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PubMed1978

15alpha-Hydroxyoestriol and other polar oestrogens in pregnancy monitoring.

Although oestriol measurements are well established for the assessment of 'at risk' pregnancies, there are a number of other oestrogens, excreted during pregnancy, which contain additional hydroxyl groups and might be more sensitive indicators of the condition of mother or fetus. Some of these result from the action of hydroxylases possibly present only in the fetus and others from maternal hydroxylations. We review the evidence for the biosynthesis of these polar oestrogens, summarise methods of measurement, and compare values obtained in normal and pathological pregnancies. There is as yet insufficient evidence to enable their potential value to be confirmed.

Catechols↗
PubMed1975

The role of estrogen in the modulation of pituitary sensitivity of LRF (luteinizing hormone-releasing factor) in men.

The role of estradiol in modulating pituitary gonadotropin release in the human male was studied by evaluating the effects of clomiphene on the pituitary gonadotropin response to synthetic LRF (150 mug) in 6 eugonadal men. Administration of clomiphene (100 mg single daily dose time 5 days) induced a significant elevation of the basal levels of LH, FSH, estradiol and testosterone. However, the pituitary release of LH and FSH in response to LRF was markedly diminished by the clomiphene treatment. This finding suggests that in men, as in women, endogenous estradiol provides feedback regulation of gonadotropin output by the pituitary.

Adult↗
PubMed1976

Effect of fluoxymesterone on the pituitary-gonadal axis: the role of testosterone-estradiol-binding globulin.

Four normal men and two agonadal men were given the oral synthetic androgen, fluoxymesterone (9alpha-fluoro-11beta, 17beta-dihydroxy-17alpha-methyl-4-androstene-3-one) for three days. Plasma testosterone (T), 17 alpha-hydroxyprogesterone (17-OHP), and LH were measured every 30 minutes on a control day and on the first day of treatment. Testosterone and LH were measured every six hours on the last day of treatment. During the first 24 hours of treatment the number of LH secretory episodes per day decreased from 10.5+/-2.5 (SD) to 6.2+/-2.9 (SD) (P less than 0.01), mean 24 hour LH decreased from 12.6+/-3.5 (SD) mlU/ml to 9.3+/-3.7 (SD) mlU/ml (P less than 0.01), and mean 17-OHP decreased from 2.33+/-1.4 (SD) ng/ml to 1.18+/-0.39 (SD) ng/ml (P less than 0.01) in all normal subjects. T was significantly decreased (P less than 0.01) from 464.5+/-76.4 (SD) ng/100 ml to 294.2+/-99.5 (SD) ng/100 ml. By the third day of treatment, LH had decreased further in four, and T in three of four normals. The number of LH spikes and the mean LH levels did not decrease in the agonadal patients. In vitro, using equilibrium dialysis, fluoxymesterone displaced T from plasma binding proteins with an apparent K=1.0 x 10(8) and 1.9 x 10(7) in female and male plasma, respectively, at 22 C; and 5.2 x 10(7) and 8.0 x 10(6) at 37 C. In polyacrylamide gel electrophoresis, a 500-fold molar excess of fluoxymesterone decreased the peak of TeBG-bound T by 45% (P less than 0.01). The in vitro data are consistent with the possibility that, in vivo, the displacement of T from TeBG by fluoxymesterone may play a role in the suppression of the pituitary-gonadal axis by synthetic oral androgens in vivo.

Adult↗
PubMed1977

Serum medroxyprogesterone acetate (MPA) concentrations and ovarian function following intramuscular injection of depo-MPA.

A sensitive radioimmunoassay measuring serum medroxyprogesterone acetate (MPA) has been developed in order to measure and correlate serum MPA concentrations and ovarian function in women following im administration of deop-MPA (DMPA), employing goat anti-MPA-3-(O-carboxymethyl) oxime-bovine serum albumin and MPA-3-(O-carboxymethyl) imino-125I-iodohistamine. In the 3 women studied, im injection of 150 mg of DMPA yielded brief initial serum MPA concentrations ranging from 1.5 to 3 ng/ml for a few days. Serum MPA concentrations gradually declined and remained relatively constant at about 1 ng/ml for 2 to 3 months, declined gradually thereafter reaching 0.2 ng/ml during the 6th month and became undetectable (less than 0.02 ng/ml) about 7-1/2 to 9 months following administration. Serum estradiol remained at early to midfollicular phase levels for 4 to 6 months after DMPA injection and rose to preovulatory levels when serum MPA levels fell below 0.5 to 0.25 ng/ml. Ovulation, however, as evidenced by serum progesterone concentrations did not occur, apparently due to suppression of the LH peak by positive feedback inhibition. Prolonged inhibition of cyclic ovarian function following DMPA injection is caused by slow MPA absorption and persists until serum MPA levels have decreased below 0.1 ng/ml or become undetectable about 7 to 9 months after DMPA administration.

