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Editorial Local drug release systems in endometriosis. 2007
Petraglia F, Luisi S. · No affiliation provided · Gynecol Endocrinol. · Pubmed #17999278 No free full text.
This publication has no abstract.
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Review Hormone-dependent gynaecological disorders: a pathophysiological perspective for appropriate treatment. 2008
Petraglia F, Musacchio C, Luisi S, De Leo V. · Obstetrics and Gynaecology, Department of Paediatrics, Obstetrics and Reproductive Medicine, University of Siena Policlinico, S. Maria alle Scotte Viale Bracci, 53100 Siena, Italy. · Best Pract Res Clin Obstet Gynaecol. · Pubmed #17804298 No free full text.
Abstract: Hormonal changes are involved in several gynaecological disorders. Correct functioning of the hypothalamus-pituitary-ovarian (HPO) axis is critical for ovulatory function, as well as the growth and differentiation of uterine tissue (myometrium and endometrium). However, the correct functioning of other endocrine glands (thyroid, adrenal cortex, pancreas) is also crucial for correct reproductive function. Genes and environmental factors have an influence on women's fertility through their effect on hormonal function. Consequently, dysfunction of the HPO axis and/or other endocrine systems may cause infertility and gynaecological disorders. The pathogenetic basis can be used to help make the correct clinical decision for treating these diseases. Disturbances related to the menstrual cycle, i.e. amenorrhoea, polycystic ovary syndrome (PCOS) and premenstrual syndrome (PMS), have a close correlation with hypo- or hypersecretion of hormones of the HPO axis. The roles of hypothalamic neurohormones and neurotransmitters in the various forms of amenorrhoea and PMS are well established. PCOS has a complex endocrine/metabolic origin, so a variety of hormonal treatments have been proposed. Hormone derangement has also been proposed as the cause of endometriosis and uterine fibroids. These disorders do not have hyper- or hyposecretion of reproductive hormones, but hyperactivity of oestrogen receptors coupled with a genetic predisposition. The relevance of the endocrine changes is confirmed by the clinical effectiveness of hormonal treatments. In order to establish the correct treatment approach in gynaecological disorders, it is important to understand the endocrine pathophysiology.
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Review Paracrine regulation of endometrial function: interaction between progesterone and corticotropin-releasing factor (CRF) and activin A. 2003
Florio P, Rossi M, Sigurdardottir M, Ciarmela P, Luisi S, ViganĂ² P, Grasso D, Fiore G, Cobellis L, Di Blasio AM, Petraglia F. · Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Policlinico Le Scotte, viale Bracci, Siena 53100, Italy. · Steroids. · Pubmed #14667971 No free full text.
Abstract: Under the influence of ovarian steroid hormones, endometrial cells aer able to produce a wide variety of growth factors and peptide hormones that area believed to promote: (1) physiological growth and differentiation during the endometrial cycle; (2) decidualization, an essential preparative event for establishment of pregnancy; and (3) pathological growth and differentiation in endometriosis and cancer. Among the local factors produced by the human endometrium, corticotropin-releasing factor (CRF) and activin A have been evaluated in terms of localization and effects. CRF is a neuropeptide expressed by the epithelial and stromal cells of the human endometrium in increasing amounts from the endometrial proliferative to the secretory phase. CRF expression also increases in the pregnant endometrium, from early in the pregnancy until term. CRF-type 1 receptor mRNA is only expressed by stromal cells. Progesterone induces CRF gene expression and release from decidualized cells and CRF decidualizes cultured stromal endometrial cells. Urocortin, a CRF-related peptide, has been identified in endometrial epithelial and stromal cells, and its function is still under investigation. Activin A is a growth factor expressed in increasing amounts throughout endometrial phases by both epithelial and stromal cells. This growth factor is secreted into the uterine cavity with higher levels in the secretory phase. Maternal decidua expresses activin A mRNA in increasing amounts from early pregnancy until term. Human endometrium also expresses activin-A receptors and follistatin, its binding protein. Activin A decidualizes cultured human endometrial stromal cells (an effect reversed by follistatin) and modulates embryonic trophoblast differentiation and adhesion. Activin A is expressed in endometriosis and endometrial adenocarcinoma.
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Article Relaxin in endometriosis. 2009
Morelli SS, Petraglia F, Weiss G, Luisi S, Florio P, Goldsmith LT. · Department of Obstetrics, Gynecology and Women's Health, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103, USA. · Ann N Y Acad Sci. · Pubmed #19416175 No free full text.
