Biomedical subjects

C Flamigni

Publications and source records attributed to C Flamigni.

At least 145 records · Page 8Linked to original sources

PubMed1988

Increased extraction of estrogens in human endometrial hyperplasia and carcinoma.

The present study was undertaken to assess in vitro the endometrial extraction of natural estrogens. Normal, hyperplastic, and neoplastic endometria were studied. This was accomplished by the use of double isotope, single-injection techniques performed during the extracorporeal perfusion of human isolated uterus. The differential permeability of vascular beds in normal and neoplastic endometrium to estrogens was evaluated. The effects of binding by human serum proteins on estrogen influx into the endometrium were also determined. When protein-free Ringer's solution was used as an injection vehicle, both normal and abnormal endometrium permitted free diffusion of estradiol (E2), estrone (E1), and estrone sulfate (E1S). In contrast, the endometrial extraction of these estrogens from human female serum was significantly lower than that obtained with Ringer's solution. The extraction of E2, E1, and E1S from human serum was significantly higher in hyperplastic and carcinomatous endometria than in normal proliferative endometria. We conclude that 1) membrane permeability to estrogenic influxes differs between normal and abnormal endometria and 2) plasma proteins decrease the endometrial uptake of estrogens.

Adenocarcinoma↗

PubMed1987

Comparative metabolism of oestrone sulphate after oral and intravenous administration in post-menopausal women.

Oestrone sulphate (E1S) is currently used in hormone replacement therapy in post-menopausal women. While isotope studies have demonstrated that E1S is metabolised in a similar way after administration by either the oral or intravenous route, pharmacokinetic studies point to its efficient extraction and metabolism by the liver. E1S was accordingly administered orally and intravenously at pharmacological dosages in a group of post-menopausal women and its conversion to oestrone (E1) and oestradiol (E2) was determined. We were able to demonstrate that E1S may cross the splanchnic area unaltered, since its conversion to E1 and E2 was similar after administration by each of the routes investigated.

Administration, Oral↗

PubMed1987

A 48-hour preservation of an isolated human uterus: endometrial responses to sex steroids.

Human uteri were perfused with Krebs-Ringer bicarbonate-glucose buffer with and without estrogens and progesterone for a period of up to 48 hours to preserve a viable organ, which was responsive to hormones. Flow rates of 12 to 35 ml/minute per artery were fully distributed into the organ, with pressure values ranging from 80 to 120 mm Hg. Arteriovenous gradients of oxygen and carbon dioxide tensions as well as the levels of lactate, lactic dehydrogenase, and creatine kinase released in the perfusate, indicators of tissue ischemia or cell necrosis, showed a good preservation of the organ for up to 48 hours. The light- and electron-microscopic examinations of endometrial and myometrial tissues taken before and during perfusion confirmed this result. The extracorporeal perfusion of uteri with buffer containing estrogens plus progesterone exhibited secretive modifications of the proliferative endometrium, thus suggesting the viability of the organ and its responsiveness to sex steroids.

Adult↗

PubMed1987

Postmenarchal evolution of endocrine pattern and ovarian aspects in adolescents with menstrual irregularities.

Ninety-five adolescents with menstrual irregularities persisting since menarche were studied and the data analyzed in relation to gynecologic age. In each year, in the premenstrual phase, luteinizing hormone (LH), testosterone (T), and androstenedione (delta 4A) values were higher than those of adults. Estrone (E1), estradiol (E2), 17-hydroxyprogesterone (17-OHP), progesterone (P), and dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) gradually increased up to adult values correlating with gynecologic age. By ultrasound, nearly half the ovaries were multicystic and ovarian volume was greater than that of adults in each gynecologic year. When the data were classified as ovulatory or anovulatory, ovulation appeared to be a dynamic process characterized by ovaries similar to those of adults and by increasing hormonal levels correlated to gynecologic age. By contrast, in anovulatory cycles, mean T, delta 4A, and LH values were stable in each year and constantly higher than in ovulatory cycles and adult controls. These findings suggest that, despite persistent irregular cycles, some adolescents normalize all endocrine and ovarian parameters toward maturity, while subjects with persistent irregular anovulatory cycles maintain marked hyperandrogenism, increasingly high LH values, and enlarged multicystic ovaries.

