[Determination of urinary pregnanediol as an ovulation parameter].
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The growth hormone, insulin and blood glucose values were measured during a glucose tolerance test in 12 women before and after 3 months' use of a contraceptive of the sequential type (11 pills containing 0.05 mg D-norgestrel and 0.05 mg ethinylestradiol and 10 pills containing 0.125 mg D-norgestrel and 0.05 mg ethinylestradiol). Neither fasting blood glucose nor glucose tolerance are altered during administration of the contraceptive steroids. On the other hand, the reactive insulin level is significantly increased in comparison to the basal value, thus showing the signs of hyperinsulinemia. Both the gestagens and the estrogens appear to contribute to this disturbance of insulin secretion. Presumably the hyperinsulinemia is an expression of decreased sensitivity of the peripheral tissue to insulin. The growth hormone, a so-called insulin antagonist, is not responsible for the "insulin resistance" observed. The values measured by us after administration of the contraceptive do not significantly differ from the basal values.
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A study was made of the excretion of the luteinizing hormone (LH) of the hypophysis and of the 5-oxyindolacetic acid in the course of 18 clinically-normal menstrual cycles. There proved to be a significant correlative association in the excretion of dophamine and of the LH in the middle of the cycle. As a rule, the peak of dophamine excretion coincided with the peak of the LH excretion. No statistically significant association between the 5-oxyindolacetic acid excretion and the LH excretion was found in the course of the cycle.
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A study was made of the dynamics of the synthesis and secretion of the luteinizing hormone in the course of the sexual cycle in female rats by its determination by the radioimmunological method. Depending on the stages of the sexual cycle there were seen regular changes in the LH content in the hypophysis and the blood of female rats. LH content in the hypophysis was the minimal at 3 p.m. at the estrus stage and the maximal at 6 p.m. at the proestrus stage.
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Plasma renin activity (PRA), Growth hormone (GH) and immunoreactive insulin (IRI) were studied in seven healthy subjects during the ovulatory menstrual cycle and during the first and third cycles of oral contraception with 0.05 mg of ethinylestradiol and 0.100 mg or 0.125 mg of a new progestogen, 17 alpha-ethinyl-18-methylene-4-estren-17 beta-ol. The PRA level in the second half of the control cycle was significantly higher than in the beginning of the cycle. At the end of the treated cycles it was significantly higher than at the end of the control cycle. Neither GH nor IRI showed significant changes during the control cycle. GH was significantly higher at the end of the first and third treated cycles than at the end of the control cycle. IRI was significantly higher both in the beginning and at the end of the first treated cycle than the corresponding IRI levels in the control cycle. IRI at the end of the third treatment cycle was not significantly different from corresponding means at the end of the control cycle or the first treated cycle.
A considerable number of women receiving antiovulatory compounds or estrogens complain of weakness and fatigability, suggesting a state of clinical hypoadrenalism. For this reason, levels of plasma ACTH and plasma cortisol were determined in 25 women with such complaints both during treatment and at various intervals after cessation of this treatment. The results obtained showed that there was a significant inhibition of ACTH secretion during long-term treatment with antiovulatory compounds or estrogens, and in half of the cases, there was a delay in normalization of the pituitary-adrenal axis following interruption of the drug, supporting a state of transitory hypoadrenalism.
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In men suffering from prostatic cancer, i.v. administration of 12 g diethylstilboestrol diphosphate within 20 days resulted in a decrease of the LH serum level to about 50% (P less than 0.05), whereas the total testosterone level decreased to less than 5% (P less than 0.001) and the apparently free testosterone level to less than 2% of the initial values (P less than 0.001). Hence, the "systemic antiandrogenic effect" of oestrogen can be explained (1) by indirect inhibition of testicular androgen secretion via diminution of hypophyseal gonadotrophin secretion, (2) by direct inhibition of testicular androgen secretion and (3) by elevation of the capacity of testosterone binding beta-globulin.
