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T Rabe

Publications and source records attributed to T Rabe.

At least 73 records · Page 4Linked to original sources

Analysis of hormonal changes during combined buserelin/HMG treatment.

Changes of serum oestradiol, LH and progesterone have been analysed in view of the effect of the GnRH analogue buserelin on the late follicular and early luteal phase of cycles stimulated with combined buserelin/HMG (n = 31) in an IVF-ET/GIFT programme. Patients undergoing cycles with HMG only (n = 57) served as the control group. With the use of the GnRH analogue buserelin, a significantly higher amount of HMG (25 versus 20 ampoules; P less than 0.001) for a significantly longer stimulation period (10 versus 8 days; P less than 0.001) was necessary to achieve the same oestradiol response as seen in HMG cycles. Serum progesterone levels during a three day period before ovulation induction tended to be lower in the combined buserelin/HMG cycles than in cycles with HMG stimulation only. We did not observe any significant difference in the luteal phase progesterone levels of the buserelin/HMG and the HMG group. On the other hand, we found that an inadequate luteal phase in buserelin/HMG cycles could be avoided by HCG administration during the luteal phase. Both the elevation of basal serum LH and a premature LH rise could also be avoided by the use of buserelin.

Adult↗

Normal values for a short-time ACTH intravenous and intramuscular stimulation test in women in the reproductive age.

Normal values in endocrine testing are the most important precondition for the recognition of disorders of the endocrine system. To establish a reference range for adrenocorticotropic hormone (ACTH) stimulation tests, an intravenous and intramuscular ACTH stimulation test was conducted in 29 female volunteers without hyperandrogenism. A total of 25 IU of ACTH were administered intravenously or intramuscularly and blood sampling was performed before, 1 h and 2 h after ACTH injection. The test was performed on days 3-5 of the menstrual cycle. The following steroid hormones were assessed in the serum: 17 alpha-hydroxyprogesterone, 17 alpha-hydroxypregnenolone, dehydroepiandrosterone, testosterone, free testosterone and 5 alpha-dihydrotestosterone. The normal range was defined by the interval between the 5th and 95th percentiles; additionally the 1st, 25th, 50th, 75th and 99th percentiles are reported. A significant increase of serum hormone levels after ACTH administration could be observed for the following hormones: cortisol, 17 alpha-hydroxyprogesterone, 17 alpha-hydroxypregnenolone and dehydroepiandrosterone. There was no rise after ACTH application for testosterone, 5 alpha-dihydrotestosterone and free testosterone. It could be shown for all hormones that there was no significant difference between the serum levels that were reached after intravenous and intramuscular ACTH injection. Neither could we find a significant difference in the relative increase of the serum hormones when stimulation values were related to basal values. Since in most studies with ACTH stimulation tests, only the serum values 1 h after ACTH application are measured, we investigated whether the measurement of steroid hormones 2 h after ACTH application gave further information. We could demonstrate that for most measured serum hormones the majority of the volunteers had the maximal response 2 h after ACTH application, no matter whether ACTH was injected intramuscularly or intravenously. As a conclusion, we recommend the measurement of the respective hormones not only 1 h but also 2 h after ACTH stimulation. Since there is no increase after ACTH stimulation for total testosterone, free testosterone and 5 alpha-dihydrotestosterone, it is sufficient to assess the basal values of these hormones. Excessive adrenal response is reflected by dehydroepiandrosterone, 17 alpha-hydroxyprogesterone, 17 alpha-hydroxypregnenolone and cortisol.

17-alpha-Hydroxypregnenolone↗

[Current approach in the diagnosis and therapy of alopecia in gynecology].

With an increasing frequency patients complaining problems with their hair show up in gynecologic office practices. We observe cases with alopecia androgenetica; both alopecia climacterica and postpartualis, being subgroups of alopecia androgenetica. From symptomatic as well as from pathogenetic point of view two other forms can be subdivided, to be named alopecia diffusa and alopecia areata. At the Department of Obstetrics and Gynecology of the University of Heidelberg an outpatients consulting programme for women with androgenetic symptoms was established some years before. The diagnostic procedures for a possible classification of the alopecia was intensified. The search for underlying internal diseases and/or endocrinopathies will be the first step towards a pathogenetically correct diagnosis, and if there is no plausible explanation reached by that, the investigation will be extended for heavy metal tracing or for the detection of other ecological damaging influences. A local treatment with thymus gland preparations (Thymu-Skin) was examined by following the conditions of a protocol. After treatment with the preparation (Thymu-Skin) 73% of all cases show improvement of the alopecia. The formula seems to be an effective alternative to the hormonal therapy. It is easy to administer and has no side-effects or contraindications. It proved also to be advisable for prophylactic use in combination with chemotherapy.

