contractile function) was 12.6 ± 5.9 % vs. 15.6 ± 5.3 % (p=0.010). In 15 patients who started enzyme replacement therapy during the study, most of the LA parameters improved at one-year follow-up (peak positive strain from 32.0 ± 13.5 % to 38.0 ± 13.5 %; p=0.006) whereas there was a trend towards deterioration in 15 patients who never received treatment (peak positive strain from 47.3 ± 10.8 % to 41.3 ± 9.3 %; p=0.058). Nine FD patients (21%) experienced new-onset atrial fibrillation or stroke during four-year follow-up. By univariate analysis, peak positive strain and early diastolic strain demonstrated significant associations with clinical events, surpassing conventional echocardiographic parameters and clinical characteristics. Conclusions: Left atrial reservoir, conduit and contractile functions by speckle-tracking echocardiography were all affected in FD. Enzyme replacement therapy improved LA function. Left atrial strain parameters were associated with atrial fibrillation and stroke.

Vision impairment and blindness are in industrialized countries primarily caused by the degeneration of the retina, the light sensing tissue inside the eye. The degeneration, occurring in diseases like age-related macular degeneration (AMD) or retinitis pigmentosa (RP), can be caused by environmental factors as well as genetic defects and thus shows diverse pathologies. In all conditions, the light detecting photoreceptors (rods and/or cones) are dying caused by either direct photoreceptor damage or as a secondary effect following degeneration of supporting cells. Although promising treatment approaches are currently under investigation, up to date it is not possible to cure these diseases. Amongst these therapeutic strategies, pre-clinical studies evaluating the replacement of degenerated cells by transplantation of new photoreceptors demonstrated promising results. First studies conducted the specific enrichment and transplantation of primary photoreceptors derived from postnatal mice and their sufficient integration and differentiation into mature photoreceptors in wild-type as well as degenerated mouse retinae. Recent experiments additionally proved the recovery of some dim-light vision after transplantation in mice lacking night sight. The in vitro differentiation of whole eye cups containing photoreceptors, out of human or mouse ES or iPS cells, peaked in the transplantation of ES-derived photoreceptors into wild-type as well as degenerated mice and the integration and maturation of these cells. These observations are encouraging, but prior to a save implementation of this strategy into a clinical routine, several further hurdles need to be challenged. Collection of photoreceptors out of whole retinal tissues prior to transplantation was shown to be an important step to reach high integration rates. Additionally, transplantation of photoreceptors derived from stem cells comprises the risk of tumor formation after transplantation and thus also requires depletion of inadvertent cells. Therefore, we established the enrichment of photoreceptors using the cell surface marker dependent method magnetic-activated cell sorting (MACS). For identification of suitable target-specific surface markers, we characterized young transplantable mouse photoreceptors using microarray analysis and screened their transcriptome. Amongst others, ecto-5´nucleotidase (Nt5e, termed CD73) was identified being a rod photoreceptor specific cell surface protein. Thus, we enriched young photoreceptors with CD73-dependent MACS with sufficient purity and transplanted these cells into the subretinal space of wild-type mice. In contrast to unsorted retinal cells, enriched photoreceptors integrated in significantly higher number into the host retina, proving that MACS is a suitable alternative for specific photoreceptor enrichment. Testing other proteins, identified as photoreceptor specific, for MACS suitability and the translation of this approach to photoreceptors, derived from mouse as well as human iPS or ES cells, should be the focus of consecutive investigations. The integration of grafted cells into the retina is a complex process dependent on a variety of influencing factors. Transplantation experiments in aging wild-type mice and a rod-depleted mouse model, containing a retina composed of cone and cone-like photoreceptors, indicated that