Efficacy and tolerability of the hormone replacement drug estradiol valerate/levonorgestrel in the treatment of menopausal syndrome in Thai women.

A prospective, open, single-center, uncontrolled phase IV study examined the efficacy and tolerability of a 6-month oral sequential hormone replacement therapy (estradiol valerate and levonorgestrel; Klimonorm in 50 outpatient peri- and postmenopausal Thai women. The clinical effectiveness of the drug was demonstrated by a rapid alleviation of the classical vasomotor menopausal complaints and a favorable effect on lipid metabolism. A rapid reduction in climacteric complaints ranging up to the complete absence of symptoms was achieved during the first 3 months of treatment. The positive effect on lipid metabolism was demonstrated by a clear reduction in total cholesterol and triglycerides as well as a slight reduction in the LDL fraction and a significant increase in the HDL fraction. The therapy resulted in stabilization of the cycle length. Cycles with regular withdrawal bleeding periods lasting 3 to 4 days with mostly mild intensity were restored in most of the women. The thickness of the endometrium measured sonographically did not change significantly. The drug was safe and well tolerated by most of the women. There were no clinically significant changes in body weight, blood pressure, hematological tests, and other laboratory parameters. Compliance was very good with a dropout rate due to undesirable side effects of only 5%.

Clinical findings with the oral contraceptive combination ethinylestradiol/dienogest in Poland.

The efficacy and safety of the low dose monophasic oral contraceptive (OC) combination containing 30 micrograms of ethinylestradiol (EE) and 2.0 mg of dienogest (DNG) (EE/DNG) was evaluated in a prospective, open-label, multicenter, uncontrolled, phase III trial. The trial was carried out in five hospitals in Poland, and included 431 healthy women (aged 18-35 years), over 12 cycles, with a total of 4608 cycles. EE/DNG provided reliable ovulation inhibition. No women became pregnant during the trial. The unadjusted Pearl index was 0. EE/DNG provided good cycle control and reduced the incidence of intermenstrual bleedings, the intensity of menstrual bleeding and frequency of dysmenorrhea. Due to the antiandrogenic properties of the progestogen component DNG, EE/DNG improved androgen-related conditions, such as skin blemishes, hair greasiness and acne vulgaris. Of 50 women with acne, 80% improved after the 6th cycle and 1 was healed. After 12 cycles, 54% were improved and 37% were healed. Breast tenderness and gastric complaints were the most frequent of the common complaints due to treatment with EE/DNG. The frequency of all complaints decreased steadily over time. Only 5.6% of subjects discontinued due to adverse reactions. No thrombophlebitic events were noticed.

Clinical findings with the oral contraceptive combination ethinylestradiol/dienogest in the Czech Republic.

The efficacy and safety of the low dose monophasic oral contraceptive (OC) combination containing 30 micrograms of ethinylestradiol (EE) and 2.0 mg of dienogest (DNG) (EE/DNG) was evaluated in a prospective, open-label, multicenter, uncontrolled, phase III trial. The trial was carried out in six hospitals by 36 investigators in the Czech Republic, and included 557 healthy women (aged 18-35 years), over 12 cycles, with a total of 6051 cycles. EE/DNG provided a reliable ovulation inhibition. The contraceptive efficacy study showed an adjusted Pearl index of 0.198 on the basis of three pregnancies occurring during 6051 cycles. EE/DNG provided good cycle control, reduced the incidence of intermenstrual bleedings, the intensity of menstrual bleeding and frequency of dysmenorrhea. Due to the antiandrogenic properties of the progestogen component DNG, EE/DNG improved androgen-related conditions, such as skin blemishes, hair greasiness and acne vulgaris. From 108 women with acne, 62 (57%) improved after the 6th cycle, and 16 (15%) were healed. Similar changes were found after cycle 12. Breast tenderness and headache were the most frequent of the common complaints due to treatment with EE/DNG. The frequency of all complaints decreased steadily over time. Only 7.7% of subjects discontinued due to adverse reactions. No thrombophlebitic events were noticed.

