Endometriosis: Petraglia F

Petraglia F, Luisi S. · No affiliation provided · Gynecol Endocrinol. · Pubmed #17999278 No free full text.

This publication has no abstract.

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.

Florio P, Rossi M, Sigurdardottir M, Ciarmela P, Luisi S, Viganò 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.

Cobellis L, Razzi S, De Simone S, Sartini A, Fava A, Danero S, Gioffrè W, Mazzini M, Petraglia F. · Department of Gynaecology, Obstetrics and Reproduction, Second University of Naples, Naples, Italy. · Eur J Obstet Gynecol Reprod Biol. · Pubmed #15294376 No free full text.

Abstract: OBJECTIVE: To evaluate the efficacy and safety of a cyclooxygenase (COX)-2 specific inhibitors versus placebo in the treatment of endometriosis-associated pelvic pain. STUDY DESIGN: A group of women (n = 28) with pelvic pain after conservative surgery for symptomatic endometriosis (Stage I and II) were enrolled at the Department of Pediatric, Obstetrics and Reproductive Medicine of University of Siena. A treatment with a COX-2 specific inhibitors (rofecoxib, 25mg per day) (n = 16) or placebo (n = 12) was given for 6 months. Pelvic pain quantification with a clinical evaluation, including Visual Analogue Scale (VAS) for pain, was performed before and up to 6 months after treatment. RESULTS: A significant improvement of both pelvic pain and dyspareunia was observed after a 6 months persisting since the end of the treatment (P < 0.0001). The efficacy of rofecoxib was higher than placebo and no recurrence occurred, while in the placebo-treatment a 16% (2/12) occurred. No significant side effects have been found with the use of rofecoxib. CONCLUSIONS: The use of COX-2 specific inhibitors was effective, safe and low cost therapy in the management of pelvic pain associated to endometriosis and might be also proposed in early stage of endometriosis.

Cobellis L, Razzi S, Fava A, Severi FM, Igarashi M, Petraglia F. · No affiliation provided · Fertil Steril. · Pubmed #15237024 No free full text.

Abstract: A danazol-loaded intrauterine device (IUD) containing 300-400 mg of danazol was inserted for 6 months in a group of women (n = 18) (median age 36.6 years; age range: 30 to 46 years) with a histologic diagnosis of endometriosis, referred for recurrent pelvic pain. Dysmenorrhea, dyspareunia, and pelvic pain significantly decreased after the first month, with a persistent effect during the 6 months of IUD insertion. These results show that a danazol-loaded IUD is an effective conservative therapy for patients with endometriosis-related pelvic pain.

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.

Torres PB, Florio P, Galleri L, Reis FM, Borges LE, Petraglia F. · Department of Pediatrics, Obstetrics and Reproductive Medicine, Section of Obstetrics and Gynecology, University of Siena, Siena, Italy. · Reprod Sci. · Pubmed #19386982 No free full text.

Abstract: Activin A is a dimeric protein that regulates endometrial functions by signaling at its receptors, namely type I (ActRI) and type II (ActRII). Nodal is an activin competitor that requires the coreceptor cripto to assemble its signaling pathway through ActRI and ActRII. In the current study, we evaluated the expression of activin A, ActRII, nodal, and cripto in eutopic and ectopic endometrium collected from women with ovarian endometrioma (n = 15) and in eutopic endometrium of healthy participants (n = 15). Eutopic endometrial samples were evaluated according to the stage of menstrual cycle. Total RNA was extracted from tissue homogenates and analyzed by real-time polymerase chain reaction (PCR). Activin A messenger RNA (mRNA) expression in eutopic endometrium of patients with endometriosis was significantly higher than in controls (P < .001) with a 10.2-fold and 7.3-fold increase in the proliferative and secretory phases, respectively. ActRII and nodal mRNA expression were found to be similar in patients with and without endometriosis, while cripto mRNA was markedly lower in eutopic (fold change = 0.03 at proliferative phase, P < .001) and ectopic endometrium (fold change = 0.14, P < .001) of women with endometriosis compared with eutopic endometrium from healthy controls. In conclusion, the altered endometrial expression of activin A and cripto during the menstrual cycle and the differences observed in the endometriotic tissue support the involvement of the activin system in endometrial changes of women with endometriosis.

