Identifying target regions for vigilance improvement under hormone replacement therapy in postmenopausal syndrome patients by means of electroencephalographic tomography (LORETA).

RATIONALE: Daytime fatigue, which at the neurophysiological level is due to vigilance decrements, is a frequent complaint in postmenopausal women. OBJECTIVES: 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. METHODS: Low-resolution brain electromagnetic tomography (LORETA) was undertaken to identify the cerebral target regions of hormone replacement therapy. RESULTS: 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. CONCLUSIONS: Electroencephalographic tomography (LORETA) identified the right-hemispheric vigilance system as the target region of Climodien.

Hormone profiles, body mass index and aging male symptoms: results of the Androx Vienna Municipality study.

Aging in the male is accompanied by steroid hormonal decline, and men may develop symptoms associated with hypogonadism. Increased awareness of 'andropause' in recent years has led to greater demand for hormonal assessments, resulting in a rising burden for health economics. We conducted a cross-sectional study to define men at risk for hypogonadism, in whom further hormonal investigation should be performed. We examined 664 blue-collar workers aged 40-60 years at their workplace and determined hormonal status and body mass index (BMI). Men with an abnormal urogenital status and those on medication that might affect endocrine status were excluded from the study. All participants completed the validated Aging Male Symptom (AMS) questionnaire and obtained scores for psychological symptoms, somatovegetative symptoms, and sexual symptoms. Multiple logistic regression analyses revealed a significantly increased risk (represented by the odds ratio) of psychological symptoms for men with low levels of testosterone and/or bioavailable testosterone (BAT). Increased BMI as well as low testosterone levels and/or low BAT levels raised the risk of somatovegetative symptoms. Each decrease of BAT by 1 ng/ml caused an approximately 1.8-fold increase of the risk (odds ratio = 1.832, p = 0.005). Additional independent risk factors were increased age and low luteinizing hormone (LH) level. Men aged 55 years with BMI > 28 kg/m2 and with somatovegetative symptoms and moderate or severe psychological symptoms had a 7.2-fold increase in the risk of a BAT level < 1.5 ng/ml compared to men without these risk factors (p < 0.001). Sensitivity and specificity were 75% and 71%, respectively. The AMS score combined with age and BMI provides an easy and convenient method to identify men with probable androgen deficiency who require hormonal assessment.

Double-blind, placebo-controlled psychometric studies on the effects of a combined estrogen-progestin regimen versus estrogen alone on performance, mood and personality of menopausal syndrome patients.

The influence of a combined estrogen-progestin regimen (Climodien) on noopsyche, thymopsyche, personality and psychophysiological measures of menopausal syndrome patients was investigated in a double-blind, placebo-controlled, comparative, randomized 3-arm trial phase (Climodien 2/3 = estradiol valerate (CAS 979-32-8) 2 mg + the progestin dienogest (CAS 65928-58-7) 3 mg = regimen A, estradiol valerate 2 mg = regimen EV, and placebo = regimen P) followed by an open-label phase in which all patients received Climodien 2/2 (estradiol valerate 2 mg + dienogest 2 mg) = regimen A*. 49 women (16, 17, 16 valid patients per arm) aged between 46 and 67 years (mean 58, 58, 56 years, respectively) with the diagnoses of insomnia (G 47.0) related to postmenopausal syndrome (N 95.1) were included in the analysis of the double-blind phase. Both the double-blind and the open-label phase lasted 2 months. Noopsychic investigations demonstrated an improvement in associative verbal memory after 2 months of regimen A, which was significant as compared with both baseline and placebo. Regarding visual memory, regimen A* induced an improvement, which was significantly different from the decline in correct reproductions in the Benton Test observed under estradiol. Errors in the Benton Test decreased significantly after regimen A* as compared with regimen EV. These findings suggest that hormone replacement therapy with estradiol, and even more in combination with dienogest, improves verbal and visual memory, which is in line with the improvement in information processing speed and capacity objectified by event-related potentials (ERP). Thymopsychic investigations demonstrated a significant improvement in somatic complaints and trait anxiety after both regimen A and regimen EV as compared with baseline. State anxiety decreased significantly under regimen A* as compared with EV. The Freiburger Personality Inventory showed an improvement in aggressivity after regimen A* as compared with the preceding placebo as well as an improvement in striving after dominancy after both regimen A and regimen EV as compared with pre-treatment, but also after regimen A* as compared with regimen EV. Extraversion increased after 2 months of regimen A as compared to regimen P. Psychophysiological findings including pupillary and skin conductance variables were not significant.

