Effects of simvastatin in prevention of pain recurrences after surgery for endometriosis (original) (raw)
Acta obstetricia et gynecologica Scandinavica, 2015
To evaluate the efficacy of dienogest + estradiol valerate (E2V) and gonadotrophin-releasing hormone analogue (GnRH-a) in reducing recurrence of pain in patients with chronic pelvic pain due to laparoscopically diagnosed and treated endometriosis. Multi-center, prospective, randomized study. Three university departments of obstetrics and gynecology in Italy. Seventy-eight women who underwent laparoscopic surgery for endometriosis combined with chronic pelvic pain. Post-operative administration of dienogest + E2V for 9 months (group 1) or GnRH-a monthly for 6 months (group 2). A visual analogue scale was used to test intensity of pain before laparoscopic surgery at 3, 6 and 9 months of follow up. A questionnaire to investigate quality of life was administered before surgery and at 9 months of follow up. The visual analogue scale score did not show any significant differences between the two groups (p = 0.417). The questionnaire showed an increase of scores for all women compared with...
The Journal of Obstetrics and Gynecology of India, 2018
Objective To compare the efficacy and safety of dienogest (DNG) with depot leuprolide acetate (LA) in patients with recurrent pelvic pain following laparoscopic surgery for endometriosis. Design Prospective randomized trial. Setting Zagazig University hospitals, Egypt. Patients Two hundred and forty-two patients with recurrent pelvic pain following laparoscopic surgery for endometriosis. Intervention Dienogest (2 mg/day, orally) or depot LA (3.75 mg/4 weeks, intramuscularly) for 12 weeks. Main Outcome Measures A visual analogue scale was used to test the intensity of pain before and after the end of treatment. Results There was highly significant reduction in pelvic pain, back pain and dyspareunia in both groups with mean of difference in dienogest group (28.7 ± 5.3, 19.0 ± 4.3 and 20.0 ± 3.08 mm, respectively) and in LA group (26.2 ± 3.01, 19.5 ± 3.01 and 17.9 ± 2.9 mm, respectively). The most frequent drug-related adverse effects in
Simvastatin protects against the development of endometriosis in a nude mouse model
Journal of Clinical …, 2009
Context: Endometriosis is a common condition associated with infertility and pelvic pain in women. Recent in vitro studies have shown that statins decrease proliferation of endometrial stroma (ES) and inhibit angiogenesis. Objective: The aim was to evaluate effects of simvastatin on development of endometriosis in a nude mouse model. Methods: Proliferative phase human endometrial biopsies were obtained from healthy donors and established as organ cultures or used to isolate ES cells. To establish endometriosis in the nude mouse, endometrial tissues were maintained in 1 nM estradiol (E) for 24 h and subsequently injected into ovariectomized nude mice. Mice (n ϭ 37) were treated with E (8 mg, SILASTIC capsule implants; made in author laboratory) alone or with E plus simvastatin (5 or 25 mg/kg ⅐ d) for 10 d beginning 1 d after tissue injection (from three donors). Mice were killed and examined for disease. Effects of simvastatin on matrix metalloproteinase-3 (MMP-3) were evaluated in cultures of ES cells. Primary Outcome: The number and size of endometriotic implants were measured. Results: Simvastatin induced a dose-dependent decrease of the number and size of endometrial implants in mice. At the highest dose of simvastatin, the number of endometrial implants decreased by 87%, and the volume by 98%. Simvastatin also induced a concentration-dependent decrease in MMP-3 in the absence and presence of inflammatory challenge (using IL-1␣). Conclusions: Simvastatin exerted a potent inhibitory effect on the development of endometriosis in the nude mouse. Mechanisms of action of simvastatin may include inhibition of MMP-3. The present findings may lead to the development of novel treatments of endometriosis involving statins.
Journal of Minimally Invasive Gynecology, 2011
Study Objective: To evaluate continuous (CON) compared with cyclic (CYC) administration of combined oral estroprogestins for 6 months after laparoscopic excision of ovarian endometriomas associated with pain. Design: Multicenter, prospective, randomized trial (Canadian Task Force classification I). Setting: Tertiary care university hospitals. Patients: Fifty-seven women aged 18 to 40 years with ovarian endometriomas associated with moderate to severe pelvic pain who underwent laparoscopic excision of the disease. Interventions: Patients were randomized to receive postoperative estroprogestins for 6 months, administered as either a CON or CYC regimen. Measurements and Main Results: At 3, 6, 12, and 24 months postoperatively, patients were evaluated for recurrence of endometriomas (defined as cysts .3 cm in greatest diameter) using ultrasonography, for recurrence of pain using a visual analog scale, and for patient satisfaction. After a minimum follow-up of 12 months (mean, 22 months), at intent-to-treat analysis, no endometrioma recurrence was observed in the CON group, whereas there was recurrence in 1 patient (4%) in the CYC group. Pain recurred in 5 and 9 patients, respectively (17% vs 32%; p 5 .23). Compared with pretreatment values, pain scores improved in both groups, with no significant difference between the 2 groups. Most patients in both groups were either satisfied or very satisfied, with no significant difference between treatment groups. However, compared with the CYC group, significantly more patients in the CON group experienced moderate to severe adverse effects, and therapy was discontinued (41% vs 14%; p 5 .03). Conclusions: Although both regimens were equally effective insofar as postoperative pain and recurrence of endometrioma, when compared with the CYC regimen, the CON regimen seems to be associated with significantly more adverse effects and discontinuation rates.
