Search PubMed⌕ Search

Biomedical subjects

S Mancuso

Publications and source records attributed to S Mancuso.

At least 91 records · Page 5Linked to original sources
PubMed1999

Gynecologic oncologic surgery in the elderly: A retrospective analysis of 213 patients.

OBJECTIVES: The aims of the study were (1) to analyze morbidity and mortality for elderly women (>/=70 years) operated on for gynecological malignancies at our department between 1985 and 1996; and (2) to compare two periods of time (years 1985-1990 versus years 1991-1996) to investigate whether new expedience in the surgical technique as well as in the perioperative management introduced by 1991 influenced the feasibility and tolerability of surgery in elderly patients. METHODS: In a retrospective analysis, we evaluated tumor site, comorbidities, surgical features, morbidity, and mortality. By 1991, several modifications in management were introduced, including: (1) early postoperative mobilization; (2) self-donation with autologous blood transfusion; (3) intraoperative antibiotic prophylaxis; (4) the retroperitoneum was left open and drains were not used after pelvic and aortic lymphadenectomy; (5) use of coagulator forceps and hemoclips for meticolous hemostasis. RESULTS: In 213 patients, tumor site distribution was uterine corpus n = 93, ovary n = 51, vulva n = 29, cervix n = 23, breast n = 15, and vagina n = 2. There were advanced stage diseases in 47%, comorbid illnesses in 76%, and high surgical risk in 48%. Sixty-nine patients (group A) and 144 patients (group B) were treated in the first and second study periods, respectively. Overall, severe postoperative morbidity and mortality were 17 and 2.8%, respectively. Group B compared to group A showed more frequent use of major surgical procedures (P < 0.01) and lymphadenectomy (P < 0.04), lower transfusion rate (P < 0.001), reduced severe morbidity (P < 0.002), lower mortality (P = 0.3), and shorter hospital stay (P < 0.001). CONCLUSIONS: Our study suggests that surgery, including very radical procedures, is reasonably feasible and well tolerated by elderly patients. The introduction of technical and medical advances in the later years of the study resulted in a significant improvement of surgical rates.

Aged↗
PubMed1999

Effect of opioid blockade on insulin and growth hormone (GH) secretion in patients with polycystic ovary syndrome: the heterogeneity of impaired GH secretion is related to both obesity and hyperinsulinism.

OBJECTIVE: To investigate the involvement of opioid tone, obesity, and hyperinsulinemia in GH secretion in women with polycystic ovary syndrome (PCOS). DESIGN: Controlled clinical study. SETTING: Catholic University of Sacred Heart School of Medicine in Rome, Italy. PATIENT(S): Twenty-two patients with PCOS and 14 healthy, normally ovulating volunteers, matched for age and body mass index. INTERVENTION(S): Patients underwent a GH-releasing hormone (GHRH) test and an oral glucose tolerance test before and after 4-5 weeks of treatment with 50 mg/d of naltrexone. MAIN OUTCOME MEASURE(S): Serum concentrations of GH, insulin, glucose, steroids, and gonadotropins, as well as the GH area under the curve (AUC-GH) and the insulin area under the curve (AUC-I), were measured before and after naltrexone treatment. RESULT(S): In patients with PCOS, the administration of naltrexone increased the GH response to the GHRH test without interfering with the insulin response to the oral glucose tolerance test. However, the GH response to the GHRH test was improved significantly only in lean patients with PCOS, whereas obese patients with PCOS did not show any improvement in GH secretion. In obese control subjects, the treatment reduced plasma basal insulin concentrations and increased the AUC-GH, whereas in lean control subjects, the treatment reduced the GHRH-induced response. In normoinsulinemic patients with PCOS, the GH response to the GHRH test increased significantly after treatment, whereas the AUC-I was not affected. In hyperinsulinemic patients with PCOS, treatment with naltrexone significantly reduced the AUC-I, whereas the AUC-GH increased only in lean hyperinsulinemic patients with PCOS. CONCLUSION(S): Naltrexone treatment improves GHRH-induced GH secretion in patients with PCOS. However, this GH response is heterogeneously represented in relation to both obesity and hyperinsulinism.

