Ovarian steroid hormones and cerebral function.
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1. Malformations and functional disturbances of the male genitalia may be caused by teratogens. 2. A short review of the prenatal development points out the possible sites of action. 3. In animals some distinct teratogens produce typical malformation syndromo spermatogenetic cells. Cyproteronacetat, an antiandrogen, suppresses the development of the accessoric genital organs and produces an external feminisation. 4. In man, cryptorchidism, agenesis of the spermatic tracts, anorchia and hypospady are known as non-hereditary malformations. 5. The teratogenic etiology of some disturbances of the spermatogenesis is discussed.
An analysis has been carried out on the basis of endocrinological and psychosomatic studies of the influence of steroid hormones, acting via probable transmitter substances, on the sexual response in women. From a review in the literature it can be concluded that among other factors the endocrine state of the women determines her sexual response and behaviour. However, the present lack of specific psychological tests is pointed out, as well as the absence of relevant hormonal data to the sexual sphere, both normal and pathological.
In male and female rats the endogenous steroid and gonadotrophin secretion was inhibited by injecting high doses of chlormadinone acetate (CmAc) from day 14 to 24 of life, i. e. during the period of brain maturation. In adulthood the males treated prepubertally with CmAc exhibited reduced sexual activity and fertility, whereas the females did not differ from the controls. More complete sex hormone deficiency during brain maturation was achieved by castration on day 14 of life. Controls were castrated at normal puberty time (40--60 days). Both groups were then substituted with androgens or oestrogens. In the females castrated on day 14 no impairment of sexual behaviour was observed as compared to the later castrated controls. In contrast, the early castrated males showed delayed onset of mounting behaviour. At autopsy, the weights of their sex organs were found to be lower than in the controls despite equal testosterone replacement for several months. These findings speak in favour of a permanently diminished responsiveness to androgens in males having been exposed to more or less severe androgen deficiency during sex specific brain maturation. Hence, the maturation of a male hypothalamus as well as the differentiation appears to depend at least in part on the presence of androgens, whereas in females it runs without hormonal influence.
Carbohydrate metabolism was examined--by means of the 100-gm-glucose standard tolerance test--in 23 patients showing a decrease in glucose tolerance during pregnancy; the examinations were carried out postpartum and after a three months' intake of a hormonal contraceptive (compound preparation: mestranol 0.1 mg, lynestrenol 1.0 mg). The peak values and the two-hour-values, being statistically significant, showed a normalization after delivery, and furthermore again a deterioration of glucose tolerance during the intake of the preparation. A remarkable increase in weight, as a possible cause for the dysbolism during contraception, was not observed.
During hormonal contraception with Deposiston (once a week pill) and with Sequenz-Ovosiston (14 days mestranol 0.1 mg, 7 days mestranol 0,08 mg and 2 mg chlormadinone acetate) doesn't take place a change of basophil granulocytes (heparinocytes) in blood. Under Deposiston the small elevation is somewhat lengthened, under Sequenz-Ovosiston the elevated phase is similar to those of the normal menstrual cycle. The smaller risk of thromboembolia under heparinocytopenia preventing contraceptives is discussed.
The number of platelets, spreading and aggregation of platelets in plasma of 102 women treated with Ovosiston, an anticonceptive agent, were investigated. A significant increase of the number of platelets, spreading and aggregation of platelets was observed. Conclusions from isolated observations are not possible.
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An increase in breathing activity has often been described for the secretory phase of the menstrual cycle, for gravidity and after intramuscular application of corpus luteum and follicle hormone. The reason for this has been assumed to be a direct interaction of the hormones in the respiratory center. A shortly published paper dealing with 50 women under long-term treatment with a combination of oestrogenes and gestagenes for oral contraception leads the author to the assumption, that a metabolic acidosis is the primary reaction, followed by an increase in breathing activity for respiratory compensation. In a long-term study it is difficult to differentiate between primary and secondary effects. Therefore in the present experiments arterial blood has been analyzed for PaO2, PaCO2, pH and hemoglobin in 49 subjects on day 1 without hormone administration and on day 2 prior to (9.00 a.m.) after (11.00 a.m., 1.00 p.m., 4.00 p.m.) administration of a combination of oestrogene and gestagene. From the measured values O2-saturation, standard-bicarbonate, buffer bases and base excess have been calculated by the Thews nomogram. By comparison of the results before and after hormone administration it was shown, that the primary effect is a metabolic acidosis, partly compensated during the next 7 h by respiratory adaptation. There is no indication for a primary respiratory alkalosis.
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The long-term effects of oral contraceptive steroids including a combination of norethindrone and ethynylestradiol, a sequential regimen of dimethisterone and ethynylestradiol, and daily administration of megestrol acetate were studied in female beagle dogs at dose levels of 1, 10, or 25 times the projected human dose levels. The major findings included cystic endometrial hyperplasia and pyometra requiring hysterectomies and alopecia for the norethindrone-ethynylestradiol and dimethisterone-ethynylestradiol treated dogs. These groups did not have accentuated mammary development or treatment-related hyperplastic or neoplastic changes. For dogs given dimethisterone-ethynylestradiol, numerous acne-like lesions occurred in the skin of the mammary areas. Dogs given the higher dose levels of megestrol acetate had marked mammary stimulation, hyperplastic and neoplastic changes in the mammary glands, and clinical and pathologic changes typical of diabetes mellitus. Mammary changes of nodular hyperplasia, benign mixed tumor, and adenocarcinoma appeared as distinct entities although constant and intense mammary stimulation may be a common denominator. Such mammary changes have not been found in long-term studies in monkeys or rats with megestrol acetate, and the relevance of the canine mammary changes to projecting potential tumorigenesis in women is questioned.
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A significant decrease in early receptivity during the night from dioestrus II to prooestrus was observed in estrogen-treated 4-day cyclic rats following bilateral ovariectomy on dioestrus II at 4-5 p.m. Early receptivity appeared then to be dependent on the presence of ovary at this stage of the cycle. The mechanism whereby the adrenals may compensate for the ovaries when removed on dioestrus I, at 10-11 a. m. (Roos et al. 1973), was not observed in the present experimental conditions.
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