Brinton LA, Sakoda LC, Sherman ME, Frederiksen K, Kjaer SK, Graubard BI, Olsen JH, Mellemkjaer L.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Room 7068, 6120 Executive Boulevard, Rockville, MD 20852-7234, USA. brinton@nih.gov
OBJECTIVE: Although endometriosis and uterine leiomyomas are common conditions, the extent to which either is associated with certain types of malignancies remains uncertain. METHODS: Using record linkage techniques, we assessed the relationships between hospital and outpatient admissions for endometriosis or leiomyomas and the development of ovarian and uterine cancers in Denmark between 1978 and 1998. Based on a population-based cohort exceeding 99,000 women, including 2,491 ovarian cancers, 860 borderline ovarian tumors, and 1,398 uterine cancers, we derived relative risks (RR) and 95% confidence intervals (95% CI) associated with overall and histology-specific tumor risks after adjustment for calendar time and reproductive characteristics. RESULTS: Endometriosis seemed to predispose to the development of ovarian cancer, with the association restricted to endometrioid or clear cell malignancies. Five or more years after the diagnosis of endometriosis, the RRs (95% CIs) were 2.53 (1.19-5.38) for endometrioid (7 exposed cases) and 3.37 (1.24-9.14) for clear cell (4 exposed cases) malignancies. Uterine leiomyomas were associated with increases in the risk of uterine malignancies, particularly sarcomas, where the RRs (95% CIs) were 20.80 (11.32-38.22) for women with 1 to 4 years of follow-up (11 exposed cases) and 5.70 (2.27-14.32) for those with more extended follow-up (5 exposed cases). CONCLUSION: In combination with clinical, pathologic, and molecular data, our results support that some endometriotic lesions may predispose to clear cell and endometrioid ovarian cancers. Uterine leiomyomas also showed a strong connection with subsequent uterine sarcomas, although it was difficult to decipher whether this reflected detection bias, shared risk factors, or an etiologic relationship.
PMID: 16365012 [PubMed – indexed for MEDLINE]
Int J Gynaecol Obstet. 2006 Feb;92(2):157-8. Epub 2005 Dec 20.
Association between ectopic pregnancy and pelvic endometriosis.
Bogdanskiene G, Berlingieri P, Grudzinskas JG.
Gynaecology and Fertility Clinic, Vilnius, Lithuania.
PMID: 16364328 [PubMed – in process]
J Reprod Med. 2005 Sep;50(9):707-14.
Nitric oxide inhibition of the proliferation of ovarian endometriotic stromal cells in vitro.
Kim KH, Kwak JY, Shin BS, Choi YM, Oh ST, Lee KS.
Department of Obstetrics and Gynecology, College of Medicine, Pusan National University, Busan, Republic of Korea.
OBJECTIVE: To investigate the effects of nitric oxide on endometrial cell proliferation and the effects of peritoneal fluid from women with and without endometriosis on the production of nitric oxide and upon the nature of nitric oxide-induced changes. STUDY DESIGN: Ovarian endometriotic and endometrial stromal cells and peritoneal fluid were obtained from endometriosis patients and controls. Cell proliferation was determined by [3H]thymidine incorporation, and nitrite was measured using Griess reagent. RESULTS: Sodium nitroprusside (SNP), a nitric oxide donor, reduced the proliferation of endometriotic and endometrial cells in primary culture in a dose-dependent manner. SNP-induced production of nitric oxide and the inhibitory effect of nitric oxide on stromal cell proliferation were reduced by peritoneal fluid from women with endometriosis, although stromal cell proliferation was still inhibited by SNP in the presence of peritoneal fluid. However, this SNP-induced inhibition of cell proliferation was unaffected by interleukin-8, 17-beta, estradiol or transforming growth factor beta1. CONCLUSION: Nitric oxide inhibits the proliferation of endometrial stromal cells in vitro, and this inhibitory effect is abrogated by peritoneal fluid from women with endometriosis.
