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Daytime fatigue, which at the neurophysiological level is due to vigilance decrements, is a frequent complaint in postmenopausal women. In a three-arm, 2-month, parallel group-design study, vigilance-promoting effects of a novel continuous combination (=Climodien 2/3) of estradiol valerate (EV; 2 mg) and dienogest (DNG; 3 mg) were compared with the effects of both EV alone and placebo in 55 insomniac, postmenopausal syndrome patients. Low-resolution brain electromagnetic tomography (LORETA) was undertaken to identify the cerebral target regions of hormone replacement therapy. An omnibus significance test revealed Climodien to increase activity in 882 of 2,394 voxels in the alpha-2 band, followed by 733, 706, and 664 voxels in the beta-2, beta-1, and beta-3 bands, and 509 voxels in the delta band, whereas 2 mg EV alone did not produce a significant suprathreshold activity. Current density increased predominantly in the right hemisphere, which had already been described in the literature as the center of the vigilance system. In the fast alpha range, which plays a major role in the context of vigilance, increased activity was found in the right prefrontal, temporal, and superior parietal cortices, i.e., those brain areas of the right-sided fronto-parietal neuronal network that are responsible for sustained attention. A further activity increase was seen in the anterior cingulate gyrus associated with attentional control and conflict monitoring. The right temporal lobe showed increased current density in all frequency bands. Electroencephalographic tomography (LORETA) identified the right-hemispheric vigilance system as the target region of Climodien.

OBJECTIVE: To define the effects of therapeutic exercise on bone density and back complaints. METHODS: A randomised controlled trial with parallel groups was conducted in an outpatient clinic, Medical School, University of Vienna. Ninety two sedentary post-menopausal women with back problems were randomly allocated to either exercise (groups 1 and 2) or control (group 3, no exercise, n = 31); the exercise group was retrospectively subdivided into compliant (group 1, n = 27) and not fully compliant patients (group 2, n = 34). Regular, initially supervised therapeutic exercise aimed at restoring biomechanical function was performed for four years. Bone density in the forearm was measured by single photon absorptiometry at entry and after four years; subjective back complaints were documented. RESULTS: A significant decrease in bone density was observed in groups 2 and 3; no change was noted in group 1; back complaints decreased in group 1 only. CONCLUSIONS: Sedentary postmenopausal women may benefit from regular long term therapeutic exercise in terms of subjective back complaints and slowed loss of bone mass.

Objective: Although epidemiological and clinical studies suggest that hormone replacement therapy (HRT) may protect against cognitive disorders and neurodegenerative diseases, the relation between estrogen and cognition in postmenopausal women remains controversial. Methods: In a double-blind placebo-controlled, parallel group design study the effects of HRT with the estrogen–progestogen combination Presomen 1.25 compositum ® (1.25 mg equine conjugated estrogens administered for 21 days plus the progestogen 5 mg medrogeston given for 11 days) on event-related potentials (ERPs) in postmenopausal patients with age-related cognitive decline (DSM-IV code 780.9, ICD-10 code R 41.8) were investigated. After a pre-drug comparison with age-matched normal postmenopausal controls, 48 psychotropic drug-free patients aged 60 ± 6 years were randomized to receive either placebo or verum for 4 months. ERPs were recorded before as well as on the 91–92 days of the study, which thus fell into the estrogen phase of the treatment during the fourth cycle. Results: At baseline, patients showed a lengthening of P300 latency and an attenuation of P300 amplitudes as compared with normal controls. After HRT with Presomen, a significant shortening of P300 latency as compared with placebo was observed. Conclusions: The baseline P300 differences suggest that in the patient group the aging process was advanced, while after HRT with Presomen a significant improvement and normalization of information processing as indexed by P300 was observed. © 2004 Elsevier Ireland Ltd. All rights reserved.