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.

Florio P, Reis FM, Torres PB, Calonaci F, Toti P, Bocchi C, Linton EA, Petraglia F. · Department of Pediatrics, Obstetrics and Reproductive Medicine, Section of Obstetrics and Gynecology, University of Siena, Siena, Italy. · Obstet Gynecol. · Pubmed #17766605 No free full text.

Abstract: OBJECTIVE: Urocortin is a neuropeptide, member of the corticotropin-releasing hormone family, that is produced by the human endometrium. Ovarian endometrioma is a prevalent gynecologic disorder still lacking specific serum markers. In the present study we measured systemic levels of urocortin to assess the diagnostic performance of its determination in distinguishing endometriomas from other benign ovarian cysts. METHODS: Plasma urocortin was measured by radioimmunoassay in women with ovarian endometrioma (n=40) and in women with benign, nonendometriotic ovarian cysts (n=40). The diagnostic accuracy of urocortin measurement was evaluated by receiver operating characteristic curve and compared with the standard marker, CA 125. To support the local origin of the peptide, we also evaluated its localization in endometriomas by immunohistochemistry and its concentrations in cyst fluid and peritoneal fluid of 12 women with endometrioma. RESULTS: Plasma urocortin levels were twice as high in women with endometrioma (median 49 pg/mL, interquartile range 41-63 pg/mL) than in the control group (19 [15-23] pg/mL, P<.001) and significantly higher in the cystic content of endometriomas than in the peritoneal fluid and plasma (P<.05). The peptide was immunolocalized in endometrioma glands and stromal capillary vessels. Elevated plasma urocortin levels detected 88% of the cases of endometrioma with 90% specificity, whereas CA 125 detected only 65% of the cases with the same specificity. CONCLUSION: Plasma urocortin is increased in women with endometriomas, and its measurement may be useful for the differential diagnosis of endometrioma compared with other benign ovarian cysts. LEVEL OF EVIDENCE: II.

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.

Torres PB, Florio P, Ferreira MC, Torricelli M, Reis FM, Petraglia F. · Section of Obstetrics and Gynecology, Department of Pediatrics, Obstetrics, and Reproductive Medicine, University of Siena, Siena, Italy. · Fertil Steril. · Pubmed #17296189 No free full text.

Abstract: OBJECTIVE: To evaluate the messenger RNA (mRNA) expression and peptide localization of follistatin and follistatin-like protein (FLRG) in ovarian endometriosis, compared to healthy human endometrium. DESIGN: Samples of ovarian endometriotic and healthy endometrial tissues were processed by semiquantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. SETTING: Academic health centers in Siena, Italy, and Belo Horizonte, Brazil. PATIENT(S): Women with endometrioma who underwent laparoscopic excision of ovarian endometriotic cysts (n = 16), and healthy, nonpregnant women (n = 18, control group). MAIN OUTCOME MEASURE(S): Immunostaining and relative quantification of follistatin and FLRG mRNA in ovarian endometriosis and eutopic endometrium. RESULT(S): Both ovarian endometriosis and healthy endometrium expressed and localized follistatin and FLRG. In endometriotic glands, follistatin immunostaining was homogeneously distributed throughout the cytoplasm of the epithelial cells, contrasting with normal eutopic endometrium, where follistatin expression was focal, irregular, and confined to the basal side of the glands. Follistatin-like protein was immunolocalized in the nuclei of both glandular epithelial cells and stromal cells, with less intense staining in endometriotic samples. The relative intensity of follistatin and FLRG immunostaining was significantly higher and lower, respectively, in endometriosis than in controls. The expression of follistatin mRNA was higher, while that of FLRG mRNA was lower, in ovarian endometriosis than in healthy eutopic endometrium. CONCLUSION(S): Ovarian endometriotic lesions show a deranged expression of FLRG and follistatin, which are activin A-binding proteins. This may result in an altered effect of activin A on angiogenesis and/or endometrial differentiation.

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.

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.

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.

