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Expert Opin Pharmacother. 2012 Oct;13(15):2157-70. doi: 10.1517/14656566.2012.725045.

Dysmenorrhea in adolescents and young adults: an update on pharmacological treatments and management strategies.

Harel Z1.

 

Abstract

INTRODUCTION:

Dysmenorrhea is the most common gynecologic complaint among adolescents/young adults. Dysmenorrhea is usually primary and is associated with normal ovulatory cycles and with no pelvic pathology. Potent prostaglandins and potent leukotrienes play an important role in generating primary dysmenorrhea symptoms. Adolescents/young adults with severe dysmenorrhea symptoms may have pelvic abnormalities, such as endometriosis or uterine anomalies (secondary dysmenorrhea).

AREAS COVERED:

This review provides an update on treatments and management strategies of dysmenorrhea in adolescents/young adults. Medical literature articles were retrieved using a Medline search on primary and secondary dysmenorrhea. Original articles from peer-reviewed journals were selected based on relevance.

EXPERT OPINION:

Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) is the preferred initial treatment for dysmenorrhea in nonsexually active adolescents/young adults. Adolescents/young adults with symptoms that do not respond to NSAIDs for three menstrual periods should be offered hormonal treatment, such as combined estrogen and progestin oral contraceptive pills (OCPs), for three menstrual cycles. If dysmenorrhea does not improve within 6 months of NSAIDs and OCPs, a laparoscopy is indicated to look for endometriosis, which is the most common reason for secondary dysmenorrhea.

 

 

Am J Reprod Immunol. 2013 Jan;69(1):73-84. doi: 10.1111/aji.12020. Epub 2012 Sep 17.

Effects of laparoscopic radical surgery for deep endometriosis on endometriosis-related pelvic pain.

Hidaka T1Nakashima AHashimoto YSaito S.

 

Abstract

Deep endometriosis is associated with severe painful symptoms that sometimes impair the quality of life in women of reproductive age. Medical therapy does not provide for adequate pain relief, and an effective management option to reduce pelvic pain appears to be complete laparoscopic removal of as many endometriotic lesions as possible. In this study, we investigated the usefulness and risks of radical laparoscopic removal of deep endometriosis for patients diagnosed as stage III/IV endometriosis during laparoscopic surgery. Forty-seven consecutive patients undergoing conservative laparoscopic surgery alone (adhesiotomy and cystectomy of ovarian endometriosis but not removal of deep endometriotic lesion; non-DEL removal group) and 151 consecutive patients undergoing radical laparoscopic removal of deep endometriotic lesions combined with conservative surgery (DEL removal group) were compared. As a result, significant improvements in pain were obtained in both groups, however, the degree of improvement was significantly higher and the rate of recurrence was significantly lower in the DEL removal group. The addition of radical removal of deep endometriotic lesions to conservative laparoscopic surgery markedly reduces the severity of dysmenorrhea and the rate of recurrent pelvic pain. Although the surgical procedure is technically demanding, the levels of peri-operative complications and morbidity are acceptable.

 

 

Minim Invasive Ther Allied Technol. 2012 Sep;21(5):355-61. doi

Association of natural killer T cells with staging of endometriosis.

Guo S1Zhang YWang LQiu W.

 

Abstract

OBJECTIVE:

To investigate the role of natural killer T cells (NKT) in the pathogenesis and staging of endometriosis(EMT).

METHODS:

Sixty EMT cases of stages I to IV were enrolled as the observation group, and 20 healthy volunteers served as the control group. NKT percentages in the peripheral blood and peritoneal effusions were detected by flow cytometry, and the levels of interferon-γ (IFN-γ) and interleukin-4 (IL-4) were examined using ELISA.

RESULTS:

Compared with the control group, EMT group showed significantly lowered NKT percentages and IFN-γ and IL-4 levels in both the peripheral blood and peritoneal effusions (P<0.05). In EMT patients, NKT percentages, IFN-γ and IL-4 levels all increased significantly with the stage of EMT in the order of I>II>III>IV (P<0.05). Spearman correlation analysis showed that NKT, IFN-γ and IL-4 were all inversely correlated with the stage of EMT (r>0.06, P<0.05).

CONCLUSION:

As a protective factor against EMT, NKT, together with its cytokines IFN-γ and IL-4, play an important role in EMT and is closely correlated with EMT staging.

 

Nan Fang Yi Ke Da Xue Xue Bao. 2012 Sep;32(9):1322-4. Chinese

Attractiveness of women with rectovaginal endometriosis: a case-control study.

Vercellini P1Buggio LSomigliana EBarbara GViganò PFedele L.

 

 

Abstract

OBJECTIVE:

To evaluate physical attractiveness in women with and without endometriosis.

DESIGN:

Case-control study.

SETTING:

Academic hospital.

PATIENT(S):

Three hundred nulliparous women.

INTERVENTION(S):

Assessment of attractiveness by four independent female and male observers.

MAIN OUTCOME MEASURE(S):

A graded attractiveness rating scale.

RESULT(S):

A total of 31 of 100 women in the rectovaginal endometriosis group (cases) were judged as attractive or very attractive, compared with 8 of 100 in the peritoneal and ovarian endometriosis group and 9 of 100 in the group of subjects without endometriosis. A higher proportion of cases first had intercourse before age 18 (53%, 39%, and 30%, respectively). The mean ± SD body mass index in women with rectovaginal endometriosis, in those with other disease forms, and in those without endometriosis was, respectively, 21.0 ± 2.5, 21.3 ± 3.3, and 22.1 ± 3.6. The median (interquartile range) waist-to-hip ratio and breast-to-underbreast ratio were, respectively, 0.75 (0.71-0.81), 0.76 (0.71-0.81), and 0.78 (0.73-0.83), and 1.15 (1.12-1.20), 1.14 (1.10-1.17), and 1.15 (1.11-1.18).

CONCLUSION(S):

Women with rectovaginal endometriosis were judged to be more attractive than those in the two control groups. Moreover, they had a leaner silhouette, larger breasts, and an earlier coitarche.

 

 

 

Gynecol Obstet Invest. 2012;74(4):288-97. doi: 10.1159/000341706. Epub 2012 Sep 19.

Endometrial stromal sarcoma arising from endometriosis: a clinicopathological study and literature review.

Lan C1Huang XLin SCai MLiu J.

 

Abstract

OBJECTIVES:

We aimed to investigate the nature of endometrial stromal sarcoma (ESS) arising from endometriosis.

METHODS:

The clinical data of 5 patients with ESS arising from endometriosis were reviewed retrospectively. The expression of CD117, HER2/neu, EGFR, VEGF, and PDGFR was analyzed by immunohistochemical staining.

RESULTS:

The median age of the 5 patients was 45 years. The primary tumor sites were the ovary in 2, the pelvis in 2, and the cervical canal in 1 patient. Three patients had disseminated disease at diagnosis. Four patients underwent complete tumor resection. All of the 5 cases received adjuvant chemotherapy and 2 received progesterone therapy, while none were treated with radiotherapy. No recurrence occurred in the 4 cases who had complete tumor resection, and the only patient who progressed was the patient in whom the tumor was unresectable. Tumor cells in all cases exhibited positive staining for PDGFR and were negative for CD117 and HER2/neu. The expression of EGFR and VEGF was observed in 2 and 4 cases, respectively.