Hormone replacement therapy is well known for its beneficial effects on climacteric symptoms and is also used for the prevention of osteoporosis. In a prospective open label study we evaluated the efficacy and safety of hormone replacement therapy with 17 beta estradiol dydrogesterone (Femoston, 17 beta estradiol/continuously and dydrogesterone/sequentially). We observed 704 women who were treated with 17 beta estradiol-dydrogesterone over three months. 448 of the women previously had not used hormone replacement therapy, 224 women had been treated with a different hormone replacement therapy before they were entered into the study; for 20 women this information was not available. The physicians were asked to assess the severity of climacteric symptoms at baseline and after three months of hormone replacement therapy. In addition, the following parameters were evaluated before and at the end of the study: blood pressure, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, blood glucose, alkaline phosphatase and gamma glutamyltransferase. Twelve women did not tolerate 17 beta estradiol-dydrogesterone and therefore dropped out of the study. Climacteric symptoms clearly improved after treatment with 17 beta estradiol-dydrogesterone. During our open label prospective study, a significant decrease in blood pressure and serum levels of total cholesterol, LDL cholesterol and the LDL/HDL ratio were observed, whereas serum levels of HDL cholesterol increased significantly. Surprisingly, triglyceride levels also decreased significantly. Serum levels of alkaline phosphatase decreased significantly in women who had received a different hormone replacement therapy before they took 17 beta estradiol-dydrogesterone. We conclude that hormone replacement therapy with 17 beta estradiol-dydrogesterone is highly effective and well tolerated. Hormone replacement therapy with 17 beta estradiol-dydrogesterone appears to have a positive effect on blood pressure and the serum lipid profile. We therefore hypothesise that prolonged treatment with 17 beta estradiol-dydrogesterone may reduce morbidity and mortality secondary to cardiovascular diseases.

In a double-blind, placebo-controlled study, the antidepressant and vigilance-promoting properties of transdermal oestrogen in post-menopausal depression were investigated utilizing hormonal, syndromal and EEG mapping evaluations. Sixty-nine menopausal women, aged 45-60 years without previous hormonal replacement therapy, diagnosed as major depression without psychotic or suicidal symptoms (DSM-III-R criteria), were randomly assigned to a 3-month treatment with transdermal oestradiol [Estraderm TTS (ETTS) 50 micrograms, applied twice weekly] or placebo. No other psychoactive medication was allowed. After removal of protocol violators, 32 patients were evaluable in each group, which did not differ in age, height or weight. As five patients discontinued prematurely in both groups and in one placebo patient a post-drug EEG could not be obtained, 27 patients remained in the ETTS and 26 in the placebo group for efficacy analysis. While in the placebo group, oestradiol (E2) and follicle stimulating hormone (FSH) remained unchanged, E2 increased and FSH decreased significantly in the ETTS group. Syndromal evaluation showed a significant improvement in the Kupperman Index (KI) as well as Hamilton Depression Rating Scale (HAMD) in both groups, with no inter-group difference. However, EEG mapping demonstrated significant inter-drug differences in brain function, mostly over the left temporal region. While ETTS patients showed an increase of alpha and alpha-adjacent theta activity and a decrease of beta activity, as well as an acceleration of the delta/theta centroid and a slowing of the alpha, beta and total power centroid, no changes occurred in the placebo-treated patients. These neurophysiological findings suggest improvement of vigilance by oestrogen, previously referred to as "mental tonic" effect. There were no changes, however, in the frontal alpha asymmetry index, reflecting left frontal hypo- and right frontal hyperactivation. Thus, this neurophysiological variable represents a state-independent marker for depression. The tolerability of ETTS was very good.

This study aimed at a possible classification of climacteric arthroses of the hand. 132 females suffering from arthralgias of the wrist and finger joints who had consulted our outpatient department originally because of climacteric complaints, were examined while asking them to complete a questionnaire with clinical criteria for classifying arthroses of the hand. The requisite number of criteria required for classification as ¿arthrosis of the hand¿ were attained in all three groups of females (premenopausal and postmenopausal women without operation, as well as hysterectomised and/or ovarectomised women¿, although the ex-ray showed no signs of degenerative arthritis. The subjective complaints voiced by the patients are opposed to the x-ray finding, so that it is not permissible to classify climacteric arthralgias of the wrist and finger joints as ¿arthritis¿.