PMID: 16363760 [PubMed – indexed for MEDLINE]
Fertil Steril. 2005 Dec;84(6):1793-6.
Effect of monocyte chemoattractant protein-1 and estradiol on the secretion of vascular endothelial growth factor in endometrial stromal cells in vitro.
Lin J, Gu Y.
Department of Gynecology, Obstetrics and Gynecology Hospital, Shanghai Medical College of Fudan University, Shanghai, China.
To explore the initial activity of endometrial stromal cells (ESCs) and the participation of monocyte chemoattractant protein-1 (MCP-1) in the histogenesis of endometriosis, vascular endothelial growth factor (VEGF) secretion of ESCs and the effect of MCP-1 on VEGF secretion of ESCs were observed in vitro. The VEGF level was detected in ESC culture media and was increased significantly when E2 or MCP-1 was added to the media, especially in the presence of E2 plus MCP-1. The VEGF secretion was higher in the ESCs of women with endometriosis than in those women without endometriosis.
PMID: 16359995 [PubMed – indexed for MEDLINE]
Fertil Steril. 2005 Dec;84(6):1705-11.
Changes in the T-helper cytokine profile and in lymphocyte activation at the systemic and local levels in women with endometriosis.
Antsiferova YS, Sotnikova NY, Posiseeva LV, Shor AL.
Laboratory of Clinical Immunology, State Research Institute of Maternity and Childhood, Ivanovo, Russia. ivniimid@ivnet.ru
OBJECTIVE: To estimate regulatory cytokine synthesis and lymphocyte activation in the peripheral blood and endometrial tissue of patients with endometriosis. DESIGN: Controlled clinical study. SETTING: Medical center. PATIENT(S): Fifteen women with laparoscopically diagnosed endometriosis; 20 gynecologically healthy women with previously documented fertility (control group). INTERVENTION(S): Peripheral venous blood sampling; laparoscopic collection of ectopic and matched eutopic endometrium. MAIN OUTCOME MEASURE(S): Messenger RNA (mRNA) for interleukin (IL)-2, IL-4, and IL-10 expression in peripheral and endometrium lymphocytes was assessed by real-time reverse transcriptase polymerase chain reaction; intracellular synthesis of these cytokines and lymphocyte phenotype profile were established by flow cytometry. RESULT(S): Both mRNA expression and intracellular synthesis of IL-4 and IL-10 were sharply increased in peripheral lymphocytes. The same changes were observed for IL-4 in ectopic endometrium of women with endometriosis. Simultaneously, elevation of the amount of pan-B cells, CD20+CD5+ B-1 cells, and activated HLA-DR+CD20+ B lymphocytes was observed in endometriosis lesions. Only an enhanced amount of B lymphocytes was seen in eutopic endometrium. CONCLUSION(S): Endometriosis development is accompanied by the activation of a T-helper type 2 immune response at the systemic and local levels. Our results support the hypothesis regarding the autoimmune nature of endometriosis and can explain the high level of autoantibody production in patients with endometriosis.
PMID: 16359969 [PubMed – indexed for MEDLINE]
Fertil Steril. 2005 Dec;84(6):1587-8.
Comment on: ? Fertil Steril. 2005 Dec;84(6):1574-8.
The dilemma of endometriosis: is consensus possible with an enigma?
Nezhat C, Littman ED, Lathi RB, Berker B, Westphal LM, Giudice LC, Milki AA.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Stanford University Medical Center, Stanford, California, USA. cnezhat@stanford.edu
Many will agree that the use of laparoscopy to diagnose and potientially treat endometriosis in patients who suffer from infertility has been superseded by IVF and sometimes oocyte donation, especially in older patients. The findings of our study add another dimension to management of endometriosis in the setting of infertility and emphasize the importance of keeping laparoscopy in the infertility management equation.
Publication Types: ? Comment ? Review
PMID: 16359950 [PubMed – indexed for MEDLINE]

Fertil Steril. 2005 Dec;84(6):1582-4.
Comment on: ? Fertil Steril. 2005 Dec;84(6):1574-8.