Effects of the combined hormonal replacement drug estradiol valerate/levonorgestrel on climacteric complaints, endometrium and lipid profile of peri- and postmenopausal women.

The effects of the combined hormone replacement (HRT) drug estradiol valerate/levonorgestrel (Klimonorm) on climacteric complaints, endometrial status and lipid profile was studied in 100 peri- and postmenopausal women aged between 41 and 57 years. The duration of therapy was 6 months. The following parameters were investigated: Kuppermann index, endometrial thickness, duration of bleeding, arterial blood pressure, body weight and serum lipids and lipoproteins (total cholesterol TC, LDL cholesterol, HDL cholesterol, and triglycerides [TG]). A separate analysis was made for 27 patients who had abnormal lipid status before treatment. Total cholesterol above 6.0 mmol/l and/or LDL of more than 3.5 mmol/l was considered abnormal and those patients were labeled as "high risk". The results showed a statistically significant reduction in the severity of climacteric symptoms (Kupperman index). A large decrease in the score was observed during the first 3 months of treatment (from 27.9 at the start to mean values of 9.3, p < 0.001). A further slight decrease of the score to 4.0 (p < 0.001) was seen after 6 months of treatment. Endometrial thickness did not change. At the start of the treatment the mean duration of bleeding was 5.1 +/- 0.3 days and at the end of the 6th month it was 3.8 +/- 0.2 days (p < 0.001) Klimonorm favorably affected the lipid profile. TC decreased significantly during the therapy: by 5.2% (p < 0.05) in all women and 7.1% (p < 0.05) in the high risk group. LDL cholesterol decreased slightly: by 4.3% (p < 0.05) in all women and was more pronounced in the high risk group (7.0%, p < 0.01). HDL cholesterol increased by 12.1% (p < 0.01) in all women and by 14.7% (p < 0.001) in the high risk group. TG were elevated slightly by 9.5% (p < 0.05) in all women and 3.9% (p > 0.05) in the high risk group. LDL/HDL ratio decreased from 2.7 to 2.3 in all women and from 3.0 to 2.4 (p < 0.05) in the high risk group. No significant changes in systolic and diastolic blood pressure were recorded. Body weight did not change significantly during the treatment period.

Changes in psychic and somatic well-being and cognitive capabilities of peri- and postmenopausal women after the use of a hormone replacement drug containing estradiol valerate and levonorgestrel.

A multicenter, prospective, open-label postmarketing surveillance study examined to what extent 2-month oral hormone replacement therapy (estradiol valerate and levonorgestrel; Klimonorm) could produce changes in psychosomatic well-being, self esteem and cognitive capabilities in 78 peri- and postmenopausal women. The women included were 42-58 years of age and had approached the physician due to climacteric symptoms. The following tests were used: Kupperman index, Menopause Rating Scale (MRS II), General Depression Scale (ADS), Zerssen's Symptom List (B-L), Frankfurt Self-Concept Scales (FSAL, FSAP, FSEG, FSSW), Digit Symbol Substitution Test (DSST), d2 Test of Attention and Number Square Test. The results showed a clear improvement in subjective psychosomatic well-being and improvements to a lesser extent in the concentration and cognitive capabilities in women in the third treatment cycle.

Estrogen replacement therapy and Alzheimer's disease.

Estrogen replacement therapy (ERT) is increasingly recommended for postmenopausal women due to its numerous beneficial effects on bone, cardiovascular system, brain function and quality of life. Data from retrospective epidemiological studies have shown that ERT has a potential to reduce the risk for developing Alzheimer's disease (AD) and to delay its progression. In addition, recent clinical studies have reported improvement of cognitive functions in women with AD. Findings from basic science indicated that the possible mechanisms of action by which estrogen may affect AD include interaction with cholinergic neurotransmitter system, cholinergic neurotrophic and neuroprotective effect, improvement of learning and memory, improvement of cerebral blood flow and metabolism, antioxidant and antiinflammatory action, and interference with beta-amyloid protein metabolism and toxicity. Estrogen use in postmenopausal women may offer a new approach for improving cognitive functions in nondemented and demented women, delaying the onset and progression of AD and reducing its occurrence. However, prospective clinical trials are required to establish the efficacy of ERT for prevention and treatment of AD.

