Endometriosis: Vigano P

Bianconi L, Hummelshoj L, Coccia ME, Vigano P, Vittori G, Veit J, Music R, Tomassini A, D'Hooghe T. · XII Committee on Hygiene and Health in the XIV Parliament of the Italian Senate, Rome, Italy. · Fertil Steril. · Pubmed #17991515 No free full text.

Abstract: Started at the grassroot level, increased awareness and investment in research has resulted in unprecedented recognition of endometriosis by the European Parliament, taken up by the Italian Senate in a 5-year action plan. This offers welcome assurance to the scientific community.

Fedele L, Somigliana E, Frontino G, Benaglia L, Vigano P. · Fondazione IRCCS Ospedale Maggiore Policlinico, Obstetrics and Gynecology, Mangiagalli e Regina Elena, Via Commenda 12, 20122 Milano, Italy. · Expert Opin Investig Drugs. · Pubmed #18616415 No free full text.

Abstract: Endometriosis is a common and enigmatic disease causing pelvic pain and infertility. Current treatment is mainly based on the use of surgery and ovarian suppressive agents. There is in particular the need for new therapeutic options able to allow a normal menstrual cycle to occur and also consent pregnancy. In the present review, we aimed to give a concise and practical overview in order to allow the clinician to clearly understand the level of development of these drugs. We have presented only treatments supported by in vivo researches with a special attention to studies in humans. Results show appealing new possibilities are emerging from agents counteracting the endometriosis-associated inflammation. Recent data also suggests that there is still the opportunity to refine the use of already available agents.

Vigano P, Somigliana E, Vignali M, Busacca M, Blasio AM. · Molecular Biology Laboratory, Istituto Auxologico Italiano, Milano, Italy. · Front Biosci. · Pubmed #17485295 No free full text.

Abstract: Family and twin studies have shown that heritability accounts for endometriosis development to an extent similar to other complex genetic diseases. Both linkage analysis and association studies have been performed to identify genetic determinants for the disease. Results from the linkage scan of 1,176 families collected thanks to a joint effort between an Australian and a UK group supported significant linkage to a novel susceptibility locus on chromosome 10q26. Although gene variants with effects on the disease predisposition have been proposed to exist and several candidates have been put forward, their effects have not been or are yet to be confirmed. The main categories of candidate genes studied have been those involved in detoxification processes, sex steroid biosynthesis and action, immune system regulation. Genetic studies on endometriosis face numerous challenges as the disease has several manifestations and different forms. Moreover, strong gene-environmental interactions might definitively influence approaches to identify genetic variants involved. Genome-wide association studies that survey most of the genome for causal genetic variants provide the potential for future progress.

Vigano P, Anonymous00212. · Istituto Auxologico Italiano and Department Ostet/Ginecol, University of Milano, Milan, Italie. · J Gynecol Obstet Biol Reprod (Paris). · Pubmed #14968065 links to  free full text

Abstract: Pathophysiology of deeply infiltrating endometriosis remains controversial whereas physiopathologic mechanism of superficial endometriosis is nearly demonstrated. Superficial peritoneal implants derive from adhesion and proliferation of endometrial cells regurgitated in peritoneum with retrograde menstruation. Peritoneal inflammation involving cytokines as TNFalpha and aromatase over-expression might be involved in the endometriosis invasion processus. Specific molecular defects of both eutopic and ectopic endometrium have been identified for each of the processes involved in the disease development. Aromatase inhibitors decrease endometriosis lesions in a mouse model of endometriosis which was induced surgically. Few studies report efficacy of aromatase inhibitors in human endometriosis. Theoretically, aromatase inhibitors should not be used alone in premenopausal women because of the resultant increase in gonadotropin levels. Nevertheless, in premenopausal women, aromatase inhibitors may be used in association with Gn-RH agonists. TNFalpha is a secretory factor of macrophages that is known to be increased in the peritoneal fluid of women with endometriosis. Granulosa cells from these women produce higher levels of TNFalpha. This cytokine can stimulate adhesion and proliferation of endometrial cells and enhances metalloproteasis expression, making thus endometrial cell invasion easier. It also stimulates angiogenesis by regulating expression of IL-8. TNFalpha is also cytotoxic to gametes. In mice and baboon models with induced endometriosis, anti-TNFalpha (TNF binding protein-1) decreases AFS score stage and reduces in size the endometriotic foci. No clinical assay has studied TNFalpha efficacy on human endometriosis.