Rossi M, Sharkey AM, Viganò P, Fiore G, Furlong R, Florio P, Ambrosini G, Smith SK, Petraglia F. · Obstetrics and Gynaecology, Department of Paediatrics, Obstetrics and Reproductive Medicine, University of Siena, Italy. · Reproduction. · Pubmed #16264101 links to  free full text

Abstract: Interleukin-1beta (IL-1b) is an important immune regulatory factor that in human endometrium plays a role in both menstruation and implantation in the event of pregnancy. It promotes inflammatory-like processes and also stimulates tissue remodelling. We present a cDNA microarray study documenting the major effects of IL-1beta on gene expression in stromal cells from human endometrium. Endometrial stromal cells from five normal healthy women at the mid secretory phase were cultured with or without IL-1beta at 50 and 500 pg/ml for 48 h. cDNA microarrays were used to compare the levels of gene expression in total RNA isolated from cells stimulated with IL-1beta. These cDNA arrays were produced containing 15 164 sequence-verified clones, which included genes known to be important in angiogenesis, immune modulators, apoptosis, cell signalling, extra-cellular matrix (ECM) remodelling and cell cycle regulation. Genes which were regulated by IL-1beta were identified by analysis of the microarray data using the Significance Analysis of Microarrays software package. Upregulated (n = 23) and downregulated (n = 6) different genes were observed, which changed at least 3-fold, at a false discovery rate of less than 2% (P < 0.02). Our results have identified genes regulated by IL-1beta, which are involved in leukocyte recruitment, ECM remodelling and other cellular functions. Changes in three genes, IL-8, colony-stimulating factor 2 and aldoketo reductase family 1 member 1, which were upregulated by IL-1beta, were verified using real-time PCR. Novel functions regulated by IL-1beta in endometrium, including genes involved in free radical protection, and fatty acid metabolism were also identified. These results also provide new insights into the role of IL-1beta in disorders of the endometrium, especially in implantation-related infertility and endometriosis, in which this cytokine plays a major role.

Razzi S, Rubegni P, Sartini A, De Simone S, Fava A, Cobellis L, Fimiani M, Petraglia F. · Department of Pediatrics, Obstetrics and Reproductive Medicine, Chair of Obstetrics and Gynecology, University of Siena, Italy. · Gynecol Endocrinol. · Pubmed #15195504 No free full text.

Abstract: To our knowledge, this is the first case reported in the literature of umbilical endometriosis in a pregnant woman. We report a case of umbilical endometriosis in a pregnant woman at 16 weeks of gestation. The patient revealed a reddish-brown polypoid nodule within the umbilical depression, with the typical history of monthly bleeding from the umbilicus. A nodule biopsy, testing of serum levels of CA-125 and a transabdominal ultrasound examination were performed. The diagnosis of endometriosis was confirmed by pathological examination. Serum levels of CA-125 were slightly increased and the pelvic ultrasound examination did not identify ovarian cysts of a possible endometriotic nature. The patient was also examined at 24 weeks' gestation, after delivery and in the late postpartum period. No therapy was given and the lesion resolved spontaneously 2 months after the biopsy was taken.

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.

Razzi S, Fava A, Sartini A, De Simone S, Cobellis L, Petraglia F. · Department of Pediatric, Obstetrics and Reproductive Medicine, University of Siena, Italy. · BJOG. · Pubmed #14723761 No free full text.

This publication has no abstract.

Cobellis L, Latini G, De Felice C, Razzi S, Paris I, Ruggieri F, Mazzeo P, Petraglia F. · Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Siena, Italy. · Hum Reprod. · Pubmed #12832380 links to  free full text

