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Biomedical subjects

C Bulletti

Publications and source records attributed to C Bulletti.

At least 73 records · Page 4Linked to original sources

Reduced conversion of dehydroepiandrosterone into estrogens in women having hypogonadotropic hypogonadism associated with weight loss.

The purpose of this study was to evaluate, without using radioisotopes, the peripheral contribution of dehydroepiandrosterone (D) to estrogens and to androstenedione (A) in patients with hypogonadotropic hypogonadism associated with weight loss (HH) and in normal menstruating women (N). Unlabelled D was infused for 48 h in 12 normal women and in 12 women affected by HH. Plasma levels of D, dehydroepiandrosterone sulfate (DS), A, estrone (E1), estrone sulfate (E1s) and estradiol (E2) were measured before and after 48 h of infusion. Metabolic clearance rates of D (MCRD), production rates of D (PRD), and increases in plasma concentration of DS, A, E1, E1s and E2, relative to the corresponding increase in plasma concentration of D, were determined. The baseline plasma levels of all steroids studied were found to be significantly lower in the patient group than in the control. The MCRD in the normal and the HH groups were similar (1420 +/- 340 l/day versus 1670 +/- 569 l/day, P greater than 0.05). No significant difference was found in PRD between the 2 groups (mean +/- SD 10.3 +/- 5 versus 13.3 +/- 5.5 mg/day, P greater than 0.05). Administration of D increased the levels of estrogen in the normal group but not in the HH group. The relative increase in plasma levels of DS resulting from infusion of D (delta cDS/delta cD) was found to be larger in the HH group than in the normal group (40.4 +/- 17 versus 26.3 +/- 11.8, P less than 0.05). Furthermore, relative increases in plasma levels of A derived from infusion of D were larger in the HH group than in the normal group (0.0495 +/- 0.0021 versus 0.192 +/- 0.0071, P less than 0.001). We conclude from these results that in the HH patients there is a blockage of the peripheral conversion of D to E1 and E1s and an enhancement of the peripheral conversions of D to DS and to A. These metabolic changes may account for the androgenization of the patients under study.

Adult↗

Treatment of endometrial hyperplasia with cyproterone acetate histological and hormonal aspects.

A regime of cyproterone acetate (CPA) (300 mg/day by the oral route for 30 days) has been used in 10 post-menopausal women with endometrial hyperplasia (8 atypical and 2 adenomatous). Androstenedione (A), estrone (E1), testosterone (T) and estradiol (E2) plasma levels were determined before and at the end of treatment. The regression of endometrial hyperplasia was ascertained histologically in all patients after 30 days of therapy. All steroids showed a significant decrease (p less than 0.05) as compared with their corresponding basal values. Moreover, the E1/A ratio was significantly lowered (p less than 0.01) following CPA administration (5.9 + 2.9% to 2.5 + 0.6%). From these data it is evident that CPA can not only act as a progestin, but may also reduce the endogenous estrogen production, lowering either the adrenal production of A (the most important estrogen precursor in the post-menopause) or the A to E1 peripheral conversion.

Androgen Antagonists↗

Preliminary report on postmenopausal endometrial hyperplasia treatment with Danazol: histological and endocrinological aspects.

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.

Danazol↗

Estrone sulphate plasma levels in postmenopausal women with and without endometrial cancer.

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.

Aged↗

Relative distribution of estrone, estradiol and estriol between fetal and maternal perfusates during perfusions of human term placentas with labelled C19 precursors.

Published results from in vivo experiments carried out in Rhesus monkeys and from in vitro perfusions of human term placentas have indicated that placental estradiol (E2) is preferentially released towards the mother whereas estrone (E1) is about evenly distributed between fetal and maternal circulation. In order to examine the distribution of estriol, relative to that of E1 and E2, we have now prepared [3H]16-hydroxyandrostenedione by incubation of [6,7-3H]androstenedione with Streptomyces roseochromogenus and perfused placental cotyledons with mixtures of these two labeled precursors. Measurement of the concentrations of tritiated E1, E2 and E3 in the maternal and fetal perfusates, flowing at approx 10 and 5 ml/min, respectively, indicated that the distribution of E3 is different from that of E2 and resembles the distribution of E1. The simple perfusion system being used shows differences in the distribution of various estrogens between fetal and maternal perfusates which may reflect the in vivo situation and offers the opportunity for experimental examination of various explanations for these differences, e.g. existence of specific carrier systems in the syncytial membranes, specific binding of the estrogens to secreted placental proteins, and actions of placental and decidual 17 beta-hydroxysteroid dehydrogenases.