Administration, Topical↗

[New progestins in oral hormonal contraceptives].

Three new progestins with a high gestagenic potency have been developed as derivatives of the levonorgestrel (in brackets: biological active substance in the human): desogestrel (3-keto-desogestrel), norgestimate (norgestimate), gestodene (gestodene). In combination with low dosages of ethinylestradiol (30-35 micrograms) an excessive steroid overload can be avoided, which is not necessary for contraceptive efficacy and control of the menstrual cycle. As an effect of dose reducing during long-time studies only a mild impact on the lipids and carbohydrates, and blood coagulation could be observed. The clinical side effects are moderate and for most patients acceptable.

Contraceptives, Oral, Hormonal↗

[Background information on contraception behavior of patients undergoing abortion as an indication of the psychosocial origin of unwanted pregnancies].

269 patients were interviewed in a private abortion clinic in Lindenfels, Hessen, West Germany on aspects of contraception and abortion. The results indicated three crucial points, which influence contraceptive behaviour: social barriers, which affect indirectly the access to and the handling of contraceptives; psychic, mainly unconscious barriers, which counteract contraception; an increasing distrust and rejection of modern medical contraception, especially in highly educated women. These barriers are evident in lack of information, differing in the various social groups; partly irrational and exaggerated fear of side effects, and lack of success of factual information. Furthermore, poor co-operation is evident on the part of the husband or partner together with considerable shortcomings in medical counselling.

Abortion, Induced↗

Epidermal growth factor stimulates luteinizing hormone and arachidonic acid release in rat pituitary cells.

Epidermal growth factor (EGF) directly enhanced luteinizing hormone (LH) release from dispersed rat pituitary cells in monolayer cultures as well as in superfusion columns. This 2.3-fold stimulatory effect was dose and time dependent and was also reconfirmed in a superfusion system. Retinal, a protein kinase C inhibitor, counteracted the EGF effect only partially. Further experiments were therefore carried out to investigate alternate EGF mechanisms. Nordihydroguaiaretic acid and chloroquine suppressed the stimulatory effect of EGF in a dose-dependent manner. Moreover, EGF (10(-7) M) stimulated [3H]arachidonate release from pre-labelled rat pituitary cells. This indicates that phospholipase A2 and arachidonic acid may be involved in EGF action on LH release from rat pituicytes.

Animals↗

[Parenteral contraceptive drugs: depot progestins].

Depot progestins as injectables, implantables or vaginal rings are suitable for contraception in those female patients, in which risk factors (e.g. cardiovascular risk) exclude the use of estrogen-progestin mixtures. In this paper the mode of action, indications, contraindications, advantages and disadvantages of the various methods using depot-progestins are discussed. Injectables contain either medroxyprogesterone acetate or norethistronenantate; both steroids are released slowly within a limited time interval (2 to 4 months) out of a depot. The major effect is a change of the cervical mucus. Side-effects are disturbances of the menstrual cycle (e.g. breakthrough bleedings) as well as an amenorrhea after frequent use (up to 50% of all cases). The subdermal implantables (Norplant 2 or 5) release levonorgestrel out of a depot over a time period of at least 5 years. Steroid plasma levels are lower than in those patients using a progestin-only pill. Side-effects of implantables are disturbances of the menstrual cycle (e.g. breakthrough bleeding); in patients who desire to conceive a child or suffer from undesirable side-effects the implantables can be removed at every time. The progestin releasing vaginal rings are in a stage of controlled clinical trials. The advantages depend on ethe easy mode of administration (implantation or removal). Side-effects are also breakthrough bleedings.

Administration, Intravaginal↗

[Risk-benefit analysis of contraception with steroids].