Laparoscopy, in vitro fertilization, and endometriosis: an enigma.
Adamson GD.
Fertility Physicians of Northern California, Palo Alto, California 94301, USA. info@fpnc.com
Studies on the respective roles of laparoscopic surgery and IVF in infertile patients with endometriosis and endometriomas are difficult to perform. Appropriate patient management is complex and requires a sophisticated understanding of individualized evidence-based decision making, surgical judgment and technical skills for laparoscopy, and thoughtful utilization of IVF technologies.
Publication Types: ? Comment ? Review
PMID: 16359948 [PubMed – indexed for MEDLINE]
Fertil Steril. 2005 Dec;84(6):1581.
Comment on: ? Fertil Steril. 2005 Dec;84(6):1574-8.
Challenges of evaluating surgical outcomes.
Diamond MP.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Wayne State University/Detroit Medical Center, University Women’s Care Inc., Detroit, Michigan, USA. mdiamond@med.wayne.edu
The role of surgery vs. IVF-embryo transfer to improve the potential for conception will vary as enhancements of these interventions occurs. Well-designed and conducted studies, controlling for the complexities of surgical trials are needed.
Publication Types: ? Comment ? Review
PMID: 16359947 [PubMed – indexed for MEDLINE]
Fertil Steril. 2005 Dec;84(6):1574-8.
Comment in: ? Fertil Steril. 2005 Dec;84(6):1579-80. ? Fertil Steril. 2005 Dec;84(6):1581. ? Fertil Steril. 2005 Dec;84(6):1582-4. ? Fertil Steril. 2005 Dec;84(6):1585-6. ? Fertil Steril. 2005 Dec;84(6):1587-8.
Role of laparoscopic treatment of endometriosis in patients with failed in vitro fertilization cycles.
Littman E, Giudice L, Lathi R, Berker B, Milki A, Nezhat C.
Department of Gynecology and Obstetrics, Stanford University Medical Center, Stanford, California, USA.
OBJECTIVE: To report our experience in patients with previous IVF failures who conceived after laparoscopic treatment of endometriosis. DESIGN: Retrospective case series. SETTING: Tertiary center IVF and endoscopy programs. PATIENT(S): Infertility patients with history of prior IVF failures. INTERVENTION(S): Laparoscopic evaluation and treatment of endometriosis by the same surgeon. MAIN OUTCOME MEASURE(S): Occurrence of conception after laparoscopic treatment of endometriosis. RESULT(S): Of 29 patients with prior IVF failures, 22 conceived after laparoscopic treatment of endometriosis, including 15 non-IVF pregnancies and 7 IVF pregnancies. CONCLUSION(S): In the absence of tubal occlusion or severe male factor infertility, laparoscopy may still be considered for the treatment of endometriosis even after multiple IVF failures.
PMID: 16359945 [PubMed – indexed for MEDLINE]
Fertil Steril. 2006 Jan;85(1):78-83.
The endometria of patients with endometriosis show higher expression of class I human leukocyte antigen than the endometria of healthy women.
Vernet-Tomas Mdel M, Perez-Ares CT, Verdu N, Molinero JL, Fernandez-Figueras MT, Carreras R.
Obstetrics and Gynecology Service, Hospital Universitari del Mar, Universitat Autonoma de Barcelona, Barcelona, Spain. mvernet@imas.imim.es
OBJECTIVE: To compare the expression of class I human leukocyte antigen (HLA I) in endometrial samples from patients with and without endometriosis. DESIGN: Cross-sectional study. SETTING: Acute-care teaching hospital in Barcelona, Spain. PATIENT(S): The endometriosis group included 32 patients for whom the only diagnosis during an operation was endometriosis. The control group included 20 women who underwent a laparoscopy and in whom no evidence of endometriosis or any other genital disease was seen. INTERVENTION(S): Samples of endometrium were obtained by curettage and immediately frozen. A pan-HLA I mouse antihuman IgG2a monoclonal antibody was used for immunohistochemical study. MAIN OUTCOME MEASURE(S): Frequency of positive glandular and stromal cells was evaluated in each section. RESULT(S): A significantly higher expression of HLA I in the endometriosis group than in controls, both in the glandular cells (median 100% vs. 80%) and in the stromal cells (median 60% vs. 20%), was observed. CONCLUSION(S): Patients with endometriosis had a significantly higher expression of HLA I molecules in endometrial cells than did the controls. This could be a possible explanation for their higher resistance to natural killer cytolysis.
