Assisted reproductive techniques: risks, contraindications, prognostic factors, therapeutic strategies.
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Female↗
Biomedical subjects
F Geisthövel
Publications and source records attributed to F Geisthövel.
[After disappointment regarding secondary cardiac prevention. What is the status of hormone replacement therapy today?].
ERT (estrogen replacement therapy) or HRT (hormone replacement therapy) can be employed for the prevention/treatment of various hormone-related conditions. The main indications are the treatment of psychovegetative deficits and--in part--primary prevention of osteoporosis. For other (hormone-related) diseases such as certain malignant tumors, the risk may increase under replacement treatment, so that a risk/benefit evaluation should always precede it prescription. Side effects of ERT/HRT include a greater risk of thrombosis and, possibly, a increase in cardiovascular events, so that this form of treatment cannot be recommended at least for the secondary prevention of cardiovascular disease. In general, treatment must be matched to the requirements and wishes of the patient. With increasing age and remitting symptoms, the dose can be reduced. Alternative substances such as phytoestrogens or selective estrogen receptor modulators (SERMs) extend the spectrum of therapeutic options.
Adult↗
[Functional hyperandrogenism--classification, etiology, diagnosis and therapy].
The classification of functional hyperandrogenism (FHA) presented in this paper is based on well known clinical experience supported by recent data of molecular biology. Functional hyperandrogenism is composed of various organ system-specific entities with consequently differential diagnostic and therapeutic strategies. The term polycystic ovary syndromes (PCOS) is misleading and should be replaced by adequate descriptions. Inspite of intense discussions and progress in molecular biology are with the exception of the here described FHA III-group the etiological consequences unresolved in terms of diagnostic and therapeutic procedures. Based on recent findings on the human genome genetic screening methods (Microarrays) may be available in the near future to allow a better understanding of the underlying pathophysiology.
Diagnosis, Differential↗
C-peptide and insulin, but not C19-steroids, support the predictive value of body mass index on leptin in serum of premenopausal women.
Hyperleptinaemia is known to be positively associated with obesity in females. Therefore, circulating leptin concentrations are predicted by body mass index (BMI). Additional effects of endogenous C19-steroids, sex hormone binding globulin (SHBG), luteinizing hormone (LH), follicle stimulating hormone (FSH), C-peptide and insulin on the predictive value of BMI on serum leptin were investigated in 56 hyperandrogenaemic and/or hyperinsulinaemic and/or obese premenopausal women. Serum concentrations (after an overnight 12 h fast) of leptin, total testosterone, free testosterone, SHBG, dehydroepiandrosterone sulphate (DHEAS), LH, FSH, and oestradiol as well as serum concentrations of C-peptide and insulin prior to, and 1 h after, an oral 100 mg glucose load (1 h values) were determined by immunoassays. Subjects with regular menstrual cycles were studied in the mid-follicular phase while the remainder were studied at random. Nineteen normotestosteronaemic, normoinsulinaemic, lean and ovulatory volunteers served as controls; in order to determine the effect of different stages of the menstrual cylce, serum concentrations of leptin (and of oestradiol in 12 out of the 19 individuals) were determined at the preovulatory, the mid-luteal and the following mid-follicular phase. Significant differences between the patients versus control were not found possibly because of the heterogeneity in the patient group. Multiple regression indicated a hyperbolic correlation between BMI and leptin concentrations. As expected, BMI was the major determinant responsible for >50% (R2=0.51) of the elevation of leptin concentrations. The combination of BMI with fasting C-peptide or fasting insulin enhanced the R2 up to 0.59. The multiple regression with two explaining parameters showed a significant regression coefficient for BMI at the 0.001 level, and for fasting C-peptide and fasting insulin at the 0.01 level, which was as statistically significant as the combination of BMI with the 1 h values of C-peptide and of insulin. In contrast, total testosterone, free testosterone, SHBG, free testosterone/SHBG ratio, DHEAS and LH/FSH ratio had no effect. Similarly, models with more than two variables did not measurably improve the explained variation. In the control group, leptin concentrations were significantly higher in preovulatory and mid-luteal phases than the two mid-follicular phases (P < or = 0.05) and must be considered when determining sampling time. In conclusion, hyperandrogenaemia does not have a predictive value on leptin concentrations in premenopausal subjects but hyperinsulinaemia exerts an effect independent of obesity that is the strongest predictor for elevation of leptin concentrations. Hyperinsulinaemia might contribute to the hyperbolic correlation of circulating leptin in obese patients.