Adult↗
PubMed1999

Antiphospholipid antibodies inhibit prostaglandin release by decidual cells of early pregnancy: possible involvement of extracellular secretory phospholipase A2.

OBJECTIVE: To investigate the effect of antiphospholipid antibodies on eicosanoid production by human decidual cells and the in vitro interaction between antiphospholipid antibodies and secretory phospholipase A2. DESIGN: Cultures of human decidual cells from early pregnancy. SETTING: All decidual specimens were obtained from the Obstetrics and Gynecology Department of the Catholic University, Rome, Italy. PATIENT(S): Patients were undergoing operative laparoscopy for extrauterine pregnancy, with a period of amenorrhea ranging from 6 to 9 weeks. INTERVENTION(S): Decidual samples were collected at laparoscopy by routine uterine curettage. MAIN OUTCOME MEASURE(S): Decidual cells were incubated with antiphospholipid antibodies, and eicosanoids (prostaglandin [PG] E2, PGF2alpha, and thromboxane B2) were assayed by RIA after 24 hours of culture. In vitro interactions between antiphospholipid antibodies and secretory phospholipase A2 were investigated with use of a modified ELISA for phospholipase A2. RESULT(S): Antiphospholipid antibodies reduced eicosanoid release from decidual cells in a dose-dependent fashion. In vitro assays showed that antiphospholipid antibodies bound secretory phospholipase A2 and that a competition occurred between antiphospholipid antibodies and secretory phospholipase A2 for the common substrate cardiolipin. CONCLUSION(S): In light of the critical role played by eicosanoids in decidual function, we suggest that an interaction between antiphospholipid antibodies and secretory phospholipase A2 occurring in vivo might impair important cellular communications at the decidual level in the antiphospholipid antibody syndrome.

Antibodies, Anticardiolipin↗
PubMed1999

Reproductive effects of dietary soy in female Wistar rats.

This study was designed to assess the effects of administration of dietary soy on reproductive function and fertility of female Wistar rats. Four groups, each of 20 females, were used. Control animals were fed a standard cereal-based diet for rats. Treated animals were fed a standard diet supplemented with 0.7%, 1.2% or 2.4% of a soy extract. Treatment started at weaning and continued until day 7 post-partum (day of sacrifice). Growth depression was seen in the 2.4% soy group. Vaginal opening occurred earlier in females receiving soy supplemented feed when compared with controls. Analysis of vaginal smears revealed that all animals were cycling, although an increase in the mean duration of each cycle was seen in the 2.4% soy group. Uterine effects were observed in high-dose females and included increases in weight, oedema, endothelial hyperplasia and leucocytic infiltration. Vaginal modifications (i.e. inflammation, hyperkeratosis and dyskeratosis) and alterations in the distribution of follicular size in the ovaries were also observed among treated animals. These data suggest that long-term exposure to high doses of phytoestrogens can produce significant agonistic actions in several oestrogen-dependent tissues and parameters, even though in this model no clear influence on reproductive processes was observed.

Animals↗
PubMed1999

Expansion of granulocyte colony-stimulating factor/chemotherapy-mobilized CD34+ hematopoietic progenitors: role of granulocyte-macrophage colony-stimulating factor/erythropoietin hybrid protein (MEN11303) and interleukin-15.

