Hypothalamic control of gonadotropin secretion in the human menstrual cycle.
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Biomedical subjects
Publications and source records attributed to C Flamigni.
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The synthetic steroid Danazol is commonly used in the hormonal treatment of endometriosis; however, little is known about its effects on human endometrium. This study was performed to verify the efficacy of Danazol on the treatment of endometrial hyperplasia in postmenopausal patients. Ten patients with histologically proven endometrial hyperplasia were treated with Danazol at a dosage of 600 mg/day for 30 days. The E1S and E1 plasma levels were also determined before and at the end of therapy. In all patients the regression of endometrial hyperplasia was observed in the endometrial biopsy specimens obtained after the treatment. Furthermore, the increased E1S/E1 ratio as compared to the basal values suggests an impairment of the peripheral sulfatase activity. The inhibition of the conversion of E1S to active unconjugated estrogens appears to be one of the mechanisms by which Danazol may act on the endometrium.
The plasma levels of the active (free) fraction of testosterone (Te) and of Te Binding Globulin (TeBG) in a group of 42 heroin addicts with similar sexual difficulties were investigated for almost 2 years. Plasma levels of free Te were significantly low and TeBG were significantly high not only in the addicts with low total Te concentrations, but also in the addicts with normal values of total Te.
Women with the polycystic ovary syndrome were treated cyclically for two years with an oral oestrogen/progestogen combination of 50 mg of cyproterone acetate and 0.05 mg of ethinyloestradiol. Ovarian volume, ovarian texture and uterine size were monitored by ultrasound before, during and after treatment. Menstrual rhythm, ovulation and the degree of hirsutism were also studied clinically. A significant decrease in the ovarian volume and in the number of cystic areas was observed during treatment. Hirsutism was also markedly improved. Some of these beneficial effects persisted after treatment was stopped. The number of subjects who had regular, ovulatory cycles increased after stopping treatment. Growth of uterine muscle occurred during treatment.
Dopamine infusion 4 micrograms/kg/min over 4 h, administered to six subjects with diagnosis of polycystic ovarian disease laparoscopically confirmed, produced a significant decrease in serum LH, FSH and PRL, suggesting a reduced dopamine activity in these subjects. The addition of naloxone 4 mg iv bolus plus 4 mg/h over 2 h, a specific opiate antagonist, does not interfere with the well-established dopaminergic inhibitory influence on LH, FSH and PRL secretion. This suggests that opiatergic pathways are not directly involved in the dopamine-induced suppressive effect on LH secretion in subjects with LH-dependent polycystic ovarian disease.
Human urinary FSH (HU-FSH) was administered during 25 treatment cycles to 21 infertile women with polycystic ovary syndrome (PCO) who had failed to conceive in response to clomiphene citrate. HCG was also given in 23 of the cycles. Twenty-two (88%) ovulations occurred, and eight (38.1%) conceptions resulted, two (25%) of which terminated in abortion and six (75.0%) in normal deliveries. No multiple pregnancies occurred. Ten instances (40%) of mild-moderate hyperstimulation also resulted. A spontaneous LH surge was observed in 12 treatment cycles. Ultrasound scanning revealed multiple ovarian follicles developing at various rates. We conclude that HU-FSH is an effective form of treatment for women with PCO. However, the response to exogenous FSH is unpredictable and depends on the stage of development and the number of follicles present prior to stimulation.
Plasma estrone sulphate ( E1S ) and estrone (E1) concentrations were determined in healthy postmenopausal women and in postmenopausal women with endometrial cancer, matched for body weight, age, and years since menopause. E1S levels (mean +/- SD) were significantly higher (P less than 0.05) in cancer patients with normal weight (511 +/- 200 pg/ml) than in control subjects (303 +/- 99 pg/ml). E1S levels were also higher in obese cancer patients (691 +/- 328 pg/ml) than in obese control subjects (610 +/- 139 pg/ml). Both cancer groups showed similar plasma E1 levels as compared with their respective controls. The E1S /E1 ratio was higher in both groups of cancer patients than in control subjects. These data suggest that estrogen conjugates should be taken into account during studies on estrogen balance and endometrial cancer.
The feasibility of using constant infusions of unlabelled oestrone sulphate (E1S) for the purposes of calculating its metabolic clearance rate (MCRE1S) and its conversion ratios to oestrone (E1) and oestradiol (E2) in post-menopausal women was exploited in this study. The results obtained by the infusion of unlabelled E1S were similar to those obtained by the infusion of labelled steroid. The MCRE1S values seen in our group of post-menopausal women fell within the range previously reported for fertile women. The contribution of E1S to circulating E1 averaged 18% (range 14-24%), indicating that the E1S-E1 equilibrium should be taken into account during studies on oestrogen balance in post-menopausal women.
