[Recommendations for substitution with estrogens and progesterones in climacteric and in postmenopause. 8th Professional Meeting of the Zurich Discussion Group, November 1992].
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Biomedical subjects
Publications and source records attributed to M Breckwoldt.
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Vascularization is a prerequisit for corpus luteum formation. Angiogenesis is supposed to be regulated by vascular growth factors. Vascular endothelial growth factor (VEGF) induces specifically endothelial cell proliferation as well as angiogenesis and increases capillary permeability. With this study we demonstrate for the first time the presence of VEGF-mRNA in human luteinized granulosa cells by Northern blot technique. Granulosa cells were obtained from 11 individual patients undergoing ovarian stimulation for in vitro fertilization procedure. Two transcripts of VEGF-mRNA at 3.9Kb and at 4.3Kb could be detected in each case. Specific transcripts were expressed in different amounts. These results indicate that VEGF may promote at least in part vascularization of the human corpus luteum.
The physiological regulation of 5 alpha-reductase (5 alpha R) as well as the complex pathogenesis of male and female androgenic disorders are still incompletely understood. Therefore, we examined the influence of various steroid hormones on the 5 alpha R activity in female and male genital skin fibroblasts in primary culture to test whether the 5 alpha R activity is identically regulated in genital skin samples of both sexes. Nine foreskin samples of male patients and 11 specimens of female genital skin were prepared and cultured as primary tissue cultures. After pre-incubation with various unlabeled steroids, [3H]-testosterone was added to the cultures and the 5 alpha R activity (conversion of testosterone to dihydrotestosterone) measured. (a) The pre-incubation of male foreskin fibroblasts with unlabeled androstenedione and androstandione both resulted in stimulation of 5 alpha R activity. Other unlabeled steroid hormones, including progesterone, testosterone, dihydrotestosterone, and estradiol had no significant effect on 5 alpha R activity. (b) In female genital skin fibroblasts, pre-incubation with testosterone also led to an increase in 5 alpha R activity, whereas pre-incubation with estradiol decreased 5 alpha R activity. None of the other unlabeled steroid hormones applied had significant effects. These data on male foreskin in culture suggest a physiologic regulatory mechanism of 5 alpha R activity independent of the concentration of the enzymatic substrate or product, whereas the results for the female genital skin suggest a cellular regulation of the androgen levels by the enzymatic substrate testosterone and a possible negative feedback mechanism of estrogens.(ABSTRACT TRUNCATED AT 250 WORDS)
The distribution of molecular forms of prolactin in serum of women during the 1st postpartum week was studied using column chromatography. Serum was analyzed 1, 4 and 7 days postpartum. Using this technique, three molecular forms of prolactin were detected with approximate molecular weights of < or = 100, 48 and 22 kDa; these were termed 'big-big', 'big' and 'little' prolactin, respectively. The relative amount of each form was measured in relation to the total amount of immunoreactive prolactin eluted from the column. Throughout the first postpartum week big-big prolactin represented a minor fraction of the total immunoreactive prolactin in the serum of lactating women: 4.9%, 5.2% and 4.6% on days 1, 4 and 7, respectively. There was a gradual decrease in the higher molecular weight forms of prolactin (big-big plus big prolactin) from the 1st to the 7th postpartum day. This was associated with a significant increase of the little prolactin from 62.8 +/- 7.2% at the 1st postpartum day to 72.6 +/- 6.5% at the 7th day (p < 0.05).
Breast vascularization was measured with an 8-MHz continuous wave Doppler pencil probe. Flow values were low in asymptomatic women and high in patients with severe pain or dysplastic changes. Mild treatment with a plant extract produced only a small decrease in breast vascularization. Treatment with norethisterone acetate showed a dose-dependent decrease in blood flow. A good response was seen with a dosage of 5 mg/d, and a dramatic decrease was seen when 10 mg/d was taken. These results showed a good correlation with the patients' symptoms.
