[Society of Obstetrics and Gynecology in Berlin. Meeting of the 13. November 1991].
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Biomedical subjects
Publications and source records attributed to J Hammerstein.
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Tubal patency was studied in 17 sterile women by means of colour-coded duplex sonography (CCDS) with local injection of an ultrasonic contrast medium. The results were compared with a conventional hysterosalpingogram. CCDS demonstrated all the soft tissues and their mobility. The ultrasonic contrast medium was SH U 454 (Schering). The colour signals generated by the air bubbles makes it possible to demonstrate tubal patency on both sides. The combination of an ultrasonic contrast medium and CCDS provides a simple, rapid, accurate and safe method for demonstrating tubal patency. Tubal patency can be demonstrated in the presence of anatomical complications and requires only a small amount of contrast medium.
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Prostanoids, leukotrienes and platelet-activating factor were measured by radioimmunoassay in menstrual blood of seven women with primary dysmenorrhea and five healthy controls. The eicosanoids and PAF concentrations in dysmenorrheic patients were significantly higher than those found in healthy women (P less than 0.005 for PGF2 alpha, 11-dehydro-TXB2, 2,3-dinor-TXB2 and LTC4/D4; P less than 0.001 for PAE; P less than 0.05 for PGE2 and 2,3-dinor-6-keto-PGF1 alpha). Whereas no relationship could be found between the concentrations of PGF2 alpha, PGE2, 11-dehydro- and 2,3-dinor-TXB2 and severity of primary dysmenorrhea, a close correlation between LTC4/D4 and PAF and severity of the disease was observed, particularly in patients who responded poorly to therapy with prostaglandin synthetase inhibitors. We conclude that the hyperstimulation of myometrial activity is not caused by selective stimulation of one metabolic pathway of arachidonic acid, but rather by an overall stimulation of phospholipid metabolism. The assessment of prostanoids, leukotrienes and PAF in menstrual blood many be useful as a direct index of primary dysmenorrhea, and the development of their antagonists may have therapeutic implications in improved treatment of the disease.
Our knowledge of the peculiarities of prohormones is rather limited, both pharmacologically and clinically. Generalizations cannot be made except that the lapse of time until peak blood values of the active drug have been reached are always greater after intake of the prodrug than after intake of the drug. This finding is presumably of no clinical importance. If pharmacokinetic differences are limited to the phase of distribution, bioequivalence may be assumed. If, on the other hand, the area under the curve during the elimination phase is smaller for the prodrug than for the drug, the potency of the former should be decreased. A shift in the spectrum of endocrine actions as a result of the biotransformation of the prodrug into the active drug is rather the exception than the rule, and so is a change in side effects. If there are major differences in this respect, metabolic pathways in addition to those leading to the respective active drug must also be taken into consideration.
Following introductory terminological clarifications, the pharmacological peculiarities of the synthetic estrogens and progestogens used in oral contraception are outlined. With the low-dose formulations containing less than 50 micrograms estrogen per pill ("micropill") coming in preferential use, the definite differences between the profiles of effects of the three major progestational categories--estranes, gonanes and pregnanes--lost much of their impact on clinical tolerance. Within the three classes of progestogens, the profiles of effects of the various compounds are, anyhow, very similar with major deviations occurring only exceptionally. As to the contraceptive estrogens, ethinyl estradiol differs from mestranol, if any, in quantitative but not in qualitative respect, the latter substance not being commonly used in Europe any longer. Besides potencies and profiles of effects of the individual contraceptive steroids, the quantitative estrogen/progestogen relationship of a "pill" is another variable of great importance for the development of unwanted side effects in the field of lipid and carbohydrate metabolism as well as of blood coagulation. Due to the lack of influence on lipid metabolism, progestogens of the pregnane series, being driven into an outsider position since long, deserve increasing attention again. As a general principle, women of all age groups should at least try to use the "micropill"--either combination-type or tristep formulations--in order to minimize risks. Only a few indications are left for the primary prescription of high-dose combination-type, sequential and step-up preparations as well as for the progestogen-only "minipill". With "micropill" becoming the oral contraceptives of the first choice, also rational reasons for changing formulations have become rare.(ABSTRACT TRUNCATED AT 250 WORDS)
