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Biomedical subjects

F Stahl

Publications and source records attributed to F Stahl.

At least 73 records · Page 4Linked to original sources

[Conservative therapy of prostate cancer using Turisteron].

Turisteron is an orally highly effective depot estrogen (ethinylestradiol sulfonate) with relatively slight side effects. The treatment with Turisteron is very effective and is well tolerated by the patient. A strong antiandrogenic effect could be produced which had as its sequel a significant increase of the survival rates of patients with carcinoma of the prostate gland. The weekly dosage of 2 mg Turisteron led to a decrease of the biologically active, free testosterone to less than 2% compared with the initial value. The decrease of the total testosterone to castration values and the decrease of the free testosterone still significantly below values of castration are evidences for the strong antiandrogenic effect in exclusive estrogen treatment with Turisteron. From this conclusions relevant to practice were derived and finally therapy recommendation for the conservative treatment of the carcinoma of the prostate gland were given.

Aged↗

[Behavior of LH, FSH, total testosterone, free testosterone and SHBG serum levels in the therapy of prostatic cancer with Turisteron (ethinyl estradiol sulfonate)].

45 patients with prostatic cancer were treated conservatively with Turisteron at a dosage of 2 mg per week. After 2 months the serum levels of total testosterone were reduced to castration values and thereafter furthermore to 6% of the pretreatment values. The free testosterone (FT) serum level did show a decrease to 2%, while the binding capacity of the sexual hormone binding globulin (SHBG) was increased from 4,1% to 97,9%. The serum levels of the two gonadotropic hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were decreased only to nearly 20% of the pretreatment value. The investigations confirm the definite "antiandrogenic" effect of Turisteron, which is 10-times higher than the antigonadotropic effect.

Ethinyl Estradiol↗

[Clinical study of ethinyl estradiol sulfonate in conservative therapy of prostate cancer].

Ethinylestradiol sulfonate is an orally applicable, potent depot estrogen with steroid structure. With a dosage of 2 mg per week it shows a distinct antigonadotropic and antiandrogenic effect. Its suitability for the hormone therapy of the carcinoma of the prostate is clinically and cytologically confirmed. It seldom has undesirable side effects. The oral application necessary only once a week guarantees a continuous supply of active substances with a good compliance by the patients.

Adenocarcinoma↗

[Inhibition of the free, biologically active testosterone level by Turisteron in patients with prostate cancer].

Apart from their antigonadotropic effect oestrogens also directly inhibit the androgen secretion of the testicles. Thus, on the 20th day of treatment the LH-level after 12 g diethylstilbestrol diphosphate (DSDP) decreases only to approximately 50% of the initial value, while the whole testosterone (T), however, is reduced to less than 5%. The sexual hormone binding globulin is significantly more increased (p less than 0.001) by the estrogen treatment than after orchidectomy only. Therefore, the free, biologically active T-level in the plasma consists of more than one third of the level after exclusive orchidectomy. The treatment with the depot estrogen Turisteron is clarly superior to the usual treatment Oestrasid implants. Both with and without orchidectomy the free testosterone level is significantly lower than after Oestrasid implants plus orchidectomy. Therefore, this therapy can successfully be used in the treatment of the carcinoma of the prostate also without orchidectomy.

Administration, Oral↗

Postovulatory sensitization to the negative oestrogen feedback in female rats is probably induced by the preceding decline of the oestrogen concentration in the medial preoptic area.

To examine the question if an endogenous oestrogen-independent rhythm is involved in the cyclic variation of sensitivity to the negative feedback of oestrogen recorded in a former study, adult female rats were ovariectomized on subsequent days of a 4-day ovarian cycle, injected with 3 micrograms oestradiol benzoate (OB)/100 g b.w. or oil three days after castration, and autopsied on the following day. Estimation of the serum LH concentration revealed a similar LH-inhibiting effect of OB in all experimental groups. Female rats were then implanted with OB or cholesterol in the medial preoptic area (MPOA) in metoestrus. In part of the rats, the implants were removed on the presumptive day of pro-oestrus to imitate the periovulatory decline of the circulating oestrogen level acting on the MPOA. Evaluation of the sensitivity to the negative oestrogen feedback during oestrus and metoestrus demonstrated that s.c. injected OB was highly effective in suppressing the LH secretion after removal of the OB implants in pro-oestrus, but not in rats with the implants left in place till autopsy. In a final experiment, the pro-oestrous progesterone surge was inactivated by the injection of specific antibodies. An influence of this treatment on the LH-inhibiting effect of OB examined during oestrus and metoestrus could not be found. Taken together the results suggest that the high sensitivity to the negative oestrogen feedback recorded during the postovulatory period in cyclic female rats is mainly induced by the periovulatory fall of the circulating oestrogen level leading to reduction of the medial preoptic oestrogen concentration.