Oral hormonal contraception is a low risk and safe form of contraception for women between 15 and 35 years of age without risk factors in the history (smoking, obesity, diabetes mellitus, hypertension, hypercholesterinemia). Women over 35 years should take the pill only when risk factors have been excluded previously. In general, low dose pills with less than 50 micrograms ethinylestradiol should be used, because they have the lowest impact on the metabolism. There should be an additional indication even after exclusion of risk factors, if women over 40 years take the pill. Besides that it could be shown that using the pill has many positive effects on health, as for example benign mamma tumors more seldomly occur, in most of the cases the dysmenorrhoea improves, anaemia and inflammatory adnex diseases are significantly more seldom, and it could be shown that there is a clearly protective effect concerning the morbidity of endometrium and ovarian cancer.

Contraceptives, Oral, Hormonal↗

Stimulation of gonadotropin release by arachidonic acid and its lipoxygenase metabolites in superfused pituitary cells.

Luteinizing hormone and follicle stimulating hormone secretion was stimulated by 4 min pulses of arachidonic acid (3 X 10(-5) to 10(-4)M) in superfused rat pituitary cells. The effect of its lipoxygenase metabolites, 5-hydroxy-6,8,11,14-eicosatetranoic acid (5-HETE) and 15-hydroxy-5,8,10,14-eicosatetranoic acid (15-HETE) was more potent on hormone release when added in the same dose. Using 3 X 10(-5)M 5-HETE, its releasing activity on gonadotropins was comparable to that of GnRH (10(-9)M). 15-HETE (3 X 10(-5)M) was even more potent on LH and FSH secretion than 5-HETE. The secretory profile induced by 5-HETE and 15-HETE was also similar to that shown for GnRH, resulting in a rapid increase and a more prolonged decline of the hormone release. The addition of these fatty acids to superfused pituitary cells did not alter the response of the cells to their physiological ligand. These findings give further support to the proposal that metabolites of arachidonic acid may be involved in receptor-mediated mechanisms of gonadotropin release in pituitary cells.

Animals↗

Contraceptive progestins and gonadotropin secretion in vitro.

In an in vitro bioassay using rat pituitary cell cultures the effect of contraceptive progestins was tested on basal and gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion in vitro. Progestins diminished gonadotropin release in pituitary cells stimulated with GnRH, but did not alter basal values. This inhibitory effect was dose dependent in a range of 10(-10)-10(-5) M tested and the inhibitory action of most of the progestins examined was more potent than that of progesterone. The maximal reduction of LH and FSH values was by 60% of GnRH-induced control levels. Progestins also caused a shift in sensitivity of cells to GnRh (10(-12)-10(-6) M). When time dependence was investigated, some progestins potentiated GnRH effect on gonadotropins in pituitary cell cultures pre-incubated for a short time (4 h) with steroids. More prolonged pre-incubations from 23 to 71 h resulted in a progressive suppression of LH and FSH response to GnRH (10(-7) M). In order to examine intracellular effects, cells were pretreated with progestins and inositol phosphate metabolism was investigated. The data obtained in pituitary cells give evidence that polyphosphoinositide breakdown is potentially an early step in the action of GnRH on gonadotropin secretion by providing diacylglycerol and inositol phosphates. Addition of gonadotropin-releasing hormone to myo-2[3H]inositol-prelabeled rat pituitary cells in primary culture evoked a dose-dependent increase of the accumulation of [3H]inositol phosphates with a rise of inositol triphosphate, inositol diphosphate and inositol monophosphate within 1 min. Using one contraceptive progestin, gestoden, inositol phosphate production was inhibited by 80% compared to controls of GnRH-treated cells without the addition of steroids. The data obtained in this study suggest that this in vitro bioassay using rat pituitary cells is a useful tool in testing progestational compounds regarding their potency on gonadotropin release. In addition, these results show that one possible site of interference of progestins with GnRH-induced gonadotropin secretion may involve polyphosphoinositide breakdown.

Animals↗

Stimulation of luteinizing hormone release by melittin and phospholipase A2 in rat pituitary cells.