[Hormone replacement therapy with 17 beta-estradiol dydrogesterone: results of a 3-month open-label study]. / Hormonersatztherapie mit 17 beta-Ostradiol-Dydrogesteron: Ergebnisse einer dreimonatigen Anwendungsbeobachtung.

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.

Reduction of intraocular pressure in a glaucoma patient undergoing hormone replacement therapy.

OBJECTIVES: To show the reducing effect of estrogens and progestins on the elevated intraocular pressure (IOP) in the case of a 56-year-old woman showing typical climacteric complaints, who was admitted to the menopause outpatient unit. She also suffered from a primary open-angle glaucoma treated with betaophtiole eye drops with intraocular pressures of 16-20 mmHg under this local therapy. METHODS: IOP patterns were monitored by means of standardised daily pressure profiles four times a day before as well as 4 and 12 weeks after the beginning of hormone replacement therapy (HRT). The local glaucoma therapy remained unchanged. RESULTS: During HRT, IOP levels were reduced from 16-20 mmHg before therapy to 12-15 mmHg at week 4 and to 13-15 mmHg at week 12 after the beginning of HRT. CONCLUSION: The finding of a close chronological relationship between the onset of menopause and the development of a glaucoma is a potentially new indication for HRT.

Treatment of menopausal keratoconjunctivitis sicca with topical oestradiol.

OBJECTIVE: To investigate the effect of 17 beta-oestradiol ophthalmic drops in comparison with a traditional tear substitute in postmenopausal women with keratoconjunctivitis sicca. DESIGN: Randomised prospective trial. SETTING: Menopause clinic. PARTICIPANTS: Eighty-four postmenopausal women suffering from keratoconjunctivitis sicca and necessitating a hormone replacement therapy (HRT) for general climacteric symptoms. METHODS: The women were randomised into two groups and were given 17 beta-oestradiol eye drops (n = 42, group 1) or a tear substitute (n = 42, group 2). Both groups received a systemic HRT. MAIN OUTCOME MEASURES: A Schirmer's test was performed immediately before the beginning of therapy and after four months. In addition, eye symptoms were assessed using a visual analogue scale. RESULTS: A comparison of visual analogue scores at four months in the women who received 17 beta-oestradiol eye drops versus those who received a tear substitute demonstrated a statistically significant difference in all observed ocular symptoms (P < 0.0001). The Schirmer's test revealed a significant difference of results before and after treatment in the oestradiol group (P < 0.0001) while in group 2 no significant difference was found. CONCLUSIONS: Our study demonstrates that topical oestrogen is successful in treating keratoconjunctivitis sicca while it seems that the blood-eye barrier prevents systemic oestrogens from acting on the conjunctivae.

Hormone replacement therapy and intraocular pressure.

OBJECTIVES: To evaluate the effect of hormone replacement therapy (HRT) on intraocular pressure (IOP) in menopausal women. METHODS: The IOP of 25 white menopausal women without an abnormal ophthalmologic history was measured before and during HRT regimen. IOP fluctations were recorded before and 1, 4, and 12 weeks after the beginning of HRT. These measurements were obtained according to a standardized time schedule (08:00, 12:00, 16:00, and 19:00 h). RESULTS: The mean IOP in the left eye decreased from 16.2 +/- 2.4 mmHg before therapy to 14.0 +/- 2.1 mmHg after 12 weeks of therapy (P < 0.001). In the right eye, whose IOP was at 15.3 +/- 2.3 mmHg before therapy there was a decrease to 14.0 +/- 1.9 mmHg after 12 weeks of therapy (P < 0.001). CONCLUSION: Hormone replacement therapy has a positive effect on IOP in menopausal women.