[Basic reproductive toxicological studies of the effect of furazolidone on the hypothalamo-hypophyseo-gonadal axis of male rats]. / Reproduktionstoxikologische Grundlagenuntersuchungen zur Wirkung von Furazolidon auf die Achse Hypothalamus--Hypophyse-Gonaden der männlichen Ratte.

The reproductive-toxic effects of furazolidone on testis, epididymis and selected nuclei of the hypothalamus of male wistar rats were investigated. After a dosage of 50 mg/kg b.w. daily over five days no changes of testis and epididymis were detected in relation to controls by means of light microscope. Using morphometric methods a significant increase of the nucleus volume of the measured nuclei of the hypothalamus (Ncl. ventromedialis, Ncl. praeopticus medialis, Ncl. infundibularis) could be shown. After the high dosage of 200 mg/kg b.w. daily for five days testis and epididymis showed marked signs of atrophy and the volume of the investigated nuclei of the hypothalamus was significantly increased. These results suggest that--contrary to the wide spread opinion the testis would react most sensitive to chemical agents--more attention should be directed to the hypothalamus in reproductive-toxicological studies.

[Computer-assisted determination of the pharmacokinetic parameters of Solupront after intrauterine administration in cattle]. / Computergestützte Ermittlung pharmakokinetischer Parameter nach intrauterinem Einsatz von Solupront beim Rind.

The drug "Solupront" a sulfonamide was clinical tested in healthy heifers and cows with endometritis, retentio secundinarum etc. The test-results were evaluated with the computer-program "Phakimo". The pharmacokinetic parameters show that there are similar relationships between the extravasal and the intravasal application of this osmochemotherapeutic. A retard of absorption is shown in dioestrus and in prooestrus. If there are pathological signs in uterus, the rate of absorption of the drug is higher and the excretion via urine is more quickly, too. The effect of the sulfonamide in the drug "Solupront" is impaired after application in the uterus in order of the quick absorption, of distribution and excretion and also in order of dilution by lochia and by interaction with p-aminobenzoic acid.

[The enteral absorption of iron (II) from humic acid-iron complexes in suckling piglets using radiolabeled iron (59Fe)]. / Untersuchungen zur enteralen Resorption von Eisen (II) aus Huminsäure-Eisen-Komplexen beim Saugferkel mit Hilfe radiomarkierten Eisens (59Fe).

Bioavailability of iron (II) bounded as a chelate to macromolecular humic acids was investigated in two different concentrations using retention rates of 59Fe in piglets (age: 24 h). Investigations period was from 3 hrs. to 21 days following application. 21 days after a single oral application of the humic-acid-iron-complexes, 25% of the total Fe was detected in the animal, distributed in the erythrocytes (80%), muscles and bones (8% respectively) and liver (4%). For the first time in veterinary medicine these results enable a combined therapy of enteric and iron-deficiency syndrome by using only one drug. Recommendation for dosing is provided.

[Pharmacologic and toxicologic properties of humic acids and their activity profile for veterinary medicine therapy]. / Pharmakologisch-toxikologische Eigenschaften von Huminsäuren und ihre Wirkungsprofile für eine veterinärmedizinische Therapie.

Humic acids derive from a class of natural substances in humic substances. The chemical properties of certain defined humic acid products enable their application in diseases of the digestive system of mammals when combined with metabolic disorders, especially in rearing age. The simple administration (via feed), their exceptional safety and the absence of side effects (e. g. allergy, resistance) as well as no residue formation in animal derived products allow a broad application of these substances in veterinary medicine, even when regarding ecotoxicological aspects.

[The absorption behavior of chemotherapeutics after intrauterine administration in cattle]. / Untersuchungen zum Resorptionsverhalten von Chemotherapeutika nach intrauteriner Applikation beim Rind.