Adult↗
Obesity in female life--from molecular to clinical aspects.
Obesity gains increasing prevalence world-wide. Multifactorially caused it presents itself in numerous heterogeneous phenotypes with a wide spectrum of clinical symptoms. The full-blown female obesity syndrome is initiated already in childhood, associated with ovarian hyperandrogenaemia (polycystic ovary syndrome) in the reproductive phase, and characterised by increasing co-morbidity (cancer; metabolic syndrome; arteriosclerosis) in the postmenopausal state leading to shortened longevity. Due to the complexity of psychic, somatic and endocrine-metabolic disturbances a causal break-through in the treatment of the disease could not be achieved yet, but the enhanced basal understanding and recently investigated pharmaceutical principles might enable to improve the therapeutical approaches.
Adolescent↗
Relationship between obesity and insulin and lipoprotein metabolism in postmenopausal women.
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Coronary Disease↗
Acarbose reduces elevated testosterone serum concentrations in hyperinsulinaemic premenopausal women: a pilot study.
In seven hyperinsulinaemic, hypertestosteronaemic premenopausal patients, we tested the effect of an attenuation of insulin serum concentrations by long-term treatment with the enteral disaccharidase inhibitor acarbose on serum concentrations of total and free testosterone, dehydroepiandrosterone sulphate (DHEAS) and sex hormone-binding globulin (SHBG). The subjects showed typical features of hyperinsulinaemia-hypertestosteronaemia syndrome, including elevated concentrations of insulin and testosterone, normal concentrations of DHEAS and suppressed SHBG concentrations. The patients were orally treated with an initial dosage of 50 mg acarbose/ day, which was gradually increased to a maximum of 300 mg/day. Blood was sampled at week 6 (under a dosage of 150 mg acarbose/day) and at week 20 of treatment. A significant reduction in the increase of glucose and insulin concentrations, determined after administration of a standard oral 100 g glucose load, was found at week 6 (P < 0.02, P < 0.00007) and at week 20 (P < 0.04, P < 0.003) of therapy and was associated with a significant decrease of total and free testosterone at week 20 (P < 0.04, P < 0.01). Concentrations of both DHEAS and SHBG remained nearly unchanged. In conclusion, it was shown that a decline of ovarian hypertestosteronaemia was achieved in association with a flattening of the postprandial glucose and insulin increase by long-term treatment with acarbose. Side effects were limited to abdominal distension and flatulence and were absent using a low dosage of 50 mg acarbose/ meal (3 x 50 mg/day).
Acarbose↗
Serum leptin and weight reduction in female obesity.
Leptin, an adipocyte-derived hormone, induces a decrease in food intake and increases energy expenditure via hypothalamic interactions. In animal models obesity can be caused by leptin deficiency or by a dysfunction of the hypothalamic leptin receptor. Using a radioimmunoassay for the determination of leptin in human serum, we measured serum leptin levels in 227 otherwise healthy normal weight (N = 78; body mass index = 16.1-27.7 kg/m2) or obese women (N = 149; body mass index = 27.8-56.7 kg/m2). Fifty-three subjects were followed over a period of 12 weeks under weight reduction (800 kcal/day) and a subgroup of 33 for another 13 weeks after termination of the diet. Body mass index and serum leptin concentrations were measured longitudinally and compared to female controls not under diet. Under baseline conditions, log serum leptin levels were positively related to body mass index with a best fit using a non-linear regression (p < 0.001), indicating an attenuated increase in serum leptin levels with high body mass index. No subgroup with low serum leptin levels could be identified. Weight reduction induced a rapid decrease in serum leptin levels within the first 3 weeks to levels significantly lower than in body mass index-matched controls under normal diet (p < 0.001). This pattern was consistent after 6 and 12 weeks. Serum leptin levels increased again after the end of the diet but remained significantly lower than in the controls despite unrestricted calorie intake over 7 weeks. The rapid and persistent decrease in serum leptin to lower levels than expected from matched controls may explain the pertinent difficulties of obese subjects to cope with weight reduction.
Adult↗
Obesity and hypertestosteronaemia are independently and synergistically associated with elevated insulin concentrations and dyslipidaemia in pre-menopausal women.