Somigliana E, Vigano P, Barbara G, Vercellini P. · Dept of Obstetrics and Gynecology, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy. · Front Biosci (Elite Ed). · Pubmed #19482659 No free full text.

Abstract: Endometriosis-associated pain represents a challenge for both the patient and the health care provider since it is often difficult to design treatment strategies resulting in improvement of the symptoms. The association between endometriosis stage and severity of pelvic symptoms is limited. Surgery is generally considered the first line treatment in women affected, at least in those who have not been previously operated, but there are several situations in which medical treatments are useful. Given their good tolerability, minor metabolic effects and low cost, progestogens with or without the addition of estrogens, can be considered the drugs of choice and are currently the only safe and inexpensive alternative to surgery. Progestogens are effective in controlling pain symptoms in approximately three of four women with endometriosis. There is little or no difference in the effectiveness of GnRH agonist and add-back treatment in comparison with other medical treatments for endometriosis while the surgical interruption of pelvic nerve pathways entail some clinically relevant risks.

Vercellini P, Somigliana E, Vigano P, Abbiati A, Barbara G, Fedele L. · Università degli Studi di Milano, Milan, Italy. · BJOG. · Pubmed #19187368 No free full text.

Abstract: OBJECTIVE: To detect a direct transition from a haemorrhagic corpus luteum to an endometriotic cyst by serial transvaginal ultrasonographic scans. DESIGN: Prospective observational study. SETTING: An academic tertiary care and referral centre for women with endometriosis. POPULATION: One hundred and nine women younger than 40 years, with regular menstrual cycles, undergoing first-line surgery for endometriomas, and not wanting postoperative oral contraception. METHODS: Three-monthly transvaginal ultrasonography during the luteal phase for 2 years after surgery. MAIN OUTCOME MEASURE: Sonographic identification of progression from a haemorrhagic corpus luteum to a recurrent endometriotic cyst. RESULTS: A haemorrhagic corpus luteum was identified in 13 women. Serial ultrasonographic scans demonstrated transition to an endometriotic cyst in 11 (85%) instances and resorption in two. A unilateral endometriotic cyst without previous detection of a cystic corpus luteum was observed in 14 women. CONCLUSIONS: Bleeding from a corpus luteum appears to be a critical event in the development of endometriomas.

Gentilini D, Vigano P, Carmignani L, Spinelli M, Busacca M, Di Blasio AM. · Molecular Biology Laboratory, Istituto Auxologico Italiano, Milan, Italy. · Fertil Steril. · Pubmed #18281038 No free full text.

Abstract: In this study, we sought to examine the association between P receptor +331G/A polymorphism and endometriosis. We excluded any relationship between endometriosis in general and the P receptor +331G/A polymorphism but found a significant association with deep-infiltrating endometriosis, supporting a potential role of this variant in the P receptor-dependent invasive behavior of endometrial cells.

Vercellini P, Somigliana E, Daguati R, Vigano P, Meroni F, Crosignani PG. · Department of Obstetrics and Gynecology, University of Milan, Milan, Italy. · Am J Obstet Gynecol. · Pubmed #18241819 No free full text.

