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C Ceccarelli

Publications and source records attributed to C Ceccarelli.

At least 19 recordsLinked to original sources
PubMed2006

Phase II study of cetuximab in combination with FOLFIRI in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma (FOLCETUX study).

BACKGROUND: The purpose of this phase II study was to evaluate the efficacy and safety of cetuximab combined with FOLFIRI as a first-line treatment of advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. PATIENTS AND METHODS: Untreated patients with confirmed advanced gastric or gastroesophageal adenocarcinoma received cetuximab at an initial dose of 400 mg/m(2) intravenously (i.v.) followed by weekly doses of 250 mg/m(2), CPT 11 180 mg/m(2) i.v. on day 1, LFA 100 mg/m(2) i.v. followed by 5-FU 400 mg/m(2) i.v. bolus, and 600 mg/m(2) i.v. 22-h continuous infusion on days 1 and 2 (FOLFIRI) every 2 weeks, for a maximum of 24 weeks, then cetuximab alone was allowed in patients with a complete response, partial response, or stable disease. Antitumor activity was assessed by computed tomography (CT) and positron emission tomography (PET) at baseline and after 6 weeks, and further by CT alone or CT and PET every 6 weeks. RESULTS: Thirty-eight patients were enrolled (median age 63.5 years, range 39-83; median Karnofsky performance status 90, range 70-100; stomach 89.5% and GEJ 10.5%; locally advanced disease 13.2% and metastatic disease 86.8%). All 38 patients were assessed for safety and survival, and 34 patients were assessed for overall response rates (ORR). The ORR was 44.1% [95% confidence interval (CI) 27.5% to 60.9%]. The median time-to-progression was 8 months (95% CI 7-9). At the median follow-up time of 11 months, 55.3% of patients were alive, with a median expected survival time of 16 months (95% CI 9-23). Grade 3-4 toxicity included neutropenia (42.1%), acne-like rash (21.1%), diarrhea (7.9%), asthenia (5.3%), stomatitis (5.3%), and hypertransaminasemia (5.3%). There was one (2.6%) treatment-related death. CONCLUSIONS: The combination of cetuximab and FOLFIRI is active in gastric and GEJ adenocarcinoma. The higher toxicity appears to be limited to neutropenia.

Adenocarcinoma↗
PubMed2006

Deuterium enhancement in H3+ in pre-stellar cores.

Deuterium enhancement of monodeuterated species has been recognized for more than 30 years as a result of chemical fractionation that results from the difference in zero-point energies of deuterated and hydrogenated molecules. The key reaction is the deuteron exchange in the reaction between HD, the reservoir of deuterium in dark interstellar clouds, and the H3+ molecular ion, leading to the production of H2D+ molecule, and the low temperature in dark interstellar clouds favours this production. Furthermore, the presence of multiply deuterated species have incited our group to proceed further and consider the subsequent reaction of H2D+ with HD, leading to D2H+, which can further react with HD to produce D3+. In pre-stellar cores, where CO was found to be depleted, this production should be increased as CO would normally destroy H3+. The first model including D2H+ and D3+ predicted that these molecules should be as abundant as H2D+. The first detection of the D2H+ was made possible by the recent laboratory measurement for the frequency of the fundamental line of para-D2H+. Here, we present observations of H2D+ and D2H+ towards a sample of dark clouds and pre-stellar cores and show how the distribution of ortho-H2D+ (1(1,0)-1(1,1)) can trace the deuterium factory in pre-stellar cores. We also present how future instrumentation will improve our knowledge concerning the deuterium enhancement of H3+.

Journal Article↗
PubMed2006

The "in situ" expression of human leukocyte antigen class I antigens is not altered by cryopreservation in human arterial allografts.