CONCLUSION:

ESS arising from endometriosis is rare. Complete tumor resection in ESS arising from endometriosis may reduce the recurrence rate.

 

 

J Med Case Rep. 2012 Sep 18;6:308. doi: 10.1186/1752-1947-6-308

Radiotherapy for inoperable and refractory endometriosis presenting with massive hemorrhage: a case report.

Nomiya T1Harada MSudo HOta IIchikawa MSuzuki MMurakami MNemoto K.

 

Abstract

INTRODUCTION:

Many patients with endometriosis are treated with medication or by surgical approaches. However, a small number of patients do not respond to medication and are inoperable because of comorbidities. This case report shows the effectiveness of radiotherapy for refractory endometriosis and includes a time series of serum estradiol levels.

CASE PRESENTATION:

A 47-year-old Asian woman presented to our facility with uncontrolled endometriosisrefractory to medication. Our patient was considered inoperable because of severe idiopathic thrombocytopenic purpura, and underwent radiotherapy for massive genital bleeding requiring blood transfusions. A radiation dose of 20Gy in 10 fractions was delivered to the pelvis, including the bilateral ovaries, uterus, and myomas. An additional 10Gy in five fractions was delivered to the endometrium to control residual bleeding. Genital bleeding was completely inhibited on day 46 after radiotherapy. Hormonal analysis revealed that radiotherapy induced post-menopausal status. Two years after radiotherapy, atypical genital bleeding had not recurred and has been well controlled without side effects.

CONCLUSIONS:

Disrupted ovarian function is an adverse effect of radiotherapy. However, radiotherapy can be useful for inducing menopause. In cases of medication-refractory or inoperable endometriosis, radiotherapy would be an effective treatment option.

 

 

Hum Reprod. 2012 Dec;27(12):3412-6. doi: 10.1093/humrep/des316. Epub 2012 Sep 17.

Diagnostic delay for endometriosis in Austria and Germany: causes and possible consequences.

Hudelist G1Fritzer NThomas ANiehues COppelt PHaas DTammaa ASalzer H.

 

Abstract

STUDY QUESTION:

What is the length of the diagnostic delay for endometriosis in Austria and Germany, and what are the reasons for the delay?

SUMMARY ANSWER:

The diagnostic delay for endometriosis in Austria and Germany is surprisingly long, due to both medical and psychosocial reasons.

WHAT IS KNOWN ALREADY:

Diagnostic delay of endometriosis is a problematic phenomenon which has been evaluated in several European countries and in the USA, but has not been reported for Germany and Austria.

STUDY DESIGN, SIZE, DURATION:

A cross-sectional, questionnaire-based multicentre study was conducted in tertiary referral centers in Austria and Germany. From September 2010 to February 2012, 171 patients with histologically confirmed endometriosis were included.

PARTICIPANTS, SETTING, METHODS:

Patients with a previous history of surgically proven endometriosis, internal diseases such as rheumatic disorders, pain symptoms of other origin, gynecological malignancy or post-menopausal status were excluded from the analysis. Patients with histologically confirmed endometriosiscompleted a questionnaire about their psychosocial and clinical characteristics and experiences. Of 173 patients, two did not provide informed consent and were excluded from the study.

MAIN RESULTS AND THE ROLE OF CHANCE:

The median interval from the first onset of symptoms to diagnosis was 10.4 (SD: 7.9) years, and 74% of patients received at least one false diagnosis. Factors such as misdiagnosis, mothers considering menstruation as a negative event and normalization of dysmenorrhea by patients significantly prolonged the diagnostic delay. No association was found between either superficial and deep infiltrating endometriosis or oral contraceptive use and the prolongation of diagnosis.

LIMITATIONS AND REASONS FOR CAUTION:

There was a possible selection bias due to inclusion of surgically treated patients only.

WIDER IMPLICATIONS OF THE FINDINGS:

Several factors causing prolongation of diagnosis of endometriosishave been reported to date. The principal factors observed in the present study are false diagnosis and normalization of symptoms. Teaching programs for doctors and public awareness campaigns might reduce diagnostic delay in Central Europe.

STUDY FUNDING/COMPETING INTEREST(S):

No competing interests exist.

 

 

Reprod Sci. 2013 Apr;20(4):456-62. doi: 10.1177/1933719112459217. Epub 2012 Sep 18.

Noninvasive imaging of the meiotic spindle of in vivo matured oocytes from infertile women with endometriosis.

Dib LA1Araújo MCGiorgenon RCRomão GSFerriani RANavarro PA.

 

Abstract

The objectives of this prospective study were to evaluate the nuclear maturation stage and the presence and location of meiotic spindles of in vivo matured oocytes from infertile women with and without endometriosis (male or tubal causes of infertility) undergoing stimulated cycles for intracytoplasmic sperm injection (ICSI). We also compared the ICSI outcomes among groups. We analyzed the meiotic spindles of oocytes from 36 patients with endometriosis I/II, 24 with endometriosis III/IV, and 60 without endometriosis (male or tubal causes of infertility). The oocytes were imaged using polarization microscopy. There were no differences in the number of oocytes in telophase I (mean [standard deviation]: 0.1 [0.5], 0.2 [0.4], and 0.2 [0.5], respectively, in the endometriosis I/II, endometriosis III/IV, and control groups), in metaphase II with visible spindles (4.2 [2.5], 3.1 [2.0], and 3.6 [2.2], respectively, in the endometriosis I/II, endometriosis III/IV, and control groups), and in spindle location among groups. We can conclude from this study that noninvasive analysis of spindles from in vivo matured oocytes of infertile patients with endometriosis did not demonstrate significant differences in terms of the nuclear maturation stage, the percentage of oocytes in metaphase II with visible spindles, and the spindle localization when compared to the control group. However, it is important to state that there are no studies evaluating the accuracy of polarization microscopy for the detection of meiotic anomalies in human oocytes, which would need to be better evaluated in future studies using an appropriate methodology.

 

 

Epidemiology. 2012 Nov;23(6):799-805. doi: 10.1097/EDE.0b013e31826cc0cf.

Perfluorochemicals and endometriosis: the ENDO study.

Louis GM1Peterson CMChen ZHediger MLCroughan MSSundaram RStanford JBFujimoto VYVarner MWGiudice LCKennedy ASun LWu QKannan K.

 

Abstract

BACKGROUND:

Environmental chemicals may be associated with endometriosis. No published research has focused on the possible role of perfluorochemicals (PFCs) despite their widespread presence in human tissues.

METHODS:

We formulated two samples. The first was an operative sample comprising 495 women aged 18-44 years scheduled for laparoscopy/laparotomy at one of 14 participating clinical sites in the Salt Lake City or San Francisco area, 2007-2009. The second was a population-based sample comprising 131 women matched to the operative sample on age and residence within a 50-mile radius of participating clinics. Interviews and anthropometric assessments were conducted at enrollment, along with blood collection for the analysis of nine PFCs, which were quantified using liquid chromatography-tandem mass spectrometry. Endometriosis was defined based on surgical visualization (in the operative sample) or magnetic resonance imaging (in the population sample). Using logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for each PFC (log-transformed), adjusting for age and body mass index, and then parity.