the activation of Müller glia cells facilitates integration of transplanted photoreceptors. Besides that, reduced outer limiting membrane (OLM) integrity, increased subretinal graft distribution or reduced retinal cell density are further suggested as potential cell engraftment enhancers. These factors might open up important possibilities of host retina manipulation to increase cell integration rates. Although retinal transplantation experiments were in addition to mice also performed using pigs or rats as hosts, the transplantation of enriched single photoreceptors, following the protocols successfully established in mice, has not been performed in other species. Nevertheless, transferring this technique is important and would allow better predictions for future application in human patients. Therefore, we transferred our protocol, using CD73 based MACS, to the rat and successfully enriched rat photoreceptors with sufficient purity. We subsequently transplanted these cells into the subretinal space of rats as well as mice and observed limited integration capacity of grafted cells. Only few transplanted rat photoreceptors were localized in the rat retina, lacking proper photoreceptor morphology. Especially regarding a perspective clinical application in humans, these data are remarkable. They imply the question, whether low integration in rat represents a general problem and might thus also be relevant for treatment in humans, or whether the rat retina forms just an exception. Thus, further detailed analysis of the cellular and molecular mechanisms underlying the integration process of transplanted photoreceptors represent an essential prerequisite for the development of a safe and efficient therapy, aiming to treat retinal degenerative diseases characterized by photoreceptor loss. / Degenerationserkrankungen der Netzhaut (Retina) sind in Industrieländern die Hauptursache für verminderte Sehfähigkeit und Blindheit. Sowohl Umweltfaktoren als auch vererbte Mutationen können Defekte wie altersbedingte Makuladegeneration (AMD) oder Retinitis pigmentosa (RP) auslösen und führen zu einem sehr variablen Krankheitsbild. Eine Gemeinsamkeit aller Formen ist das Absterben der lichtdetektierenden Fotorezeptoren (Stäbchen und/oder Zapfen). Dieses kann entweder durch direkte Schädigung, oder als Sekundäreffekt nach Degeneration der unterstützenden Zellen erfolgen. Obwohl im Moment vielversprechende Behandlungsansätze untersucht werden, ist es zurzeit nicht möglich, retinale Degenerationserkrankungen dieser Art zu heilen. Ein erfolgversprechender Ansatz könnte jedoch der Ersatz der degenerierten Zellen durch transplantierte Fotorezeptoren sein. Erste Studien demonstrierten die spezifische Anreicherung von primären Fotorezeptoren aus der Netzhaut neugeborener Mäuse und deren subretinale Transplantation in Wildtyp-Mäuse und Mausmodelle mit retinaler Degeneration. Die transplantierten Zellen integrierten in die Empfängernetzhaut und entwickelten sich in ausgereifte Fotorezeptoren und konnten unter anderem bei nachtblinden Mäusen die Sehfähigkeit bei Dunkelheit verbessern. Die Differenzierung von humanen oder murinen ES- und iPS-Zellen in vitro in vollständige Retinae und die Transplantation daraus gewonnener Fotorezeptoren in Mäuse, bilden vorläufig den Höhepunkt dieser Entwicklung. Obwohl die Fortschritte der jüngsten Vergangenheit beeindruckend sind, sollten vor der sicheren und effektiven Anwendung einer retinalen Zellersatztherapie als therapeutische Maßnahme beim Menschen noch einige wissenschaftliche Fragestellungen beantwortet werden. Studien zeigen, dass Zellpopulationen, die direkt aus der Spendernetzhaut entnommen und transplantiert wurden, auf Grund ihrer Heterogenität in geringeren Zahlen in die Empfängerretina einwandern als angereicherte Fotorezeptoren. Zusätzlich besteht bei unsortierten Zellen, die aus Stammzellpopulationen gewonnen wurden, das Risiko einer Tumorbildung. Daher haben wir die magnetisch-aktivierte Zellsortierung (MACS) zur Anreicherung junger Fotorezeptoren etabliert. Die dabei benötigten, für Fotorezeptoren spezifischen, Oberflächenproteine wurden mit Hilfe von Microarray-Analysen des Transkriptoms junger Stäbchen von Mäusen identifiziert. Dabei wurde unter anderem die 5\'-Nukleotidase (Nt5e, CD73) entdeckt, die uns die erfolgreiche Anreicherung junger Mausfotorezeptoren mit Hilfe von