Androstenedione↗

Metabolic clearance rate of oestrone sulphate in post-menopausal women.

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.

Estradiol↗

Estrone sulfate, estrone and estradiol concentrations in normal and cirrhotic postmenopausal women.

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.

Estradiol↗

Androstenedione metabolism in human uterine tissues: endometrium, myometrium and leiomyoma.

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.

Adult↗

Estrogen provocation test: lack of correlation between LH and 17-beta-estradiol basal levels and LH peak response in hypothalamic chronic anovulation.

Estrogen provocation test was performed in 27 women with hypothalamic chronic anovulation: all patients received I mg of estradiol benzoate (EB) as a single im injection. Plasma 17-beta-estradiol (E2) levels were monitored during the test performed and then compared; no significant correlation was found between mean basal values of LH and E2 and the LH peak response (r = 0.246, P = 0.108 for LH; r = 0.124, P = 0.278 for E2). These data seem to indicate that basal LH values reflect the tonic secretion but not the hypothalamic responsiveness to the estrogen positive feedback; moreover, this latter seems not be influenced by the endogenous E2 levels.

Adult↗

Estrone sulphate and estrone splanchnic extraction in postmenopausal women.

The splanchnic extraction of estrone sulphate (E1 S) and estrone (E1) was calculated in post-menopausal women undergoing cardiac catheterization for diagnostic purposes. The results showed a net uptake for E1 by the splanchnic area, liver included, whereas the splanchnic extraction of E1 S was not similar for each subject. Anyway the results clearly showed that the splanchnic area does not release significant amount of E1 S into the blood in the post-menopausal women.

Estrone↗

Reproductive failure due to spontaneous abortion and recurrent miscarriage.

The epidemiology, aetiology, diagnosis and clinical management of spontaneous and recurrent abortion and of the failure of embryo implantation are discussed in a retrospective overview of the major studies conducted since 1975 identified through a Medline search. Infertile women who experienced spontaneous single (32%) and recurrent (0.5%) abortion as well as those who became pregnant after induction of ovulation with gonadotrophins (abortion rate 17-31%) and those who underwent assisted fertilization programmes (abortion rate 18-34%) are considered. Causes and treatments are here reported. Medical treatments for immunologically mediated abortion (IMA) are based on prednisolone, heparin, aspirin and intravenous immunoglobulin. Efficacy of the medical treatment of patients with a history of IMA has yet to be completely demonstrated. Genetic disorders are possible causes of both failure in implantation and early abortion; this cause is more prominent with advanced age and currently cannot be treated. Endocrine factors may also be responsible for miscarriage, and correction of hormone abnormalities is discussed. Infections, endometriosis and psychological factors are other possible important causes of embryo loss without specific widely accepted treatments. Prominent areas of research are the identification of genetic preimplantation abnormalities, and pharmacological intervention for abnormal spontaneous uterine contractility. The data here reported are encouraging, but the efficacy of different treatments is still not convincing. The information available is sufficient to develop new diagnostic and therapeutic tools to evaluate their efficacy in reducing spontaneous abortion at an early stage.

Abortion, Habitual↗

Danazol reverses endometrial hyperplasia to normal endometrium.

Danazol, an isoxazol derivate of ethinyltestosterone, was used in the treatment of thirtyone postmenopausal patients with endometrial hyperplasia at the dose of 400 mg/day for three months. A profound growth-inhibitory effect of danazol on human endometrium was previously suggested. The present study shows that this compound is effective to reverse the endometrial hyperplasia to normal endometrium in 97% of cases. Atrophic changes of endometrial hyperplasia to normal endometrium after danazol-treatment were observed in 68% of patients. These results strongly suggest that danazol has a significant antiproliferative effect on the endometrium.

Danazol↗