Ex vivo stroma-free static liquid cultures of granulocyte colony-stimulating factor (G-CSF)/chemotherapy-mobilized CD34+ cells were established from patients with epithelial solid tumors. Different culture conditions were generated by adding G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF), Flt3 ligand (Flt3), megakaryocyte growth and development factor (Peg-rHuMGDF), GM-CSF/erythropoietin (EPO) hybrid protein (MEN11303), and interleukin-15 (IL-15) to the basic stem cell factor (SCF) + interleukin-3 (IL-3) + EPO combination. This study showed that, among the nine different combinations tested in our 5% autologous plasma-containing cultures, only those containing IL-3/SCF/Flt3/MEN11303 and IL-3/SCF/Flt3/MEN11303/IL-15 significantly expanded colony-forming unit granulocyte-macrophage (CFU-GM), burst-forming unit erythroid (BFU-E), long-term culture-initiating cells (LTC-IC), CD34+, and CD34+/CD38- cells after 14 days of culture. Particularly, the addition of IL-15 to IL-3/SCF/Flt3/MEN11303 combination produced a significant increase of LTC-IC, with an average 26-fold amplification as compared to input cells, without any detrimental effect on CFU-GM and BFU-E expansion. This combination also produced a statistically significant 3.6-fold expansion of primitive CD34+/CD38- cells. Moreover, this study confirms the previously described erythropoietic effect of MEN11303, which, in our experience, was the only factor capable of expanding BFU-E. Compared to equimolar concentrations of GM-CSF and EPO, MEN11303 hybrid protein showed a significantly higher capacity of expanding CFU-GM, BFU-E, LTC-IC, CD34+, and CD34+/CD38- cells when these cytokines were tested in combination with IL-3/SCF/Flt3. These cultures indicated that Peg-rHuMGDF addition to IL-3/SCF/EPO/Flt3 does not affect CFU-GM and BFU-E expansion but, unlike G-CSF or GM-CSF, it does not decrease the ability of Flt3 to expand primitive LTC-IC. These studies indicate that, starting from G-CSF/chemotherapy-mobilized CD34+ cells, concomitant expansion of primitive LTC-IC, CFU-GM, BFU-E, CD34+, and CD34+/CD38- cells is feasible in simple stroma-free static liquid cultures, provided IL-3/SCF/Flt3/MEN11303/IL-15 combination is used as expanding cocktail in the presence of 5% autologous plasma.

Adolescent↗
PubMed1999

Dilute ornitin vasopressin and a myoma drill for laparoscopic myomectomy.

To improve enucleation of uterine myomas, we designed a reusable 5-mm laparoscopic drill with a distal forked pin and locking system. Because the device is jointed, it can apply traction not only along its own axis, but also along planes, depending on its bending radius. We compared enucleation time for myomas 5 to 8 cm in size before and after introduction of the drill. The last 23 procedures performed with this instrument were easier, with a reduction in operating time of about 28.5% for the enucleation part of the procedure (p <0.001). (J Am Assoc Gynecol Laparosc 6(2):189-193, 1999)

Adult↗
PubMed1999

Tamoxifen induces oxidative stress and apoptosis in oestrogen receptor-negative human cancer cell lines.

Recent data have demonstrated that the anti-oestrogen tamoxifen (TAM) is able to facilitate apoptosis in cancer cells not expressing oestrogen receptor (ER). In an attempt to identify the biochemical pathway for this phenomenon, we investigated the role of TAM as an oxidative stress agent. In two ER-negative human cancer cell lines, namely T-leukaemic Jurkat and ovarian A2780 cancer cells, we have demonstrated that TAM is able to generate oxidative stress, thereby causing thiol depletion and activation of the transcriptional factor NF-kappaB. As described for other oxidative agents, TAM was able to induce either cell proliferation or apoptosis depending on the dose. When used at the lowest dose tested (0.1 microM), a slight proliferative effect of TAM was noticed in terms of cell counts and DNA synthesis rate, whereas at higher doses (10 microM) a consistent occurrence of apoptosis was detected. Importantly, the induction of apoptosis by TAM is not linked to down-regulation or functional inactivation by phosphorylation of the antiapoptotic bcl-2 protein.