Exercise therapy for osteoporosis: results of a randomised controlled trial.

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.

Hormonal, syndromal and EEG mapping studies in menopausal syndrome patients with and without depression as compared with controls.

UNLABELLED: The aim of the study was to investigate brain function in menopausal depression by EEG mapping, as compared with menopausal syndrome patients without depression and normal controls, and to correlate neurophysiological with clinical and hormonal findings in order to elucidate the pathogenesis of depression in the menopause. METHODS: One hundred and twenty-nine menopausal women, aged 45-60 years, with no previous hormonal replacement therapy were investigated in regard to hormones (estradiol [E2], follicle stimulating hormone [FSH]), clinical symptomatology (Kupperman Index [KI], Hamilton depression score [HAMD]) and brain function (EEG mapping). Based on KI and DSM-III-R research criteria for major depression, 3 groups were available for statistics (after removal of protocol violators): group A had a KI of <15 and no depression (n = 29); group B had a KI of > or = 15 and no depression (n = 29) and group C had a KI of > or = 15 and fulfilled the criteria for major depression (n = 60). RESULTS: EEG maps of depressed patients demonstrated less total power and absolute power in the delta, theta and beta band, more relative delta and less alpha power as well as a slower delta/theta and faster alpha and beta centroid than controls, suggesting a vigilance decrement. Group B did not differ from group A. Correlation maps showed significant relationships between estradiol levels and EEG measures (the lower the E2, the worse the vigilance) and between the EEG measures and the Hamilton depression (HAMD) score (the worse the vigilance, the higher the depression score). There were no correlations between the hormones E2 and FSH and the syndromes KI and HAMD. In the target variable, the asymmetry index, depressed patients showed less alpha power over the right than left frontal lobe, whereas normal controls exhibited the opposite. Group B did not differ from group A. The frontal asymmetry index was significantly correlated with the Hamilton depression score and suggests right frontal hyper- and left frontal hypoactivation in depression. CONCLUSIONS: Although hormonal findings are not directly linked to psychic changes, low estradiol levels do contribute to a decreased vigilance at the neurophysiological level , which is in turn correlated with higher depressive and menopausal symptomatology at the behavioural level. Depression is further correlated to a right frontal hyper- and left frontal hypoactivation.

Double-blind, placebo-controlled, hormonal, syndromal and EEG mapping studies with transdermal oestradiol therapy in menopausal depression.

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.

[Climacteric arthralgia and hand arthrosis]. / Klimakterische Arthralgien und Handarthrose.

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¿.

Hysterectomy increases the symptomatology of postmenopausal syndrome.

The purpose of our investigation was to verify whether or not women who have undergone hysterectomy react differently to the menopause compared with women who have not. The study was performed in a prospective documentation on 203 women, and the assessments of discomforts were provided by the patients themselves using questionnaires. For statistical purposes, the Mann-Whitney test and chi 2 test were used. In both groups of patients--with and without hysterectomy--a determination was made concerning the significance of differences in the degree of intensity of problems: breast tension (p < 0.05), muscle pains (p < 0.05), palpitations (p < 0.05) and dizziness (p < 0.01). Concerning the frequency of climacteric symptoms, a significant difference was noted for urogenital ailments. While only 29.6% of women who had not been operated on complained about discomfort caused by atrophy of the urogenital tract, the number of women with such discomfort who had had a hysterectomy was 42.6% (p < 0.01). In other words, women who underwent hysterectomy suffered more discomfort and showed frequent symptoms of urogenital atrophy.

Forearm bone density and grip strength in women after menopause, with and without estrogen replacement therapy.