Abstract: BACKGROUND: Emerging evidence suggests a potential role for ubiquitous environmental contaminants in the physiopathology of endometriosis. Di-(2-ethylhexyl)-phthalate (DEHP), the most commonly used plasticizer in flexible polyvinylchloride (PVC) formulations, is a widespread environmental contaminant with potentially adverse effects on fertility in animal models. In the present study, we tested the hypothesis that DEHP and/or and its main metabolite, mono-ethylhexyl phthalate (MEHP), play a role in the pathogenesis of endometriosis. METHODS: Specimens of blood and peritoneal fluid were collected in a group of women with endometriosis (n = 55), and in age-matched control women (n = 24). Concentrations of DEHP and MEHP were measured in plasma and peritoneal fluid by using high performance liquid chromatography (HPLC). Differences between groups were tested using the Fisher's exact test, Wilcoxon-test, and Kruskal-Wallis analysis of variance. RESULTS: Endometriotic women showed significantly higher plasma DEHP concentrations than controls (median 0.57 micro g/ml, interquartile range: 0.06-1.23; values range: 0-3.24 versus median 0.18 micro g/ml, interquartile range: 0-0.44; values range: 0-1.03; P = 0.0047) and 92.6% of them had detectable DEHP and /or MEHP in the peritoneal fluid. No significant differences in either the DEHP/MEHP plasma concentrations (P >/= 0.31) or DEHP/MEHP peritoneal fluid concentrations (P >/= 0.66) were observed in the endometriotic patients as a function of the disease stage at the time of diagnosis. CONCLUSIONS: The present findings showed for the first time an association between DEHP plasma concentrations and endometriosis, suggesting a possible role for phthalate esters in the pathogenesis.

Inaudi P, Mazzini M, D'Aniello G, Trusso P, Joghtapour A, Petraglia F. · Department of Pediatrics, Obstetrics and Reproductive Medicine, Chair of Obstetrics and Gynecology, University of Siena, Viale Bracci, 53100 Siena, Italy. · Gynecol Endocrinol. · Pubmed #12587535 No free full text.

Abstract: Ovarian hyperstimulation after a single dose of gonadotropin-releasing hormone (GnRH) analog is a rare phenomenon. A case of ovarian hyperstimulation-like syndrome after sole administration of triptorelin (Decapeptyl 3.75 mg) is reported in a woman who had undergone surgery for an endometriotic cyst. After administration of the drug, abdominal pressure increased with nausea and diffuse pelvic pain. Ultrasound examination showed bilateral enlargement of the ovaries (right 74 x 62 mm, left 62 x 53 mm), more than 10 follicles ranging in diameter from 15-25 mm, proliferative endometrium 7 mm thick and fluid in the Douglas pouch up to 25 x 23 mm thick. Estradiol plasma level was in the normal range. The syndrome spontaneously resolved in the course of treatment and a spontaneous pregnancy occurred when the triptorelin effect disappeared.

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.

Reis FM, Di Blasio AM, Florio P, Ambrosini G, Di Loreto C, Petraglia F. · Department of Obstetrics and Gynecology, University of Siena Policlinico Le Scotte, 53100 Siena, Italy. · Fertil Steril. · Pubmed #11172841 No free full text.

Abstract: OBJECTIVE: To evaluate the expression of inhibin A and activin A in ovarian endometriosis. DESIGN: Uncontrolled cross-sectional study and controlled prospective in vitro study. SETTING: Academic health centers in Siena, Udine, Sassari, and Milan, Italy. PATIENT(S): A group of women (n = 19) who underwent laparoscopic excision of ovarian endometriotic cysts. INTERVENTION(S): Specimens of serum, peritoneal fluid, and cystic fluid, ovarian tissue for immunohistochemistry, and endometriotic cells for primary culture were collected. Cell cultures were also prepared from proliferative endometrium of women without endometriosis. MAIN OUTCOME MEASURES: Dimeric inhibin A and activin A concentrations in biological fluids; immunostaining of alpha and betaA subunits in ovarian endometrioma; alpha and betaA gene expression in cultured endometriotic cells compared with normal endometrium. RESULT(S): Inhibin A and activin A concentrations in the cystic fluid were slightly higher than in peritoneal fluid and significantly higher than in serum (P<.05). Immunoreactive alpha and betaA subunits were strongly expressed both in the epithelial and stromal components of ovarian endometrioma. The relative abundance of betaA mRNA was significantly decreased in endometriotic cells compared with eutopic stromal cells. CONCLUSION(S): The results of the present study provide evidence for a local production and secretion of inhibin A and activin A in ovarian endometriotic cysts.