Abstract: Endometriosis is an important contributing factor to chronic pelvic pain and infertility. Matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) have each been implicated in the establishment of endometriotic lesions. Since relaxin regulates the expression of MMPs and VEGF in the endometrium, we tested the hypothesis that relaxin plays a role in endometriosis by comparing the expression of relaxin mRNA and its LGR7 (RXFP1) receptor mRNA in normal human endometrium to those in samples from patients with endometriosis.
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Article Low serum and peritoneal fluid concentration of interferon-gamma-induced protein-10 (CXCL10) in women with endometriosis. 2009
Galleri L, Luisi S, Rotondi M, Romagnani P, Cobellis L, Serio M, Petraglia F. · Division of Obstetrics and Gynecology, Department of Pediatrics, Gynecology and Reproductive Medicine, University of Siena, Siena, Italy. · Fertil Steril. · Pubmed #18281042 No free full text.
Abstract: OBJECTIVE: To evaluate serum and peritoneal fluid concentrations of interferon-gamma-inducible protein-10 (CXCL10), a chemokine involved in local immune function, in women with endometriosis. DESIGN: Prospective study. SETTING: Division of Obstetrics and Gynecology, University of Siena. PATIENT(S): A total of 147 women were divided in two groups: women with (n = 77) and without (n = 70) endometriosis. INTERVENTION(S): Serum and peritoneal fluid were collected from all patients undergoing laparoscopy. MAIN OUTCOME MEASURE(S): CXCL10 concentrations were measured by a specific ELISA. RESULT(S): Serum CXCL10 concentrations in women with endometriosis were significantly lower than in those without endometriosis. No statistically significant difference between women with early endometriosis and those with advanced endometriosis was found. CXCL10 concentrations in peritoneal fluid of women with advanced endometriosis were significantly lower than in that of women with an early stage of, or without, endometriosis. CONCLUSION(S): The decreased concentrations of CXCL10 in serum and peritoneal fluid of women with endometriosis indicate an impaired immune activity in women with endometriosis.
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Article Efficacy of vaginal danazol treatment in women with recurrent deeply infiltrating endometriosis. 2007
Razzi S, Luisi S, Calonaci F, Altomare A, Bocchi C, Petraglia F. · Division of Obstetrics and Gynecology, Department of Pediatrics, Gynecology and Reproductive Medicine, University of Siena, Siena, Italy. · Fertil Steril. · Pubmed #17544421 No free full text.
Abstract: OBJECTIVE: To describe a safe long-term medical treatment for deeply infiltrating endometriosis, a critical condition characterized by multiple painful symptoms and a high recurrence rate after surgical treatment. DESIGN: Prospective study. SETTING: University of Siena. PATIENT(S): Twenty-one women with deeply infiltrating endometriosis. INTERVENTION(S): In a nonrandomized prospective study a low dose of vaginal danazol (200 mg/d) was self-administered for 12 months. After a previous laparoscopic surgery, these patients had reported recurrent severe dyspareunia, dysmenorrhea, and pelvic pain (in five cases also painful defecation). MAIN OUTCOME MEASURE(S): Before and every 3 months during the treatment a visual analogue pain scale was used. Transvaginal and transrectal ultrasound examinations were performed before and after 6 and 12 months of treatment. Adverse effects were registered, and serum concentration of cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, glycemia, protein S, protein C, antithrombin III, and homocysteine was evaluated before and after 12 months. RESULT(S): Dysmenorrhea, dyspareunia, and pelvic pain significantly decreased within 3 months and disappeared after 6 months of treatment, with a persistent effect during the 12 months of treatment. A relief of painful defecation was also shown. Ultrasound examination showed a reduction of the nodularity in the rectovaginal septum within 6 months. The medical treatment did not affect metabolic or thrombophilic parameters; few local vaginal adverse effects were reported. CONCLUSION(S): Vaginal danazol resulted in effective medical treatment for the various painful symptoms in women with recurrent deeply infiltrating endometriosis, and because of the lack of significant adverse effects it may be proposed as an alternative to repeated surgery.
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Article Use of a progestogen only preparation containing desogestrel in the treatment of recurrent pelvic pain after conservative surgery for endometriosis. 2007
Razzi S, Luisi S, Ferretti C, Calonaci F, Gabbanini M, Mazzini M, Petraglia F. · Chair of Obstetrics and Gynecology, Department of Pediatric, Obstetrics and Reproductive Medicine, University of Siena, Policlinico Le Scotte, 53100 Siena, Italy. · Eur J Obstet Gynecol Reprod Biol. · Pubmed #16963174 No free full text.