This study was aimed to establish whether the cryopreservation procedure we currently use in clinics can modify arterial homograft antigenicity. To this purpose, we performed an immunohistochemical study on fresh and cryopreserved human arterial homografts to visualize the expression of HLA class I heavy and light chains "in situ" by using the HC-10 and Namb-1 monoclonal antibodies. Human femoral arteries and thoracic aortas were harvested from 18 heart-beating donors and sampled before and after cryopreservation. Arterial segments were frozen in liquid nitrogen vapors in a controlled rate freezing system. After thawing, samples were processed for routine immunohistochemistry. To standardize immunostaining, flow-cytometry indirect immunofluorescence analysis was performed on HUVEC; immunohistochemistry of human ovarian cortical vessels was performed as an additional positive control. Negative controls were performed by omitting tissue incubation with primary antibodies. HLA-class I antigens were markedly expressed by endothelial cells lining surface intima and adventitial vasa vasorum; a moderate expression was found in medial smooth muscle cells. Except for the surface unreactivity caused by loss of endothelium, results from cryopreserved arterial allografts were strictly comparable to those observed in fresh, unfrozen tissues. These results support the view that cryopreserved arterial allografts are immunogenic as their fresh counterparts; apart from smooth muscle cells which retained a moderate expression of HLA class I antigens following cryopreservation, our study suggests that the highly HC-10 positive endothelial cells we found to line the rich adventitial network of vasa vasorum are expected to be one of the major targets of the serological response in the recipient.

Adult↗
PubMed2006

Dyskerin expression influences the level of ribosomal RNA pseudo-uridylation and telomerase RNA component in human breast cancer.

Dyskerin is a nucleolar protein, altered in dyskeratosis congenita, which carries out two separate functions, both fundamental for proliferating cells. One function is the pseudo-uridylation of ribosomal RNA (rRNA) molecules, necessary for their processing, and the other is the stabilization of the telomerase RNA component, necessary for telomerase activity. A significant feature of dyskeratosis congenita is an increased susceptibility to cancer; so far, however, no data have been reported on dyskerin changes in human tumours. Therefore, in this study, the distribution of dyskerin in a large series of human tumours from the lung, breast, and colon, as well as from B-cell lymphomas, was analysed by immunohistochemistry. Dyskerin proved never to be lost or delocalized outside the nucleolus. A quantitative analysis of dyskerin mRNA expression was then performed in 70 breast carcinomas together with the evaluation of telomerase RNA component levels and rRNA pseudo-uridylation. Dyskerin mRNA levels were highly variable and directly associated with both telomerase RNA component levels and rRNA pseudo-uridylation. Dyskerin gene silencing in the MCF-7 human breast carcinoma cell line reduced telomerase activity and rRNA pseudo-uridylation. Significantly, patients with low dyskerin expression were characterized by a better clinical outcome than those with a high dyskerin level. These data indicate that dyskerin is not lost in human cancers and that the levels of its expression and function are associated with tumour progression.

Breast Neoplasms↗
PubMed2005

Radioiodine ablation of thyroid remnants after preparation with recombinant human thyrotropin in differentiated thyroid carcinoma: results of an international, randomized, controlled study.

CONTEXT: After surgery for differentiated thyroid carcinoma, many patients are treated with radioiodine to ablate remnant thyroid tissue. This procedure has been performed with the patient in the hypothyroid state to promote endogenous TSH stimulation and is often associated with hypothyroid symptoms and impaired quality of life. OBJECTIVE AND INTERVENTION: This international, randomized, controlled, multicenter trial aimed to compare the efficacy and safety of recombinant human TSH (rhTSH) to prepare euthyroid patients on L-thyroxine therapy (euthyroid group) to ablate remnant thyroid tissue with 3.7 GBq (100 mCi) 131I, compared with that with conventional remnant ablation performed in the hypothyroid state (hypothyroid group). Quality of life was determined at the time of randomization and ablation. After the administration of the 131-I dose, the rate of radiation clearance from blood, thyroid remnant, and whole body was measured. RESULTS: The predefined primary criterion for successful ablation was "no visible uptake in the thyroid bed, or if visible, fractional uptake less than 0.1%" on neck scans performed 8 months after therapy and was satisfied in 100% of patients in both groups. A secondary criterion for ablation, an rhTSH-stimulated serum thyroglobulin concentration less than 2 ng/ml, was fulfilled by 23 of 24 (96%) euthyroid patients and 18 of 21 (86%) hypothyroid patients (P = 0.2341). Quality of life was well preserved in the euthyroid group, compared with the hypothyroid group, as demonstrated by their lower pretreatment scores on the Billewicz scale for hypothyroid signs and symptoms, 27 +/- 7 vs. 18 +/- 4 (P < 0.0001) and their significantly higher Short Form-36 Health Assessment Scale scores in five of eight categories. Euthyroid patients had a statistically significant one third lower radiation dose to the blood, compared with patients in the hypothyroid group. CONCLUSIONS: This study demonstrates comparable remnant ablation rates in patients prepared for 131I remnant ablation with 3.7 GBq by either administering rhTSH or withholding thyroid hormone. rhTSH-prepared patients maintained a higher quality of life and received less radiation exposure to the blood.