Adolescent↗

PubMed1987

Circadian variations of luteinizing hormone can have two different profiles in adolescent anovulation.

The circadian profile of plasma LH concentrations was investigated in 12 healthy anovulatory adolescent women by drawing blood samples every 20 min for 24 h during the early follicular phase. Plasma 17 beta-estradiol, testosterone, and androstenedione levels were measured in the first sample. Ovarian size was measured by ultrasound. According to their mean plasma LH levels, the adolescents were divided into two groups, those with a high plasma LH level (2 Sd or greater than the mean adult value) and those with a normal plasma LH level. The mean plasma estradiol (P less than 0.001) and testosterone (P less than 0.05) levels were higher in the women with high plasma LH levels compared to those in women with normal plasma LH levels. The LH pulse amplitude was greater (P less than 0.05) and the interpulse interval shorter (P less than 0.025) in the high LH group compared to those in the normal LH group. A 24-h periodicity with the highest plasma LH levels and the greatest pulse amplitude in the afternoon was found in high LH group. In the normal LH group, the highest plasma LH levels and greatest pulse amplitude occurred in the first hours of the morning. An accentuated 24-h LH periodicity is typical of puberty, but disappears in adulthood. We have recorded the persistence of pronounced LH circadian changes in anovulatory adolescent women which might be a marker of a continuing maturational process. Furthermore, LH circadian changes have opposing profiles according to the mean LH values, suggesting the presence of different central nervous system pubertal programs.

Adolescent↗

PubMed1987

Different gonadotropin pulsatile fashions in anovulatory cycles of young girls indicate different maturational pathways in adolescence.

To characterize the spectrum of pulsatile gonadotropin secretion during the postmenarchal period, we studied 24 adolescents whose gynecological age was 1-4 yr. Six women with ovulatory cycles formed a control group. Eighteen women with anovulatory cycles were grouped on the basis of mean plasma LH values: group 1 (n = 8) with high LH values and group 2 (n = 10) with normal LH values. In all women, plasma gonadotropin concentrations were measured at 10-min intervals for 8 h on day 4 of the cycle. Pulsatile gonadotropin secretion was also studied a second time in 7 women from group 1 and 7 from group 2 after 5 days of progesterone (P) in oil treatment to assess the role of P in regulating gonadotropin secretion in the postmenarchal period. Group 1 had more frequent and greater LH pulses than the other two groups (which were very similar) and had the highest plasma 17 beta-estradiol, testosterone (T), androstenedione (A), and 17-hydroxyprogesterone concentrations. In all anovulatory women, basal LH values were correlated with the LH interpulse interval (r = -0.65; P less than 0.01) and pulse amplitude (r = 0.86; P less than 0.001). LH pulse amplitude was correlated with basal 17 beta-estradiol values (r = 0.74; P less than 0.001), and LH interpulse interval with basal T (r = -0.83; P less than 0.001), A (r = -0.51; P less than 0.05), and 17-hydroxyprogesterone (r = -0.79; P less than 0.001) values. P administration decreased LH pulse frequency and increased LH pulse amplitude more in group 2 than in group 1 with high LH values; a clear reduction was also found in A, T, and 5 alpha-dihydrotestosterone values. These results indicate that 1) anovulatory young women with high plasma LH values have an alternative maturational pathway, different from that of anovulatory women with normal plasma LH values, who are similar to ovulatory adolescents; 2) the pulsatile pattern of gonadotropin secretion has specific roles linked separately to amplitude and frequency in controlling ovarian steroidogenesis, which accounts for the endocrine differences between groups; and 3) in the postmenarchal period, by modulating LH and FSH pulsatility and thus reducing androgen levels and their atretic action on follicles, P may be a basic regulatory factor in enhancing functional cyclicity.

Adolescent↗

PubMed1987

Effects of alpha 1-adrenergic blockade on pulsatile luteinizing hormone, follicle-stimulating hormone, and prolactin secretion in polycystic ovary syndrome.