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In this century, paramount progress has been made in many areas of medicine, not least in the field of contraception, with landmarks such as the introduction of intrauterine contraceptive devices (IUDs), hormonal contraceptives (OCs), and laparoscopic sterilization. The general optimism of the 1960s about overcoming the problems of global overpopulation with these new tools has subsequently been replaced by growing concern about the risks of contraception in general and of OCs especially. It was not before the 1980s that the benefit-risk balance of hormonal contraception turned out to be much more favorable than was formerly suspected. The wide variation from country to country in the prevalence of contraceptive methods has economic, political, religious, sociological, educational, and legal rather than medical reasons. Former misjudgments have led to a ban on valuable tools such as the sequential regimen or the use of 17-acetoxyprogestogen analogues as components in OCs, or to a ban on the licensing of depot progestogens in some countries but not in others. The recent decision of U.S. firms to cease production and sale of IUDs for legal reasons is unique and hopefully will not be imitated elsewhere. Just after the introduction of oral contraception, tremendous inventive dynamics led to the discovery of several new contraceptive principles. Most of these have reached the stage of clinical application and are being used satisfactorily, at least in some parts of the world. Later contraceptive concepts are still in the stage of experimentation and no breakthrough appears to be directly ahead. If contraception means more than just meeting individual wants--if it is also to be an instrument for handling the increasing problems of overpopulation--then much more must be done to deepen our knowledge of reproductive physiology, to popularize efficient means of contraception, and to make them available to everyone. Otherwise, all efforts to improve health standards throughout the world according to the "WHO Global Strategy for Health for All by the Year 2000" will be in vain.
The growth fraction (GF) and estrogen receptor (ER) status of 76 cases of breast cancer were investigated on frozen sections of the same tissue block by immunostaining with monoclonal antibodies (Ki-67 and anti ER antibody). In 55 cases of this series, the ER status was also determined by standard biochemical methods. Our study revealed an inverse correlation between GF and ER status. This negative relationship was most significant when both variables were determined immunohistologically in the same tissue block and less significant when GF was analyzed by immunohistology and ER status by biochemical methods. These data suggest that the immunohistologically assessed ER values characterize the receptor status of a given carcinoma better than the biochemical values, which leads to the conclusion that the immunohistologically determined close negative relationship between GF and ER reflects the actual in vivo situation of a given breast carcinoma case. However, the immunohistologic analysis also revealed that there is a proportion of exceptional cases, ie, those with a positive ER status and a large or moderately large GF. Because only half of the ER-positive breast carcinomas respond to endocrine therapy with objective remission., it is hypothesized that it might be preferentially these mentioned exceptional cases that fail to positively respond to endocrine treatment protocols.
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GnRH double stimulation (2 X 25 micrograms i.v. at a two-hour interval) was used to assess the dynamics of LH and FSH release in 25 healthy women on oral contraceptives, all containing 50 micrograms of ethinylestradiol (EE). The study included two sequential regimens (50 micrograms EE X 7 days, 50 micrograms EE + 0.125 mg desogestrel X 15 days; 50 micrograms EE X 7 days, 50 micrograms EE + 2.5 mg lynestrenol X 15 days) and three combined preparations (biphasic: 50 micrograms EE + 1 mg norethisterone acetate (NETA) X 11 days, 50 micrograms EE + 2 mg NETA X 10 days; monophasic: 50 micrograms EE + 2 mg cyproterone acetate X 21 days; 50 micrograms EE + 2.5 mg lynestrenol X 21 days). The tests were always performed on days 19 to 21 of the first treatment cycle and compared to results obtained in normally cycling controls and in women receiving 50 micrograms EE daily alone. It was found that the EE-induced augmentation of pituitary responsiveness to GnRH is diminished by the addition of progestins. LH and FSH reactions to stimulation were both affected. The degree of inhibition depended not only on the chemical structure and daily dose of the progestin component, but also on the duration of its administration per treatment cycle.