Adolescent↗
PubMed2005

Presence and type of oncogenic human papillomavirus in classic and in differentiated vulvar intraepithelial neoplasia and keratinizing vulvar squamous cell carcinoma.

The presence and type of oncogenic papillomavirus (HPV) in classic warty/basaloid vulvar intraepithelial neoplasia and in differentiated vulvar intraepithelial neoplasia and keratinizing vulvar squamous cell carcinoma was investigated using three techniques, that is, histology, in situ hybridization, and PCR-ELISA. HPV typing was performed using in situ hybridization and PCR-ELISA. Differentiated vulvar intraepithelial neoplasia and invasive keratinizing vulvar squamous cell carcinoma proved completely negative for HPV by PCR-ELISA, in situ hybridization, and histologic examination, while in classic vulvar intraepithelial neoplasia, a HPV positivity of 66.1% was found. HPV 16 was the predominant type, with HPV 35, 33, and 52 types found rarely and sometimes together with HPV 16. PCR-ELISA proved to be the most suitable method to detect and type mucosal oncogenic HPVs. The absolute absence of HPV DNA in differentiated vulvar intraepithelial neoplasias and in keratinizing vulvar squamous cell carcinoma suggests a strong HPV-independent pathway of malignant progression to invasive carcinoma.

Adult↗
PubMed2005

Concurrent EGFr and Cox-2 expression in colorectal cancer: proliferation impact and tumour spreading.

BACKGROUND: Many reports were produced on single epidermal growth factor receptor (EGFr) and cyclo-oxygenase-2 (Cox-2) evaluation using immunohistochemical techniques (IHC), but very few works considered concurrent expression of these two proteins in the light of their impact on proliferation and tumour spreading. At least three molecular pathways (EGFr, Cox-2, and APC/beta-catenin molecular cascade) may interact in this malignancy giving rise to cross talking effects on proliferation and cancer spreading. PATIENTS AND METHODS: To better detail these two latter aggressive features, we studied 205 sporadic colorectal cancer patients, comparing concurrent expression of EGFr, Cox-2, Ki-67, Cyclins D1-A, and E, with tumour spreading (budding) (BUD) and pN status. RESULTS: Our results point to a different aggressive molecular profile due to Cox-2 expression. Cox-2 High expressing cases showed a clear EGFr proliferation-promoting role. On the contrary, EGFr seems directly involved in cancer cells spreading rather than in promoting cancer proliferation in Cox-2 Low/Negative cases. CONCLUSIONS: Immunohistochemical profiling of colorectal cancer seems to be a promising approach, not only to define prognostic impact, but also to detail proliferation-related molecular interplays between EGFr and Cox-2 pathways, with these two latter proteins, at present, being the hottest pharmacological targets for colorectal cancer (CRC) chemoprevention and therapy.

Adult↗
PubMed2005

Suppressor of cytokine signalling 2 (SOCS-2) expression in breast carcinoma.

AIMS: To investigate SOCS-2 (suppressor of cytokine signalling 2) protein expression in breast carcinoma samples in relation to biopathological parameters and survival. METHODS: A polyclonal antibody against SOCS-2 was used to study 50 archival breast carcinoma samples, collected from 1993 to 1995. The presence of SOCS-2 protein was investigated in relation to clinical and biological parameters used in breast cancer pathology. Fluorescence in situ hybridisation (FISH) was used to study whether SOCS-2 expression was related to SOCS-2 gene copy number. RESULTS: SOCS-2 protein was expressed in 34 of 50 breast carcinoma samples and was positively associated with low grade, low nuclear grade, and p27 protein. SOCS-2 expression was inversely related to Ki-67, cyclin A, retinoblastoma protein (pRb), and the epidermal growth factor receptor (EGFR). No relation with overall survival was demonstrated. SOCS-2 amplification was found in three samples. No relation between the number of FISH signals and SOCS-2 expression was found. CONCLUSIONS: The significant correlation seen between SOCS-2 expression, grade, nuclear grade, p27, Ki-67, cyclin A, pRb, and EGFR labelling strongly supports the hypothesis that SOCS-2 loss might be related to cell proliferation and tumour growth in breast carcinoma. Gene copy number changes did not seem to play a role in SOCS-2 regulation and expression; other mechanisms might be involved and deserve further study.

Adult↗
PubMed2005

[Workplace injuries and professional mobility correlated with health problems. The potential and limitations of the ISTAT Labour Force survey--July 1999].