Dual energy X-ray absorptiometry of bone density in the lumbar vertebral column was performed in 32 young women (mean age 24.6 [19-34] years) with hypergonadotropic hypogonadal amenorrhoea. There was a significantly lower bone density (0.74 +/- 0.27 g/cm2) than in a control group of 27 women of similar age (1.17 +/- 0.081 g/cm2; P less than 0.001). Subsequently 21 of the 32 women received cyclical hormone substitution therapy for 24 months (day 1-30: 0.625 mg conjugated oestrogens; additionally, on days 20-30: 5 mg medrogestone; followed by a seven-day pause). After 6 months bone density, compared with that of the 11 untreated women, had increased significantly (P less than 0.001). It is therefore recommended that young hypoestrogenemic women should receive early and continuous hormone substitution treatment.

In the last few years several studies have been published raising the question whether hormonal factors are co-responsible for the female prevalence of certain joint diseases. From our own clinical experience we know that more than half of the women seen at our outpatients department because of disorders of the post menopausal syndrome complain about arthralgies (especially of the PIP-joints). We have introduced the term "arthropathia climacterica" for it. Moreover the positive results of two clinical studies on which effects hormone replacement therapy had on these complaints indicate a relation between estrogens and joints.

Bone density was evaluated in 182 healthy climacteric women. Women were recruted from a general prevention program. The results show deviation from 58.2 to 218.6--mean value 128.28, SD 30.91 mg/ccm K2HPO4. 28% of bone density values are under the fracture risk level citated in literature. No statistical relationship was found between bone density and anamnestic data--only the age at hysterectomy shows statistical correlation. The follow up after one year shows no predictive value of anamnestic data to the lost of bone mineral density.

The menopausal syndrome consists of a variety of psychic and physical signs of different intensity. At our outpatient department for problems in menopause and prevention of osteoporosis (1. Dept. of Gynaecol. and Obstetrics, Vienna) 1287 women who were consulting this department for the first time because of prevailing complaints or prophylactic reasons, were registered during the years 1988 and 1989. In the course of this work we paid particular attention to the symptom "eye complaint" as a sign of the beginning of the menopausal period. 98 out of 430 patients with eye complaints were examined ophthalmologically. Referring to our patient population we tried to analyse epidemiologically the frequency and the degree of severity of menopausal eye complaints as well as the therapeutical response to a hormone substitution therapy. To what extent an endocrinological explanation can be found and which facts lead us assume such a statement, we have tried to demonstrate in the discussion.

Anti-thrombin III is the major inhibitor of intravasal coagulation. Patients with AT III activity less than 80% are at risk for thromboembolic complications. We have examined 224 women with climacteric symptoms (flush, urogenital complaints, osteoporosis) who received estrogen replacement therapy for one year. 105 women (group I) received conjugated estrogens at 0.626 mg. 52 women (group II) were given conjugated estrogens at 1.25 mg. 67 women (group III) were treated with transdermal estrogen replacement (TTS 50 mcg). AT III activity was measured before and one year after replacement therapy. No significant alterations of AT III activity were noted between the different modalities of application. This supports epidemiologic findings suggesting that no increase in the incidence of thromboembolic complications was seen in women who received estrogen replacement therapy over several years.

Among the variety of symptoms of the postmenopausal syndrome joint pain seems to be an important problem for the patient as well as for her doctor. Because of the excellent response of the hormone substitution therapy it is asked if the synovial membrane is a target organ for oestradiol. Biopsies from the knee joint of ten women (not having any hormone therapy)--excised during knee joint surgery--were examined. Only in two cases oestrogenreceptors were found. Accordingly the synovial membrane cannot be seen as a direct target organ for oestradiol and so other mechanisms must play a role in the pathogenesis of postmenopausal joint pain.

In 21 patients, suffering from amenorrhoeic hypergonadotropic ovarian insufficiency (age 27 +/- 3 years [FSH: 43 +/- 10, LH: 40 +/- 8]), the bone density was measured by single-photon densitometry (SPA), before starting a hormonal replacement therapy with oestrogen/progesterone. Every 5 months, the trend in bone density change was measured in all cases. The bone density before hormonal treatment was lower in the WHO III-group (1.36 +/- 0.21 g/cm; 1.09 +/- 0.26 g/cm2) than in the age-matched group (1.57 +/- 0.21 g/cm; 1.28 +/- 0.31 g/cm2). Bone density increased after hormonal therapy (p less than 0.05). These results point to the necessity of hormonal replacement therapy in cases of WHO III.

