Rosanna Apa

Recombinant versus Urinary Follicle-Stimulating Hormone in the Low-Dose Regimen in Anovulatory Patients with Polycystic Ovary Syndrome: A Safer and More Effective Treatment

Background: We studied polycystic ovarian syndrome (PCOS) in fifty 25- to 37-year-old women who failed to conceive with clomiphene citrate treatment. Methods: Twenty patients were submitted to treatment with low-dose (75 IU) urinary FSH (uFSH) in order to achieve ovulation and 30 patients were treated with recombinant FSH (rFSH) according to the same protocol. Results: Ovulation was achieved in 75 and 97% of the cycles after uFSH and rFSH, respectively (p < 0.02). The length of treatment needed to achieve ovulation, the number of ampules given and dose per kilogram were significantly lower in the rFSH group. Mild ovarian hyperstimulation syndrome (OHSS) was observed in 9 uFSH cycles, whereas only 1 of the women treated with rFSH developed an OHSS (1/38 vs. 9/36; p < 0.01). Conclusion: rFSH is more efficient than uFSH in inducing ovulation in PCOS patients. The high prevalence of ovulatory cycles using a lower dose guaranteed greater safety of treatment and significantly reduced the incidence of OHSS.

The effects of nitric oxide on prostanoid production and release by human umbilical vein endothelial cells

Human umbilical vein endothelial cells (HUVEC) express and synthesize both constitutive and inducible nitric oxide synthase (NOS) and cyclo-oxygenase (COX) enzymes, and have been extensively used as an in vitro model to investigate the role of these enzymes in the patho-physiology of placenta-fetal circulation. In this study we investigated the role of NO in regulating prostanoid production and release from HUVEC. Both untreated and IL-1beta-treated HUVEC were exposed to various NOS inhibitors and NO donors in short-term (1 or 3 hours) experiments, and the effects on prostanoid production were evaluated through the measurement of prostaglandins (PG) I2, E2 and F2alpha released in the incubation medium. We found that the inhibition of inducible NOS but not endothelial NOS antagonizes the IL-1beta-induced increase in PGI2 release. However, NOS inhibitors do not modify baseline PGI2 production. Pharmacological levels of NO, obtained with various NO donors, inhibit basal and IL-1beta-stimulated PG release.

Effect of Luteal Metoclopramide-Induced Hyperprolactinemia on Pituitary and Luteal Responsiveness to Gonadotropin-Releasing Hormone

The pituitary and corpus luteum responses to acute gonadotropin-releasing hormone (GnRH) administration at the mid-luteal phase (LP) were studied in 24 infertile women. Patients were randomly divided into two groups. In one group (n = 12) metoclopramide (MCP, 10 mg orally 3 times daily) was administered from day 0 or 1 of the LP for 7 days. On day 7 or 8 of LP blood samples were taken every 15 min for 180 min; then 25 micrograms GnRH were acutely administered intravenously and blood samples taken at 185, 195, 210, 225, 240, 255, 270, 285 and 300 min. In the other 12 patients the same experimental design was performed on day 7 or 8 of an untreated LP. Plasma prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone and estradiol (E2) were assayed. The responsiveness of the different hormones to GnRH was evaluated as the integrated secretory area for 120 min after injection (sISA = stimulated integrated secretory area) and as the percentage increase (delta A) with respect to the area under basal conditions before GnRH administration (bISA = basal integrated secretory area). MCP-treated women showed higher basal PRL levels (p less than 0.01) and lower basal plasma concentrations and bISA (p less than 0.01) values of LH than controls. After GnRH a more marked response of LH secretion was observed in the treated group (p less than 0.01), so that the absolute values of sISA were superimposable in both groups. Basal and stimulated FSH secretion did not differ significantly in the study groups. Basal plasma and bISA values of progesterone were also decreased in MCP-treated subjects. After GnRH injection the absolute values of progesterone sISA were greater in controls (p less than 0.01), but delta A values were similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

ESP Bulletin Board

The ESPE Research Fellowship Grant is a highly prestigious research grant supported by Novo Nordisk A/S which is given to young investigators within the area of paediatric endocrinology enabling a 2-year research stay abroad in research centers of excellence. The two recipients in 2001 were: Dr. Mäkitie Outi from Helsinki in Finland who trained by Professor Perheentupa. She will go to the Hospital of Sick Children in Toronto, Canada, to work with Dr. W.G. Cole and Professor Daneman on a project named ‘Clinical and genetic aspects of infantile cortical hyperostosis’. Dr. Birgit Köhler from Marburg in Germany who was trained by Professor Grüters. She will go to INSERM Institution in Montpellier, France, to work in the laboratory of Professor Sultan on a project named ‘Interaction of the Wilms tumor suppressor (WT1) protein and the androgen receptor gene?’ Deadline for applications for the 2002 ESPE Research Fellowship Grants is March 1, 2002. Applications should be sent to:

Plasmatic and Intracellular Markers of Oxidative Stress in Normal Weight and Obese Patients with Polycystic Ovary Syndrome

Introduction Insulin resistance (IR) is associated with polycystic ovary syndrome (PCOS). Oxidative stress (OS) is, in turn, related to IR. Studies in PCOS evidenced an increase in OS markers, but they are mainly performed in obese patients, while the complex picture of normal weight PCOS is still poorly investigated. Matherials and Methods To investigate OS in PCOS and relationship with hormonal and metabolic picture, we performed a case-control study in 2 PCOS groups: normal weight (N-PCOS, n=21, age 18-25 ys, mean±SEM BMI 20.7±0.2 kg/m2) and obese (OB-PCOS, n=15, 20-30 ys, BMI 32.8±1.1), compared with control groups matched for BMI: normal (N-C, n=10, 20-30 ys, BMI 21.6±0.9) and obese (OB-C, n=20, 21-31ys, BMI 36.8±1.0). Malondialdehyde (MDA) in blood plasma and peripheral mononuclear cells, obtained by density-gradient centrifugation, was assayed spectrophotometrically by TBARS assay. CoenzymeQ10 (CoQ10) in plasma and cells was assayed by HPLC. Plasma Total Antioxidant Capacity (TAC) was also measured by spectrophotometric method. Results PCOS patients exhibited higher Testosterone levels than controls, but OB-PCOS had highest HOMA (Homeostasis Model Assessment) index, suggesting marked insulin resistance. Despite plasma MDA levels were not significantly different (N-PCOS 3380±346.94 vs. N-C 7 120±541.66; OB-PCOS 5 517.5±853.9 vs. OB. 3 939.66±311.2 pmol/ml), intracellular MDA levels were significantly higher in N-PCOS than controls (mean 3 259±821.5 vs. 458±43.2 pmol/106/cells) and higher than OB-PCOS, although not significantly (1363.1±412.8 pmol/106/cells). Intracellular CoenzymeQ10 was higher in N-PCOS than in N-C, but the highest levels were found in OB-C. Conclusions Our data, while confirming the presence of OS in obese PCOS patients in agreement with literature, suggest that OS could be present also in normal weight PCOS, but it can be revealed in tissue rather than in plasma. The relationship with metabolic status remains to be established, but could be a physiopathological basis for antioxidant treatment in such patients.