BACKGROUND: Knowledge on the occupational and social factors that influence the relationship between illness, absence from work and occupational mobility is at present insufficient. OBJECTIVES: To map out, by social class and occupational group, the impact of health problems on work and the distribution of accidents and morbidity associated with occupation. METHODS: Using data from the National Survey of the Italian Labour Force (ISTAT, 1999), covering a sample of 200,384 subjects, prevalence odds ratios of morbidity, work injuries and change of occupation due to health problems were calculated by social class and occupation, adjusting for age and residence. RESULTS: The working class showed a higher risk, due to health problems, of a reduction in time worked (OR = 3.70 in men and OR = 4.10 in women), of choosing to work part-time (OR = 2.04 in men and OR = 2.27 in women), or of withdrawing from the workforce (for artisans, skilled manual workers, farmers and agricultural labourers OR = 1.63 in men and OR = 1.47 in women). This class was also at a greater disadvantage not only with respect to accident rates (OR = 1.85 in men and OR = 1.88 in women), but also with respect to the time needed for post-trauma rehabilitation and return to work (for absences of one week to one month: OR = 1.67 and 1.83 for men and women, respectively; for absences of more than one month: OR = 1.29 and OR = 1.69). Moreover, the working class, when compared to other social classes, had a higher rate of suffering from illness, physical impairment or other physical and psychological problems caused or aggravated by working activity (25% in men and 32% in women). CONCLUSIONS: The ISTAT National Survey provides an estimate of minor accidents with prognoses of less than three days, including those not reported to the National Institute for Insurance against Occupational Accidents and Diseases (INAIL). This allows a preliminary exploration of the relationship between health problems and occupational mobility; however, it seems necessary to collect more detailed information in order to more exhaustively explore the mechanisms which generate the inequalities observed.

Accidents, Occupational↗
PubMed2004

Mutations in the SLC26A4 (pendrin) gene in patients with sensorineural deafness and enlarged vestibular aqueduct.

Pendred syndrome and the enlarged vestibular aqueduct (EVA) are considered phenotypic variations of the same entity due to mutations in the SLC26A4 (pendrin) gene. Pendred syndrome consists in sensorineural deafness, goiter and impaired thyroid hormone synthesis while in EVA thyroid function seems to be preserved. The aim of this study was to evaluate thyroid function and morphology and to look for mutations in the SLC26A4 gene in patients presented with EVA. Among 57 consecutive patients with sensorineural deafness 15 with EVA, as assessed by magnetic resonance imaging (MRI), were identified and studied. A complete evaluation of thyroid function including thyroid echography and perchlorate discharge test was carried out in all patients with EVA; all exons of the SLC26A4 gene were amplified from peripheral leukocytes and directly sequenced, using specific intronic primers. Out of 15 patients with EVA, goiter was present in 8 (53%), hypothyroidism in 7 (47%), increased serum thyroglobulin levels in 8 (53%) and a positive perchlorate discharge test in 10 (67%). Nine alleles of the SLC26A4 gene were mutated: 2 novel mutations (L465W and G497R) and 4 already known mutations (T410M, R409H, T505N and IVS1001+1G>A) were found. Four subjects were compound heterozygous and 1 heterozygous (G497R/wt). All patients harbouring mutations in the SLC26A4 gene had goiter and a positive perchlorate discharge test: 3 were slightly hypothyroid and 2 euthyroid. The remaining 10 patients had no mutations in the SLC26A4 gene: 4 of them were hypothyroid, 2 with goiter and positive perchlorate discharge test, 2 without goiter and with negative perchlorate discharge test. Two patients without mutations were euthyroid with positive perchlorate discharge test. Patients with mutations in the SLC26A4 gene had larger thyroid volume (p<0.002), higher serum thyroglobulin (Tg) levels (p<0.002) and greater radioiodine discharge after perchlorate (p=0.09) than patients without mutations. The results of the present study lend support to the concept that all patients with mutated SLC26A4 gene have abnormalities of thyroid function tests.

Adolescent↗
PubMed2004

Location of functioning metastases from differentiated thyroid carcinoma by simultaneous double isotope acquisition of I-131 whole body scan and bone scan.