Animals↗

Successful treatment of prostatic cancer with the orally active depot estrogen ethinylestradiol sulfonate (Turisteron).

Ethinylestradiol sulfonate (Turisteron) is an orally highly active depot-estrogen with relatively low side effects. In men with prostatic cancer, weekly administration of 2 mg Turisteron resulted in a striking decrease of the biologically active free testosterone level to less than 2% of the basal level; i.e., even significantly lower than after orchidectomy. Turisteron was able to normalize the 5 year survival rate in men with advanced non-metastatic cancer (T3NxM0) and to increase the survival rate significantly in men with metastatic cancer (T3-4, Nx, M1). Hence, due to our experience, Turisteron treatment is a very effective, non-expensive and well tolerated therapy for prostatic cancer.

Aged↗

Serum levels of FSH, LH and estradiol-17 beta in female rats around the time of puberty onset.

Groups of female rats were autopsied at daily intervals from 27 days of age through the first vaginal cycle and the serum FSH and LH and plasma estradiol-17 beta (E2) concentrations were estimated. Fluctuating hormone concentrations were recorded between days 27 and 31. Both gonadotropins and E2 dropped to a very low level on days 32 and 33 and showed then a progressive increase that commenced on day 34 and terminated for LH and E2 on day 39, i.e. in proestrus, whereas FSH declined from day 37 to day 39. The circulating gonadotropin level was lower during the first postpubertal diestrus than during most of the prepubertal phase. The findings suggest that a high sensitivity to the gonadotropin -inhibiting effect of estrogen prevented completion of an ovarian cycle up to day 33. After that, desensitization to the negative estrogen feedback as indicated by the simultaneous rise of E2 and gonadotropins makes final maturation of ovarian follicles and the first ovulation possible. In part of the rats aged 27-38 days cell nuclear volumes of medial preoptic neurons were evaluated, because recent results suggest that estrogen induces the desensitization process by an inhibitory action on the medial preoptic area. In accordance with this assumption, an inverse relationship between nuclear size and the E2 level in the blood could be revealed.

Animals↗

A sensitive direct enzyme immunoassay for cortisol in plasma and saliva.

A sensitive enzyme immunoassay for cortisol in plasma and saliva without extraction has been developed. An antibody was raised in rabbits against cortisol-3-CMO-BSA and compared with anti-cortisol-21-HS-HSA. The enzyme label was a covalently linked cortisol-horseradish peroxidase conjugate. Solvent extraction was avoided by use of heat denaturation of transcortin and dilution of plasma 1:300. This assay had a limit of detection of 3 fmol/tube and satisfied the standard criteria of accuracy and precision. The test requires only a simple photometer. The normal values of cortisol in plasma and saliva before and after ACTH, dexamethasone or metyrapone application were determined. Saliva, being easily collected by a noninvasive, stress-free technique is an alternative to plasma. The cortisol concentrations were significantly increased in plasma and saliva of patients with Cushing's syndrome and decreased in patients with Addison's disease.

Addison Disease↗

Plasma testosterone levels in rats under various conditions.

A radioimmunoassay (RIA) for testosterone (T) was found to be suitable for determination in plasma of rats. Since the cross-reactive dihydrotestosterone levels were extremely low both in males (130.8 +/- 27.6 pmol/l) and females (189.4 +/- 41.3 pmol/l), the procedure measured T equally well, whether or not chromatography preceded the RIA. The method met all requirements of precision, sensitivity, accuracy and specificity. Basal levels of 5 male control groups (n approximately equal to 10) showed considerable variations from a low of 6.86 +/- 4.68 nmol/l to a high of 16.26 +/- 5.06 nmol/l. This high variability may be the reason, at least in part, for the fact that moderate stress did not produce always a significant decrease of T levels in males. However, after forced stress or administration of adrenaline plasma T was significantly (p less than 0.01) lower than in controls. Gonadectomy lowered extremely plasma T levels both in males and females, whereas adrenalectomy had no significant effect. These data demonstrate that the gonads are the main sources of T in both sexes. The significant (p less than 0.01) decrease of T levels after administration of adrenaline, dexamethasone and ACTH in adrenalectomized males indicated that these substances affect mainly the testicular synthesis of T. In cyclic females, administration of ACTH produced no significant change in plasma T levels. During pregnancy, there was a significant (p less than 0.01) increase of plasma T values from day 10 to day 18-19, followed by a decrease to day 22.