The association of obesity and hypertestosteronaemia with elevated insulin concentration and dyslipidaemia was studied in 15 non-obese and 15 obese, hypertestosteronaemia patients; 14 non-obese and 10 obese, normotestosteronaemic subjects served as controls. Data were subjected to multivariate analysis. Enhanced body mass index (BMI kg/m2) resulted in a significant elevation of basal insulin (b-Ins), glucose-stimulated (delta) insulin (del-Ins), triglycerides (TG), very low density lipoprotein (VLDL), low density lipoprotein (LDL), and LDL/high density lipoprotein (HDL) ratio, and in a significant reduction of HDL. Furthermore, it was shown that BMI was positively correlated with TG, VLDL, LDL and LDH/HLD ratio, and negatively correlated with HDL in the normotestosteronaemic groups. Hypertestosteronaemia was associated with a significant increase of del-Ins, VLDL and LDL/HDL ratio, and with a significant decrease of HDL concentration. Testosterone was directly associated with del-Ins and LDL/HDL ratio, and inversely related to HDL in the non-obese groups. Summation effects of obesity and hypertestosteronaemia were found for del-Ins and VLDL. The data suggest that obesity and hypertestosteronaemia are independently and jointly associated with insulin resistance and dyslipidaemia, indicating an increased risk for coronary heart disease. The highest risk rate was found in obese hypertestosteronaemic patients. Serum testosterone may be a useful marker in detecting metabolic disorders connected with cardiovascular risk.
Adult↗
[Climacteric--trigger for obesity?. Interview by U. Fuchs].
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Climacteric↗
[Contraception by cyclic treatment with buserelin and progesterone].
Hormonal contraception with a combination of a GnRH-agonist (Buserelin) and progesterone was achieved in 47 high risk patients in 547 cycles. In these patients, oral contraceptives were contraindicated because of severe cardiovascular diseases, thromboembolic complications, benign liver tumours, advanced diabetes, terminal kidney insufficiency and severe migraine. Buserelin was administered intranasally in one daily dose of 300-400 micrograms from the 1st day to the 21st day, one dose of 100 mg of Progesterone was given intravaginally daily from the 12th day to the 21st day. Under these conditions, average E2 concentrations were found in the range of 50-60 pg/ml. The discontinuation of progesterone replacement resulted in withdrawal bleeding. Cycle control was acceptable. In 4 cases, this contraceptive regimen had to be discontinued because of side effects or paradox reactions. One patient conceived. In conclusion, GnRH-analogues in a moderate dose can be used to inhibit ovulation without inhibiting follicular maturation and adequate oestrogen production. This costly regimen of contraception requires strict indication and careful monitoring.
Administration, Intranasal↗
Oral contraception in disease states.
Oral contraceptives are clearly contraindicated in patients with a history of thromboembolic disease, ischemic heart attack, or cerebral stroke. Patients requiring long-term anticoagulant treatment can be treated with gonadotropin-releasing hormone analogs to prevent ovulation, because ruptured follicles can cause massive intraperitoneal bleeding. Patients with essential hypertension and severe liver diseases should also discontinue treatment 4 weeks before major elective surgery. Migraine and diabetes mellitus are regarded as relative contraindications, depending on the individual situation. Long-term diseases, such as Crohn's disease, epilepsy, and sickle cell anemia, also require individualized consultation.
Cerebrovascular Disorders↗
[GnRH-analogs in the therapy of uterine myomatosis].
Uterine fibroids are the commonest tumors of the female genital tract. Hysterectomy is the typical therapy in patients whose families are complete. In women desirous of children GnRH-analogues can effect a shrinkage of leiomyomata before a myomectomy. Furthermore, GnRH-A treatment can be an alternative to hysterectomy in inoperable patients or in premenopausal women with symptoms of uterine fibroids. In this study eleven patients were treated with 3.2 mg triptorelin monthly and ten patients with 900 micrograms buserelin daily for 6 months. With triptorelin, a 50% reduction of the uterus volume can be observed after 3 months. A further treatment has no benefit. With buserelin, a regression in the same range as with triptorelin can be reached only after 6 months. In contrast, fibroid volumes revealed a regression of 28% with triptorelin and 21% with buserelin in the same time. In this period all fibroid-associated symptoms disappeared. Less bleeding resulted in an increase of hemoglobin. Therefore, treatment with GnRH analogues can be an important factor in the management of uterine fibroids patients in at-risk.