CD73-vermitteltem MACS erlaubte. Die Transplantation dieser angereicherten Zellpopulation in die Netzhaut von Empfängertieren resultierte in einer signifikant erhöhten Integrationsrate im Vergleich zu nicht-angereicherten retinalen Zellen. Die Überprüfung der Nutzbarkeit weiterer identifizierter Oberflächenproteine zur Zellanreicherung bzw. die Übertragung der etablierten Protokolle zur Zellsortierung und Transplantation auf Fotorezeptoren aus ES- und iPS-Zellkulturen, sollten im Fokus nachfolgender Experimente stehen. Die Integration transplantierter Zellen in die Empfängernetzhaut ist ein komplexer Prozess und von unterschiedlichen Einflussfaktoren abhängig. Durch Transplantationsexperimente in alternden Wildtyp-Mäusen und einem Mausmodell, dessen Fotorezeptorschicht keine Stäbchen und stattdessen nur Zapfen und zapfenähnlichen Fotorezeptoren aufweist, konnte gezeigt werden, dass vor allem die Aktivierung von Müllerzellen die Integrationsrate der Fotorezeptoren erhöht. Neben dieser sogenannten Gliose werden weitere Faktoren, wie die reduzierte Stabilität der äußeren Grenzmembran, die flächenmäßig größere Verteilung der transplantierten Zellen im subretinalen Raum oder die reduzierte Dichte der Zellen in der äußeren Körnerschicht, als potentielle integrationsfördernde Komponenten in Betracht gezogen. Diese bilden interessante Schwerpunkte für weitere Forschungen, um eine ausreichende Zellintegration durch Manipulation der Empfängernetzhaut, auch in der klinischen Anwendung, zu erreichen. Obwohl Transplantationsexperimente zusätzlich zur Maus auch in anderen Empfängerspezies, wie Ratten und Schweinen, durchgeführt wurden, liegen bis jetzt keine Studien vor, die die in der Maus erfolgreich etablierten Protokolle der Zellanreicherung und Transplantation von Fotorezeptor-Suspensionen in diesen Spezies reproduzierte. Der Transfer dieser Technik und eine Generalisierung der Anwendbarkeit eines Fotorezeptorersatzes durch Transplantation in verschiedenen Säugetierarten geben jedoch wichtige Hinweise für eine mögliche Translation dieser Technologie für klinische Anwendungen. Deshalb haben wir unser bereits an der Maus getestetes Protokoll auf die Ratte übertragen und erfolgreich Fotorezeptoren der Ratte mit Hilfe von CD73-vermitteltem MACS angereichert. Nach deren Transplantation in die Netzhaut von Ratten und Mäusen zeigten die Rattenfotorezeptoren aber eine stark verminderte Integrationsfähigkeit und das Fehlen einer reifen Fotorezeptormorphologie. Speziell in Hinsicht auf eine zukünftige klinische Anwendung sind diese Ergebnisse relevant, da sie die Frage aufwerfen, ob die mangelnde Integration in der Ratte ein generelles Problem darstellt und daher auch beim Menschen zu erwarten ist, oder ob sie nur eine Ausnahme im Rattenmodell bildet. Aus diesem Grund bildet die weitere Erforschung der zellulären und molekularen Mechanismen der Integration transplantierter Fotorezeptoren eine wichtige Grundlage für die Entwicklung einer sicheren und effizienten Therapie mit dem Ziel, degenerative Netzhauterkrankungen zu heilen.

Neurological disorders affect more than 14% of the population worldwide and together with traumatic brain and spinal cord injuries represent major health, public and economic burden of the society. Incidence of inherited and idiopathic neurodegenerative disorders and acute CNS injuries is growing globally while neuroscience society is being challenged by numerous unanswered questions. Therefore, research of the CNS disorders is essential. Since animal models of the CNS diseases and injuries represent the key step in the conversion of the basic research to the clinics, we focused our work on generation of new animal models and on their use in pre-clinical research. We generated and characterized transgenic minipig model of Huntington's disease (HD) which represents the only successful establishment of a transgenic model of HD in minipig which should be valuable for testing of long term safety of HD therapeutics. Next, we crossed the well characterized R6/2 mouse HD model with the gad mouse model which lacks the expression of UCHL1 which led to results that support the theory of "protective" role of mutant huntingtin aggregates and suggest that UCHL1 function(s) may be affected in HD disturbing certain branches of Ubiquitin Proteasome System. Traumatic spinal cord injury and Amyotrophic Lateral...