Antineoplastic Agents, Hormonal↗
PubMed1999

hMSH2 and GTBP expression in advanced stage epithelial ovarian cancer.

Defects in DNA mismatch repair have been associated with both hereditary and sporadic forms of human cancer. Most of the attention has been focused on the incidence and genetics of mismatch repair defects, while little is known about the expression levels of the mismatch repair proteins and their significance in cancer cell biology. In this study, both the expression levels of hMSH2 and GTBP proteins were investigated by Western blotting in 20 untreated epithelial ovarian cancers. For these analyses, a commercial anti-hMSH2 monoclonal antibody and a newly generated mouse monoclonal anti-GTBP antibody were used. hMSH2 and GTBP proteins were detected by Western blotting in 19 out of 20 (95%) samples analysed and were found to be directly correlated (r= +0.51, P = 0.025). hMSH2 expression was significantly higher in ovarian cancer cells originating from solid tumours than from ascites (H = 4.5, P = 0.033), whereas GTBP content did not significantly differ according to the origin of cancer cells. No statistically significant differences were found in the distribution of hMSH2 and GTBP levels according to the age of the patients, grade of differentiation, histotype and extent of surgical debulking. The amount of hMSH2 protein was demonstrated to be significantly lower in stage IV than in stage III patients (H = 7.35, P = 0.007). Moreover, significantly lower hMSH2 levels were observed in non-responding patients compared to patients who achieved complete or partial response to cisplatin-based chemotherapy (H = 4.88, P = 0.027). Conversely, GTBP levels were not distributed differently according to stage of disease and chemotherapy response. Our study suggests a possible involvement of hMSH2 in ovarian cancer cell biology and susceptibility to chemotherapy. The possible biological and/or clinical role of GTBP expression in ovarian cancer patients remains to be elucidated.

Adult↗
PubMed1999

p53 overexpression is associated with cytoreduction and response to chemotherapy in ovarian cancer.

The aim of this study was to assess the association of p53 status with primary cytoreduction, response to chemotherapy and outcome in stage III-IV primary ovarian cancer patients. Immunohistochemical analysis of p53 was performed on formalin-fixed, paraffin-embedded specimens from 168 primary ovarian carcinomas by using the DO-7 monoclonal antibody. p53 nuclear positivity was found in 84 out of 162 (52%) malignant tumours. A higher percentage of p53 nuclear positivity was observed in patients with advanced stage of disease than in stage I-II (57% vs 23% respectively; P = 0.0022) and in poorly differentiated versus well/moderately differentiated tumours (59% vs 32% respectively; P = 0.0038). The multivariate analysis aimed to investigate the association of FIGO stage, grade and p53 status with primary cytoreduction in 136 stage III-IV patients showed that stage IV disease may influence the possibility to perform primary cytoreduction in ovarian cancer patients. p53-positivity also maintained a trend to be associated with poor chance of cytoreduction. In patients who underwent pathologic assessment of response, cases who did not respond to chemotherapy were much more frequently p53-positive than p53-negative (86% vs 14% respectively; P = 0.012). Moreover, patients with stage III disease and < 2-cm residual tumour were more likely to respond to treatment. In multivariate analysis, FIGO stage and p53 expression were independently correlated with pathologic response to chemotherapy. Time to progression and survival rates were shown not to be different in p53-positive versus p53-negative patients.

Adult↗
PubMed1999

The prognostic role of salpingoscopy in laparoscopic tubal surgery.

