[Sex hormone replacement following menopause--for all women? A plea for prevention using estrogens and gestagens]. / Sexualhormonsubstitution nach der Menopause--für alle Frauen? Plädoyer für die Prävention mit Ostrogenen und Gestagenen.

After the menopause, a growing proportion of women will have a good chance to add three decades or more to their lifetime. They must decide whether to start long-term hormonal replacement therapy or to accept the risks of osteoporosis, fracture, cardiovascular disease, and a variety of psychological and physical problems as 'natural' destiny. The syndrome of postmenopausal endocrine deficiency is a primary glandular insufficiency, which in principle requires substitution with the secretory product of the gland. Postmenopausal osteoporosis and fractures are consequences of a pathological dysfunction of calcium metabolism. After estrogen withdrawal, the impaired hepatic and renal synthesis of calcitriol will result in a reduced intestinal resorption of calcium. Parathyroid hormone may initiate a vicious circle by acceleration of bone resorption, mobilization of bone calcium and a tendency to hypercalcemia. The failure to preserve circulating calcium due to 'escape' from calcitonin and a decreased renal tubular back-resorption are followed by an increased loss of calcium from a 'renal calcium leak', resulting in hypercalcuria. In order to maintain homeostasis, additional calcium is required, which will be supplied from accelerated bone resorption. Thus, the circle is closed by renewed osteolysis. The process is associated with accelerated bone turnover and a negative balance of calcium and bone. After a variable time interval which depends on the individual bone mass and rate of bone loss, these events will inevitably result in osteoporosis. Estrogen replacement will interrupt the circle, decelerate bone turnover, and re-establish a positive balance of calcium and bone. Estrogen withdrawal also favors an 'atherogenic' set of lipoproteins, which is strongly associated with increased coronary risk. Substitution with estrogens will favor a 'protective' profile of lipoproteins and cut the cardiovascular risk to about one half. Progestogens, in particular the 17 alpha-alkylated 19-nor-steroids, may reduce the favorable effects of estrogens on lipoproteins in a dose-dependent manner; however, they do not impair the antiatherogenic estrogen effects, even in presence of an atherogenic profile of lipoproteins. Thus, these anti-estrogenic effects of progestogens, at least in nonhuman primates, do not have clinical significance.(ABSTRACT TRUNCATED AT 400 WORDS)

[Indications for the therapeutic use of contraceptive steroids]. / Therapeutische Indikationen kontrazeptiver Steroide

PIP: Therapeutic indications of contraceptive steroids are described. Menstrual cycle disturbances may benefit from the regularizing effects of combined or sequential contraceptives. Other gynecological conditions for which steroid hormone treatment may be indicated are: functional dysmenorrhea, premenstrual syndrome, endometriosis, and benign breast conditions. Seborrhea oleosa, acne, alopecia, and hirsutism may respond to steroid hormone treatment; neoplastic etiology and pregnancy must be eliminated before such treatment, however. Precocious puberty and pseudopuberty may also be treated with steroid hormones, which repress or inactivate body hormones responsible for the symptomatology. Estrogens are also used to limit the adult height of girls; this procedure must still be regarded as experimental.^ieng

[Are you prescribing fatal hormones? Bremen professor accuses physicians with unsubstantiated claims]. / Verschreiben Sie tödliche Hormone? Bremer Professor verunglimpft Arzte mit unhaltbaren Vorwürfen.

The present study uses arbitrary projections based on non-representative local polls of women insured by the AOK (an insurance carrier) to construct a fictitious Pan-German data base, which is then used to make pronouncements on the hormone exposure, hysterectomy status and the prevalence of estrogen monotherapy in non-hysterectomied women in all the German Bundesländern (States). Using the data of the Saarland cancer registry the yearly incidence of approximately 42,000 mammary carcinomas (MC) and approximately 8700 endometrial carcinomas (EC) were extrapolated to the whole of Germany. Relative risks obtained from US literature were arbitrarily used as factors for calculations showing a yearly attributive risk of approximately 5000 MC and approximately 3000 EC due to the use of exogenous sex hormones. Although the numerical details of the calculations are not given, the information the authors provide on the acquisition and processing of the data--as also the interpretation of the results--leaves no room for doubt that here the minimum formal, content-related and methodological standards required of epidemiological studies have not been met. Since the quality of the basic data makes the results, even as "preliminary estimations" [2], unacceptable, they merely add to the already existing contradictory and inconsistent data material.

[Endocrine regulation of the menstrual cycle]. / Die endokrine Regulation des menstruellen Zyklus

Physiological data concerning the serum concentrations and the pituitary content of varian steroids and gonadotropins, respectively, are reviewed. On the basis of these physiological data results from experimental studies are critically evaluated as far as their significance for the understanding of the physiology of the cycle is concerned. Data from the literatur and results from own studies are incorporated in a concept of the endocrine regulation of the human menstrual cycle.

Falsely low results in CA 125 determination due to anti-idiotypic antibodies induced by infusion of [131I]F(ab')2 fragments of the OC125 antibody.

