Advanced Stage Endometriosis Research Articles

Pleiotrophin (PTN) and midkine (MK) mRNA expression in eutopic and ectopic endometrium in advanced stage endometriosis.

Endometriosis is characterized by the ectopic implantation of endometrium on peritoneal surfaces. Angiogenic and growth factors may play a significant role in the pathogenesis of endometriosis. Midkine (MK) and pleiotrophin (PTN) are two related peptides associated with carcinogenesis and angiogenesis. To test the hypothesis that a higher expression of MK and PTN in ectopic and eutopic endometrium from women with endometriosis might favour increased angiogenesis and growth with subsequent ectopic implantation, we investigated PTN and MK expression by quantitative competitive PCR (QC-PCR) in endometrium from 30 women with severe, stages III and IV endometriosis and from 30 women without endometriosis. Total RNA was extracted and reverse transcribed into cDNA, and QC-PCR was performed to evaluate PTN and MK mRNA expression. Results were analysed by analysis of variance. Eutopic endometrium from endometriosis patients showed increased expression of MK and PTN mRNA compared with endometrium from normal women in the luteal phase (P < 0.05). MK and PTN mRNA expression in ectopic endometrium was significantly lower than that in eutopic endometrium from women with and without endometriosis (P < 0.05). Our results suggest increased MK and PTN expression may be related to the initiation of ectopic endometrial implants and peritoneal invasion.

Regulation of steroidogenic acute regulatory protein expression and progesterone production in endometriotic stromal cells.

The regulation of steroidogenic acute regulatory protein (StAR) gene expression and the synthesis of steroids from cholesterol in ectopic endometriosis tissues were investigated. Peritoneal fluid and endometrial tissues were collected from patients with endometriosis and otherwise healthy women. Peritoneal progesterone and 17 beta-E2 concentrations were highest in early stage endometriosis compared with those in advanced stage endometriosis and in normal women. In concordance with the profile of peritoneal steroids, StAR mRNA and protein were greatest in ectopic implants of early endometriosis. In the advanced stage, concentrations of StAR mRNA and protein were also greater compared with those in normal endometrium. In contrast, P450 side-chain cleavage enzyme and 3 beta-hydroxysteroid dehydrogenase transcripts were not different between normal endometrium and ectopic endometriotic implants. Expression of StAR mRNA was detected in purified stromal, but not epithelial, cells. Treatment with PGE(2), but not TNF alpha, or IL-1 beta significantly increased StAR expression and thus induced progesterone production in cultured endometriotic stromal cells. These results demonstrated that aberrant expression of StAR in ectopic endometriotic tissues leading to increased peritoneal progesterone is associated with the formation of endometriosis. Induction of StAR gene expression by peritoneal PGE(2) in endometriotic stromal cells may further contribute to the development of endometriosis.

Increase in the expression of killer cell inhibitory receptors on peritoneal natural killer cells in women with endometriosis

Objective: Malfunction of peritoneal natural killer cells (NK) may result in endometriosis. The present study was designed to determine whether the decrease in NK cytotoxicity occurs at early and advanced stages of endometriosis and is due to the increase in the NK inhibition receptors. Design: A case control study. Setting: A tertiary-care infertility center. Patient(s): A total of 44 women (controls, n = 11; women with early-stage endometriosis, n = 11; and women with advanced-stage endometriosis, n = 22) were included in this study. Intervention(s): Laparoscopic examination. Main Outcome Measure(s): NK cytotoxicity was determined by assay of 51Cr release against K562 cells, and the expression of killer cell inhibitory receptors (KIR, including NKB1, GL183, and EB6) in NK cells was examined by flow cytometry. Result(s): Women with endometriosis showed a decrease in peritoneal NK cytotoxicities against K562 at early and advanced stages of endometriosis. The expression of KIR (NKB1 and EB6) was significantly elevated in the peritoneal NK cells of women with advanced-stage endometriosis compared with controls. KIR (NKB1) was also significantly increased in peritoneal NK cells of women with advanced-stage endometriosis, compared with those of women with early-stage endometriosis. Conclusion(s): The results of this study suggest that the decrease in peritoneal NK cytotoxicities against K562 is observed and that this disease may be partially due to the increased expression of KIR on these NK cells.