The present study was designed to evaluate the prognostic value of salpingoscopy in patients undergoing tubal laparoscopic surgery for infertility due to periadnexal adhesion or distal tubal occlusion. In addition, the clinical value of salpingoscopy was compared with a current classification system of adnexal adhesions and distal tubal occlusion. A total of 51 patients with either adnexal adhesions (24 patients) or hydrosalpinx (27 patients) were prospectively evaluated. Salpingoscopy was performed concomitantly with salpingo-ovariolysis or salpingoneostomy at the time of operative laparoscopy. There was no significant correlation between salpingoscopic classes and the classification system used for both the salpingo-ovariolysis and the salpingoneostomy groups of patients. The patients had a mean follow-up of 33 months. Patients with a normal tubal mucosa (salpingoscopic classes I and II) had a 71% cumulative term pregnancy rate in the salpingo-ovariolysis group and a 64% cumulative term pregnancy rate in the salpingoneostomy group. No intrauterine pregnancies were obtained in patients with intratubal damage (salpingoscopic classes III to V). There was a statistically significant correlation between the occurrence of a term pregnancy and the salpingoscopic classes, but not with the classification system used. These results suggest that patients with tubal infertility should be offered operative laparoscopy with salpingoscopy as the first step of treatment.

Adnexa Uteri↗
PubMed1999

Changes in luteinizing hormone and insulin secretion in polycystic ovarian syndrome.

Uncertainties regarding the pathogenetic changes underlying the polycystic ovarian syndrome (PCOS) have been reported. The aim of this study was to investigate the endocrine and metabolic features of PCOS patients in relation to luteinizing hormone (LH) secretion. Androgen assays, oral glucose tolerance tests, hyperinsulinaemic euglycaemic clamps and gonadotrophin releasing hormone (GnRH) tests were performed in 100 patients. Sixty-six patients scheduled as hyperinsulinaemic and 34 as normoinsulinaemic showed similar concentrations of LH, follicle stimulating hormone (FSH), LH/FSH ratio, and LH response to GnRH testing. Hyperinsulinaemic subjects showed higher body mass index (BMI), insulin resistance, testosterone and free androgen index levels compared with those of normoinsulinaemic subjects; when clustered in relation to their LH basal concentrations, the two groups obtained differed only in androstenedione concentrations. Considering both insulin and LH plasma concentrations, four groups were obtained. Hyperinsulinaemia and hyper-LH secretion were not related in 54% and coexisted in the same subjects in 26% of cases. Hyperinsulinaemia as well as hyper-LH secretion affected the expression of the syndrome; the insulinaemia was directly correlated with testosterone concentrations and all metabolic parameters that affected the free androgen index. The LH concentrations were related to androgen production and were independent of BMI and insulin concentrations. It is concluded that the degree of hormonal alteration is the final sum of such pathogenetic factors.

Adult↗
PubMed1999

HIV infection: oral lesions, CD4+ cell count and viral load in an Italian study population.

The aims of this study were to assess types and prevalence of HIV-related oral lesions and to correlate these lesions to the main laboratory parameters such as CD4+ cell count and plasma HIV-RNA. The study population consisted of 104 consecutive HIV+ patients living in Sicily (M=67, 64.4%; F=37, 35.6%; median age=35 years). CD4+ cell count and viral load were measured within 24 h of oral examination. Data were managed and analysed by Epi-Info 6.0. HIV-related oral lesions, as classified by the EC-Clearinghouse, were diagnosed in 35.6% of patients: these were of the Strongly Associated (SA) type in 22.1%, the Less Common Associated (LCA) type in 12.5%, and the Lesions Seen in HIV Infection (LS) type in 3.8%. CD4+ cell counts <200 x 10(6)/l were significantly associated only with SA lesions (P=0.03); median values of CD4+ cell count were also significantly correlated (P=0.02). Viral load, expressed both by median values of copies/ml (P=0.0001) and log10 copies/ml (P=0.0003), was significantly associated only with SA lesions. Treatment failure was significantly correlated to SA lesions (P=0.04). Besides the confirmed correlation with CD4 depletion, the strong association with a high level of viral load could make SA oral lesions a useful tool for identifying progression of HIV infection and could be of value in monitoring antiretroviral therapy.

Adult↗
PubMed1999

Effect of anticardiolipin antibodies on prolactin and insulin-like growth factor binding protein-1 production by human decidual cells.