We investigated a one-step immunometric CA 125 assay, which employs new anti-CA 125 antibodies as capture antibodies and OC125 antibodies for detection, for interference due to antibodies induced by repeated administration of F(ab')2 fragments of the anti-CA 125 antibody OC125. Testing 33 samples, obtained from 13 patients treated with OC125 fragments, we found falsely high CA 125 concentrations only in samples with exceptionally high concentrations of both anti-idiotypic antibodies and non-specific human anti-mouse antibodies. In contrast, the recovery of added CA 125 was already diminished in the presence of low anti-idiotypic antibody concentrations. Both interferences disappeared after removal of serum IgG. It was possible to eliminate the falsely high results, but not the reduction in recovery rate, by adding non-specific murine IgG. When the binding of the detector antibodies was performed in a separate incubation step, no reduction in recovery rate was observed. Our results suggest that non-specific human anti-mouse antibodies are responsible for falsely high results. The reduction in the recovery rate is obviously due to an inhibition of the binding of OC125 detector antibodies by anti-idiotypic antibodies. In patients receiving OC125 antibodies CA 125 can be measured using OC125 detector antibodies if a two-step assay is performed. An increase in CA 125 following OC125 infusion should be confirmed after the addition of non-specific murine IgG.

Experimental studies on the endocrine regulations during the periovulatory phase of the human menstrual cycle. The effects of exogenous 17 -oestradiol and progesterone on the release of pituitary luteinizing and follicle stimulating hormones.

PIP: In order to simulate some parts of the progesterone and estrogen patterns of the normal menstrual cycle in a normal women, im injections of progesterone and estradiol benzoate were used in 7 amenorrheic, castrated, postmenopausal, or eugonadal women who were receiving 60 mcg of ethinyl estradiol orally per day. Both progesterone and estradiol benzoate were found to produce a positive feedback on the hypothalamic cycle center as measured by the plasma LH surge. Subsequent LH peaks could be induced by either hormone after an estradiol-induced peak, but neither hormone could induce an LH peak after the first progesterone-induced peak. Progesterone-induced LH peaks were always immediate and short-lived with the duration of the LH release appearing to be inversely related to the dose. Estradiol-induced LH peaks did not appear until at least 24 hours after the injection. Only progesterone induced a significant increase in plasma FSH levels. It is inferred from these experiments and the steroid pattern of the normal mentrual cycle that 17-beta-estradiol is the initial triggering stimulus in the cycle leading to an LH surge. This in turn results in an increase in plasma progesterone which regulates the amount of LH release in the second part of the biphasic midcycle peak, which is a possible periovulatory mechanism for mono-ovulation in the human female.^ieng

[LH, FSH and ovarian steroids in serum during normal menstrual cycles and cycles with corpus luteum insufficiency in the human female (author's transl)]. / Hypophysäre Gonadotropine und ovarielle Steroide im Serum während des normalen menstruellen Cyclus und bei Corpus-luteum-Insuffizienz

LH, FSH, estradiol-17beta, progesterone, 20alpha-dihydroprogesterone, 17alpha-hydroxyprogesterone, delta4-androstenedione and testosterone are determined by radioimmunoassay in serum daily during 11 menstrual cycles. Three of them had to be considered as cycles with corpus luteum insufficiency on the basis of basal body temperature, length of the luteal phase and the pattern of progesterone concentration in serum. One woman conceived during the investigated cycle. The present concepts of the regulation of ovulation are discussed on the basis of the chronological relationshp of changing endocrine parameters in serum during the cycles. The analysis of the hormone concentrations in serum during the cycles with corpus luteum insufficiency supports the view that corpus luteum insufficiency could be caused by an insufficient stimulation of the growing follicle, but other ethiological factors have also to be considered.

[Estradiol-17beta, estrone, LH and FSH in serum after administration of estradiol-17beta, estradiolbenzoate, estradiol-valeriate and estradiol-undecylate in the female (author's transl)]. / Untersuchungen zur Pharmakokinetik von Ostradiol-17beta, Ostradiol-Benzoat, Ostradiol-Valerianat und Ostradiol-Undezylat bei der Frau: Der Verlauf der Konzentrationen von Ostradiol-17beta, Ostron, LH und FSH im serum

Estradiol-17beta, estradiol-benzoate, estradiol-valerianate, and estradiol-undecylate were injected intravenously and intramuscularly to postmenopausal woman and to female castrates. Equal doses were used corresponding to 20 mg of free estradiol-17beta. Estradiol-17beta, estrone, FSH and LH were measured in serum by radioimmunoassay before and after application of the hormone and the estradiol esters. Thus the depot effect of the different esters could be compared.

Experimental studies on the positive feedback effect of progesterone, 17 alpha-hydroxyprogesterone and 20 alpha-dihydroprogesterone on the pituitary release of LH and FSH in the human female. The estrogen priming of the progesterone feedback on pituitary gonadotropins in the eugonadal woman.