Although glucocorticoids have been universally implemented to stimulate fetal lung maturity, their effectiveness and side effects are still widely contested. In search of alternative drugs a double-blind study was conducted between June 1981 and June 1984 comparing betamethasone, a conventional corticoid, and ambroxol, a bromhexine metabolite for efficacy and tolerance in prenatal prevention of the respiratory distress syndrome (RDS) in premature infants and full-term neonates. The therapeutic efficacies of betamethasone and ambroxol for this indication proved to be comparable. Since the possible risks of corticoid therapy in abnormal pregnancies are repeatedly discussed in the literature and in daily clinical practice. 137 patients with EPH gestosis, placental insufficiency, diabetes mellitus, and premature rupture of the membranes were selected from the original group of 308 patients. Only minor side effects (e.g. nausea) were present in a few of the 137 cases undergoing treatment with the 2 test substances. No side effects were observed in the neonates. The incidence of fetal RDS was comparable in both groups (2.9% with ambroxol, 2.2% with betamethasone). Transient and mild RDS cases were slightly more frequent in the ambroxol group than in the betamethasone group. To date, contraindications to ambroxol treatment in abnormal pregnancies are unknown and since generally the rate of potential side effects is considered to be lower in comparison with corticoid treatment, the use of ambroxol especially in abnormal pregnancies corresponding indication can be recommended.

Die Prophylaxe der postmenopausalen Osteoporose war der erste grose Erfolg der Hormonersatztherapie. Obwohl der Ernahrung, dem Ausschlus von Risikofaktoren und auch der Bewegung grose Bedeutung in der Vorbeugung der Osteoporose zukommt, ist bei gefahrdeten Patientinnen der Ausgleich des Ostrogenmangels die wichtigste Intervention, um einer Knochenerweichung vorzubeugen. Vor allem auch bei jungen Frauen kann ein Ostrogenmangel zu einer Reduktion der Knochenmasse fuhren. Im klinischen Management hat sich die Knochendichtemessung – bei all ihrer technischen Problematik – doch am besten zur Abschatzung eines Osteoporoserisikos bewahrt, was fur die gynakologische Praxis von hoher Wichtigkeit ist, da die Kenntnisse der Knochendichte dem Arzt eine Moglichkeit gibt, die Beratung zur Hormonersatztherapie – auch was die Dauer betrifft – effizienter vorzunehmen. Die Reaktion des Knochens auf Sexualsteroide ist zytokinmediiert, wodurch sich die Osteoporose im Rahmen einer neuen Kategorisierung in eine Gruppe von Erkrankungen stellt, die durch die Interaktion von Sexualsteroiden und parakrinen Faktoren bedingt sind. Dazu gehoren neben der Osteoporose auch Erkrankungen, in die Geschlechtshormone –ahnlich wie bei der Osteoporose – ebenfalls via Zytokinen eingreifen. Obwohl die postmenopausale Osteoporose am besten durch eine Hormonersatztherapie verhindert werden kann, ist trotzdem die Kooperation mit anderen medizinischen Disziplinen angezeigt, vor allem um zu verhindern, das seltene, nicht sexualhormonabhangige Formen der Osteoporose ubersehen werden. In kaum einem anderen Bereich konnte das interdisziplinare Engagement der Gynakologie sich im letzten Jahrzehnt so deutlich beweisen wie bei der Prophylaxe der Osteoporose. Es waren vor allem die grundlegenden Arbeiten von Albright nach dem 2. Weltkrieg und spater dann die Moglichkeit der praktikablen Knochendichtemessung mittels Photonendensitometrie, die diesen Bereich der gynakologischen Endokrinologie zu einem festen Bestandteil der Gynakologie und zu einem wesentlichen Fundament fur die weitere differenzierte diagnostische, therapeutische und prophylaktische Betrachtung des Klimakteriums bzw. der Postmenopause hat werden lassen. Auch wissen wir nun, das Sexualhormonmangelsituationen in allen Lebensabschnitten – also nicht nur in der Postmenopause – relativ rasch zu einem Knochendichteverlust fuhren konnen und, das nicht nur die Ostrogene, sondern auch Androgene und Gestagene fur eine verminderte Knochendichte verantwortlich sein konnen. Die Knochendichtemessung hat bei aller ihrer methodischen Relativitat sicherlich bedeutsam zur Thematisierung der Osteoporoseprophylaxe beigetragen. Wie bei allen neu eingefuhrten Methoden ist es anfangs oft zu einer Uberbewertung der Aussage gekommen – von Seiten des Arztes, aber auch der betroffenen Frauen. Es ist gerade jetzt ein Gebot der Stunde, hier eine Relativierung der Knochendichtemessung vorzunehmen. Aufgrund der grosen Abhangigkeit der Knochendichte von den Sexualhormonen kommt dem Gynakologen in der Prophylaxe der Osteoporose eine besondere Bedeutung zu. Bei bereits bestehender Osteoporose, oder wenn ein fortschreitender Knochendichteverlust durch eine Hormonsubstitution nicht hinangehalten werden kann, sollte immer ein osteologisch ausgerichteter Internist zur genaueren Abklarung (z. B. sekundare Osteoporose!) bzw. zu einer Osteoporosetherapie, welche meist additiv zur Hormonersatztherapie erfolgt, beigezogen werden.