European Journal of Obstetrics & Gynecology and Reproductive Biology, 2011
To investigate factors that might influence the recurrence of both painful symptoms and endometriotic lesions following laparoscopic treatment of endometriosis. Study design: Retrospective cohort study in a University teaching hospital. We reviewed data from patients referred for laparoscopy between March 1993 and November 2007. We selected women who were followed up throughout Transvaginal-ultrasound (TV-US) after a first conservative laparoscopy for endometriosis. After laparoscopy, all patients were followed up according to an internal protocol: a standard gynaecologic examination, the assessment of painful symptoms and a TV-US scan that were repeated at 3, 6, and 12 months, and subsequently on a yearly basis. Sixteen factors were assessed by univariable and multivariable Cox proportional hazards models to evaluate their associations with recurrence of endometriotic lesions and pain related-endometriosis. Results: 401 women were enrolled. A total of 154 (38.4%) experienced moderate or severe pain after laparoscopy; endometriotic lesions were observed by TV-US in 74 (18.4%) patients. In the multivariable model, age at menarche, severity of chronic pelvic pain (CPP) and dysmenorrhoea prior to surgery were significant risk factors for recurrence/occurrence of pain. Age at the first laparoscopy, stage of disease, pre-operative severity of CPP, and pregnancy were predictive factors of the recurrence for such lesions. Conclusion: The severity of CPP prior to the first laparoscopy showed the only significant factor in the overall prediction of recurrence of pain and endometriotic lesions. Patients with severe CPP at the time of their first surgery might represent a subgroup of women with a more aggressive form of endometriosis.
BMC Women's Health, 2017
Background: Simvastatin is a promising new drug for the treatment of endometriosis. It is a cholesterol-lowering drug that acts by inhibiting HMG-CoA reductase, resulting in a decrease in mevalonate, a precursor of cholesterol and monocyte chemoattractant protein-1 (MCP-1). This study investigated the effect of pre-operative oral simvastatin administration on MCP-1 gene expression and serum MCP-1 protein levels in patients with endometriosis. Methods: A prospective, randomized, controlled study was conducted at the Reproductive Endocrinology Unit of the Department of Obstetrics and Gynecology at the Faculty of Medicine Ramathibodi Hospital. Forty women (mean age: 18-45 years) scheduled for laparoscopic surgery who had been diagnosed with endometriosis were recruited and randomly assigned to either a treatment group (20 mg/d of orally administered simvastatin for 2 weeks before surgery) or an untreated control group. Serum was collected before and after treatment and protein levels of MCP-1 were determined. MCP-1 and CD68 transcript levels were also quantified using real-time PCR on endometriotic cyst tissues. Results: MCP-1 gene expression on endometriotic cyst was not significantly different between the simvastatin-treated and untreated groups (P = 0.99). CD68 expression was higher in the treatment group compared to the control group, but this was not statistically significant (P = 0.055). Serum MCP-1 levels following simvastatin treatment were higher than in samples obtained before treatment (297.89 ± 70.77 and 255.51 ± 63.79 pg/ml, respectively) (P = 0.01). Conclusions: Treatment with 20 mg/d of simvastatin for 2 weeks did not reduce the expression of either the chemokine MCP-1 gene or macrophage-specific genes. Cumulatively, this suggests that simvastatin is not ideal for treating endometriosis because a higher dose of simvastatin (40-100 mg/d) would be needed to achieve the target outcome, which would significantly increase the risk of myopathy in patients.