Gonadotropin release in rat pituitary monolayer cultures was stimulated by phospholipase A2, as well as by its activator melittin. A dose-dependent stimulation of luteinizing hormone secretion by melittin was observed in a dose range of 10(-8) to 10(-4) M. A higher dose (1 mM) melittin had a sub-optimal effect. The stimulatory action of melittin was calcium-dependent and blocked by phospholipase A2 inhibitors, chloroquine and quinacrine. Similar to melittin, phospholipase A2 enhanced the effect of LH release in a dose range of 0.1-100 units/ml. The effect of this enzyme was also calcium-dependent with optimal calcium concentrations at 1.5 mM, as obtained also for melittin. In superfusion experiments, the stimulatory action of melittin and phospholipase A2 was reproducible in their effects on LH release in gonadotrophs. In addition, melittin (10(-7) M) stimulated LH and 3H-arachidonic acid efflux in superfused pituicytes following prelabelling with radiolabelled arachidonate. These data suggest that phospholipase A2, which releases arachidonic acid from phospholipids, may participate in controlling gonadotropin secretion in gonadotrophs, since arachidonic acid and its metabolites have previously been found to enhance gonadotropin release.

Animals↗

New progestogens in oral contraceptives.

The aim of using new synthetic progestogens (gestodene and norgestimate) in oral hormonal contraceptives is to find a combination that has a more beneficial effect on metabolism and endometrium than presently available formulations. Our studies with low-dose pills containing 30 micrograms ethinyl estradiol/150 micrograms levonorgestrel or 30 micrograms ethinyl estradiol/150 micrograms desogestrel compared with the new pills with 35 micrograms ethinyl estradiol/250 micrograms norgestimate or 30 micrograms ethinyl estradiol/75 micrograms gestodene revealed no significant alterations of serum glucose after glucose loading. With all four combination pills, insulin levels were slightly elevated when compared with controls. Studies of the lipid metabolism showed that depending on the type and estrogen combination, progestogens have different effects on lipid metabolism. The new progestogens seem to have a more pronounced effect on triglycerides, whereas total cholesterol and high-density lipoprotein cholesterol remain almost unchanged. In general, it could be shown that low-dose oral contraceptives have little impact on lipid metabolism. Studies with low-dose monophasic preparations, including the new formulations, reveal only a low effect on blood coagulation. According to our and other data on the new progestogens in oral contraceptives available so far, it can be expected that such low-dose monophasic and triphasic combination pills will be beneficial during longtime use with respect to side effects on the cardiovascular system and control of the menstrual cycle.

Contraceptives, Oral, Combined↗

[Risk-benefit analysis of a hCG-500 kcal reducing diet (cura romana) in females].

The British physician A.T.W. Simeons described in 1954 a new method for dieting. He combined a reduction diet (500 kcal per day) with daily injections of the pregnancy hormone human chorionic gonadotropin (hCG) (125 IU i.m.). According to Simeons the patient should not lose more weight during a 4-to-6 weeks' diet than without hCG, but the injections should facilitate to maintain the diet and to lose body weight at specific parts of the body (e.g. hip, belly, thigh). After the first publication various studies conducted with male and female patients analysed the efficacy of the "Cura romana". 10 of these studies showed positive and another 10 studies negative results with regard to hCG-related weight reduction. Two of these studies with positive results were double-blind studies (hCG vs. placebo). Most of them were reports on therapeutical experiences and were not controlled studies. According to these reports the body proportions normalized and the feeling of hunger was tolerable. Four out of 10 studies with negative results were controlled studies (hCG vs. control without hCG), whereas 6 were double-blind studies. These studies showed a significant weight reduction during dieting, but no differences between treatment groups in respect of body weight, body proportions and feeling of hunger. One of them is the only German study conducted by Rabe et al. in 1981 in which 82 randomised premenopausal volunteers had been dieting either with hCG or without hCG injections. In recent publications describing mostly well-documented double-blind studies authors largely reject hCG administration in dieting. Supporters of the hCG diet must prove the efficacy of this method in controlled studies according to the German Drug Law. Until then the opinion of the German steroid toxicology panel is still valid, that hCG is ineffective in dieting and should not be used (Bolt 1982 a, 1982 b).

Appetite↗

[Effect of the PGE1 methyl analog misoprostol on the pregnant uterus in the first trimester].