Ziel dieser vorliegenden, vergleichenden Literaturarbeit ist es, den heutigen Wissensstand in Bezug auf den Kohlenhydratstoffwechsel einer Frau darzustellen. Hierbei werden die physiologischen Veränderungen des Metabolismus zu verschiedenen Zeitpunkten im Leben einer Frau, begonnen mit der Kindheit und Pubertät, über Menstruation und Schwangerschaft bis hin zur Menopause, betrachtet und es werden die Ursachen und möglichen Mechanismen aufgezeigt, die zu Abweichungen der Insulinresistenz und der Insulinsekretion und damit möglicherweise zu einer Glukoseintoleranz bzw. einem Typ-2 Diabetes mellitus führen können. Der Kohlenhydratstoffwechsel wird nicht nur bezüglich der physiologischen, sondern auch in bezug auf die iatrogen verursachten Veränderungen, d.h. unter oraler hormonaler Kontrazeption, unter Hormonersatztherapie im Klimakterium, sowie hinsichtlich bestimmter Pathologien, wie dem zur Infertilität führenden polyzystischem Ovarsyndrom oder dem Gestationsdiabetes, untersucht. Ergebnis: Es scheint eine starke Verknüpfung zwischen dem weiblichen Reproduktionssystem und dem Kohlenhydratstoffwechsel zu geben, deren Interaktion von den unterschiedlichsten Faktoren beeinflusst wird. Der Frauenarzt sollte sich bei der Verschreibung hormoneller Kontrazeptiva, der Hormonersatztherapie und im Besonderen bei der Therapie des polyzystischen Ovarsyndroms sowie bei der Untersuchung seiner Patientinnen bewusst sein, dass verschiedene Lebensphasen, wie Pubertät, Schwangerschaft und Klimakterium und die damit verknüpften Veränderungen des Reproduktionssystems und der Sexualhormone auch deutliche metabolische Veränderungen nach sich ziehen können. Besonders eine erhöhte Insulinresistenz, die mit einer gesteigerten Insulinsekretion einhergeht, muss bedacht werden. Nicht nur das Syndrom X, eine Zusammenfassung von metabolischen Abnormitäten (Dyslipidämie, Insulinresistenz, Adipositas, Hypertonie), die mit einem deutlich erhöhten Risiko kardiovaskulärer Krankheiten und besonders der Atherosklerose einhergehen, sondern die daraus folgende steigende Prävalenz von Typ-2 Diabetes mellitus und das stark vermehrte Auftreten von Adipositas verlangen nach einer fachübergreifenden Zusammenarbeit zwischen Frauenärzten und Internisten. / The aim of this comparative review is to reveal the current standard of knowledge concerning carbohydrate metabolism in women. The study demonstrates the physiological changes in metabolism at various stages in a female life, from childhood and puberty, through menstruation and pregnancy and ending with the menopause, whilst also evaluating different causes and possible mechanisms that lead to aberrance in insulin resistance and insulin secretion and thereby potentially to glucose intolerance and/or type 2 Diabetes mellitus. In addition to presenting physiological alterations in glucose metabolism, this work also analyses changes generated by iatrogenic treatment such as oral contraceptives and hormone replacement therapy, as well as those caused by different pathologies like polycystic ovary syndrome or gestational diabetes. The results indicate a strong correlation between the female reproduction system and the carbohydrate metabolism. The interaction is influenced by the many very different factors. Before prescribing oral contraceptives, hormone replacement therapy in climacteric (especially during the treatment of infertility in PCOS), or examining patients, the gynaecologist needs to be aware of the fact that different phases in life along with sex steroids and connected changes in the reproductive system, might lead to severe metabolic diversifications. Special attention should be paid to an increased insulin resistance, associated with an augmentation in insulin secretion. Not only the metabolic syndrome, the simultaneous appearance of metabolic abnormalities (dyslipidaemia, insulin resistance, adiposity, hypertonia), which holds a higher risk of cardiovascular diseases, especially arteriosclerosis, but also the consequential increased prevalence of type 2 diabetes mellitus and the highly increased prevalence of adiposity, demand for a multidisciplinary collaboration between gynaecologists and internists.