Adult↗
Management of multiple conceptions after gonadotropin-releasing hormone analog/human menopausal gonadotropin/human chorionic gonadotropin therapy.
The treatment course of a 31-year-old infertility patient due to PCO disease is presented. Because the patient failed to conceive after various treatment cycles with CC, she was subjected to a combined GnRHa/hMG/hCG therapy. After plasma E2 levels had reached 2400 pg/ml, three leading follicles, with diameters of 20 to 24 mm, were detected. Induction of ovulation was achieved by 10,000 IU hCG. The patient conceived and developed ovarian hyperstimulation. At 8 weeks of gestation, seven cystic structures were detected within the uterine cavity, five containing single embryos, and two with twin embryos. All nine embryos were vital, as evidenced by their heart beats. Embryo reduction was achieved by transabdominal puncture on three occasions. The three surviving fetuses were carried to the 34th week of gestation. After delivery by cesarean section, three healthy babies developed normally. This communication illustrates the complications that can be associated with ovulation induction in PCO disease: ovarian hyperstimulation, polyovulation, multiple conceptions, and their clinical management.
Adult↗
[Stimulation of ovarian function with gonadotropins following suppression of endogenous gonadotropin secretion by long-term infusion of the LHRH analog buserelin].
The treatment of infertile women by gonadotropins is more effective in hypogonadotropic than in normogonadotropic ovarian insufficiency. In order to induce a hypogonadotropic state the luteinizing hormone-releasing hormone analog (LHRHA) buserelin was administered in eight cycles of four infertile patients suffering from luteal phase defect. Buserelin was infused subcutaneously in a dosage of 400 micrograms/d for 26-44 days using a portable external osmotic minipump system. Following suppression of estradiol-17 beta below 35 pg/ml within 11 +/- 5 days, gonadotropins were injected intramuscularly to stimulate ovarian function. In all cycles treated, ovulation and formation of a functional corpus luteum were observed without signs of premature luteinization. Whereas constant administration of LHRHA by a slow release system seems very useful for long-term reversible suppression of follicular maturation, further studies should evaluate the clinical usefulness of combined LHRHA/gonadotropin treatment in cases of infertility.
Adult↗
Pharmacology and experimental basis of therapy with LHRH agonists in women.
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Administration, Intranasal↗
[Non-puerperal mastitis. Etiology, clinical aspects and therapy].
Non-puerperal mastitis was diagnosed in 79 patients (aged 12-77 years) over the years 1974-1984. Malignant neoplasm was not present. Bacterial infection in the region of the areola was the most frequent finding (40%), followed by abacterial inflammation without involvement of the nipples (29%). The other cases, bacterial or nonbacterial, occurred at different sites. The histological picture or clinical features of an increased secretory activity of the mammary gland (galactorrhoea, mastodynia) in addition to the mastitis was noted in 54 women. Causative organisms were proven in 53% of cases: Staph. aureus (41%) and coagulase-negative staphylococcus (41%), or anaerobic organisms (11%). Physical measures, antibiotics and bromocriptine were used as treatment. At the onset of treatment abscesses were already present or developed in 34 instances. In 28 cases one to six recurrences set in after the end of the treatment period. In 22 patients treated with bromocriptine prophylactically there were only two recurrences. In the majority of patients an increased alveolar secretion was important in the pathogenesis of the bacterial or abacterial inflammation. Prolactin-lowering treatment seems reasonable by itself in cases of abacterial mastitis, or in combination with antibiotics in bacterial mastitis. Recurrences can be prevented by long-term lowering of the peripheral prolactin level.
Adolescent↗
Ovarian hyperstimulation due to long-term pulsatile intravenous GnRH treatment.
Pulsatile long-term gonadotropin releasing hormone (GnRH) therapy with an average dosage of 8 micrograms/pulse i.v. in intervals of 90 min induced in a patient with hypothalamic amenorrhea the development of multiple ovarian cysts as visualized by ultrasonography. Estradiol (E2) plasma concentration reached values of 5000 pg/ml. These findings indicate that pulsatile GnRH application can induce ovarian hyperstimulation.
Adult↗