Peripheral plasma concentrations of 6-keto-PGF1 alpha and TXB2 were measured in patients with benign and malignant tumours of the breast, in patients with non-gynecological diseases, and in healthy female controls. The values were significantly higher in female patients with malignant tumours of the breast than in healthy controls (146 +/- 28 vs 13 +/- 2.5 pg/ml for 6-keto-PGF1 alpha p less than 0.01 and 78 +/- 17 vs 11 +/- 2 pg/ml for TXB2, p less than 0.01). Benign tumours of the breast were also associated with significantly raised plasma levels of 6-keto-PGF1 alpha and TXB2 compared to normal controls (52 +/- 5 vs 13 +/- 2.5 pg/ml for 6-keto-PGF1 alpha, p less than 0.01 and 26 +/- 5 vs 11 +/- 2 pg/ml for TXB2, p less than 0.05). The high levels of 6-keto-PGF1 alpha and TXB2 were not found to be correlated with clinical and histopathological data. The surgical removal of the primary tumour has apparently no effect on the plasma concentrations of 6-keto-PGF1 alpha and TXB2 over a follow-up period of 9 days after operation. The lack of alterations in the ratio of TXB2:6-keto-PGF1 alpha in the cancer patients and other subjects studied before and after surgery is indicative of the regulatory power of metabolic systems to preserve the homeostatic balance.
This study compares the clinical, biochemical and laparoscopic findings in androgenized patients with (n = 33) and without (n = 17) polycystic ovaries (PCO). It included selective ovarian-adrenal vein catheterisation with measurement of testosterone, dihydrotestosterone, delta 4-androstendione, dehydroepiandrosterone and its sulfate, 17 alpha-hydroxyprogesterone and cortisol in peripheral and glandular venous samples; determination of free testosterone, oestradiol, oestron, LH, FSH and prolactin in peripheral blood; GnRH and TRH double stimulation, as well as dexamethasone suppression tests. There was no correlation between the morphological, clinical, and endocrine changes. A PCO-specific hormonal pattern was not identifiable. Based on catheterisation data, combined ovarian-adrenal androgen hypersecretion was found in 46% of PCO cases; purely ovarian (21%) or adrenal (12%) overproduction were not as frequent. The dynamic function tests proved to be non-specific; e.g., dexamethasone suppressed not only adrenal, but also ovarian androgen output. It is concluded from these data that PCO are not a nosologic entity, but rather a non-obligatory sign of hyperandrogenism. Laparoscopy is, therefore, without clinical relevance in these patients with non-neoplastic hyperandrogenaemia.
Bilateral ovarian-adrenal vein catheterization and androgen measurements in the efferent samples were utilized to directly assess glandular steroid release in 8 healthy volunteers with proven ovulatory cycles during the early follicular phase. Side effects did not occur in any of the women. Hormone levels were as follows (mean +/- SD; ng/ml) T: peripheral vein (PV) 0.36 +/- 0.16, ovarian veins (OV) 0.39 +/- 0.13, adrenal veins (AV) 0.85 +/- 0.63; dihydro-T (DHT): PV 0.25 +/- 0.09, OV 0.29 +/- 0.10, AV 0.93 +/- 0.65; delta 4-androstendione (A): PV 0.88 +/- 0.34, OV 1.82 +/- 1.04, AV 9.22 +/- 8.04; DHEA; PV 5.13 +/- 1.96, OV 6.73 +/- 2.69, AV 146.79 +/- 217.24; DS PV 1860 +/- 850, OV 1937 +/- 1039, AV 2567 +/- 1201; 17 alpha-hydroxyprogesterone (17P): PV 0.60 +/- 0.19, OV 1.46 +/- 1.64, AV 6.94 +/- 6.20; F: PV 170 +/- 50, OV 130 +/- 21, AV 788 +/- 1320; the bilateral differences of effluent levels were not significant. Glandular-peripheral vein steroid gradients served as semiquantitative estimates of momentary secretory activity; they were as follows (mean +/- SD; ng/ml) T: ovarian-peripheral vein gradient (OPG) 0.03 +/- 0.09, adrenal-peripheral vein gradient (APG) 0.48 +/- 0.57; DHT: OPG 0.05 +/- 0.05, APG 0.69 +/- 0.60; A: OPG 0.97 +/- 1.13, APG 8.33 +/- 7.86; DHEA: OPG 1.70 +/- 1.80, APG 141.80 +/- 216.60; DS: OPG 191 +/- 72, APG 706 +/- 824; 17P: OPG 0.87 +/- 1.67, APG 6.30 +/- 6.10; F: OPG 38 +/- 11, APG 610 +/- 1329. Gradient, analysis revealed that the ovaries produced significant quantities of A, DHEA and 17P, but no T, DHT or F between day 3-7 of the cycle; direct gonadal DS output was detected in 2 individuals. A significant OPG for DS was detected in two individuals possibly indicating its partially gonadal origin. The adrenals released larger amounts of A, DHEA and 17P than the ovaries at this stage (P less than 0.05); also, they consistently secreted T, DHT, DS and F.