The effect of misoprostol, a PGE1 methyl analogue, on the pregnant human uterus was unknown at dosage levels normally used in the treatment of gastric and duodenal ulceration. Data from animal fertility and teratology studies suggested no activity at an anti-ulcer dosage level. In a double-blind placebo-controlled study, 300 patients (9.-12. week of gestation) were treated with two doses of misoprostol (study A: 2 X 400 micrograms; study B: 2 X 200 micrograms) or placebo during the evening before a legally permitted termination of first-trimester pregnancy. A partial or complete abortion occurred spontaneously in 11% of patients receiving misoprostol 2 X 400 micrograms, 9% of patients receiving misoprostol 2 X 200 micrograms and none of the patients receiving placebo. The incidence of vaginal bleedings (A: 45%, B: 34%), abdominal pain (A: 42%, B: 43%) and the softening of the cervix were all significantly increased by misoprostol treatment. These results show that the sensitivity of the human pregnant uterus to prostaglandin analogues cannot be reliably predicted from animal studies. Furthermore, misoprostol should not be used in human first-trimester pregnancy. The effect of misoprostol on second and third-trimester pregnancy (e.g. labour induction) is still unknown.

Abortifacient Agents↗

Arachidonic acid and its lipoxygenase metabolites stimulate prolactin release in superfused pituitary cells.

The direct effect of leukotrienes and other lipoxygenase products on prolactin release has been assessed. Arachidonic acid and its lipoxygenase metabolites 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) and 15-hydroxy-5,8,10,14-eicosatetranoic acid (15-HETE) stimulated the release of prolactin in superfused rat pituitary cells in a dose-dependent manner. Leukotrienes (LT) A4, B4, C4 and E4 provoked a very marked biphasic and dose-dependent secretion of prolactin from superfused cells. Maximal effects were achieved with leukotrienes at a concentration of 3 X 10(-11) to 3 X 10(-10) M but LTD4 did not affect peptide release under these conditions. The metabolites were more potent than arachidonic acid in affecting hormone secretion. Pulses of 4 minutes duration of these fatty acids may even elicit a more pronounced response than thyrotrophin-releasing hormone (TRH). Nordihydroguaiaretic acid (NDGA 10(-6) M), a lipoxygenase inhibitor, prevented the effect of arachidonic acid on peptide secretion. Repeated TRH (10(-7) M) administration to pituitary cells led to a reduction in cell response, which may also be observed in cells pre-treated with pulsatile 5-HETE or 15-HETE. These data support previous findings that arachidonic acid and its lipoxygenase metabolites may play a role in the secretory mechanism of prolactin release in pituitary cells.

Animals↗

Freezing-thawing behaviour and cell membrane ultrastructure of mouse embryos pre-cultured in B2-Menezo medium before cryopreservation.

Mouse embryos were pre-cultured from the 2-cell to the 8-cell stage inserum-free B2-Menezo medium and in B2-Menezo medium with 15% fetal cord serum before cryopreservation with a slow freezing-thawing method (-0.3 degree C/min in 1.5 M DMSO). Viability after freezing-thawing was tested by continuing in-vitro culture and evaluating the percentage of embryos developing to the blastocyst stage. An extreme decrease in viability after freezing and thawing was found for the embryos pre-cultured in serum-free B2-Menezo medium compared with the embryos pre-cultured in B2-Menezo medium with 15% fetal cord serum (12 versus 81% blastocysts). Ultra-thin sections of the pre-cultured embryos and of freshly collected controls were prepared for transmission electron microscopy before and after the freezing-thawing procedure. A drastic decrease in the number of microvilli on the cell surface and a high degree of cell damage after freezing and thawing was observed in the embryos pre-cultured in serum-free B2-Menezo medium. In contrast a high number of microvilli and an intact cell structure after cryopreservation was observed in the embryos pre-cultured in B2-Menezo medium with 15% fetal cord serum and in the non-pre-cultured controls. It is suggested that the smaller cell surface and the resulting lower permeability of the cell membrane in the embryos with few microvilli are due to sub-optimal culture conditions and are the main reasons for the extremely decreased viability after freezing and thawing.

Animals↗