A competitive, sensitive, and rapid enzyme-linked immunoadsorbent assay (ELISA) was developed for the determination of estriol in saliva and in plasma. Horseradish peroxidase (HRP) was used as the label enzyme; separation between free and bound steroid was carried out by insolubilized antibody prepared by adsorbing purified IgG of rabbit anti-6-oxoestriol-6-(O-carboxymethyl)oxime-BSA on polystyrene balls. The enzyme activity was measured by a colorimetric reaction using o-phenylenediamine dihydrochloride and hydrogen peroxide as substrate. The sensitivity of the assay was 12 pg/tube. In order to compare ELISA to RIA estriol estimations in different biological fluids, we selected six women during normal pregnancy, from the 30th to the 40th week of gestation. Salivary estriol was assayed by direct and extraction methods, while the corresponding plasma samples of the same subjects were analyzed only for unconjugated estriol by an extraction method. A good agreement was found between the results obtained by RIA and ELISA: r = 0.897, p less than 0.001 between direct RIA and direct ELISA in saliva; r = 0.909, p less than 0.001 between extraction RIA and direct ELISA in saliva; and r = 0.916, p less than 0.001 between extraction RIA and extraction ELISA in plasma. A good correlation (r = 0.793, p less than 0.001) was present between plasma samples by RIA and saliva samples by ELISA (direct method). These results indicate that: ELISA is a reliable method for the determination of estriol in plasma and saliva. Saliva samples can be used for the assay of estriol and therefore for the assessment of fetal conditions during pregnancy.
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Five infertile patients with polycystic ovarian disease were treated to induce ovulation with pure human urinary follicle-stimulating hormone and human menopausal gonadotropin consisting of follicle-stimulating hormone and luteinizing hormone in 1:1 ratio. No substantial differences were seen between the two types of treatment regarding plasma values of follicle-stimulating hormone, prolactin, testosterone, dihydrotestosterone, progesterone, and 17-hydroxyprogesterone. Estrone, estradiol, and androstenedione values were higher during human urinary follicle-stimulating hormone treatments. Luteinizing hormone levels dropped in both treatments, but the fall was greater during human urinary follicle-stimulating hormone. No real differences were observed concerning number of ovulations, length of treatments, and follicle-stimulating hormone amounts administered; no hyperstimulations were observed. These data do not confirm the observation that more controlled responses of the ovaries can be elicited when low luteinizing hormone gonadotropin preparations are used.
Women with polycystic ovarian disease were treated with oral estrogens and progestogens and their ovarian volume, ovarian texture and uterine size were studied by ultrasound before and during treatment. A significant decrease in the volume and in the number of follicles in the ovaries was seen. Hormone therapy thus temporarily restores normal ovarian morphology in subjects with polycystic ovaries. The uterus did not change significantly during treatment.
Nine infertile patients, suffering from polycystic ovaries, were treated with human urinary FSH and hCG (eight cases) to induce ovulation. Oestrone, oestradiol, 17 alpha-hydroxyprogesterone, testosterone and androstenedione serum levels increased during the treatment. A decrease in luteinizing hormone serum levels was noticed, and in five cases a spontaneous peak was observed. No changes were noted in 5 alpha-dihydrotestosterone serum levels. Ultrasound scanning of the ovaries often revealed multiple follicles at different speeds and stages of growth and their marked turnover was observed. The beginning of the LH spontaneous surge was precocious compared to the normal ovulating follicular sizes: it does not appear that an optimum size exists but when the LH peak occurred too prematurely, ovulation did not take place. Administration of hCG seems to be necessary as spontaneous peaks of LH are not always followed by rupture of the follicle. Ultrasound scanning plays an important role in monitoring ovulation induction, while oestradiol and 17 alpha-hydroxyprogesterone serum levels are not good indicators of follicular maturity in multifollicular growth. Ovulation occurred in eight patients; four conceptions were obtained, one of which resulted in abortion. No ovarian hyperstimulations were observed.
Circulating levels (mean +/- SD) of estrone sulfate (E1S), estrone (E1) and estradiol-17 beta (E2) were measured in normal and cirrhotic postmenopausal women matched for body weight and age. In cirrhotic postmenopausal women, the E1S concentrations (201 +/- 46 pg/ml), while both E1 and E2 levels showed an increase (46 +/- 7 and 30 +/- 8 pg/ml) compared to control subjects (32 +/- 6 and 18 +/- 7 pg/ml). These data suggest that the liver plays an important role on the control of estrogen sulfation.
Bromocriptine was used to test the hypothesis that the abnormality of the dopaminergic system described in haemodialysis patients may cause enhanced sympathetic activity and high blood pressure. Bromocriptine significantly reduced supine mean blood pressure and plasma noradrenaline. Moreover, although the increments in plasma noradrenaline during tilt tests were reduced by bromocriptine there was a significant improvement in the response of blood pressure. These results suggest that dopaminergic control of sympathetic activity may be impaired in haemodialysis patients and may be a cause of high blood pressure. Moreover, a restoration of a normal relationship between noradrenaline and adrenergic receptors would be consistent with the present results.
Androstenedione was metabolized in vitro by human endometrium, myometrium and leiomyoma, to its 5 alpha-reduced metabolites: 5 alpha-androstan-3,17-dione (5 alpha-androstanedione) and androsterone as well as to testosterone, 17 beta-hydroxy-5 alpha-androstan-2-one (5 alpha-DHT) and 5 alpha-androstan-3 alpha,17 beta-diol (3 alpha-diol). Uterine tissue showed a similar enzymatic profile to the androgen responsive tissues; these data suggest that androgens may have a functional role in the uterine pathophysiology.
In a 38-year-old white woman with a virilizing mesovarium hilus cell tumor and polycystic ovaries, serum levels of 13 hormones were measured under different conditions. Endocrine studies showed that testosterone was the principal secretory product of tumor cells. Androstenedione, 17-hydroxyprogesterone, and dehydroepiandrosterone sulfate were normal. Light and electron microscopic investigations of the tumor showed polygonal cells containing intracytoplasmic Reinke crystalloids. Immunoperoxidase studies demonstrated the presence of testosterone within tumor cells.