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In four cases of one twin pregnancy and three triplet pregnancies, efforts were made to prolong the pregnancy after the death of one foetus between 15th and 26th weeks of gestation. Two patients had a history of spontaneous abortion, three patients had undergone infertility treatment. In a further three cases the membranes ruptured prematurely in association with severe disturbance of the vaginal flora. Treatment consisted of rest in bed, sedation, and administration of magnesium and antibiotics. Neither cervical cerclage nor general IV tocolysis were performed. Although the pregnancies could be prolonged for 4, 22, 28, and 76 days, they all terminated before the 27th week, mainly due to ascending infection. Of the 11 children, two survived with no morbidity, two children (B and C of the third triplet pregnancy), died 2 and 19 days after delivery, respectively, and seven were stillborn. A comparison with prolongations of twelve twin and four triplet pregnancies reported in the literature, reveals the various concepts for treatment. After infection has been ruled out and the parents have been fully informed, efforts could be made to prolong the multiple pregnancy after the death of one foetus until the surviving child is viable. This requires intensive supervision.
A case of pseudovaginal perineoscrotal hypospadia (PPSH) is presented. This autosomal recessive disorder, also termed incomplete male pseudohermaphroditism type 2, is mostly caused by a deficiency of 5 alpha-reductase, which controls the conversion of testosterone to 5 alpha-dihydrotestosterone. In genital skin fibroblasts, the activity of the 5 alpha-reductase was strongly reduced, compared with a normal male. The 5 alpha-reductase activity in nongenital skin fibroblasts, however, was in the range of the normal male control. For complete diagnostic evaluation of PPSH 5 alpha-reductase activity it should be determined simultaneously in genital and non genital skin fibroblasts. The conversion of T to DHT in genital skin fibroblasts of a patient with testicular feminisation (Tfm) was found to be of the same order of magnitude as in PPSH. This suggests, that the expression of 5 alpha-reductase is androgen-dependent.
Explored by structured dialogue, miscarriage meant for 31 women, a psychosocial stress but not a medical stress. They tried to convince themselves of the non-normative event via subjective causal attributions to obtain cognitive control. Social support, especially by the partner, minimising the importance of the miscarriage, and social comparisons were the main modes of coping with their problem. Doctors and nurses significantly undervalued the degree of psychosocial stress, which resulted in negative consequences in the doctor-patient-relationship.
In 3 cases of severe twin transfusion syndrome we demonstrate that the concentration of atrial natriuretic factor (ANF) in the cord blood of recipient twins is significantly elevated compared to that of donor twins. The discrepancy between recipient and donor concentration correlates with the volume of transfusion. The following pathophysiological mechanism for explaining polyhydramnios in recipient twins is proposed: chronic overload in recipient twins causes enhanced release of ANF from the fetal heart. Consequently, increased fetal urine production leads to polyhydramnios, which is additionally enhanced by inhibition of ADH release.
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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.
Since 1 October 1990, German legislation requires compulsory counselling of an infertile couple before artificial insemination on the medical and psychosocial aspects, by a doctor not performing the treatment. A prerequisite of successful counselling, which enables the couple to take a decision and helps coping with the psychosocial stress of sterility and its consequences, is, in addition to the intrinsic motivation of the couple, also the empathy and the discussion with the doctor. Subject for counselling should be the burdens of therapy, effects of the sterility upon sexuality, partnership, and communication, motivations for wanting a child and the functions of the child for both partners individually and as a partnership. As a prophylactic measure against the development of a neurotic desire for a child and a fixation upon sterility therapy, alternative resolving strategies for therapy failure should be discussed and developed.
We describe two cases of autoimmune polyendocrinopathy syndrome as a cause of primary ovarian failure. Antibodies against various endocrine organs cause pluriglandular insufficiency, in most cases hypoparathyroidism. Addison's disease, and primary ovarian insufficiency. In these patients, careful examination of all endocrine organs is necessary in order to provide an adequate hormone replacement.