Abstract: OBJECTIVE: The purpose of this study was to compare the postoperative risk of endometrioma recurrence in women using oral contraception and in those undergoing simple observation. STUDY DESIGN: After laparoscopic excision of ovarian endometriotiomas, a cyclic, low-dose, monophasic oral contraceptive pill (OCP) was offered to women not seeking pregnancy. One month after surgery, and every 6 months afterward, the patients underwent clinical and ultrasonographic assessment. RESULTS: Of the 277 patients who entered the study, 102 used OCP for the entire follow-up period (always users), 129 used OCP discontinuously (ever users), and 46 declined treatment (never users). The median follow-up was 28 months. Recurrent endometriotic cysts were detected in 74 subjects (27%). The 36-month cumulative proportion of subjects free from endometrioma recurrence was 94% in the always users compared with 51% in the never users (P < .001); adjusted incidence rate ratio (IRR) = 0.10 (95% CI, 0.04-0.24). CONCLUSION: Regular postoperative use of OCP effectively prevents endometrioma recurrence.

Gentilini D, Somigliana E, Vigano P, Vignali M, Busacca M, Di Blasio AM. · Molecular Biology Laboratory, Istituto Auxologico Italiano, Cusano Milanino, Milan, Italy. · Hum Reprod. · Pubmed #17977866 links to  free full text

Abstract: BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent stimulus of angiogenesis potentially contributing to the pathogenesis of endometriosis. The aim of this study was to investigate the potential association between the single nucleotide polymorphism +405G>C of the VEGF gene with the risk of endometriosis, for the first time in the Caucasian population. METHODS: The polymorphism +405G>C of the VEGF gene was examined in n = 203 Italian women affected by endometriosis and in n = 140 women without laparoscopic evidence of the disease. All the women were genotyped by PCR-restriction fragment length polymorphism from venous blood samples. We then performed a meta-analysis including results from the present study and from the two previously published studies on this topic. RESULTS: The distribution of the three different genotypes significantly differed between women with and without the disease (P = 0.03). The odds ratio (95% confidence interval) for endometriosis in women carrying the C allele was 1.8 (1.2-2.8). The Breslow-Day test revealed statistically significant heterogeneity among the studies performed so far thus indicating inconsistency among studies and excluding the possibility of obtaining a common estimation of the effect. CONCLUSIONS: Results obtained herein are in keeping with those obtained previously and support a role for the +405G>C VEGF polymorphism in endometriosis development, although a further, larger study is required to confirm our findings. However, this effect may depend on the population studied. Ethnicity and the characteristics of endometriosis are likely to influence this association.

Somigliana E, Panina-Bordignon P, Murone S, Di Lucia P, Vercellini P, Vigano P. · Infertility Unit, Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Via M. Fanti 6, 20122 Milan, Italy. · Hum Reprod. · Pubmed #17548365 links to  free full text

Abstract: BACKGROUND: An immune-mediated defect in recognition and elimination of endometrial fragments refluxed in the peritoneal cavity has been hypothesized to play a crucial role in endometriosis development. Since vitamin D is an effective modulator of the immune system, we have hypothesized that the vitamin D status may have a role in the pathogenesis of endometriosis. METHODS: Women of reproductive age selected for surgery for gynecological indications were enrolled in this prospective cohort study. Serum levels of 25-hydroxyvitamin-D(3), 1,25-dihydroxyvitamin-D(3) and Ca(2+) were assessed. RESULTS: Eighty-seven women with endometriosis and 53 controls were recruited. Mean (+/- SD) levels of 25-hydroxyvitamin-D(3) in women with and without endometriosis were 24.9 +/- 14.8 ng/ml and 20.4 +/- 11.8, respectively (P = 0.05). The Odds Ratio (95% Confidence Interval) for endometriosis in patients with levels exceeding the 75th percentile of the serum distribution of the molecule (28.2 ng/ml) was 4.8 (1.7-13.5). A positive gradient according to the severity of the disease was also documented. A trend towards higher levels of 1,25-dihydroxyvitamin-D(3) and Ca(2+) was observed in women with endometriosis, but differences did not reach statistical significance. As expected, serum concentrations of 25-hydroxyvitamin-D(3) and 1,25-dihydroxyvitamin-D(3,) but not Ca(2+), are influenced by the season (P < 0.001, P = 0.004, P = 0.57, respectively), while levels of the three molecules did not vary according to the phase of the menstrual cycle. CONCLUSIONS: Endometriosis is associated with higher serum levels of vitamin D.