RESULTS:

Serum perfluorooctanoic acid (PFOA; OR = 1.89 [95% CI = 1.17-3.06]) and perfluorononanoic acid (2.20 [1.02-4.75]) were associated with endometriosis in the operative sample; findings were moderately attenuated with parity adjustment (1.62 [0.99-2.66] and 1.99 [0.91-4.33], respectively). Perfluorooctane sulfonic acid (1.86 [1.05-3.30]) and PFOA (2.58 [1.18-5.64]) increased the odds for moderate/severe endometriosis, although the odds were similarly attenuated with parity adjustment (OR = 1.50 and 1.86, respectively).

CONCLUSIONS:

Select PFCs were associated with an endometriosis diagnosis. These associations await corroboration.

 

 

Acta Med Croatica. 2011 Dec;65(5):435-44. Croatian.

Acute compartment syndrome as a complication of prolonged surgery in the Lloyd Davies position.

Mrsić V1Rasić ZVelnić DAdam VNStojcić EGSmiljanić A.

 

Abstract

Acute compartment syndrome of the muscle is condition in which prolonged increase of tissue pressure in closed unyelding fascial compartments reduces capillary perfusion below a level necessary for tissue viability leading to muscle and nerve ischaemia for few hours. There are wide variety different clinical settings associated with compartment syndrome. Acute lower limb compartment syndrome that occur during and after prolonged surgical procedures in Lloyd Davies position is rare but potentially devastating complication that can lead serious local complications and life threatening situations as, rabdomyolysis, kidney failure and death. In this article we summarize pathophysiology, clinical staging and diagnostic procedures of acute compartment syndrome in Lloyd Davies position. We present female patient developed limb compartment sindrome after surgical procedure which lasted 6,5 hours in the Lloyd Davies position for extensive rectovaginal endometriosis. In this article we rewiev different contributing factors that may predispose to compartment syndrome during Lloyd Davies position and undescore importance of recognise the risk factor and prevent the esthablishment of acute compartment syndrome during and after surgery in the Lloyd Davies position.

 

 

Histopathology. 2012 Nov;61(5):955-65. doi: 10.1111/j.1365-2559.2012.04290.x. Epub 2012 Sep 20.

Mammaglobin 1: not only a breast-specific and tumour-specific marker, but also a hormone-responsive endometrial protein.

Classen-Linke I1Moss SGröting KBeier HMAlfer JKrusche CA.

 

Abstract

AIMS:

The secretoglobin mammaglobin 1 (MGB1) is strongly expressed in breast tumours, and is therefore used to detect breast cancer metastases, although it has also been detected in other tissues. The aim of this study was to examine MGB1 expression and its hormonal regulation in human endometrium to further investigate the use of MGB1 as a marker molecule.

METHODS AND RESULTS:

Mammaglobin 1 expression was assessed immunohistochemically in endometrial samples from 60 normal fertile patients throughout the menstrual cycle, in 49 endometriotic tissue samples, in 15 endometrial adenocarcinomas, and in 36 breast carcinomas. In addition, 25 endometrial samples were analysed by western blot and quantitative real-time reverse transcription polymerase chain reaction. To prove hormonal regulation, primary endometrial epithelial cells were cultured with 17β-oestradiol and promegestone. MGB1 was detected in human endometrial tissue, with peak expression during the luteal phase, in 31% of endometriotic samples, in 53% of endometrial adenocarcinomas, and in 64% of breast carcinomas. MGB1 mRNA expression was increased in vitro by hormonal treatment.

CONCLUSIONS:

Our data show that MGB1 expression is not restricted to normal and malignant breast tissue. Besides its documented occurrence in endometriotic and malignant endometrial tissues, MGB1 is also expressed in normal human endometrium, and such expression is controlled by steroid hormones.

 

 

New insights into the pathogenesis of ovarian carcinoma: time to rethink ovarian cancer screening.

Chan A1Gilks BKwon JTinker AV.

 

Abstract

Recent discoveries about the pathogenesis of ovarian cancer have suggested that it can no longer be thought of as a single entity, but that the histologically defined ovarian cancer subtypes are different diseases, with different precursor lesions and distinct biomarker expression profiles. Most serous carcinomas probably arise from the fallopian tube. Clear cell and endometrioid carcinomas are associated with endometriosis and likely originate from ectopic endometrium. The focus of large ovarian cancer screening trials has been detection of macroscopic ovarian abnormalities by ultrasonography and detection of serum biomarkers associated with the most common (serous) subtype of ovarian cancer. The only completed and phase three randomized controlled trial failed to achieve the objective of reducing ovarian cancer mortality and was not able to demonstrate a stage migration effect of the screening. Future screening strategies have to incorporate our growing understanding of each subtype of pelvic (ovarian or fallopian tube) cancer, its organ of origin, and disease-specific biomarkers. We review how our current understanding of pathogenesis should prompt a reexamination of data from ovarian cancer screening studies and discuss potential designs for future screening strategies.

 

 

Case Rep Pathol. 2012;2012:742035. Epub 2012 Sep 11.

Endometriosis of the terminal ileum: a diagnostic dilemma.

Karaman K1Pala EEBayol UAkman OOlmez MUnluoglu SOzturk S.

 

Abstract

Endometriosis is characterized by the presence of endometrial tissue consisting of glands and/or stroma located outside the uterus. Involvement of the terminal ileum is extremely rare. Preoperative distinction of ileal endometriosis from other diseases of the ileocecal region is difficult in terms of clinical presentation, symptomatology, radiological appearance, and surgical and pathological findings. We report a case initially diagnosed as Crohn’s disease due to a longstanding diarrhea with subsequent intestinal obstruction, but finally diagnosed as ileal endometriosis by histopathological evaluation after resection of the involved segment.

 

 

Sichuan Da Xue Xue Bao Yi Xue Ban. 2012 Jul;43(4):517-9. Chinese.

The expression of Caspase-3 in granulosa cells of endometriosis treated with mifepristone.

Qiao L1Chen BXu KHXiong YCai LR.

 

Abstract

OBJECTIVE:

To investigate the effect of mifepristone on the expression of Caspase-3 in the granulosa cells.

METHODS:

Forty Sprague-Dawley (SD) female rats with (230 +/- 20) g weight were divided into four groups, low-dose group with 1.04 mg/(kg x d) of mifepristone, middle-dose group with 2.604 mg/(kg x d) of mifepristone, high dose group with 10.4 mg/(kg x d) of mifepristone, as well as blank group. Mifepristone tablets were given through gastromy in diestrus of rat for four weeks. Rats were sacrificed after the treatment, and the the expression of Caspase-3 in the granulosa cells of developing follicles was detected by immunohistochemical staining.

RESULTS:

The Caspase-3 protein expression was observed in granulosa cells of developing follicles, while the positive expression level and integrated optical density (IOD) value were increased along with the dosage of mifepristone increasing. The difference among the three dosage groups were significant (P < 0.05).

CONCLUSION:

Regulating Caspase-3 protein expression may be one of the ways for mifepristone inducing granulosa cell apoptosis.

 

Urology. 2012 Nov;80(5):1033-8. doi: 10.1016/j.urology.2012.07.036. Epub 2012 Sep 19.

Laparoscopic treatment of intrinsic endometriosis of the urinary tract and proposal of a treatment scheme for ureteral endometriosis.

Lusuardi L1Hager MSieberer MSchätz TKloss BHruby SJeschke SJanetschek G.

 

Abstract

OBJECTIVE:

To discuss the contemporary management of urinary tract endometriosis and report our experience concerning laparoscopic treatment of intrinsic urinary tract endometriosis.