Central noradrenergic mechanisms may participate in the regulation of pulsatile gonadotropin secretion in women with the polycystic ovary syndrome (PCO). To examine this possibility we measured serum LH, FSH, and PRL concentrations at 10-min intervals and total testosterone and 17 beta-estradiol at 60-min intervals for 8 h basally and during the infusion of the alpha 1-adrenoceptor antagonist thymoxamine (10 micrograms/kg X min) in 10 young women with PCO. Mean and integrated serum LH concentrations as well as LH pulse frequency were not significantly altered (P = NS) during the thymoxamine infusion. However, we found an increase in LH pulse amplitude as both net (P less than 0.002) and percent (P less than 0.002) increment, as well as mean LH peak values (P less than 0.05) during alpha 1-adrenergic blockade. There were no significant changes in pulsatile FSH and PRL secretion or gonadal sex steroids during these experimental conditions. These data suggest that in PCO patients, 1) brain noradrenergic mechanisms do not play a stimulatory role in regulating the frequency of pulsatile LH secretion, 2) central noradrenergic activity inhibits LH pulse amplitude, and 3) PRL and FSH pulsatility are not altered by central noradrenergic blockade.

Adolescent↗

PubMed1987

Evidence for a physiological reduction in brain dopamine but not norepinephrine metabolism during the preovulatory phase in normal women.

To investigate the role of brain catecholamine (CA) activity in the mechanisms related to physiological ovulatory function, we used high-performance liquid chromatography with electrochemical detector to measure the levels of urinary dopamine (DA), norepinephrine (NE), epinephrine (E), vanillylmandelic acid (VMA), homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), and total 3-methoxy-4-hydroxy-phenylglycol (MHPG) in a group of 12 normal women during both the early follicular and pre-ovulatory phases of the menstrual cycle. The mean (+/- SEM) concentrations of HVA and DOPAC were significantly lower (P less than 0.001) during the pre-ovulatory phase than during the early follicular phase, whereas those of DA, NE, E, VMA and total MHPG were unaltered. A significant negative correlation between urinary HVA and plasma LH (r = -0.70, P less than 0.01) was also found during the pre-ovulatory period, whereas no significant negative correlations were found between urinary HVA and plasma PRL, progesterone and oestradiol. These data show: 1) reduced brain DA activity and 2) unchanged brain NE activity at the time of the midcycle surge in normal women, suggesting a physiological variation of the central DA metabolism in ovulatory function.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1986

Reduced conversion of dehydroepiandrosterone into estrogens in premenarchal girls.

The purpose of this study was to evaluate the increases in plasma levels of E1, E1S and E2 during constant infusion of dehydroepiandrosterone (D) in premenarchal girls (PG) and in normal menstruating women (AW). Unlabelled D was infused for 48 h in 10 premenarchal girls and in 10 normal menstruating women. Plasma levels of D, estrone (E1), estrone sulfate (E1S) and estradiol (E2) were measured before and during 48 h infusion. Metabolic clearance rates of D (MCRD), production rates of D (PRD), and increases in plasma concentration of E1, E1S and E2, relative to the corresponding increase in plasma concentration of D, were determined. The baseline plasma levels of D were found significantly lower in premenarchal girls than in normal menstruating women. MCRD was found significantly higher in premenarchal girls than in normal menstruating women (2565 +/- 467 L/day versus 1317 +/- 242 L/day, p less than 0.01). Administration of D increased the plasma levels of E1 and E1S in the group of normal menstruating women but not in the premenarchal girls. Considering all subjects studied, the increases in plasma levels of E1 and E1S during the infusion of D were significantly correlated with body weight (p less than 0.01 and p less than 0.001, respectively). From these results, we conclude that in premenarchal+ girls there is: a reduced peripheral contribution of D to E1 and E1S, and/or a higher MCRE1 and MCRE1S than in normal menstruating women.

Adult↗

PubMed1986

Effects of obesity on gonadotropin secretion in patients with polycystic ovarian disease.