In this experimental study, the feelings of climacterium in two groups of menopausal women were compared (a test group with climacteric complaints vs a control group without complaints). 70 patients were given a questionnaire: EWL by Janke and Debus, FPI and Giessen-test. The evaluation of the socio-economic data exhibited the fact, that patients in the group with complaints took more drugs than the other group and were more inclined to weight gain. Gynecological data showed significant differences in the beginning and the experience of menstruation. Psychological tests of the group with complaints showed a lack of self-assurance and increased anxiety. These women had also a tendency toward psychosomatic disorders and were less assertive in their social contacts. The discriminant analysis of menopausal and personality variables classified the women equally into the group with complaints compared to the control group.

Hot flushes are not caused by a hypergonadotrophinemia. Peaks of gonadotrophin in the serum do not coincide with the cutaneously measured hot flushes. There is an occurrence of hot flushes in hypophysectomized women as well. GnRH and other neurotransmitters (beta-endorphin?) effect the thermoregulation. -During the climacteric period changes of neurotransmitters, a decrease of catecholestrogens, a decrease of alpha-2-adrenoceptor activity and the ceasing of the ovarian steroid production lead to changes of the endogenous opiate activity and thus to disturbances of the thermoregulation resulting in the occurrence of hot flushes. Low beta-endorphin levels in the peripheral plasma, which increase again after a treatment with estrogens, are found during the climacteric period. On the other hand women with severe hot flushes as an expression of a stress event show enormously increased beta-endorphin values, which normalize again after a hormone substitution therapy, effected by still unknown neuroendocrinological feedback mechanisms.

Three couples were selected for this preliminary sperm injection study with their consent, since in all three cases the zona free hamster egg penetration test was negative and in one couple previous attempts of in vitro fertilization were unsuccessful. Of 22 eggs, recovered from three patients, 9 from each patient 3 were injected with sperm, while the others were inseminated by the standard IVF-protocol. Before manipulating human eggs extended experiments were performed with animals eggs, so decreasing the rate of damage to under 10%. Additionally we optimized the method by using an individual adapted equipment. Manipulation was performed by penetration of the zona pellucida with a 5 to 7 mu thick injection pipet into the perivitilline space so damaging of the egg cytoplasm was avoided. This special technique for sperm injection was not used till now in this indication. From the nine eggs used in this experiment one egg developed a pronucleus and one egg developed to a four-cell stage. We could not achieve a pregnancy.