Abstract: OBJECTIVE: To assess the effect of a new progestin progestogen only pill (desogestrel) versus an oral contraceptive in the treatment of recurrent endometriosis. STUDY DESIGN: A randomized prospective clinical study. A group of women with endometriosis (n=40) who showed recurrent dysmenorrhea and/or pelvic pain after conservative surgery, and did not desire a pregnancy. Continuous treatment for 6 months with desogestrel (75 microg/d) (n=20) versus a combined oral contraceptive (ethinyl estradiol 20 microg plus desogestrel 150 microg) (n=20) was performed. RESULTS: A significant improvement of both pelvic pain and dysmenorrhea was observed following each type of treatment (P<0.001). The use of desogestrel progestogen only pill was associated with a breakthrough bleeding in 20% patients, while a significant body weight increase was observed in 15% after oral contraceptive. CONCLUSIONS: Both desogestrel and an oral estro-progestinic were effective, safe and low cost therapy of pain symptoms after endoscopic surgery for endometriosis, the former showing an impact on breakthrough bleeding, the later an incidence on body weight increase.
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Article Surgical scar endometriosis after Cesarean section: a case report. 2006
Luisi S, Gabbanini M, Sollazzi S, Calonaci F, Razzi S, Petraglia F. · Chair of Obstetrics and Gynecology, Department of Pediatric, Obstetrics and Reproductive Medicine, University of Siena, Siena, Italy. · Gynecol Endocrinol. · Pubmed #16785151 No free full text.
Abstract: BACKGROUND: Cutaneous endometriosis is a rare condition. CASE REPORT: A 37-year-old woman came to our observation 3 years after Cesarean section for a nodule under the scar that became spontaneously painful during menstrual bleeding. Transabdominal ultrasound examination, serum CA125 determination and histopathological analysis of the nodule were performed. Ultrasound revealed the presence of an oval-shaped hypoechogenic neoformation, while the serum CA125 level was slightly increased, and a diagnosis of endometriosis was confirmed by the histopathological analysis of a surgical specimen. CONCLUSION: This is an interesting case of surgical scar endometriosis, and the etiopathogenetic mechanism of this location may be explained by a dissemination of endometrial tissue during the Cesarean section.
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Article Estrogen receptor gene polymorphisms are associated with recurrence of endometriosis. 2006
Luisi S, Galleri L, Marini F, Ambrosini G, Brandi ML, Petraglia F. · Department of Pediatrics, Gynecology and Reproductive Medicine, University of Siena, Siena, Italy. · Fertil Steril. · Pubmed #16500359 No free full text.
Abstract: The presence of gene polymorphisms of the estrogen receptors ERalpha (PvuII and XbaI) and ERbeta (AluI) in 61 women with endometriosis was investigated. A statistically significant correlation between PvuII ERalpha gene polymorphism (PvuII), both in homozygosity (PP) and in heterozygosity (Pp), and a recurrence of endometriosis was found. In conclusion, women affected by endometriosis with the ERalpha polymorphic allele, even if heterozygous, have a worse prognosis, and these results suggest that the ERalpha gene polymorphisms may be included among the genetic risk factors for endometriosis.
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Article High concentrations of activin A in the peritoneal fluid of women with epithelial ovarian cancer. 2004
Cobellis L, Reis FM, Luisi S, Danero S, Pirtoli L, Scambia G, Petraglia F. · Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Siena, Italy. · J Soc Gynecol Investig. · Pubmed #15120692 No free full text.
Abstract: OBJECTIVE: The aim of the present study was to evaluate the concentrations of activin A in the peritoneal fluid of women with epithelial (serous) ovarian cancer. METHODS: A group of 160 women was studied and divided in four subgroups as follows: 1) serous ovarian carcinoma (n = 32); 2) serous ovarian cystadenoma (n = 20); 3) endometriosis (n = 53); and 4) healthy controls (n = 55), including both fertile (n = 32) and postmenopausal women (n = 23). Specimens of peritoneal fluid were collected during surgical interventions, and activin A was quantified using a specific two-site enzyme immunoassay. RESULTS: Peritoneal fluid activin A concentrations in women with ovarian carcinoma were about five-fold higher than those found in the control group (median [interquartile range] = 7.60 [2.85-10.15] and 1.50 [1.00-2.50] ng/mL, respectively, P <.001). In contrast, the women with benign serous cystadenoma had peritoneal fluid activin A concentrations (1.50 [1.0-2.70] ng/mL) similar to those of the control group. High peritoneal fluid activin A levels (>2 multiples of the mean) distinguished carcinoma from cystadenoma with a sensitivity of 72% and a specificity of 80%. The follow-up of nine patients with stage IIIc ovarian cancer showed no apparent relationship between the peritoneal fluid activin A levels and overall survival. No significant difference in peritoneal fluid activin A concentrations between patients with endometriosis and control women was observed. CONCLUSION: Most women with serous ovarian carcinoma had high concentrations of activin A in the peritoneal fluid, supporting a possible role of this growth factor in ovarian cancer.