Fertility and Sterility, 2011
Objective: To compare efficacy of the levonorgestrel-releasing intrauterine system (LNG-IUS; Mirena) with depot GnRH analogue (GnRH-a; gosareline acetate; Zoladex) on endometriosis-related chronic pelvic pain (CPP) in patients with severe endometriosis during 12 months. Design: Prospective, randomized, controlled study. Setting: The reproductive endocrinology unit of a tertiary, research and education hospital. Patient(s): Forty women with severe endometriosis (revised The American Fertility Society [AFS] classification >40) and endometriosis-related CPP and control groups were enrolled in the study. Intervention(s): The patients were treated with either LNG-IUS (n ¼ 20) or GnRH-a (n ¼ 20). The GnRH-a dose was repeated every 4 weeks for 24 weeks. Main Outcome Measure(s): Scores of CPP were evaluated using a visual analogue scale (VAS) and total endometriosis severity profile (TESP). Result(s): The TESP score decreased in the LNG-IUS group at first, third, and sixth month follow-up visits, whereas at the 12th month follow-up visit, the TESP scores were increased to values similar to pretreatment values. Although the VAS score had no significant alteration during the follow-up period in the LNG-IUS group, the GnRH-a group showed a significant decrease in the VAS score and TESP score at the end of 1 year. The LNG-IUS treatment showed a lower patient satisfaction. Conclusion(s): Both treatment modalities showed comparable effectiveness in the treatment of CPP-related endometriosis.
Indonesian Journal of Obstetrics and Gynecology, 2019
Objective : To evaluate the correlation between the American Society of Reproductive Medicine (ASRM) score in endometriosis and severity pelvic pain in a group of women with endometriosis. Methods : A total of 131 patients with pelvic pain who: conduct laparoscopy for diagnosis and therapy of endometriosis, have pain symptoms>3 months, and absence of pelvic anomalies. Dysmenorrhea, deep dyspareunia, dyschezia, dysuria, and chronic pelvic pain were evaluated using a 10-point visual analogue scale. The data was collected by assessing the medical record, and retrospective analysis was performed. Disease stage according to the American Society of Reproductive Medicine, the presence of adhesion, lesion type (Deep Infi ltrating Endometriosis (DIE) or without DIE), and severity of pain symptoms were analysed by Spearman analysis. Different VAS between DIE vs non DIE group was analysed by Mann-Whitney analysis. Results : Stage IV endometriosis accounts for 79.4%. Based on the macroscopic appearance, ovarian endometriosis accounts for 92.4%, peritoneal endometriosis 82.4%, DIE was 40.5%, and adenomyosis was 19.1%. There was signifi cant correlation between total ASRM, ovarian endometriosis, peritoneal lesion, Douglas pouch obliteration, adnexal adhesion score and VAS dysmenorrhea (r=0.303; 0.187; 0.203; 0.278; 0.266, p<0.05). There was signifi cant VAS difference of DIE vs non DIE group; the difference was on dyspareunia (5.18±2.4 and 4.58±1.0, p<0.001] and dyschezia [5.28±2.2 and 4.86±0.7,p<0.001] Conclusions : There was a positive correlation between ovarian endometriosis score and severity of dysmenorrhea. There was also a difference in the degree of endometriosisassociated pain between DIE and non DIE group.
Journal of Obstetrics and Gynaecology Research, 2009
Objective evaluation of pelvic pain symptoms using a standard pain questionnaire is essential to assessing the treatment of endometriosis and related pain. Aim: To evaluate the McGill Pain Questionnaire (MPQ) as a multi-dimensional verbal scale in providing information about chronic pelvic pain associated with endometriosis, before and after laparoscopic surgery. Methods: Fifty-five women undergoing laparoscopy for severe endometriosis were asked to complete the MPQ before surgery and at the 6-month follow up. All patients presented with preoperative pain symptoms of variable severity. We obtained the pain indexes and studied their relation with: patients' characteristics (age, body mass index, parity, qualification, occupation); operative findings (number, site and size of endometriotic lesions and presence of pelvic adhesions); and postoperative evolution of variable MPQ pain indexes at the 6-month follow up. Results: Median present pain index (PPI) (index of pain intensity), before surgical treatment was 3 (2-4): preoperative PPI was <2 in 25% of patients while 25% of patients had PPI > 4. Overall median PPI after surgical treatment was 1 (0-2): postoperative index of pain intensity was <1 in 50% of patients, >2 in 25% of patients while 25% of patients did not experience postoperative pain. Overall pain intensity significantly decreased after laparoscopic treatment of endometriosis (Wilcoxon test P < 0.0005). None of the patients' characteristics were found to be significantly correlated with the severity or improvement of preoperative pain at postoperative follow up (P > 0.05), and the intensity of preoperative pain was not correlated to any of the operative variables. There was a significant reduction in all individual MPQ pain indexes; however 18.2% of women did not show improvement of pain symptoms after laparoscopic surgery. An increasing endometrioma diameter was associated with a significant decrease in the difference in evaluative rank score of pain rating index between pain indexes at the 6-month follow up and preoperatively (P = 0.04, Spearman's rank correlation Rho = -0.277).