Sclerotherapy: A Less Invasive Alternative for the Treatment of Ovarian Endometriomas Prior to IVF

Sclerotherapy: A Less Invasive Alternative for the Treatment of Ovarian Endometriomas Prior to IVF

Peritoneal interleukin-10 increases with decrease in activated CD4+ T lymphocytes in women with endometriosis.

This study was performed to determine whether peritoneal T cells are suppressed in the CD4+ or CD8+ T cell subpopulation and whether they are Th1 or Th2 predominant in women with endometriosis. Immune cells in the peritoneal fluid (PF) were obtained from women undergoing laparoscopy for endometriosis or tubal ligation. Three-colour flow cytometry was utilized for immunophenotyping of peritoneal fluid mononuclear cells (PFMC). Concentrations of interleukin (IL)-4, IL-5 and interferon-gamma (IFN-gamma) produced by PFMC with and without mitogen stimulation and concentrations of IL-10 and IL-12 were measured in PF. The peritoneal T lymphocytes were predominantly of the Th1 type that produced much more IFN-gamma but less IL-4 or IL-5 in women with or without endometriosis. The decrease in peritoneal lymphocytes was significant in the HLA-DR+ CD4+ CD3+ subpopulation and the concentrations of peritoneal IL-10 and IL-12 were significantly elevated in women with early stage endometriosis. There was impaired IL-5 production by PFMC after phytohaemagglutinin stimulation in women with advanced stage endometriosis. We concluded that the activated peritoneal CD4+ Th1 cells from the women with endometriosis were decreased in number. The suppression of these T cells may be due to the elevation of IL-10 and IL-12 in the peritoneal fluid.

Combined use of a long-acting gonadotropin-releasing hormone agonist and low-dose danazol in advanced stage endometriosis

In this preliminary study, the safety and efficacy of a combined GnRHa and low-dose danazol regimen was evaluated in patients with advanced stage endometriosis. Five patients with stage IV endometriosis were administered triptorelin 3.75 mg intramuscularly with monthly intervals in combination with oral danazol 100 mg/day for 6 months. Laparoscopy was performed before and after therapy to assess the change in endometriotic lesions. During controls, patients were evaluated for the change in hormonal and biochemical parameters and the side effects of the treatment. In 4 patients with ovarian endometriomas, cysts were drained during initial laparoscopy. None of the endometriomas persisted after therapy. Total scores, according to the revised American Fertility Society classification of endometriosis were, 54.8 ± 10.9 before treatment and decreased to 31.6 ± 10.3 ( P < 0.05), whereas, endometriotic implants scores changed from an initial value of 22.8 ± 12.1 to 1.2 ± 1.1 ( P < 0.05). No adverse effect was observed on lipid and liver metabolism. Estrogen deprivation symptoms and oily skin were the most prominent complaints and one patient had a weight gain of 6 kg. Based on these results we conclude that a combination of GnRHa and low dose danazol is an effective alternative treatment modality in the treatment of severe endometriosis without any serious side effect.

Ovarian preservation at hysterectomy for endometriosis

Traditionally, definitive treatment for symptomatic endometriosis has been total abdominal hysterectomy with bilateral salpingo-oophorectomy. However, aggressive excision of all endometriotic implants at the time of hysterectomy with preservation of one or both ovaries may be an acceptable alternative. All hysterectomies performed between 1988 and 1993 were retrospectively reviewed. Fifty-two women underwent laparoscopic hysterectomy for pelvic pain from advanced stage endometriosis with preservation of at least one ovary. The majority of women had significant to total relief of pelvic pain postoperatively. Average follow-up was 36 months. This series suggests that ovarian preservation at the time of hysterectomy can be considered in women with endometriosis. Patient benefits include avoidance of symptoms of surgical castration and subsequent exogenous hormone replacement.