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Article Serum inhibin A, inhibin B, and pro-alphaC levels are altered after surgically or pharmacologically induced menopause. 2002
Cobellis L, Luisi S, Pezzani I, Reis FM, De Leo V, Petraglia F. · Chair of Obstetrics and Gynecology, University of Siena, Siena, Italy. · Fertil Steril. · Pubmed #11937127 No free full text.
Abstract: OBJECTIVE: To evaluate the course of changes in serum inhibin A, inhibin B, and pro-alphaC levels in women with surgically or pharmacologically induced menopause. DESIGN: Longitudinal study. SETTING: Academic Health Center of Siena, Siena, Italy. PATIENT(S): Four groups of women were studied: [1] surgical menopause including bilateral oophorectomy (n = 15), [2] amenorrhea induced by GnRH-analogue for treatment of endometriosis (n = 13), [3] amenorrhea induced by antineoplastic chemotherapy before (n = 15) and after chemotherapy (n = 13), and [4] control physiological menopause (n = 67). INTERVENTION(S): Collection of blood specimens. MAIN OUTCOME MEASURE(S): Serum inhibin A, inhibin B, and pro-alphaC concentrations were measured by using specific two-site ELISAs. RESULT(S): Following oophorectomy, serum inhibin A, inhibin B, and pro-alphaC levels were decreased on the first postoperative day; on the fifth postoperative day they were still significantly reduced. Women with amenorrhea induced by GnRH-analogue treatment exhibited serum inhibin A and pro-alphaC levels that were significantly higher than those observed in physiological menopause. Patients undergoing antineoplastic chemotherapy had higher serum inhibin A levels than those in physiological menopause, whereas inhibin B and pro-alphaC levels did not differ. During the course of chemotherapy, median serum inhibin A concentrations were similar to those of patients evaluated after the suspension of treatment. In postmenopause, inhibin A, and inhibin B levels were low, whereas levels of pro-alphaC were still detectable. CONCLUSION(S): Circulating levels of inhibin A, inhibin B, and pro-alphaC are reduced after oophorectomy. Women with amenorrhea induced by GnRH-analogue treatment or by antineoplastic chemotherapy still produce inhibin A and pro-alphaC. This probably reflects a residual ovarian function and hormone synthesis. Therefore, the ovary may be a source of pro-alphaC after menopause; significant amounts of pro-alphaC are present in circulation after natural menopause, but not after oophorectomy.
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Article Vascular endothelial growth factor and interleukin-8 in ovarian cystic pathology. 2001
Fasciani A, D'Ambrogio G, Bocci G, Luisi S, Artini PG, Genazzani AR. · Department of Reproductive Medicine and Child Development, Division of Gynaecology and Obstetrics, University of Pisa, Pisa, Italy. · Fertil Steril. · Pubmed #11384653 No free full text.
Abstract: OBJECTIVE: To determine the levels of the angiogenic factors vascular endothelial growth factor (VEGF) and interleukin (IL-8) in ovarian cysts. DESIGN: Prospective descriptive study. SETTING: University hospital. PATIENT(S): One hundred women, of whom 9 had ovarian carcinomas, 38 had ovarian endometriomata, 43 had serous ovarian cysts, and 10 had follicular ovarian cysts. INTERVENTION(S): Sampling of serum and ovarian cystic fluid before and during surgery. MAIN OUTCOME MEASURE: Levels of VEGF and IL-8 in cystic fluid and serum. RESULT(S): Levels of both VEGF and IL-8 were found to be significantly higher in the cystic fluid of ovarian carcinomas and endometriomata than in serous and follicular cysts. In endometriomata fluid, levels of VEGF and IL-8 were found to be directly correlated (r = 0.68; P=.0074). Serum levels of VEGF were significantly higher in women with ovarian carcinomas and endometriomata than in those with serous and follicular cysts. Ovarian cancers and endometriomata were similar in terms of cystic concentrations of VEGF and IL-8 and in serum levels of VEGF. CONCLUSION(S): An increase in angiogenic factors that differentiate ovarian carcinomas and endometriomata from other kinds of ovarian pathology is demonstrated.
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