METHODS:

We performed a retrospective, multicenter study of data collected from March 2006 to March 2011. Ten women were referred from gynecology, seven with ureteral involvement and hydronephrosis and three with bladder involvement, for urologic management. Of the 7 women with hydronephrosis, 5 were symptomatic, with recurrent urinary tract infections or pain. All 3 women with bladder endometriosis had hematuria. All patients had previously undergone unsuccessful hormonal therapy. Ureteral endometriosis was extensively investigated and treated by laparoscopic excision of endometriotic plaques and excision of intrinsic endometriosis of the ureter. Bladder endometriosis was treated by partial cystectomy. Some patients also had endometriosis in other organs and underwent, for example, wedge resection of sigmoid colon and oophorectomy.

RESULTS:

The median age of the patients was 30 years (range 25-44). Seven patients with intrinsic endometriosis of the ureter all had hydronephrosis and proximal hydroureter and underwent laparoscopic ureteral segment excision and either end-to-end, spatulated uretroureterostomy or ureteral reimplatation with psoas hitch. Three patients had hematuria, and cystoscopic biopsy of the bladder lesions confirmed intrinsic endometriosis. They were treated with laparoscopic partial cystectomy. One patient with bowel symptoms also underwent laparoscopic wedge resection of the sigmoid colon and another underwent oophorectomy for a chocolate cyst. Most patients also had peritoneal endometriotic plaques excised. We did not perform simple ureterolysis. No complications were encountered. The median follow-up was 26.5 months (range 4-53), with no return of symptoms or recurrence. The annual follow-up examinations included urinalysis and ultrasonography of the urinary tract.

CONCLUSION:

Intrinsic endometriosis can be successfully managed with minimally invasive techniques to provide relief of symptoms, protect renal function, and prevent recurrence. We describe a classification of ureteral endometriosis determined from staging investigations.

 

Fertil Steril. 2012 Dec;98(6):1370-9. doi: 10.1016/j.fertnstert.2012.08.053. Epub 2012 Sep 19. Review.

Aromatase inhibitors for the treatment of endometriosis.

Pavone ME1Bulun SE.

 

 

Abstract

OBJECTIVE:

To review the use of aromatase inhibitors (AIs) for the treatment of endometriosis.

DESIGN:

Literature review.

CONCLUSION(S):

Most studies show that in reproductive-age women, the combination of AI with conventional therapy alleviates endometriosis-related pain. In postmenopausal women, using an AI alone has been shown to be an effective treatment, although more studies are needed in this subgroup. Side effects of using AIs appear to be tolerable in most women, although special consideration should be given to monitoring bone mineral density. More studies need to be done examining pregnancy rates and outcomes after AI treatment for endometriosis. In addition, larger randomized clinical trials using AIs need to be done. In summary, AIs may be effective in treating endometriosis-related chronic pelvic pain in both reproductive-age and postmenopausal women.

 

 

Fertil Steril. 2013 Jan;99(1):231-40. doi: 10.1016/j.fertnstert.2012.08.038. Epub 2012 Sep 19.

Dysmenorrhea and its severity are associated with increased uterine contractility and overexpression of oxytocin receptor (OTR) in women with symptomatic adenomyosis.

Guo SW1Mao XMa QLiu X.

 

Abstract

OBJECTIVE:

To evaluate uterine contractility, oxytocin receptor (OTR) expression in myometrial smooth muscle cells (MSMCs) derived from uterine tissues from women with and without adenomyosis correlate OTR expression with uterine contractility and dysmenorrhea severity, and see whether trichostatin A (TSA) and andrographolide inhibit OTR expression.

DESIGN:

Laboratory study using human tissues.

SETTING:

Academic hospital.

PATIENT(S):

Twenty patients (cases) with histologically confirmed adenomyosis and 10 (controls) with leiomyomas, cervical dysplasia, and cancer but no adenomyosis or endometriosis.

INTERVENTION(S):

Dysmenorrhea severity was scored by Visual Analog Scale. Uterine tissue samples were collected during hysterectomy. Myometrial smooth muscle cells derived from tissue samples were cultured and OTR protein levels were measured. The effect of TSA (0.5 or 1 μM) and andrographolide (15 or 30 μM) on OTR expression was evaluated.

MAIN OUTCOME MEASURE(S):

Visual Analog Scale scores, and contractile amplitude and frequency. The OTR protein levels in MSMCs were quantified by Western blot analysis.

RESULT(S):

The contractile amplitude and OTR expression levels were significantly higher in cases than in controls. Dysmenorrhea Visual Analog Scale scores correlated positively with contractile amplitude and OTR expression level. Both TSA and andrographolide dose-dependently inhibit OTR expression in MSMC.

CONCLUSION(S):

Oxytocin receptor overexpression in MSMCs may be responsible for increased uterine contractility and adenomyosis-associated dysmenorrhea. Both histone deacetylase inhibitors and andrographolide are therapeutically promising.

 

 

 

 

Reprod Biomed Online. 2012 Nov;25(5):543-8. doi: 10.1016/j.rbmo.2012.07.020. Epub 2012 Aug 8.

History of  endometriosis may adversely affect the outcome in menopausal recipients of sibling oocytes.

Prapas Y1Goudakou MMatalliotakis IKalogeraki AMatalliotaki CPanagiotidis YRavanos KPrapas N.

 

Abstract

Due to the known adverse effect of endometriosis on gamete quality, it has always been difficult to demonstrate a direct effect of endometriosis on implantation. In order to eliminate these confounding effects, this prospective comparative study studied a population of menopausal recipients with and without endometriosis sharing sibling oocytes coming from the same donor. The aim was to understand the impact of endometriosis on implantation, pregnancy and live birth rates in menopausal recipients. A total of 240 menopausal recipients of donated sibling oocytes, were divided in two groups. Group I consisted of 120 recipients diagnosed with endometriosis and group II consisted of 120 controls. The implantation and pregnancy rates were significantly lower in the endometriosisgroup compared with the control group (23.81% versus 31.48%, P=0.019; 45.00% versus 58.33%, P=0.039, respectively). In oocyte donation cycles, a recipient’s history of endometriosis might have a negative impact on implantation, pregnancy and live birth rates, even in menopausal women. Infertility in endometriosis may be due to poor oocyte quality or embryos with decreased ability to implant due to impaired fertilization. There are no conclusive data on the impact of endometriosis on implantation. The already-known adverse effect of endometriosis on gamete quality makes it more difficult to demonstrate a direct effect of endometriosis on implantation. In order to eliminate these confounding effects we studied a population of menopausal recipients with and without endometriosis sharing sibling oocytes coming from the same oocyte donor. The oocyte donation model was used in an attempt to understand whether the endometrium, the oocytes or both are affected by endometriosis. The aim of the present study was to understand the impact of endometriosis on implantation, pregnancy and live birth rates in menopausal recipients. A total of 240 menopausal recipients of donated sibling oocytes were divided into two groups. Group I consisted of 120 recipients diagnosed with endometriosis and group II consisted of 120 controls. The pregnancy and implantation rates were significantly lower in the endometriosisgroup compared to the control group (45.00% versus 58.33%, P=0.039) and (23.81% versus 31.48%, P=0.019) respectively. In oocyte donation cycles, a recipient’s history of endometriosis might have a negative impact on implantation, pregnancy and live birth rates, even in menopausal women.