Adult↗
PubMed1977

Hormonal evaluation of the intrauterine progesterone contraceptive system.

Nine women were studied for one menstrual cycle prior to the insertion of an intrauterine progesterone contraceptive system (IPCS) delivering 65 microng progesterone/day into the uterus and again at 1 month after its insertion. Eight of these women were again studied between 6-8 months after the insertion of the IPCS. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol-17beta, progesterone, prolactin and relaxin were measured in each plasma sample. The data from each study were combined according to the day of the LH peak. Ovulation occurred in all the cycles studied in spite of an elevation in plasma estradiol-17beta and a depression of prolactin and relaxin immunoactivities at the 6-8 month follow up. Menstruations noted at the 6-8 month of use occurred while levels of estradiol-17beta and progesterone were elevated.

Adult↗
PubMed1978

The relationship of changes in serum estradiol and progesterone during the menstrual cycle to the thyrotropin and prolactin responses to thyrotropin-releasing hormone.

The responses of serum TSH and PRL to TRH (500 microgram) were studied in normal young women in the early follicular, periovulatory, and midluteal phases of the menstrual cycle in order to examine the relationship of these responses to the levels of estradiol relationship of these responses to the levels of estradiol (E2) and progesterone. Each woman was studied twice in each phase in order to assess intraindividual variability. There was no significant difference in either the TSH or PRL responses among the phases of the menstrual cycle nor was either response affected by the periovulatory rise in E2 or by the luteal rise in both E2 and progesterone. Thus, the interpretation of the TSH and PRL responses to TRH in normal women is not affected by the menstrual cycle although both responses are greater in women that in men. Both the peak TSH and peak PRL after TRH were highly correlated with the basal levels of TSH (r = 0.85; P less than 0.01) and PRL (r = 0.67; P less than 0.01), respectively, indicating that the TSH and PRL responses to TRH in women are directly proportionate to the basal levels of the respective hormones, as previously shown for the TSH response in men. The mean intraindividual variability (coefficient of variation) of the TSH response to TRH was 18%, but ranged as high as 56%, while that of the PRL response was 16% and ranged up to 31%; variability was not affected by the phase of the menstrual cycle. The normal range of the peak TSH after TRH in women is 7-33 microU/ml (mean +/- 2 SD); however, because of the variability, a normal woman may sometimes have a peak TSH after TRH as low as 4 microU/ml. Repeating the test will result in a normal value if the woman is truly normal. Similarly, the normal peak PRL after TRH in women is 22-111 ng/ml (mean +/- 2 SD); usually, however, the lower limit is 30 ng/ml with lower values due to intraindividual variation. The data suggest that the higher average level of E2 in women compared to women, but that the cyclic changes in serum E2 or progesterone in women have little or no additional effect.

Adult↗
PubMed1979

Failure of estrogen-induced discharge of luteinizing hormone in lactating women.

Pituitary-ovarian relationships were studied in seven lactating women by measuring the basal plasma concentrations of pituitary and ovarian hormones and their responses to an estrogen provocation test at 7, 30, and 100 days after delivery. The results were compared to a similar group of seven women who did not breast feed. The first ovulation occurred in five of the nonlactating women beteen 43-87 days after delivery, as judged by the urinary excretion of total estrogen and pregnanediol. In all lactating women, ovarian cyclicity was suppressed for at least 150 days after delivery or until weaning. The basal concentration of PRL in lactating women was significantly higher than in the nonlactating women at all three times measured. At 30 and 100 days, the concentration of estradiol was significantly lower in the lactating women, although the basal concentrations of FSH were similar in the two groups. After an injection of 1 mg estradiol benzoate, the concentrations of FSH and LH in plasma were suppressed to a greater extent in lactating than in nonlactating women. In addition, fewer of the lactating group (one of seven and none of seven at 30 and 100 days, respectively) than the nonlactating group (two of seven and five of seven) subsequently showed a rise in the concentration of LH 58--96 h after the estrogen injection (positive feedback). These results suggest that during lactation the hypothalamic-pituitary system is more sensitive to the negative feedback and relatively insensitive to the positive feedback of estrogen.