To investigate the interrelationships between body weight and gonadotropin secretion of polycystic ovarian disease (PCO), basal hormonal pattern and responses of gonadotropins and 17 beta estradiol (E2) to 25 micrograms (bolus) and 175 micrograms (4-h infusion) of synthetic luteinizing hormone-releasing hormone (LHRH) were studied in two age-matched groups of 18 obese (OB-PCO) and 18 normal-weight (NO-PCO) women suffering from the syndrome. Unlike other hormone levels, plasma LH and the LH/FSH ratio values were significantly higher (p less than 0.001) in NO-PCO than in OB-PCO females. Moreover, LH response to both stimuli was significantly greater in NO-PCO with respect to OB-PCO. No differences were found in FSH response, whereas E2 response was significantly higher (p less than 0.05) in the NO-PCO group during the continuous infusion test. These results emphasize the role of body weight in the development of PCO in obese females.

Adolescent↗

PubMed1986

Extracorporeal perfusion of the human uterus.

Uterine specimens specially prepared for extracorporeal perfusions (arterial and venous stumps available for catheterization) were perfused with oxygenated Krebs-Ringer bicarbonate-glucose buffer for periods of up to 12 hours to investigate the feasibility of obtaining constant flow, stability of biochemical parameters, and adequate distribution of the perfusion fluid. Flow rates of 10 to 30 ml/min per artery could be maintained at pressures ranging from 80 to 120 mm Hg. Arteriovenous gradients of oxygen and carbon dioxide tensions were relatively stable and levels of lactate, lactic dehydrogenase, and creatine kinase released to the medium, indicators of tissue hypoxia or cell lysis, declined after 30 minutes of perfusion, remaining low and stable up to 12 hours. Distribution of methylene blue and radiopaque solutes was practically complete throughout the fundus and upper two thirds of the uterus. A mixture of tritium-labeled estrone sulfate and carbon 14-labeled estrone was injected as a bolus through an arterial catheter during perfusion. Perfusate samples were collected for 30 minutes, and tissue samples were taken at the end of this period. Tritium/carbon 14 ratios in myometrium and perfusate indicated preferential uptake of the unconjugated estrogen. Tritium/carbon 14 ratios were higher in endometrium than in myometrium, which suggests an enhanced permeability of endometrial capillaries to estrone sulfate.

Catheterization↗

PubMed1986

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↗

PubMed1986

Triplet pregnancy after low-dose pulsatile gonadotropin-releasing hormone in polycystic ovarian disease.

In a patient with polycystic ovarian disease, low-dose intravenous pulsatile gonadotropin-releasing hormone (5 mcg every hour) and no exogenous human chorionic gonadotropin induced multiple follicular development and elevated estrogen levels and resulted in a triplet pregnancy. Patients with polycystic ovarian disease may have a higher risk of complications and should be monitored more closely during ovulation induction with pulsatile gonadotropin-releasing hormone.

Adult↗

PubMed1986

Human urinary follicle-stimulating hormone and human menopausal gonadotropin in induction of multiple follicle growth and ovulation.

Five normally menstruating women were treated, in an attempt to induce development of multiple follicles, with pharmacologic doses of purified human urinary follicle-stimulating hormone (hU-FSH) and (in another instance) with human menopausal gonadotropin (hMG) administered on the second and third days after the onset of menses. All of the cycles were ovulatory: the follicular phase was short and the luteal phase length was normal in both hMG and hU-FSH treatment. No substantial differences were seen between the two types of treatment in regard to plasma values of FSH, luteinizing hormone (LH), estradiol (E2), testosterone, and progesterone (P). FSH, E2, and P increased to supraphysiologic levels, and LH fluctuated within the normal range. On ultrasound examination, a large number of growing and matured follicles were visualized during both treatments: at human chorionic gonadotropin administration, multiple preovulatory follicles (greater than or equal to 15 mm) and only a few small follicles (less than 10 mm) were imaged, without any difference between the two types of treatment. Multiple corpora lutea were often obtained. These data underline that pharmacologic doses of FSH alone are able to induce the growth of multiple preovulatory follicles when the initiation of stimulation is timed early. Besides this, exogenous LH does not seem to interfere with follicular recruitment, and it is not required for follicular maturation and ovarian steroidogenesis when endogenous normal LH mean values are present.

Adult↗

PubMed1986

The successful use of human amniotic fluid for mouse embryo culture and human in vitro fertilization, embryo culture, and transfer.