In a young patient with differentiated thyroid carcinoma (DTC), previously submitted to total thyroidectomy and I-131 therapy for ablation of thyroid remnant, a follow-up 1-131 diagnostic whole body scan (WBS) demonstrated four small abnormal I-131 uptake areas. Two of these were projected over the thoracic region and corresponded to lung nodules, as later demonstrated by lung computerized tomography (CT)-scan. The remaining two areas were found in the lumbar-pelvic region, but their precise location could not be determined. Standard bone Rx examination and bone scan were negative. After I-131 therapy, we simultaneously acquired a I-131 WBS and a Tc-99m oxidronate bone scan by setting a dual window on the gamma camera. Comparing the I-131 and bone images we were able to identify the 4th lumbar vertebra and right ilium as the bone segments to be studied by a radiological approach. Eventually, the thin slice CT-scan demonstrated the presence of two small osteolytic lesions in these areas. In conclusion, the simultaneous acquisition of images both from I-131 and a bone-seeking agent may be useful to locate functioning bone metastases from DTC.

Adult↗
PubMed2004

The prognostic value of the AgNOR parameter in human breast cancer depends on the pRb and p53 status.

BACKGROUND: The amount of argyrophilic nucleolar organiser regions (AgNORs) represents a cell kinetics parameter used in tumour pathology for prognostic purposes. AgNOR expression is directly related to the rate of ribosome biogenesis, which has been recently shown to be controlled also by the tumour suppressor proteins pRb and p53. AIMS: To ascertain the relative prognostic value of AgNORs and of pRb and p53 expression in breast carcinoma. METHODS: This study was carried out on 335 human primary breast carcinomas with a median follow up time of 108 months. AgNORs were measured by morphometric analysis on sections that had been selectively silver stained; expression of p53 and phosphorylated and non-phosphorylated pRb forms was assessed by immunohistochemistry. RESULTS: Patients were divided into groups with low (249) and high (86) AgNOR values; with normal (267) and mutated p53 (68); and with normal (256) and hyperphosphorylated or deleted pRb (79). Univariate analysis of disease free survival showed that AgNORs and the status of pRb and p53 were significantly related to the patients' clinical outcome. However, among the four groups characterised by different pRb and p53 status, the AgNOR parameter was not capable of distinguishing subgroups of patients with different clinical outcomes. CONCLUSIONS: These findings indicate that the prognostic value of the AgNOR parameter depends on the status of the tumour suppressor proteins pRb and p53, and it cannot be ascribed to the relation between AgNORs and the cell proliferation rate.

Biomarkers, Tumor↗
PubMed2003

Thyroid color flow doppler sonography and radioiodine uptake in 55 consecutive patients with amiodarone-induced thyrotoxicosis.

Amiodarone-induced thyrotoxicosis (AMT) is a life-threatening condition, the appropriate management of which is achieved by identifying its different subtypes. Type 1 AIT develops in patients with underlying thyroid abnormalities and is believed to be due to increased thyroid hormone synthesis and release; Type 2 AIT occurs in patients with a normal thyroid gland and is an amiodarone-induced destructive process of the thyroid. Management differs in the two forms of AIT, since Type 1 usually responds to combined thionamides and potassium perchlorate therapy, while Type 2 is generally responsive to glucocorticoids. Mixed forms, characterized by coexistence of excess thyroid hormone synthesis and destructive phenomena, may require a combination of the two therapeutic regimens. In this cross-sectional prospective study, 55 consecutive untreated patients, whose AIT was subtyped according to clinical and biochemical criteria, were evaluated to assess the specificity of color flow doppler sonography (CFDS) and thyroidal radioiodine uptake (RAIU) in the differential diagnosis of AIT. Sixteen patients (6 men, 10 women, age 66+/-13 yr), who had diffuse or nodular goiter with or without circulating thyroid autoantibodies, were classified as Type 1 AIT; 39 patients (27 men, 12 women, age 65+/-13 yr) with apparently normal thyroids were classified as Type 2 AIT. All Type 1 patients had normal or increased thyroidal vascularity on CFDS, while Type 2 AIT patients had absent vascularity (p<0.0001). Thirteen Type 1 AIT patients had inappropriately normal or elevated thyroidal 3-h and 24-h RAIU values (range 6-37% and 10-58%, respectively), in spite of elevated values of urinary iodine excretion; the remaining 3 patients (two with nodular goiter, one with a thyroid adenoma) had low 3-h and 24-h RAIU values (range 1.1-3.0% and 0.9-4.0%, respectively). The latter patients, who were unresponsive to the combination of methimazole and potassium perchlorate, became euthyroid after the addition of glucocorticoids. Thirty-eight Type 2 AIT patients had low 3-h and 24-h RAIU values (range 0.4-3.7% and 0.2-3.0%, respectively), but one had inappropriately normal 3-h and 24-h RAIU values (6% and 13%, respectively). In conclusion, CFDS can accurately distinguish between Type 1 and Type 2 AIT, and in general the CFDS pattern is concordant with the thyroid RAIU. However, in 4 out of 55 patients (7%) the thyroid RAIU was discrepant, probably reflecting the coexistence of Type 1 and Type 2 AIT. Thus, assessment of both CFDS and RAIU may provide a more accurate subtyping of AIT and help in selecting the appropriate therapy. Finally, in long standing iodine sufficient areas, such as the United States, where the thyroid RAIU is consistently low irrespective of the etiology of the AIT, CFDS offers a rapid and available method to differentiate between Type 1 and Type 2 AIT.