PMID: 16412734 [PubMed – indexed for MEDLINE]
Fertil Steril. 2006 Jan;85(1):71-7.
Short synthetic endostatin peptides inhibit endothelial migration in vitro and endometriosis in a mouse model.
Becker CM, Sampson DA, Short SM, Javaherian K, Folkman J, D’Amato RJ.
Department of Surgery, Vascular Biology Program, Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA.
OBJECTIVE: To determine the active peptide regions inside the angiogenesis inhibitor endostatin that can inhibit endothelial migration in vitro and also inhibit endometriosis in a mouse model. DESIGN: Pharmacologic intervention in a surgically induced mouse model of endometriosis and endothelial migration assay. SETTING: Animal research and laboratory facility. SUBJECT(S): Eight-week-old, female C57BL/6 mice and human microvascular endothelial cells. INTERVENTION(S): Eight overlapping synthetic peptides were tested for inhibitory potential on endothelial migration in vitro. The peptides with significant activity then were given for 4 weeks to mice after implantation of autologous endometrium. MAIN OUTCOME MEASURE(S): Inhibition of vascular endothelial growth factor-induced endothelial migration for in vitro studies. In vivo studies examined the growth rate of endometriotic lesions after 4 weeks of treatment, as well as the effect on estrous cycling and ovulation as assessed by corpus luteum formation. RESULT(S): The N-terminal mP-1 peptide and the internal mP-6 peptide inhibited endothelial migration in a dose-dependent manner. Additionally, both synthetic peptides suppressed growth of endometriotic lesions significantly in vivo. However, estrous cycling and corpus luteum formation were normal in both groups. CONCLUSION(S): Short endostatin fragments may be promising as a new, nontoxic therapeutic strategy for the treatment of endometriosis without inhibition of normal estrous cycles.
PMID: 16412733 [PubMed – indexed for MEDLINE]
Fertil Steril. 2006 Jan;85(1):63-70.
Expression of the proto-oncoprotein breast cancer nuclear receptor auxiliary factor (Brx) is altered in eutopic endometrium of women with endometriosis.
Hearns-Stokes R, Mayers C, Zahn C, Cruess D, Gustafsson JA, Segars J, Nieman L.
Reproductive Biology and Medicine Branch, National Institute of Child Health and Human Development, National Institute of Health, Bethesda, Maryland, USA.
OBJECTIVE: To evaluate the expression of estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta), and breast cancer nuclear receptor auxiliary factor (Brx) in eutopic endometrium of normal women and women with endometriosis. DESIGN: Prospective observational study. SETTING: Tertiary care and research center. PATIENT(S): Twenty-nine women with endometriosis and 35 healthy ovulatory volunteers of similar ages. INTERVENTION(S): Endometrial biopsy. MAIN OUTCOME MEASURE(S): Expression of immunohistochemical staining intensity and localization of ERalpha, ERbeta, and Brx proteins in eutopic endometrium during the menstrual cycle. RESULT(S): Expression of ERalpha and ERbeta was highest in the proliferative phase and was similar in both groups. Brx expression differed between healthy volunteers and those with endometriosis. During the proliferative phase, immunostaining intensity of Brx was greater in both the glandular and the stromal compartments of biopsies from patients with endometriosis compared to healthy volunteers; nuclear stromal Brx staining was more common in patients with endometriosis. CONCLUSION(S): The spatiotemporal expression of Brx was altered in eutopic endometrium of women with endometriosis. These findings suggest a fundamental alteration in the endometrium of women who have endometriosis. The role of Brx in ectopic implantation of endometrium deserves further study.