Peaking in young adulthood, both bone mass and muscle strength decrease with ageing, but bone loss may accelerate after the menopause and can be delayed by estrogen replacement therapy (ERT). This study was designed to evaluate whether, like bone density, the muscle strength was affected by the onset of menopause and/or ERT. First grip strength (GS) of young female adults (group III; n = 18; age (+/- S.E.M.) 21.8 +/- 0.4 years) was compared to that of postmenopausal women, who were divided into two groups. Group I (n = 22; age 59.6 +/- 1.6 years) was 12.5 +/- 1.7 years after the menopause and received no ERT, and group II (n = 21; age 59.5 +/- 1.1 years) was 8.3 +/- 1.2 years after the menopause and had received ERT for 3.9 +/- 2.3 years at the time of the study. GS of the postmenopausal women was significantly (P < 0.005) lower than that of the young female adults. GS did not differ significantly between both postmenopausal groups. Further analysis revealed a weak negative correlation of years since menopause with forearm bone density (r = -0.37, P < or = 0.023 for group II and III together), but not with GS. It is concluded that the later onset of menopause and estrogen replacement therapy do not seem to have a noticeable influence on muscle strength.

The role of prolactin in the menopause.

Within a study on menopausal discomforts, 2322 women were seen for the first time at the Outpatients Department for Climacteric Disturbances and Prophylaxis of Osteoporosis at our clinic. Amongst routine hormonal examination we measured prolactin levels. We found hyperprolactinemia in 23 women. Furthermore, in 224 women who initially had normal hPRL values, an estrogen-gestagen replacement therapy was administered and within this we found a significant increase of the prolactin levels (P < 0.005). The role of prolactin in the climacteric period as well as the mechanism of the estrogen effect upon prolactin secretion are subjects of discussion.

Hormone replacement therapy: lipid responses to continuous combined oestrogen and progestogen versus oestrogen monotherapy.

Fifty-five postmenopausal women with climacteric complaints were randomly assigned to treatment with either 2 mg oestradiol valerate (E2V) (cyclic regimen: 21 days of treatment followed by a 7-day treatment-free interval), or 2 mg E2V combined with 1 mg cyproterone acetate (E2V+CPA) daily, over a 6-month period. Treatment was by the oral route in both cases. The aim was to compare the influence of these two hormone replacement therapy regimens on lipid metabolism. Blood samples were obtained before and after 1 and 6 months of treatment. Serum was analyzed for total cholesterol (TC), high-density lipoproteins (HDL), apolipoproteins A1 and B and triglycerides. The low-density lipoprotein (LDL) concentrations were derived by calculation. All parameters were evaluated in terms of mean +/- S.D. There was no significant difference in the response of the blood lipids to the two treatments, as assessed by analysis of variance (P greater than 0.05). Serum levels of TC were found to have fallen after month 1 and 6 by 5.3 and 5.6%, respectively, during E2V treatment and by 2.4 and 0.2% during E2V+CPA treatment. Serum HDL levels had increased after months 1 and 6 by 9.7 and 5.2%, respectively, in the E2V group and by 6.9 and 2% in the E2V+CPA group, which was also confirmed by the increase in apolipoprotein A1 levels. There was, however, a borderline increase in LDL and apolipoprotein B in the E2V+CPA group. Serum triglycerides were reduced and serum levels of SHBG increased during treatment in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

[Bone density before and after the hormonal therapy of young women with hypergonadotropic hypogonadal amenorrhea]. / Knochendichte vor und nach Hormontherapie bei jungen Frauen mit hypergonadotroper hypogonader Amenorrhoe.

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.

[A main symptom of the climacteric manifestation complex: arthropathia climacteria]. / Ein Hauptsymptom des klimakterischen Beschwerdenkomplexes: Arthropathia climacteria.

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.

[Menopausal bone density in healthy females of Voralberg. Lack of relation to anamnesis]. / Menopausale Knochendichte bei gesunden Voralbergerinnen. Fehlende Beziehung zur Anamnese.

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.