The development of mouse and human embryos was assessed in human amniotic fluid to determine its suitability as a culture medium for human in vitro fertilization (IVF). Two-cell mouse embryos developed to blastocysts after 72 hours at rates similar to that in Whittingham's T6 + 10% fetal calf serum. Significantly more mouse embryos hatched in amniotic fluid. No difference was found between individual patient's amniotic fluids obtained at 16 to 21 weeks' gestation. A preliminary trial comparing amniotic fluid with T6 + maternal serum in human IVF showed no significant difference in fertilization rate and embryo development during 42 to 48 hours in vitro. Expanded blastocysts were obtained in amniotic fluid after 5 days in vitro. Four pregnancies were obtained in 9 patients' transferred embryos grown in amniotic fluid and with 2 or 12 patients' transferred embryos grown in T6 + maternal serum.

Amniotic Fluid↗

PubMed1986

Menstrual irregularities in adolescents: hormonal pattern and ovarian morphology.

The endocrine pattern and ovarian characteristics of 110 healthy adolescents with menstrual irregularities were investigated during the early follicular and premenstrual phases and were compared to those of 14 adolescents with regular menstrual cycles and 20 adults. Over a period of six gynecological years a low ovulation rate (49%) was found in the group of subjects with irregular cycles and regular ovulation was noted in only a few subjects. Slight differences in endocrine pattern and ovarian morphology were observed between the group of adolescents with regular cycles and the group of adults. In contrast, adolescents with irregular menses had higher mean values of luteinizing hormone (LH), testosterone (T), and androstenedione (A) in comparison with the other two groups both in follicular and premenstrual phases. Nearly 35% of the subjects with irregular cycles had levels of T, A and LH which were higher than the upper limit of the adult normal range. Lower progesterone (P), 17P and oestradiol values were observed in the premenstrual phase. Within the group of subjects with irregular menses, LH levels were higher in anovulatory than in ovulatory cycles, in both phases of the cycle, while T and A levels were higher and prolactin levels were lower in the premenstrual phase of anovulatory cycles. Unlike irregular anovulatory cycles, irregular ovulatory cycles showed a hormonal pattern similar to that found in the adult group. By ultrasound evaluation, a high percentage of subjects with irregular menses had multicystic ovaries (57.9%) and the mean (+/- SEM) ovarian volume was higher (10.6 +/- 0.5 cm3) than that found in adolescents with regular menses (6.7 +/- 0.8 cm3) and in the adult group (7.7 +/- 0.3 cm3). With the increase in frequency and continuity of ovulation an improvement in the direction of adult volume and ovarian structure was observed. Besides the endocrine similarity the data emphasize the striking similarity, already documented by histological studies, between pubertal ovaries and those seen in micropolycystic ovary syndrome. These endocrine and ovarian characteristics are typical of a large number of adolescents with irregular menstrual cycles: these features may be representative of a developmental step toward adult normality, although the possibility of a pathological evolution for some subjects cannot be excluded.

Adolescent↗

PubMed1986

Ovarian multifollicularity, high LH and androgen plasma levels, and anovulation are frequent and strongly linked in adolescent irregular cycles.

Ninety-seven adolescents (0.5-6.0 years in gynaecological age) suffering from various kinds of menstrual irregularities were studied and compared with 20 adults by performing ovarian ultrasonography and plasma hormonal determinations. High percentages of multifollicularity (57.7%) and enlarged ovaries (46.3%) were found in the entire group of adolescents. Adolescents with multifollicular ovaries (more than 4 cystic areas) showed higher percentages of luteinizing hormone (LH: 32%), testosterone (T: 34%), and androstenedione (A: 43%) levels exceeding the upper normal adult range than subjects with homogeneous (less than 4 cystic areas) ovaries (LH: 12%, T: 10%, A: 19%, respectively). Ovulation can further discriminate the adolescents: in fact, adolescents with homogeneous ovaries and ovulatory cycles have a hormonal pattern almost identical to that of adults. On the contrary, subjects with multifollicular ovaries and anovulatory cycles show low values of follicle-stimulating hormone (FSH) and high values of LH, T and A, significantly different from those in ovulatory subjects with homogeneous ovaries (P less than 0.005) and from those in adults (P less than 0.005).

Adolescent↗

PubMed1986

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↗