Adult↗
PubMed1979

Estrogen and progestin regulation of the progesterone receptor concentration in human endometrium.

The concentration of the progesterone receptor (PR), both cytosol and nuclear, has been measured in the endometrium of 31 normal menstruating women during the 2 phases of their menstrual cycle and compared with the plasma 17 beta-estradiol and progesterone concentrations. There was no relationship between PR concentrations and the plasma steroid levels when the 2 phases of the cycle were considered; however, a statistically significant correlation (r = 0.70; P less than 0.005) was observed between PR concentration and plasma 17 beta-estradiol when only the follicular phase was considered. PR was then measured in the endometrium of 14 postmenopausal patients treated with ethinylestradiol at increasing doses with or without association of chlormadinone acetate. Ethinylestradiol was shown to increase PR concentration (P less than 0.05), and chlormadinone acetate was found to prevent this increase. These data suggest that in humans, as in other mammalian species, the endometrial PR concentration is under estrogen and progestin control.

Chlormadinone Acetate↗
PubMed1976

Some aspects on pituitary function in human and rat anovulatory cycles.

To investigate the anterior pituitary function of human anovulatory cycles, hormonal environments were analyzed in an animal experimental model and women with anovulatory cycles. A specific antiserum to hypothalamic luteinizing hormone-releasing factor (LH-RF) was prepared in rabbits. Intravenous injection of 1.0 ml of this antiserum to 4-day cycling female rats on the proestrous day blocked ovulation in the following cycles without changing regular estrous cycles on vaginal smear. Thus experimental anovulatory cycles were induced in antiLH-RF serum-treated rats. In this experimental model, LH surge on the proestrous evening was blocked but LH and FSH were maintained at the basal levels. In human anovulatory cycles, serum LH and FSH levels were also not significantly reduced except during the period of LH surge, and blood estradiol-17beta levels were similar to the levels of women with normal ovulation. Serum progesterone levels were higher in the normal women after the expected day for ovulation. These data may indicate that the anterior pituitary is able to secrete its gonadotropins without stimulation by LH-RF and this tonic discharge of gonadotropins would maintain the basal levels of ovarian secretion of steroids.

Adult↗
PubMed1976

Estrogens in maternal plasma following intraamniotic injection of (3H)-dehydroepiandrosterone-sulfate in midpregnancy.

In 4 patients with normal pregnancies between the 18th and 20th week of gestation (3H7alpha)-dehydroepiandrosterone-sulfate ([H]-DHEA-S) was injected intraamniotically. Maternal venous blood was drawn before and at regular intervals for 240 minutes after DHEA-injection. Thereafter, legal abortion was performed by intraamniotic instillation of prostaglandine. The conjugated steroids were hydrolyzed enzymatically and the total steroids were isolated and identified. The following labelled metabolites were determined quantitatively: Estriol (e3, estradiol-17beta (E2-17beta), estrone(E1), 16alpha-hydroxy-estrone, (16alpha-OH-DHEA), ALPHA4-androstenedione (AD) and testosterone (T). The maximal increase of all estrogen fractions in matermal plasma occurred 120-180min after intraamniotic injection of the precursor. The most prominent rise of the C18-steroids could be shown for estriol. 60-70% of all metabolites were C16-hydroxylated.

Amnion↗
PubMed1977

Influence of LH/FSH releasing hormone (LRH) on the basal secretion of gonadotrophins in relation to plasma levels of oestradiol, progesterone and prolactin during the post-partum period in lactating and in non-lactating women.