Administration of progesterone eugonadal women during the midfollicular phase of the menstrual cycle failed to induce a positive feedback effect on the serum concentrations of LH and FSH. The levels of estradiol in serum decreased following the injection of progesterone without a parallel change in LH and FSH concentrations indicating a direct ovarian effect of the exogenous progesterone. In the late follicular phase of the cycle, when preovulatory levels of estradiol were present in serum, or under a ethinyl estradiol treatment progesterone was able to induce an LH discharge indicating the requirement of an estradiol priming of the positive feedback of progesterone in eugonadal women. In order to establish the time required for a sufficient estrogen priming with preovulatory levels of estradiol in serum 3 mg of estradiol-benzoate were administered i.m. 1, 12 and 24 h prior to the administration of 30 mg of microcristalline progesterone in the midfollicular phase of the menstrual cycle, when progesterone alone did not cause an LH surge. Only when estradiol-benzoate was injected 24 h prior to the progesterone administration an LH surge reproducible in time course and magnitude occurred. Administration of estradiol-benzoate alone under these conditions did not cause an LH surge within the elapse of time after the injection when the progesterone induced LH surge occurred. Thus, these experiments demonstrate that a defined estrogen priming is required for the positive feedback effect of progesterone on the gonadotropin release in eugonadal women. Furthermore, progesterone levels in serum of about only 1--2 ng/ml were required for the induction of an LH surge indicating that under physiological conditions progesterone may have an supplementory effect on the primarily estradiol induced LH midcycle peak. 17-hydroxyprogesterone administered during the mid follicular phase of the menstrual cycle and under pretreatment with ethinyl estradiol failed to induce a positive feedback effect on the serum concentrations of LH and FSH, indicating that this steroid does not play a regulatory role on the midcycle LH release in women. 20alpha-dihydroprogesterone administered under the same experimental conditions as 17-hydroxyprogesterone seems to be able to induce an LH surge in serum provided there is an adequate estrogen priming.

PIP: The hypothesis that progesterone (P) is involved in the regulation of the estradiol-induced midcycle surge of luteinizing hormone (LH) was investigated in eugonadal women. The administration of P during the midfollicular phase did not exert a positive feedback effect on serum levels of LH and follicle stimulating hormone (FSH). Serum estradiol levels fell after the administration of P, though levels of LH and FSH were not altered. This indicates a direct ovarian effect of P. Administration of P, in the presence of preovulatory levels of estradiol or exogenous ethinyl estradiol, induced an LH discharge indicative of the necessity of estradiol priming for the positive feedback effect of P. It was found that estradiol benzoate had to be adminstered at least 24 hours prior to the administration of P during the midfollicular phase for the LH surge to occur. In his latter experiment, neither P nor estradiol by themselves were able to produce an LH surge, thus indicating the estrogen priming is required for the positive feedback effect of P on LH release. 20alpha-dihydroprogesterone, but no 17-hydroxyprogesterone, was able to induce an LH surge with adequate estrogen priming.

[Clinical aspects and diagnosis of intrauterine growth retardation]. / Klinik und Diagnostik der intrauterinen Mangelentwicklung

Low birthweight infants add to a great extent to perinatal mortality. Among this group children with intrauterine growth retardation differ from premature children with respect to their pre-, intra- and postnatal risk. Early prenatal diagnosis and monitoring is of great importance for the outcome and later development of these children.

Effect of long-term testosterone oenanthate administration on male reproductive function: clinical evaluation, serum FSH, LH, testosterone, and seminal fluid analyses in normal men.

The effect of long-term testosterone administration on male reproductive function has been investigated in seven healthy young men age 20 to 27 years. Testosterone oenanthate (TOe) was administered in doses of 250 mg per week for 21 weeks. No toxic side-effects were observed. Libido, sexual potency, frequency of sexual intercourse and body hair development generally remained unaffected, but there was a reversible mean weight gain of 3.6 kg during TOe administration. Seminal fluid parameters and radioimmunoassayable serum FSH, LH, testosterone, and androstenedione levels were monitored before, during, and after TOe administration. The serum testosterone rose approximately by a factor of two, while the serum FSH and LH were rapidly suppressed after the initiation of the TOe therapy. The mean sperm concentration fell to values below three million spermatozoa per ml, and changes in sperm motility, the percentage of normal sperm morphology, and seminal fructose concentrations generally paralleled those of the mean sperm concentrations. In contrast, the mean seminal fluid volume and serum androstenedione levels did not change significantly during TOe administration. The mean sperm concentration showed a marked recovery 13 to 16 weeks after TOe withdrawal, but sperm counts remained below pre-treatment levels in three out of seven subjects 25 to 28 weeks after discontinuation of TOe.

The role of testosterone in the feedback control of male FSH and LH secretion.

Intramuscular administration of 250 mg testosterone oenanthate per week over a period of 21 weeks treatment rapidly and sustainedly suppressed serum LH as well as FSH levels in seven normal males, while serum testosterone rose by a factor of approximately two. These together with other data provide increasing evidence for a feedback control of FSH secretion by gonadal steroids in the male in addition to the already described but as yet undefined tubular testicular factor.