 

 

 

Hum Immunol. 2013 Jan;74(1):93-7. doi: 10.1016/j.humimm.2012.09.007. Epub 2012 Sep 20.

TYK2 rs34536443 polymorphism is associated with a decreased susceptibility to endometriosis-related infertility.

Peluso C1Christofolini DMGoldman CSMafra FACavalcanti VBarbosa CPBianco B.

 

Abstract

INTRODUCTION:

Tyrosine kinase 2 gene (TYK2) is part of the janus kinase (JAK) that binds to the type I interferon-α receptor (IFNAR) on the cell surface of IFN-producing cells, and have crucial importance in the etiology of autoimmune and inflammatory diseases. Many polymorphisms of the TYK2 gene have been identified, and recently, a number of case-control studies were conducted to investigate the association of these polymorphisms with autoimmune and inflammatory diseases, with conflicting results. Based on these observations, we hypothesized that the TYK2 polymorphisms (rs34536443, rs2304256, rs280523, rs12720270 and rs12720356) might be involved in the pathogenesis of endometriosis and/or infertility.

METHODS:

Genetic association study comprising 275 infertile women with endometriosis, 92 women with idiopathic infertility and 307 fertile women as controls. TYK2 polymorphisms were identified by TaqMan PCR. Genotype distribution, allele frequency and haplotype analysis of the TYK2 polymorphisms were performed. A p-value <0.05 was considered significant.

RESULTS:

Single-marker analysis revealed that TYK2 rs34536443 was significantly associated with protection against endometriosis-related infertility, especially in moderate/severe disease (p = 0.002; OR = 0.24, 95% IC = 0.09-0.62). No difference was found considering the infertile group without endometriosis. No associations were found considering rs2304256, rs280523, rs12720270 and rs12720356 either for endometriosis-related infertility group or idiopathic infertility group. Haplotype analysis of five TYK2 polymorphisms identified a haplotype “CTATG” associated with protection against endometriosis-related infertility, especially in moderate/severe disease (p = 0.027).

CONCLUSION:

This is the first study to report an association between TYK2 polymorphisms and endometriosisand/or infertility. These findings require replication in other populations but suggest the TYK2 rs34536443 polymorphisms and “CTATG” haplotype can be associated with a decreased susceptibility to endometriosis-related infertility in Brazilian women.

 

 

 

Arch Gynecol Obstet. 2013 Feb;287(2):301-5. doi: 10.1007/s00404-012-2565-2. Epub 2012 Sep 22.

Clinical manifestations of abdominal wall endometriosis: a single center experience.

Kang J1Baek JHLee WSCho THLee JNLee WKChung M.

 

Abstract

OBJECTIVE:

This study aimed to investigate the clinical manifestations and treatment outcomes of abdominal wall endometriosis (AWE).

MATERIALS AND METHODS:

Patients diagnosed with AWE at the Gil Medical Center from January 2002 to September 2010 were retrospectively reviewed.

RESULTS:

Thirty-seven women were treated for AWE during the study period. Median age was 34 (range 24-45) years, and median duration from last pelvic surgery until symptom onset was 30 (range 6-96) months. The most common initial symptom was a palpable mass (36, 97.2 %), followed by cyclic or spontaneous pain (21, 56.8 %). Preoperative diagnoses were accurate in 20 of 29 patients (68.9 %), who underwent a preoperative imaging study. The accuracy of abdominal US was 80 % (12/15). All patients underwent wide excision, and the median tumor size was 3.5 (range 1.0-10.0) cm. One patient experienced recurrence at 34 months postoperatively.

CONCLUSIONS:

Physicians should be aware of AWE in any woman presenting with palpable mass and/or pain at the abdominal wall, especially after pelvic surgery. Adequate preoperative estimation and wide excision might be essential for the treatment of AWE.

 

 

Hum Reprod. 2012 Dec;27(12):3432-9. doi: 10.1093/humrep/des332. Epub 2012 Sep 20.

How common is adenomyosis? A prospective study of prevalence using transvaginal ultrasound in a gynaecology clinic.

Naftalin J1Hoo WPateman KMavrelos DHolland TJurkovic D.

 

Abstract

STUDY QUESTION:

What is the prevalence of adenomyosis in a population of women attending a general gynaecological clinic?

SUMMARY ANSWER:

Adenomyosis was present in 206 of 985 [20.9%; 95% confidence interval (CI): 18.5-23.6%] women included in the study.

WHAT IS KNOWN ALREADY:

Previous studies of occurrence of adenomyosis have been limited to women who underwent hysterectomy, which is likely to overestimate its prevalence compared with the general population of women. There are no large prospective studies on the prevalence of adenomyosis, either in the general population of women or in a general gynaecology clinic setting.

STUDY DESIGN, SIZE, DURATION:

This was a prospective observational study set in the general gynaecology clinic of a university teaching hospital between January 2009 and January 2010.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

There were 985 consecutive women who attended the clinic and underwent structured clinical and transvaginal ultrasound examination in accordance with the study protocol. Morphological features of adenomyosis were systematically recorded with the ultrasound scan to determine its prevalence and factors which may affect its occurrence.

MAIN RESULTS AND THE ROLE OF CHANCE:

Adenomyosis was present in 206/985 [20.9% (95% CI: 18.5-23.6%)] women included in the study. Multivariate analysis showed that the prevalence of adenomyosis was significantly associated with women’s age, gravidity and pelvic endometriosis (P< 0.001). In women who subsequently underwent hysterectomy, there was a good level of agreement between the ultrasound and histological diagnosis of adenomyosis [κ = 0.62 (P = 0.001), 95% CI (0.324, 0.912)].

LIMITATIONS, REASONS FOR CAUTION:

Our estimate of prevalence of adenomyosis is likely to be higher than in the general population as we studied symptomatic women attending a gynaecology clinic.

WIDER IMPLICATIONS OF THE FINDINGS:

Better estimates of the prevalence of adenomyosis can improve our understanding of the burden of the disease, help to identify women at high risk of developing the condition and facilitate the development of preventative strategies and effective treatment.

STUDY FUNDING/COMPETING INTEREST(S):

The authors have no competing interests to declare. The study was not supported by an external grant.

 

 

 

Hum Reprod. 2012 Dec;27(12):3417-24. doi: 10.1093/humrep/des331. Epub 2012 Sep 20.

Role of prostaglandin E2 in bacterial growth in women with endometriosis.

Khan KN1Kitajima MYamaguchi NFujishita ANakashima MIshimaru TMasuzaki H.

 

Abstract

STUDY QUESTION:

Can prostaglandin E(2) (PGE(2)) in menstrual and peritoneal fluid (PF) promote bacterial growth in women with endometriosis?

SUMMARY ANSWER:

PGE(2) promotes bacterial growth in women with endometriosis.

WHAT IS KNOWN ALREADY:

Menstrual blood of women with endometriosis is highly contaminated with Escherichia coli (E. coli) compared with that of non-endometriotic women: E. coli-derived lipopolysaccharide (LPS) promotes the growth of endometriosis.

STUDY DESIGN, SIZE AND DURATION:

Case-controlled biological research with a prospective collection of body fluids and endometrial tissues from women with and without endometriosis with retrospective evaluation.