Standardized bilateral ovarian-adrenal vein catheterization was utilized to assess directly glandular steroid release in 60 androgenized women without evidence of a functional neoplasm. Testosterone (T), dihydrotestosterone (DHT), androstenedione (delta 4 A), dehydroepiandrosterone (DHEA), DHEA sulfate (DHEA-S), 17-hydroxyprogesterone (17-OHP), and cortisol (F) were measured by radioimmunoassay in samples obtained from a peripheral vein and the four glandular veins (all values are given as nanograms per milliliter, mean +/- standard deviation). Peripheral values were as follows: T, 0.68 +/- 0.43; DHT, 0.32 +/- 0.13; delta 4 A, 2.2 +/- 2.0; DHEA, 8.8 +/- 8.9; DHEA-S, 3137 +/- 1774; 17-OHP, 2.0 +/- 3.0; and F, 216 +/- 121. Peripheral elevations of at least one androgen were found in 80% of the 60 cases (T, 38%; DHT, 18%; delta 4 A, 50%; DHEA, 45%; and DHEA-S, 37%). Ovarian-peripheral vein gradients ( OPGs ) and adrenal-peripheral vein gradients ( APGs ) served as semiquantitative estimates of glandular secretion. OPGs were as follows: T, 0.4 +/- 1.1; DHT, 0.1 +/- 0.2; delta 4 A, 3.4 +/- 7.0; DHEA, 14.6 +/- 100; DHEA-S, -288 +/- 523; 17-OHP, 4.5 +/- 8.4; and F, -35 +/- 47. APGs were as follows: T, 0.88 +/- 1.3; DHT, 1.1 +/- 0.9; delta 4 A, 14.4 +/- 38.4; DHEA, 327 +/- 367; DHEA-S, 854 +/- 1223; 17-OHP, 20.8 +/- 41.3; and F, 1252 +/- 2023. Excess ovarian and/or adrenal androgen output was assumed in a given individual when one or more of the respective T, DHT, delta 4 A, DHEA, and DHEA-S gradients exceeded the upper 95% confidence limits of normal previously established in this laboratory.(ABSTRACT TRUNCATED AT 250 WORDS)
Standardized bilateral ovarian-adrenal vein catheterization was utilized to preoperatively assess glandular steroid release in seven consecutive cases of occult virilizing gonadal neoplasms. Peripheral testosterone (T) exceeded 1.5 ng/ml in all instances (range, 1.51 to 8.67 ng/ml). Endoscopy and radiography failed to locate the functional lesions. Catheterization showed a unilateral elevation of the ovarian-peripheral vein gradient for T greater than 2.7 ng/ml in six women. In the remaining patient, gradient analysis ruled out an adrenal tumor but did not facilitate lateralization of the gonadal lesion due to subselective ovarian effluent sampling. In addition to the consistent hypersecretion of T, variable excess gonadal output of dihydrotestosterone, androstenedione, dehydroepiandrosterone, and 17 alpha-hydroxyprogesterone was evident. Associated adrenal androgenic hyperfunction was documented in three subjects. Histologic evaluation of the implicated ovaries revealed three lipid cell, two Leydig cell, and two Sertoli-Leydig cell tumors, respectively, measuring between 0.6 and 2.2 cm in diameter. No correlation was found between any of the following parameters: peripheral or glandular vein steroid levels, androgen gradients, severity of symptoms, tumor morphology, and tumor size. In conclusion, appropriate application of selective catheterization may considerably reduce the frequency and extent of operative intervention.
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