The pituitary responsiveness to LH/FSH releasing hormone (LRH) was studied in the puerperium in lactating and in non-lactating women. The response of both groups of patients to 25 mug LRH iv was tested 8-10 days, 15-17 days, and 29-32 days after a normal delivery at full term. The basal levels of FSH were low during the first 10 days after delivery. A rise was then observed, and about 4 weeks after delivery levels above or in the upper normal range of a normal follicular phase were recorded. The levels were significantly higher in the lactating group. When compared with the normal follicular phase, the relative increase in FSH basal levels was higher than the increase in LH basal levels in both groups of patients. The period of non-responsiveness of the pituitary to LRH was found to be of equal length in the two groups. In both groups the FSH response returned more rapidly than the LH response. About 2 weeks after delivery a reverse pattern of gonadotrophin response to LRH was seen with a FSH response that was greater than the LH response compared with what is generally observed in the various phases of the menstrual cycle in eumenorrhoeic women. This pattern was more pronounced in the lactating group about 4 weeks after delivery. Oestradiol levels were low and roughly equal on the three test occasions in each group, but in the non-lactating group there was a tendency to higher concentrations. Prolactin levels were highest about one week after delivery and then showed a tendency to decrease, and this was more pronounced in the non-lactating group. Progesterone levels were invariably low in both groups.

Adult↗
PubMed1977

Pituitary gonadotrophin secretion during the first weeks of pregnancy.

A longitudinal study of basal plasma LH and FSH and their responses to 25 microng LRH iv as well as basal levels of oestradiol, progesterone, prolatin and HCG was performed every week in 3 women, pregnant after heterologous insemination, from conception until the 6th week of gestation. A comparative study was carried out in 7 women in cycles in which no conception occurred after insemination. All hormones were assayed with radioimmunoassay. LH was measured with a specific assay for native HL, which did not cross-react with HCG. A decrease in basal levels of LH and FSH as well as decreasing responses to LRH was found during the first 2 weeks of gestation. These changes did not differ from what was observed during the luteal phase in the non-conception cycles. One week later the basal FSH levels and the FSH response in the pregnant women showed a further decrease, while in the non-pregnant women, now reaching the early follicular phase, a rise in FSH basal levels occurred. The basal levels of LH and the LH response, however, did not differ from that found in the non-pregnant woment at this time. FSH basal levels remained below the lower normal limit in eumenorrhoic women from the 3rd week of gestation. By this time the FSH response was almost completely inhibited. The LH basal levels, however, remained above the lower normal limit in eumenorrhoic women, but the LH response to LRH progressively decrease and was completely inhibited by the 5th week of gestation. In the non-conception cycles the LH response varied with the levels of oestradiol in plasma. This was not found in the pregnant women as the decrease in gonadotrophin response occurred while oestradiol remained at mid-cycle levels during the first 4 weeks of gestation. Rather it seems that the increasing and continuously elevated level of progesterone, in the presence of appropriate levels of oestradiol, might be the main go nadal steroid responsible for the diminishing pituitary secretion. The contribution of HCG to the further decrease in gonadotrophin secretion after the 2nd week of pregnancy cannot be answered by the present studies. Prolactin remained at non-pregnant levels until the 6th week of gestation, and appeared to have no influence on the secretion of gonadotrophins during early pregnancy.

Adult↗
PubMed1977

Interaction of rifampicin treatment with pharmacokinetics and metabolism of ethinyloestradiol in man.

[6,7-3H]Ethinyloestradiol (50 microng) was administered intravenously to volunteers and the free extractable ethinyloestradiol in the plasma was measured. The compound showed a biphasic plasma decline. The half-life of the second phase was 7.5+/-1.7 (SD) hours. Administration of rifampicin (600 mg for 6 days) shifted the half-life of ethinyloestradiol to 3.3+/-0.9 h while the apparent volume of distribution for the second phase of elimination was not changed. When [2,4,6,7-3H]ethinyloestradiol (100 microng) was administered orally, some of the tritium was released by oxidative metabolism from the steroid and transformed to tritiated water (HTO) which equilibrated with whole body water. This portion, normally 7.17+/-1.66% of the tritium dose, was increased by previous administration of rifampicin to 10.62+/-2.27%. The initial rate of oxication of [2,4,6,7-3H]ethinyloestradiol was increased more than twofold by rifampicin treatment. The results are consistent with previous findings that rifampicin induces the oestrogen-2-hydroxylase in the endoplasmic reticulum of human liver, and explain the reduced effectiveness of ethinyloestradiol in oral contraceptives, if the patients are treated with rifampicin.

Administration, Oral↗