In early pregnancy up the 7th week of pregnancy PGF2alpha was infused and 15(S)-methyl-PGF2alpha was applied i. m. to induce menstruation in 20 or 19 cases, respectively. In the tested form of application 15(S)-methyl-PGF2alpha is effective in 89 per cent of the cases and in 74 per cent complete abortion was achieved. PGF2alpha produced bleeding in 80 per cent only and complete abortion in 55 per cent. The differences in these two groups were not statistically significant. The steroid hormones estradiol and progesterone decrease in a successful application of PGs for induction of abortion and reach a value of 75 per cent at the onset of bleeding. The LH concentration in plasma becomes smaller too. In some cases there is a temporary increase in hormones shortly after starting treatment. The results could indicate that the considerable decrease in hormones before the onset of bleeding might be caused by an alteration of the corpus luteum, which is effective during early pregnancy.
The authors have studied the long-term effects of combined oestrogen-progestogen on the secretion of gonadotrophins and on ovarian function. Estimation of the radio-immune levels of the plasma concentrations of the pituitary luteinizing hormone (LH), of oestradiol (E2), of progesterone (P) and of 20 alpha hydroxyprogesterone (20 alpha OHP) and of testosterone (T) served as a base for this study. A test cycle and 8 cycles in which a combination of 50 micrograms of ethinyl-oestradiol and 0.5 mg of norgestrel were administered were studied in 4 normal volunteer women. A pituitary stimulation test using 50 micrograms of gonadotrophin "releasing factor" (LH-RH) was given during the 7th cycle. Ovarian stimulation using human menopausal gonadotrophins (HMG) was given during the 8th cycle of treatment in 3 of the women and in 3 other subjects. Pituitary secretion of LH and ovarian secretion of E2 and P are partially inhibited. Pituitary response to the injection of LH-RH stays normal but 5 out 6 patients had no response to stimulation by gonadotrophins. These results allow us to conclude that the lowering of production of gonadotrophins during treatment with combination oestrogen and progestagens is responsible for inhibition of ovarian activity, and that there is a delay before the latter respond to stimulation by either endogenous or exogenous gonadotrophins.
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The magnitude and frequency of episodic LH-fluctuations have been observed to change during the different phases of the menstrual cycle. A hypothalamic control center appears to be responsible for these variations. Disturbances of the hypothalamus often make themselves known through a lack of LH-episodes. Ahypothalamic derangement in women with functional amenorrhoea can result in a disregulation of gonadotropins as well as prolactin, thereby leading to hyperprolactinemia. One finds an inverse relationship between high prolactin secretion and cessation of or decreased pulsatile LH-secretion (spiking). LH-spiking was tested in physiological post partum, functional pathological and TRH-induced hyperprolactinemias. No LH-episodes were observed post partum after the end of HCG clearance although prolactin had returned to normal levels at 12 days p.p. The mode of LH-secretion in a group of functionally amenorrhoic patients was changed by a TRH-induced prolactin increase: the previously observed LH-spikes in these women could no longer be seen. Normal cycling women, however, were not affected. In patients with hyperprolactinemic anovulatory syndromes, prolactin suppressed LH-fluctuations reappeared after administration of 2-Bromo-alpha-ergocryptin. The inhibitory influence of hyperprolactinemia on the function of the gonadostat will be discussed. High plasma prolactin levels influence the cyclic and tonic hypothalamic function. Furthermore, prolactin appears to have a peripheral inhibitory influence on ovarian gonadotropin stimulation. Post partum anovulation and amenorrhoea can be caused by an antigonadotropic and antigonadic effect of prolactin.
Retrospective analysis of 103 samples of amniotic fluid was performed. Twenty-four samples were obtained prior to midtrimester abortion, 31 were from patients who delivered spontaneously, 14 were from patients in whom labor was induced, and the remaining samples were obtained from patients who were delivered by cesarean section. In all normal pregnancies, there was a rising trend in corticosteroid levels in amniotic fluid as the gestation advanced. This was less marked in abnormal pregnancies. There is a suggestive fetal role in initiation of normal spontaneous labor, as reflected by a significant increase in amniotic fluid corticosteroid levels, in patients immediately prior to vaginal delivery as opposed to abdominal delivery. There was a significant correlation between the birthweight of babies born vaginally with the amniotic fluid corticosteroid levels, as compared to the weight of babies born by cesarean section.