PMID: 16412732 [PubMed – indexed for MEDLINE]
Med Hypotheses. 2006;66(5):945-949. Epub 2006 Jan 10.
Endometriosis associated with defective handling of apoptotic cells in the female genital tract is a major cause of autoimmune disease in women.
Seery JP.
Department of Medicine and Therapeutics, University College Dublin, St Vincent’s University Hospital, Elm Park, Dublin 4, Ireland.
Several autoimmune diseases are far more common in women than men. The reasons are unknown. Recent studies have shown that many autoimmune diseases which predominantly affect females are characterized by the production of autoantibodies against components of apoptotic cells. Furthermore, in experimental animals, defective clearance of apoptotic cells in a pro-oxidant inflammatory environment can trigger the production of these autoantibodies and related autoimmune disease. Endometriosis is characterized by defective clearance of apoptotic endometrial cells in a pro-oxidant inflammatory environment. It is proposed that this combination of abnormalities triggers autoantibody production in women affected by endometriosis. A proportion of these women will be genetically predisposed to develop overt autoimmune disease. As endometriosis affects at least 4% of the female population of reproductive age, this phenomenon will have a major effect on the gender prevalence of several related autoimmune syndromes. The hypothesis is supported by epidemiological studies which show a strong association between endometriosis and female-predominant autoimmune disorders.
PMID: 16412582 [PubMed – as supplied by publisher]
Colorectal Dis. 2006 Feb;8(2):102-11.
Self-expanding metallic stents in the treatment of benign colorectal disease: indications and outcomes.
Forshaw MJ, Sankararajah D, Stewart M, Parker MC.
Department of Surgery, Darent Valley Hospital, Dartford, UK.
OBJECTIVE: The use of stents for benign colorectal obstruction is considered controversial because of a lack of data and perceived high failure and complication rates. The aim of this study was to evaluate the indications and outcomes following stent placement for benign colorectal disease in a UK district general hospital and to review the published literature. PATIENTS AND METHODS: Between 1997 and 2004, 11 of 90 attempted stent insertions were performed for benign colorectal disease (diverticular disease, 4; anastomotic strictures, 4; idiopathic rectal stricture, 1; rectal endometriosis, 1; caecal volvulus, 1). Complications and outcomes were analysed from a prospective database. RESULTS: Stent insertion was successful in nine patients. Early complications occurred in two patients (both with diverticular disease): one patient failed to decompress and needed a colostomy and laparotomy was performed in a second patient who developed peritonitis after five days although no stent perforation of the bowel was identified. Two patients were successfully decompressed and underwent subsequent elective surgery with full bowel preparation. Stent placement resulted in symptomatic improvement in three out of four patients with anastomotic strictures (allowing closure of defunctioning stomas) and in the one patient with an idiopathic rectal stricture. Stent migration occurred in two of these patients without recurrence of symptoms. Stent fracture occurred in one patient, who remained symptomatic. CONCLUSIONS: Self-expanding metallic stents are an effective treatment for benign colorectal obstructions, especially anastomotic strictures with long-term patency. Stents should be avoided in acute diverticular disease because of a higher incidence of complications.
Publication Types: ? Review
PMID: 16412069 [PubMed – indexed for MEDLINE]
Reprod Biomed Online. 2005 Nov;11(5):641-50.
Oxidative stress and its implications in female infertility – a clinician’s perspective.
Agarwal A, Gupta S, Sharma R.