The uterus of cattle is an organ of excellent absorptive properties, as has been demonstrated by the examples of a sulphonamide and of penicillin. This is true for all cyclic phases. Absorption was somewhat delayed, when animals were in di-oestrus or pro-oestrus. A comparison between rates of absorption by clinically intact and pathomorphologically altered uteri showed absorption of Solupront and Ursopen 40,000 to be much faster in cases of disease. Experimental results as well as knowledge so far obtained on protein binding capacity are likely to support the conclusion that in the pathologically altered uterus bacteriostatic effects of sulphonamides are low due to the high amount of p-aminobenzoic acid which is present as a direct antagonist in pus and cellular detritus.

[The fermentation diagnosis and histologic studies in blood and the liver of surviving rats after 1 and 2 administrations of a median toxic dose of parathion methyl. 1. Results of studies on the activities of the plasma enzymes AlAT, AsAT, AP, and gamma-GT]. / Fermentdiagnostische und histologische Untersuchungen im Blut und an der Leber überlebender Ratten nach 1- und 2maliger Verabfolgung mittlerer tödlicher Dosen von Parathionmethyl. 1. Mitteilung: Ergebnisse der Untersuchungen zur Aktivität der Plasma-enzyme AlAT, AsAT, AP, gamma-GT.

Clearly pronounced changes in plasma enzyme activities were observed 24 hours after one and two applications of parathion methyl (PM). The most strongly pronounced rise was in activity of aspartate-amino transferase and was recorded from both sexes. PM application caused sizeable changes in male rats. Comparison between reactions after one and two applications revealed more intensive changes in males after the 1st application. Somewhat larger differences were recordable in some cases between the 1st and 2nd applications. Closer agreement between reaction intensities after the 1st and 2nd PM applications was recordable from female rats. In either sex in response to one single and repeated application parameters returned to normal within nearly one and the same period of time. No secured relationships between activities prior to and after application of PM could be derived from the assays of gamma-glutamyl transpeptidase (gamma-GT). Both increase and decrease of determined enzyme activities were actually recorded. Activities were highly variable in the control groups. Extreme rises were recordable in some cases from both control and experimental groups. No conclusions so far can be drawn as to "normal values" in rat plasma, possible sex-related differences, and behaviour of enzyme activity in response to one single or repetitive applications. Hence, within common investigations of acute toxicity of alkylphosphates, gamma-GT was found to be not suitable for detection of damage to the liver or other organs.

[The fermentation diagnosis and histologic studies in blood and the liver of surviving rats after 1 and 2 administrations of a median toxic dose of parathion methyl. 2. Tyrosine aminotransferase and pathologico-morphological findings in the liver]. / Fermentdiagnostische und histologische Untersuchungen im Blut und an der Leber überlebender Ratten nach 1- und 2maliger Verabfolgung mittlerer tödlicher Dosen von Parathionmethyl. 2. Mitteilung: Tyrosin-Amino-Transferase und pathologisch-morphologische Befunde der Leber.

Tyrosine-amino transferase, an enzyme induced to the liver via glucocorticoids, caused clearly measurable activity rises in either sex, 24 hours after 1 and 2 applications. Increased levels continued to recordable from males on the 3rd day from application, whereas enzyme activities in females had already returned to normal by that time. Histological examination of liver sections, following 1 and 2 applications of parathion methyl (PM), revealed the tissue pattern of clearly manifest toxic hepatosis with detectable mesenchymal reactions. Histologically detectable damage reached its maximum on the 2nd and 3rd days from application. Sex-related differences were not recordable. Damage in response to the 2nd application was characterised by faster mesenchymal activation and higher frequency of cell necroses. The morphological picture of the liver was rated as having returned to normal, 14 days after 1 and 2 applications of PM. These results should not be interpreted as evidence to the involvement of specific, non-cholinergic mechanisms in the processes of damage observed. The alterations might rather be attributed to unspecific disorders in the energy balance or to the effect of "stress" during intoxication.