PROBLEM: The effect of anticardiolipin antibodies (ACAs) on basal- and growth factor-stimulated prolactin and insulin-like growth factor (IGF) binding protein (BP)-1 production by cultured human decidual cells was investigated. METHOD OF THE STUDY: Decidual cells were cultured for 24, 48, or 96 hr in medium supplemented with 5% ACA-containing or 5% control serum and increasing concentrations of insulin (1-10 micrograms/mL) or IGF-1 (10-100 ng/mL). RESULTS: No significant increase in prolactin production was observed after addition of increasing doses of insulin and IGF-I in the presence of ACA-containing serum, while a dose-dependent stimulation was seen with control serum. Time-dependent prolactin accumulation was also reduced when cells were cultured in the former conditions. IGF BP-1 release was not affected by insulin and IGF-I in the presence of both sera. However, lower IGF BP-1 levels and a less pronounced time-dependent accumulation were observed in the presence of ACA-positive serum. CONCLUSIONS: Our data suggest that ACAs affect cellular transduction mechanisms regulating critical events, such as decidual cell differentiation. These cellular dysfunctions might be relevant in the induction of some obstetric disorders typical of this syndrome.

Antibodies, Anticardiolipin↗
PubMed1999

IL-6, M-CSF and IAP cytokines in ovarian cancer: simultaneous assessment of serum levels.

The aim of this study was to simultaneously determine IL-6, M-CSF and IAP levels in 61 serum samples of previously untreated ovarian cancer patients. A direct correlation between IL-6 and M-CSF has been found in our patient population (r = +0.41, p = 0.013), while IAP serum levels failed to correlate with M-CSF (r = +0.15, p = 0. 24) and IL-6 (r = +0.17, p = 0.18) levels. Since IL-6 and M-CSF have been demonstrated to be both induced in response to the same agents, it is conceivable that a mechanism of coregulation in the production of these cytokines by tumor cells and macrophages might occur. The direct correlation between IL-6 and M-CSF also suggests that tumor-derived cytokines can potentially lead to a self-maintaining cytokine network by recruiting cytokine-producing host cells and by perpetuating cytokine production.

Biomarkers, Tumor↗
PubMed1999

Erythropoietin addition to granulocyte colony-stimulating factor abrogates life-threatening neutropenia and increases peripheral-blood progenitor-cell mobilization after epirubicin, paclitaxel, and cisplatin combination chemotherapy: results of a randomized comparison.

PURPOSE AND METHODS: The ability of granulocyte colony-stimulating factor (G-CSF) plus erythropoietin (EPO) treatment was compared in a randomized fashion with that of G-CSF treatment alone in promoting hematologic recovery and peripheral-blood progenitor-cell (PBPC) mobilization in previously untreated patients with advanced ovarian cancer who underwent their first course of epirubicin, paclitaxel, and cisplatin (ETP) chemotherapy during a phase II study of intensive outpatient ETP chemotherapy followed by high-dose carboplatin, etoposide, and melphalan (CEM) late intensification with PBPC support. RESULTS: Comparative analysis of hematologic recovery of 50 randomized patients, after ETP chemotherapy, showed that life-threatening neutropenia occurred in 88% of the patients treated with G-CSF alone, whereas it occurred in only 4% of patients treated with G-CSF + EPO. Significantly different WBC and polymorphonuclear leukocyte (PMN) counts were observed in the two distinct arms on the day of WBC nadir (P <.0001 and P <.0001, respectively). Moreover, the addition of EPO to G-CSF increased PBPC mobilization and collection as compared with that in G-CSF-treated patients (P =.0009 and P =.0026, respectively), who required a significantly higher number of leukaphereses than G-CSF + EPO-treated patients (P =.0076) to obtain the planned minimum dose of PBPCs. Qualitative analysis by cloning assay of PBPCs collected in both arms revealed that G-CSF- and G-CSF + EPO-mobilized PBPCs have comparable in vitro functional properties. CONCLUSION: This randomized comparison revealed that EPO significantly increases most of the hematologic effect produced by G-CSF administration after chemotherapy. This biologic property of EPO translated in vivo into a global improvement of patients' hematologic status.