Centre for Advanced Research in Human Reproduction, Infertility, and Sexual Function, Department of Obstetrics-Gynecology and Glickman Urological Institute, The Cleveland Clinic Foundation, OH 44195, USA. agarwaa@ccf.org
Reactive oxygen species (ROS) have a role in the modulation of gamete quality and gamete interaction. Generation of ROS is inherent in spermatozoa and contaminating leukocytes. ROS influence spermatozoa, oocytes, embryos and their environment. Oxidative stress (OS) mediates peroxidative damage to the sperm membrane and induces nuclear DNA damage. ROS can modulate the fertilizing capabilities of the spermatozoa. There is extensive literature on OS and its role in male infertility and sperm DNA damage and its effects on assisted reproductive techniques. Evidence is accumulating on the role of ROS in female reproduction. Many animal and human studies have elucidated a role for ROS in oocyte development, maturation, follicular atresia, corpus luteum function and luteolysis. OS-mediated precipitation of pathologies in the female reproductive tract is similar to those involved in male infertility. OS influences the oocyte and embryo quality and thus the fertilization rates. ROS appears to play a significant role in the modulation of gamete interaction and also for successful fertilization to take place. ROS in culture media may impact post-fertilization development, i.e. cleavage rate, blastocyst yield and quality (indicators of assisted reproduction outcomes). OS is reported to affect both natural and assisted fertility. Antioxidant strategies should be able to intercept both extracellular and intracellular ROS. This review discusses the sources of ROS in media used in IVF-embryo transfer and strategies to overcome OS in oocyte in-vitro maturation, in-vitro culture and sperm preparation techniques.
Publication Types: ? Review
PMID: 16409717 [PubMed – indexed for MEDLINE]
Reprod Biomed Online. 2005 Nov;11(5):615-9.
Effects of peritoneal fluid on preimplantation mouse embryo development and apoptosis in vitro.
Esfandiari N, Falcone T, Goldberg JM, Agarwal A, Sharma RK.
Department of Obstetrics and Gynaecology, The Cleveland Clinic Foundation, OH 44195, USA.
To evaluate the effect of peritoneal fluid (PF) on preimplantation mouse embryo development and apoptosis, PF was obtained from women presenting with (n = 7) and without endometriosis (n = 7). Mouse embryos were cultured to the blastocyst stage in human tubal fluid medium alone (control) or 10% PF. Embryo development was assessed and the total cell number per embryo was determined by Hoechst 33258 staining. Allocation of inner cell mass and trophectoderm in blastocysts, and incidence of apoptosis were determined using confocal microscopy. The blastocyst development rate was significantly lower in the presence of 10% PF (P < 0.01). Total cell number and trophectoderm in blastocysts cultured in culture media alone was significantly higher than in the presence of PF (P = 0.034 and P = 0.01 respectively). A higher incidence of apoptosis was seen in blastocysts cultured in culture media alone, compared with those cultured in the presence of PF (P = 0.04). PF decreases the development of early mouse embryos to the blastocyst stage, as well as the incidence of apoptosis in the resulting mouse blastocysts. No difference was seen in the effect of PF from women with and without endometriosis on mouse embryo development and apoptosis.
PMID: 16409713 [PubMed – indexed for MEDLINE]
Gynecol Obstet Fertil. 2006 Jan;34(1):8-13. Epub 2006 Jan 6.
[Abdominal wall endometriosis after caesarean section: report of fifteen cases] [Article in French] Picod G, Boulanger L, Bounoua F, Leduc F, Duval G.