PARTICIPANTS/MATERIALS, SETTING AND METHODS:

PF and sera were collected from 58 women with endometriosis and 28 women without endometriosis in an academic research laboratory. Menstrual blood was collected from a proportion of these women. Macrophages (Mφ) from PF and stromal cells from eutopic endometria were isolated in primary culture. The exogenous effect of PGE(2) on the replication of E. coli was examined in a bacterial culture system. Levels of PGE(2) in different body fluids and in the culture media of Mφ and stromal cells were measured by ELISA. The effect of PGE(2) on the growth of peripheral blood lymphocytes (PBLs) was examined.

MAIN RESULTS AND THE ROLE OF CHANCE:

The PGE(2) level was 2-3 times higher in the menstrual fluid (MF) than in either sera or in PF. A significantly higher level of PGE(2) was found in the MF and PF of women with endometriosis than in control women (P < 0.05 for each). Exogenous treatment with PGE(2) dose dependently increased E. coli colony formation when compared with non-treated bacteria. PGE(2)-enriched MF was able to stimulate the growth of E. coli in a dilution-dependent manner; this effect was more significantly enhanced in women with endometriosis than in control women (P < 0.05). PGE(2) levels in the culture media of LPS-treated Mφ/stromal cells were significantly higher in women with endometriosis than in non-endometriosis (P < 0.05 for each). Direct application of PGE(2) and culture media derived from endometrial Mφ or stromal cells significantly suppressed phytohemagglutinin-stimulated growth of PBLs.

LIMITATIONS AND REASONS FOR CAUTION:

Further studies are needed to examine the association between PGE(2)-stimulated growth of E. coli and endotoxin level and to investigate the possible occurrence of sub-clinical infection within vaginal cavity.

WIDER IMPLICATIONS OF THE FINDINGS:

Our findings may provide some new insights to understand the physiopathology or pathogenesis of the mysterious disease endometriosis and may hold new therapeutic potential.

STUDY FUNDING/COMPETING INTEREST(S):

This work was supported by grants-in-aid for Scientific Research from the Ministry of Education, Sports, Culture, Science and Technology of Japan. There is no conflict of interest related to this study.

 

 

Ultrasound Obstet Gynecol. 2013 Jun;41(6):685-91. doi: 10.1002/uog.12305.

Prediction of pouch of Douglas obliteration in women with suspected endometriosis using a new real-time dynamic transvaginal ultrasound technique: the sliding sign.

Reid S1Lu CCasikar IReid GAbbott JCario GChou DKowalski DCooper MCondous G.

 

Abstract

OBJECTIVE:

To evaluate preoperative real-time dynamic transvaginal sonography (TVS) in the prediction of pouch of Douglas (POD) obliteration in women undergoing laparoscopy for suspected endometriosis.

METHODS:

This was a multicenter prospective observational study undertaken from January 2009 to November 2011. All women with symptoms suggestive of endometriosis who were scheduled for laparoscopy underwent detailed preoperative TVS, in particular to ascertain whether the POD was obliterated. POD obliteration was assessed using a real-time TVS technique called the ‘sliding sign’. Preoperative TVS sliding sign findings were then compared to gold standard laparoscopic POD findings.

RESULTS:

One hundred consecutive women with preoperative TVS and laparoscopic outcomes were included in the final analysis. Mean age was 32.8 years and mean age at diagnosis of endometriosis was 27.4 years. At laparoscopy, 84/100 (84%) were found to have some form of endometriosis (73% peritoneal endometriosis, 35% ovarian endometrioma(s), 33% deep infiltrating endometriosis). At laparoscopy, 30/100 (30%) had an obliterated POD and 19/30 (63.3%) of these women also had evidence of bowel endometriosis. The sonographic sliding sign technique had an accuracy of 93.0%, sensitivity of 83.3%, specificity of 97.1%, positive predictive value of 92.6%, negative predictive value of 93.2%, positive likelihood ratio of 29.2 and negative likelihood ratio of 0.17 in the prediction of POD obliteration (P = 1.8E-16).

CONCLUSIONS:

Preoperative real-time dynamic TVS evaluation using the sliding sign seems to establish with a high degree of certainty whether the POD is obliterated. Given the increased risk of deep infiltrating endometriosisin women with POD obliteration, the TVS sliding sign technique may also be useful in the identification of women who may be at a higher risk for bowel endometriosis.

 

 

 

Biometrics. 2012 Dec;68(4):1294-302. doi: 10.1111/j.1541-0420.2012.01789.x. Epub 2012 Sep 24.

Estimating diagnostic accuracy of raters without a gold standard by exploiting a group of experts.

Zhang B1Chen ZAlbert PS.

 

Abstract

In diagnostic medicine, estimating the diagnostic accuracy of a group of raters or medical tests relative to the gold standard is often the primary goal. When a gold standard is absent, latent class models where the unknown gold standard test is treated as a latent variable are often used. However, these models have been criticized in the literature from both a conceptual and a robustness perspective. As an alternative, we propose an approach where we exploit an imperfect reference standard with unknown diagnostic accuracy and conduct sensitivity analysis by varying this accuracy over scientifically reasonable ranges. In this article, a latent class model with crossed random effects is proposed for estimating the diagnostic accuracy of regional obstetrics and gynaecological (OB/GYN) physicians in diagnosing endometriosis. To avoid the pitfalls of models without a gold standard, we exploit the diagnostic results of a group of OB/GYN physicians with an international reputation for the diagnosis of endometriosis. We construct an ordinal reference standard based on the discordance among these international experts and propose a mechanism for conducting sensitivity analysis relative to the unknown diagnostic accuracy among them. A Monte Carlo EM algorithm is proposed for parameter estimation and a BIC-type model selection procedure is presented. Through simulations and data analysis we show that this new approach provides a useful alternative to traditional latent class modeling approaches used in this setting.

 

 

 

Reprod Biol Endocrinol. 2012 Sep 24;10:84. doi: 10.1186/1477-7827-10-84

Genome-wide expressions in autologous eutopic and ectopic endometrium of fertile women with endometriosis.

Khan MA1Sengupta JMittal SGhosh D.

 

Abstract

BACKGROUND:

In order to obtain a lead of the pathophysiology of endometriosis, genome-wide expressional analyses of eutopic and ectopic endometrium have earlier been reported, however, the effects of stages of severity and phases of menstrual cycle on expressional profiles have not been examined. The effect of genetic heterogeneity and fertility history on transcriptional activity was also not considered. In the present study, a genome-wide expression analysis of autologous, paired eutopic and ectopic endometrial samples obtained from fertile women (n=18) suffering from moderate (stage 3; n=8) or severe (stage 4; n=10) ovarian endometriosisduring proliferative (n=13) and secretory (n=5) phases of menstrual cycle was performed.

METHODS:

Individual pure RNA samples were subjected to Agilent’s Whole Human Genome 44K microarray experiments. Microarray data were validated (P<0.01) by estimating transcript copy numbers by performing real time RT-PCR of seven (7) arbitrarily selected genes in all samples. The data obtained were subjected to differential expression (DE) and differential co-expression (DC) analyses followed by networks and enrichment analysis, and gene set enrichment analysis (GSEA). The reproducibility of prediction based on GSEA implementation of DC results was assessed by examining the relative expressions of twenty eight (28) selected genes in RNA samples obtained from fresh pool of eutopic and ectopic samples from confirmed ovarian endometriosis patients with stages 3 and 4 (n=4/each) during proliferative and secretory (n=4/each) phases.