Adult↗
PubMed1999

Paracrine regulation of insulin-like growth factor I (IGF-I) an IGF-II on prostaglandins F2alpha and E2 synthesis by human corpus luteum in vitro: a possible balance of luteotropic and luteolytic effects.

The existence of a complete intraovarian insulin-like growth factor (IGF) system replete with ligands, receptors, and binding proteins has been demonstrated as well as the ability of IGF-I to positively affect steroidogenesis in human granulosa cells. Furthermore, we recently showed that IGF-I and IGF-II stimulate progesterone secretion by human luteal cells. As the PGs, PGE2 and PGF2alpha, are classically known to have luteotropic and luteolytic effects, we wanted to determine whether the IGFs could affect the human luteal phase by influencing the PG system. For this reason, human luteal cells were cultured for different times (12, 24, and 48 h) with IGF-I, IGF-II (10-100 ng/mL), and GH (100 ng/mL), and both PGs were assayed in the medium culture. We found that both IGF-I and IGF-II were able to stimulate PGE2 synthesis in a time- and dose-dependent way, whereas they both inhibited PGF2alpha production. GH, too, significantly reduced PGF2alpha synthesis; this effect was IGF-I mediated because it was reverted by increasing dilutions of an anti-IGF-I antibody. On the contrary, no GH effect was observed on PGE2 production. In conclusion, based on these data and on our previous results, we speculate that IGFs could influence luteal steroidogenesis through PG system.

Adult↗
PubMed1999

Differential effect of transdermal estrogen plus progestagen replacement therapy on insulin metabolism in postmenopausal women: relation to their insulinemic secretion.

OBJECTIVE: To evaluate the impact on glucose and insulin metabolism of transdermal estrogen patches before and after the addition of cyclic dydrogesterone in postmenopausal women. DESIGN: We studied 21 postmenopausal women seeking treatment for symptomatic menopause. All patients received transdermal 50 micrograms/day estradiol for 24 weeks. After 12 weeks of treatment, 10 mg/day dydrogesterone were added. METHODS: During both regimens, insulin and C-peptide plasma concentrations were evaluated after an oral glucose tolerance test (OGTT); insulin sensitivity was evaluated by a hyperinsulinemic euglycemic clamp technique. Insulin and C-peptide response to OGTT were expressed as area under the curve (AUC) and as incremental AUC; insulin sensitivity was expressed as mg/kg body weight. Fractional hepatic insulin extraction (FHIE) was estimated by the difference between the incremental AUC of the C-peptide and insulin divided by the incremental AUC of the C-peptide. Plasma hormone and lipid concentrations were assessed at baseline and at 12 and 24 weeks of treatment. RESULTS: Nine patients proved to be hyperinsulinemic and 12 were normoinsulinemic. Transdermal estrogen treatment significantly decreased the insulin AUC (P < 0.05) and the insulin incremental AUC in hyperinsulinemic patients; addition of dydrogesterone further decreased both the AUC and incremental AUC of insulin. Estrogen alone and combined with dydrogesterone evoked a significant increase in C-peptide AUC in hyperinsulinemic (79.2%) and normoinsulinemic (113%) patients. The treatment increased the values for FHIE and insulin sensitivity in all patients (P < 0.04) and in the hyperinsulinemic group (P < 0.01), whereas it did not affect such parameters in normoinsulinemic patients. CONCLUSIONS: Transdermal estrogen substitution alone and combined with cyclical dydrogesterone may ameliorate hyperinsulinemia in a selected population of postmenopausal women.

Administration, Cutaneous↗