Service de chirurgie gynecologique, hopital Jeanne-de-Flandre, CHRU de Lille, avenue Avinee, 59037 Lille cedex, France. g.picod@caramail.com
OBJECTIVE: Parietal endometriosis is an uncommon pathology. It can occur on all the scars, most often after a surgical procedure with hysterotomy. Surgical scar endometriosis following caesarean section has an incidence of 0.03 to 0.4%. PATIENTS AND METHODS: This retrospective study reviewed all the cases of parietal endometriosis seen during a 7-year period in the department of visceral surgery of the Armentiere’s hospital center. A pathological analysis has confirmed each lesion retained. RESULTS: 15 women were treated during this period. The mean age is 32 years. All the women have one or two antecedents of caesarean with Pfannenstiel’s laparotomy. The interval between the caesarean and the appearance of the first symptoms is on average of 5 years and 11 months. Only 66.6% of cases presented the classical symptoms with cyclic pain. For 66.6% of patients, the diagnosis of parietal endometriosis was suspected before the treatment. The treatment is a surgical one with exeresis for all the women. In 13.3% of the cases, the lesion is pre aponeurotic. In 46.6% of the cases, it overgrows the rectus abdominis muscle, in 33.3% of the cases the external abdominal oblique and at last a lesion overgrows the transversus abdominis and one is in an inguinal localization. The mean size of lesions is 2.48 cm. We have not notified complications and no recurrence was noted. DISCUSSION AND CONCLUSION: The local endometrial cell transplant is the most likely mechanism to explain the physiopathology of parietal endometriosis. The classical symptoms associate a painful swelling and cyclic pain related to the menstrual period, but all of these symptoms are not always associated. The contribution to the diagnosis of the imaging studies is weak. The surgical treatment has to be sufficiently wide to avoid all recurrence. No means of prevention has proved its efficiency. In 26.6% of cases the parietal endometriosis is associated to pelvic endometriosis. This localization is more often asymptomatic. Then the realization of a laparoscopic exploration is not indicated immediately.
PMID: 16406732 [PubMed – in process]
Gynecol Obstet Fertil. 2006 Jan;34(1):71-9. Epub 2006 Jan 6.
[Recommendations of good practice on drug therapy for endometriosis (except adenomyosis) (November 2005)] [Article in French] Agence Francaises de securite sanitaire des produits de sante, Afssaps.
PMID: 16406660 [PubMed – in process]
: Mol Cell Endocrinol. 2006 Mar 27;248(1-2):94-103. Epub 2006 Jan 10.
Progesterone resistance in endometriosis: Link to failure to metabolize estradiol.
Bulun SE, Cheng YH, Yin P, Imir G, Utsunomiya H, Attar E, Innes J, Julie Kim J.
Division of Reproductive Biology Research, Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, 303 East Superior Street, Chicago, IL 60611, United States.
Endometriosis is the most common cause of pelvic pain and affects an estimated 5 million women in the US. The biologically active estrogen estradiol (E(2)) is the best-defined mitogen for the growth and inflammation processes in the ectopic endometriotic tissue that commonly resides on the pelvic organs. Progesterone and progestins may relieve pain by limiting growth and inflammation in endometriosis but a portion of patients with endometriosis and pelvic pain do not respond to treatment with progestins. Moreover, progesterone-induced molecular changes in the eutopic (intrauterine) endometrial tissue of women with endometriosis are either blunted or undetectable. These in vivo observations are indicative of resistance to progesterone action in endometriosis. The molecular basis of progesterone resistance in endometriosis may be related to an overall reduction in the levels of progesterone receptors (PRs) and the lack of the PR isoform named progesterone receptor B (PR-B). In normal endometrium, progesterone acts on stromal cells to induce secretion of paracrine factor(s). These unknown factor(s) act on neighboring epithelial cells to induce the expression of the enzyme 17beta-hydroxysteriod dehydrogenase type 2 (17beta-HSD-2), which metabolizes the biologically active estrogen E(2) to estrone (E(1)). In endometriotic tissue, progesterone does not induce epithelial 17beta-HSD-2 expression due to a defect in stromal cells. The inability of endometriotic stromal cells to produce progesterone-induced paracrine factors that stimulate 17beta-HSD-2 may be due to the lack of PR-B and very low levels of progesterone receptor A (PR-A) observed in vivo in endometriotic tissue. The end result is deficient metabolism of E(2) in endometriosis giving rise to high local concentrations of this local mitogen. The cellular and molecular mechanisms underlying progesterone resistance and failure to metabolize E(2) in endometriosis are reviewed.
PMID: 16406281 [PubMed – in process]
Gynecol Obstet Fertil. 2006 Jan;34(1):1-2. Epub 2006 Jan 5.
[Surgeons! Pity patients who suffer from endometriosis!] [Article in French] Mage G, Canis M.
Publication Types: ? Editorial
PMID: 16403667 [PubMed – in process]

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