We examined the ocular fundus in 100 unselected pregnant women with EPH-gestosis of different severity. In 52 women there were no retinal changes, in 32 women we saw I hypertensive changes according to the classification of Keith-Wagener, in 10 cases II, and in 6 cases III or IV retinal changes. There was no direct relationship between the severity of EPH-gestosis and I and II retinal changes; however, severe retinal changes (III IV) were associated with moderate or severe EPH-gestosis. We found a significant relationship between the degree of hypertensive retinal changes and fetal mortality. In the group of gravidae with severe retinal changes 4 out of 6 infants died. The examination of the ocular fundus permits the direct evaluation of fundal changes and the early recognition of fetal jeopardy.

In the literature you can find several therapeutic possibilities in the treatment of carcinoma by additive ozone therapy. We investigated the consequences of ozone therapy for the immunological status, lysozyme and vitamin A. 21 women with progressive cervical cancer (Stage III, IV) got besides the conventional irradiation therapy also an additive ozone therapy. After irradiation and ozone therapy a small decrease in IgG, IgA and IgM can be seen. A statistical significance could not be evaluated. There was no difference to the control group in lysozyme and vitamin A.

The diagnosis of tubal pregnancy has undergone important changes in recent years: the introduction of new non-invasive methods like the LH/hCG test1 or ultrasound equipment with high-dissolution capacity, and invasive methods like laparoscopy. Thus diagnosis of ectopic pregnancy has been made possible at a very early stage, sometimes even before the onset of clinical symptoms.

The aim of the study was to investigate the influence of long-term administration of oral contraceptives on bone density in climacteric women. Two hundred (n = 200) climacteric women were allocated to three study groups (I, II, III). The first (n = 30) one had been using oral contraceptives for more than 10 years, the second (n = 50) one for between 2 and 9 years, while the third (n = 120) one had never used oral contraceptives. Bone mineral content (BMC) of the left forearm was measured by single photon absorptiometry. The results demonstrate that osteoporosis occurs later and is less frequent during the peri-menopause (p less than 0.05) in women who have used oral contraceptives on a long-term basis (greater than 10 yr). Our findings confirm that there is an important correlation between longterm use of oral contraceptives and bone density.

Im Rahmen des Zyklusmonitorings ist fur die Sterilitatspatientin die Beurteilung des Endometriums neben den ublichen Hormonbestimmungen von groser Bedeutung. In der normalen Follikelphase andert sich das Endometrium durch die ansteigende Hormonproduktion aus dem Ovar. Sechs verschiedene Endome-triumtypen konnten in der ersten Zyklusphase beschrieben werden. Diese Endo-metriumveranderungen korrelieren mit dem Plasma-β-Ostradiol und dem Progesteron [1]. Man versuchte anhand von Messungen der Endometriumdicke in der Lutealphase im Ultraschall bei Frauen des In-vitro-Fertilisierungsprogrammes eine bevorstehende Graviditat fruhzeitig zu erkennen [4]. Endometriumverande-rungen im Ultraschall wurden auch beim Endometriumkarzinom beobachtet [2]. Ziel unserer Studie war es, das Endometrium in der lutealen Phase bei Frauen mit normaler Lutealfunktion und bei lutealinsuffizienten Frauen zu beschreiben. Als weitere Frage stellt sich, ob das Endometrium bei Frauen in der Postmenopause sonographisch beurteilbar ist, ob sich das Endometrium unter einer hormonellen Stimulation im Klimakterium verandert und ob es Kriterien gibt, ein beginnendes Endometriumkarzinom sonographisch fruhzeitig zu erkennen.

In Biostack III B, flown in the Apollo-Soyuz Test Project, AgCl detectors were used to study ionizing effects of HZE particles on spores of Bacillus subtilis or eggs of Artemia salina. The tracks of these particles inside the detectors are used to extrapolate the path of the particle near the biological objects which are fixed at the detector surface. The closest distance to the geometric centre of the object, the so-called impact parameter, is determined with a mean accuracy of 0.3 micrometers for 1 micrometers spores. From knowledge of the lateral distribution of the energy transferred by primary and secondary ionization effects of the particle, the energy deposit and its localization at the objects can be determined. We describe some technical aspects of a video-electronic scanning system, Quantimet 720, which has been adjusted to the particular requirements of these experiments. The main improvements achieved are increased precision of coordinate measurements, objective focusing of the microscopic image combined with measurements of the density profile of particle tracks, and finally speeding up of the measurements by automatic data transfer.