RESULTS:

Higher clustering effect of pairing (cluster distance, cd=0.1) in samples from same individuals on expressional arrays among eutopic and ectopic samples was observed as compared to that of clinical stages of severity (cd=0.5) and phases of menstrual cycle (cd=0.6). Post hoc analysis revealed anomaly in the expressional profiles of several genes associated with immunological, neuracrine and endocrine functions and gynecological cancers however with no overt oncogenic potential in endometriotic tissue. Dys-regulation of three (CLOCK, ESR1, and MYC) major transcription factors appeared to be significant causative factors in the pathogenesis of ovarian endometriosis. A novel cohort of twenty-eight (28) genes representing potential marker for ovarian endometriosis in fertile women was discovered.

CONCLUSIONS:

Dysfunctional expression of immuno-neuro-endocrine behaviour in endometrium appeared critical to endometriosis. Although no overt oncogenic potential was evident, several genes associated with gynecological cancers were observed to be high in the expressional profiles in endometriotic tissue.

 

 

 

Skinmed. 2012 Jul-Aug;10(4):248-50.

Umbilical endometriosis in a woman with bicornuate uterus.

Baird D1Klepeiss SWehler AHarkins GAnderson B.

 

Abstract

A 39-year-old woman presented for evaluation of a tender nodule on the umbilicus that had been present for 6 months. She stated that it had slowly been increasing in size and would occasionally open up and crust over with dried blood. Physical examination revealed a 4-mm firm, tender, brown papule in the umbilicus (Figure 1). She had a history of chronic pelvic pain and exploratory laparoscopy for endometriosis 10 years prior, at which time the diagnosis ofa bicornuate uterus was made. Subsequently, hysterectomy was performed (Figure 2) at which time the entire umbilical lesion was excised. Histopathology revealed branching tubular glands in the dermis lined by stratified columnar epithelium, surrounded by small cells with scant cytoplasm, characteristic of proliferative-phase endometrial stroma (Figure 3 and Figure 4). These findings were consistent with a diagnosis of umbilical endometriosis (Villar’s nodule). Subsequent examination revealed no evidence of recurrence.

 

 

 

Hum Reprod. 2012 Dec;27(12):3616-21. doi: 10.1093/humrep/des329. Epub 2012 Sep 25

No evidence for genetic association with the let-7 microRNA-binding site or other common KRAS variants in risk of endometriosis.

Luong HT1Nyholt DRPainter JNChapman BKennedy STreloar SAZondervan KTMontgomery GW.

 

Abstract

STUDY QUESTION:

Is there a contribution of the minor allele at the KRAS single nucleotide polymorphism (SNP) rs61764370 in the let-7 microRNA-binding site to endometriosis risk?

SUMMARY ANSWER:

We found no evidence for association between endometriosis risk and rs61764370 or any other SNPs in KRAS.

WHAT IS KNOWN ALREADY:

The rs61764370 SNP in the 3′ untranslated region of the KRAS gene is predicted to disrupt a complementary binding site (LCS6) for the let-7 microRNA, and was recently reported to be at a high frequency (31%) in 132 women of varying ancestry with endometriosis compared with frequencies in a database of population controls (up to 7.6% depending on ancestry), suggesting a strong effect of this KRAS SNP in the aetiology of endometriosis.

STUDY DESIGN, SIZE AND DURATION:

This was a case-control study with a total of 11 206 subjects. The study was performed between February 2012 and July 2012. PARTICIPANTS/MATERIALS, SETTINGAND METHODS: We first investigated a possible association between common markers in KRAS and endometriosis risk from our genome-wide association (GWA) data in 3194 surgically confirmed endometriosis cases and 7060 controls of European ancestry. Although rs61764370 was not genotyped on the GWA arrays, five SNPs typed in the study were highly correlated with this variant. The rs61764370 and two SNPs highly correlated with rs61764370 were then genotyped in 933 endometriosis cases and 952 controls using the Sequenom MassARRAY platform.

MAIN RESULTS AND THE ROLE OF CHANCE:

There was no evidence for an association between rs61764370 and endometriosis risk P = 0.411 and odds ratio = 1.10 (95% confidence intervals: 0.88-1.36). We also found no evidence for an association between the highly correlated SNP rs17387019 and endometriosis. Their minor allele frequencies in cases and controls were of 0.087-0.091 similar to the population frequency reported previously for this variant in controls. Analyses of endometriosis cases with revised American Fertility Society stage III/IV disease also showed no evidence for an association between these SNPs and endometriosis risk.

LIMITATIONS AND REASONS FOR CAUTION:

The GWA and genotyped data sets were not independent since individuals and cases from some families overlap. Controls in our GWA study were not screened for endometriosis.

WIDER IMPLICATIONS OF THE FINDINGS:

The key SNP, rs61764370, was genotyped in a subset of samples. Our results do not support the suggestion that carrying the minor allele at rs61764370 contributes to a significant number of endometriosis cases and rs61764370 is, therefore, unlikely to be a useful marker of endometriosis risk.

STUDY FUNDING/COMPETING INTEREST(S):

The research was funded by grants from the Australian National Health and Medical Research Council and Wellcome Trust. None of the authors has competing interests for the study.

 

 

Virchows Arch. 2012 Nov;461(5):589-99. doi: 10.1007/s00428-012-1301-4. Epub 2012 Sep 6.

Survivin, MMP-2, MT1-MMP, and TIMP-2: their impact on survival, implantation, and proliferation of endometriotic tissues.

Londero AP1Calcagno AGrassi TMarzinotto SOrsaria MBeltrami CAMarchesoni DMariuzzi L

 

Abstract

In order to study survivin, matrix metalloproteinases (MMP-2), membranous type 1 matrix metalloproteinase (MT1-MMP), and tissue inhibitor metalloproteinase-2 (TIMP-2) expression immunohistochemically in endometriotic tissues and normal endometrium, our retrospective study considered 194 patients affected by endometriosis and 71 patients with normal endometrium. Tissue microarrays were created from paraffin-embedded blocks; immunohistochemistry was used to assess protein expression. In endometriotic tissues, survivin was expressed at a higher level than in normal endometrium; its glandular expression level was higher in non-ovarian than in ovarian endometriotic tissues and lower in stromal components. Endometrial tissues from women without endometriosisand endometriotic tissues had different matrix metalloproteinase expression profiles. MMP-2 and MT1-MMP correlated with TIMP-2 in endometriotic tissues. Furthermore, in endometriotic tissues, expression of survivin, aurora B kinase, and Ki-67 showed a significant positive correlation, which indicates a role in cellular proliferation that could be closely linked to its anti-apoptotic activity in endometriosis development. Our results imply a role for matrix metalloproteinases in endometriosis invasiveness; correlation of their expression with that of TIMP-2 underscores its possible key regulatory role.

 

 

Cell Death Dis. 2012 Sep 27;3:e392. doi: 10.1038/cddis.2012.116.

TP53 PIN3 and PEX4 polymorphisms and infertility associated with endometriosis or with post-in vitro fertilization implantation failure.

Paskulin DD1Cunha-Filho JSSouza CABortolini MCHainaut PAshton-Prolla P.