Adult↗
PubMed2003

Recombinant human thyrotropin-stimulated serum thyroglobulin combined with neck ultrasonography has the highest sensitivity in monitoring differentiated thyroid carcinoma.

Recombinant human TSH (rhTSH)-stimulated thyroglobulin (Tg) measurement and (131)I whole body scan (WBS) have been validated as informative tests in the postsurgical follow-up of differentiated thyroid carcinoma. We report the diagnostic accuracy of Tg measurement and diagnostic WBS, alone or in combination, after rhTSH stimulation in a retrospective, consecutive series of patients undergoing follow-up for differentiated thyroid cancer. Routine procedures also include neck ultrasound in every patient and post-therapy WBS when indicated. We studied 340 consecutive patients with differentiated thyroid carcinoma, previously treated with near-total thyroidectomy and (131)I thyroid ablation, scheduled for routine diagnostic tests. At baseline on L-T(4)-suppressive therapy, 294 patients had undetectable (<1 ng/ml) serum Tg and negative anti-Tg autoantibodies (TgAb), 25 patients had undetectable serum Tg and positive TgAb, and 21 patients had detectable serum Tg and negative TgAb. These patients were tested for the presence of active disease by rhTSH stimulation. The results of our study showed that rhTSH-stimulated Tg alone had a diagnostic sensitivity of 85% for detecting active disease and a negative predictive value (NPV) of 98.2%. After adding the results of neck ultrasound, sensitivity increased to 96.3%, and the NPV to 99.5%. rhTSH-stimulated WBS had a sensitivity of only 21% and a NPV of 89%. The combination of rhTSH-stimulated Tg and WBS had a sensitivity of 92.7% and a NPV of 99%. We conclude that the rhTSH-stimulated Tg test combined with neck ultrasonography has the highest diagnostic accuracy in detecting persistent disease in the follow-up of differentiated thyroid carcinoma. A detectable level of serum Tg on L-T(4), its conversion from undetectable to detectable after rhTSH, and/or a suspicious finding at ultrasound will allow the identification of patients requiring therapeutic procedures without the need for diagnostic WBS.

Adolescent↗
PubMed2003

Effect of different hormonal replacement therapies on circulating allopregnanolone and dehydroepiandrosterone levels in postmenopausal women.

The effects of hormone replacement therapy (HRT) on the central nervous system in postmenopausal women might be mediated by changes in neurosteroid synthesis and/or release. The aim of this study was to evaluate the impact of HRT on the levels of allopregnanolone, a sedative anxiolytic GABA(A) agonist steroid, and dehydroepiandrosterone (DHEA), a GABA(A) antagonist steroid. We evaluated allopregnanolone and DHEA circulating levels after 1, 3, 6, 9 and 12 months of HRT with ten different estrogen or estrogen-progestin molecules, regimens and routes of administration in 186 postmenopausal women. Cortisol, luteinizing hormone, follicle stimulating hormone, estradiol and progesterone levels were also evaluated. Allopregnanolone levels significantly increased during follow-up with all HRT preparations. The addition of progestin molecules (except for 19-nor derivatives) to transdermal estradiol administration alone determined a higher increase in allopregnanolone levels. Transdermal HRT showed a significantly higher percentage change in allopregnanolone levels compared with oral HRT. DHEA levels showed a progressive decline starting from the 3-month follow-up, without significant differences between the transdermal and oral groups, as well as among the ten groups, independently of the presence and type of progestin molecule used. In conclusion, HRT strongly modifies circulating neurosteroid levels in postmenopausal women.

Administration, Cutaneous↗