Adrenalectomy↗

[Significance and mechanism of desensitization to the gonadotropin-inhibiting effect of estrogen. 1. Studies on prepubertal desensitization].

In immature female rats, both a distinctive diminution of the gonadotrophin-inhibiting effect of s. c. or intrahypothalamically implanted estradiol and a simultaneous rise of the estrogen and gonadotrophin levels in the blood were revealed during the last days preceding the onset of puberty. Based on these findings, studies on the neurohormonal mechanism underlying this prepubertal desensitization to the negative estrogen feedback were performed. Bilateral lesioning of the medial preoptic area (MPOA) which induced precocious puberty also diminished significantly the gonadotrophin-inhibiting effect of s. c. or intrahypothalamically administered estrogen. Similar responses were recorded following the implantation of very low quantities of estrogen into the MPOA, whereas medial preoptic implants of the antiestrogen clomiphene citrate impaired the spontaneous prepubertal desensitization and delayed the onset of puberty. It is concluded from the results that the prepubertal increase of the estrogen concentration in the blood itself induces the desensitization to estrogen by an inhibitory effect on medial preoptic neurons. Preliminary clinical and experimental findings suggest that a comparable mechanism may be operative in humans, too.

Animals↗

The influence of adrenaline on plasma testosterone in adult and newborn male rats.

In adult male intact and adrenalectomized rats a significant decrease of plasma testosterone was found following five days of subcutaneous treatment with adrenaline. LH was significantly decreased in adrenalectomized, adrenaline treated males. Plasma testosterone was also found to be diminished in the male offspring of females treated with adrenaline during pregnancy. In view of these findings catecholamines may also play a role in the stress-induced drop of plasma testosterone in adult animals as well as in the production of androgen deficiency in male fetuses and newborns of stress-exposed pregnant females.

Adrenalectomy↗

Effects of tamoxifen on the levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), 17 beta-oestradiol (E2), total and free testosterone (T) and total and free dihydrotestosterone (DHT) in blood of patients with benign prostatic hyperplasia.

Treatment of 9 patients with benign prostatic hyperplasia with 20 mg tamoxifen daily for 6 weeks resulted in a significant increase of LH (211%), FSH (215%), E2 (231%), total T (157%), free T (148%) and total DHT (148%) levels in blood. The increase of plasma free DHT (152%) levels was not significant and PRL concentrations in serum were unchanged during treatment. Comparison of the increases between total T and free T, total T and total DHT as well as free T and free DHT failed to reveal any significant differences. These results imply (1) a marked anti-oestrogenic effect of tamoxifen at the level of hypothalamo-hypophysial axis (2) no effect at the hepatic oestrogen receptor sites indicated by unchanged SHBG-bound T and DHT in plasma and (3) no significant inhibitory effect of tamoxifen on 5 alpha-reductase activity concluded from the T/DHT ratio in peripheral circulation. In view of these findings tamoxifen appears to be unsuitable for therapy of benign prostatic hyperplasia.

Dihydrotestosterone↗

Responses of salivary cortisol levels to stress-situations.

A procedure is described for determining salivary cortisol levels by a competitive protein-binding assay using horse transcortin. The collection of saliva was performed by means of filter paper-strips. Filter paper samples are more than 5 days stable after air-drying. In this form, the samples could be stored without refrigerator or deep-freezer and, if necessary, sent by post to the laboratory without any special precaution. Stressful situation of either painful or anxious origin were associated with an adequate increase of salivary cortisol levels. The increases were 157 to 230% of the initial or normal values dependent on the kind of stress. The mean values in 4 cases of Cushing's syndrome were 380% and 1 hour after 25 I.U. ACTH 690% higher than those in normal persons. In normal persons, a well-defined circadian rhythm has been observed.

Adrenocorticotropic Hormone↗