 

Abstract

p53 has a crucial role in human fertility by regulating the expression of leukemia inhibitory factor (LIF), a secreted cytokine critical for blastocyst implantation. To examine whether TP53 polymorphisms may be involved with in vitro fertilization (IVF) failure and endometriosis (END), we have assessed the associations between TP53 polymorphism in intron 2 (PIN2; G/C, intron 2), PIN3 (one (N, non-duplicated) or two (D, duplicated) repeats of a 16-bp motif, intron 3) and polymorphism in exon 4 (PEX4; C/G, p.P72R, exon 4) in 98 women with END and 115 women with post-IVF failure. In addition, 134 fertile women and 300 women unselected with respect to fertility-related features were assessed. TP53 polymorphisms and haplotypes were identified by amplification refractory mutation system polymerase chain reaction. TP53 PIN3 and PEX4 were associated with both END (P=0.042 and P=0.007, respectively) and IVF (P=0.004 and P=0.009, respectively) when compared with women both selected and unselected for fertility-related features. Haplotypes D-C and N-C were related to higher risk for END (P=0.002, P=0.001, respectively) and failure of IVF (P=0.018 and P=0.002, respectively) when compared with the Fertile group. These results support that specific TP53 haplotypes are associated with an increased risk of END-associated infertility and with post-IVF failure.

 

 

J Med Case Rep. 2012 Sep 26;6:327. doi: 10.1186/1752-1947-6-327.

Chronic abdominal pain, appendiceal mucinous neoplasm, and concurrent intestinal endometriosis: a case report.

Kurogochi T1Fujita TIida NEtoh KOgawa MYanaga K.

 

Abstract

INTRODUCTION:

Although both appendiceal tumor and intestinal endometriosis have been reported as rare causes of abdominal pain, the coexistence of appendiceal mucinous neoplasm and ileal endometriosis has not previously been reported.

CASE PRESENTATION:

A 41-year-old Japanese woman presented with a positive fecal occult blood test and a 3-year history of menstruation-related lower abdominal pain. A colonoscopy demonstrated extrinsic compression of the cecum, suggesting a mass arising from the appendix or adjacent structures. Abdominal imaging showed a 6-cm cystic mass with intraluminal thick fluids originating from the appendix. At ileocecal resection for an appendiceal tumor, a 2-cm mass in the terminal ileum was incidentally found, which was included in the surgical specimen. Microscopic examination confirmed a diagnosis of a mucinous neoplasm of the appendix with endometriosis of the terminal ileum.

CONCLUSIONS:

To avoid urgent surgery for subsequent serious events associated with disease progression, appendiceal tumor and intestinal endometriosis should be ruled out in patients with chronic abdominal pain.

 

 

 

Aust N Z J Obstet Gynaecol. 2012 Dec;52(6):513-22. doi: 10.1111/j.1479-828X.2012.01480.x. Epub 2012 Sep 27.

Endometriosis and infertility – a consensus statement from ACCEPT (Australasian CREI Consensus Expert Panel on Trial evidence).

Koch J1Rowan KRombauts LYazdani AChapman MJohnson N.

 

Abstract

Endometriosis is common in women with infertility but its management is controversial and varied. This article summarises the consensus developed by a group of Australasian subspecialists in reproductive endocrinology and infertility (the Australasian CREI Consensus Expert Panel on Trial evidence group) on the evidence concerning the management of endometriosis in infertility. Endometriosis impairs fertility by causing a local inflammatory state, inducing progesterone resistance, impairing oocyte release and reducing sperm and embryo transport. Medical treatments have a limited role, whereas surgical and assisted reproductive treatments improve pregnancy rates. The role of surgery for deep infiltrative endometriosis and repeat surgery requires further evaluation and there is insufficient evidence for the use of anti-adhesives to improve fertility. Intrauterine insemination (IUI) and in vitro fertilisation (IVF) improve pregnancy rates but women with endometriosis have lower pregnancy rates than those with other causes of infertility. The decision about whether to operate or pursue assisted reproduction will depend on a variety of factors such as the patient’s symptoms, the presence of complex masses on ultrasound, ovarian reserve and ovarian access for IVF, risk of surgery and cost. Some women with infertility and endometriosis may benefit from a combination of assisted reproduction and surgery.

 

 

 

Eur J Obstet Gynecol Reprod Biol. 2013 Jan;166(1):81-5. doi: 10.1016/j.ejogrb.2012.09.003. Epub 2012 Sep 25.

Polymorphic variants of DNMT3A and the risk of endometriosis.

Szczepańska M1Mostowska AWirstlein PMalejczyk JPłoski RSkrzypczak JJagodziński PP.

 

Abstract

OBJECTIVE:

Overexpression of DNA methyltransferase 3A (DNMT3A) and aberrant methylation of various genes in eutopic endometrium have been demonstrated in women with endometriosis. We aimed to study whether DNMT3A polymorphisms could be a genetic risk factor for endometriosis and endometriosis-related infertility.

STUDY DESIGN:

We studied 5 SNPs (rs2289195, rs7590760, rs13401241, rs749131 and rs1550117) located in the DNMT3A gene in 357 women with endometriosis and 640 controls.

RESULTS:

We did not observe significant differences between genotype and allele frequencies of rs2289195, rs7590760, rs13401241, rs749131 and rs1550117 SNPs in women with endometriosis, endometriosis-related infertility, and controls. The lowest p values of the trend test were observed for DNMT3A rs1550117 in endometriosis and endometriosis-related infertility (p(trend)=0.049 and p(trend)=0.055, respectively).

CONCLUSIONS:

Our results did not supply evidence for the contribution of SNPs located in DNMT3A to either endometriosis or endometriosis-related infertility.

 

 

Int J Gynecol Pathol. 2012 Nov;31(6):517-23. doi: 10.1097/PGP.0b013e31824fe269.

Immunohistochemical localization of HE4 in benign, borderline, and malignant lesions of the ovary.

Georgakopoulos P1Mehmood SAkalin AShroyer KR.

 

Abstract

Despite advances in the development of novel methods to improve treatment, ovarian carcinoma is still the leading cause of gynecologic cancer death in the United States and other industrialized nations. Improvements in the clinical outcome of ovarian cancer will be achieved if methods can be developed to enable the detection of these tumors at the earliest possible stage. Thus, it is critically important to identify and validate new biomarkers of ovarian cancer. HE4 expression was defined by immunohistochemical analysis of a wide range of benign, borderline, and malignant ovarian lesions, including serous, endometrioid, mucinous, and clear cell lesions of the ovary and in primary tubal carcinomas and the normal fallopian tube. At the cellular level, HE4 was highly expressed in malignant ovarian tumors and in a wide range of benign and borderline ovarian lesions. In addition, HE4 was highly expressed in primary fallopian tube carcinomas and benign fallopian tubal epithelial cells. These results support the conclusion that HE4 is widely expressed in most benign, borderline, and malignant lesions of the ovary and the fallopian tube. The detection of HE4 expression at high levels in some benign lesions and normal tissues suggests that HE4 could have limited specificity as a marker of ovarian or tubal carcinoma. Furthermore, the relatively weak expression that was observed in many ovarian carcinomas indicates that HE4 could fail to detect some cases of primary or recurrent disease.

 

 

 

 

nt J Gynecol Pathol. 2012 Nov;31(6):524-31. doi: 10.1097/PGP.0b013e31824fe2aa.

Prevalence of loss of expression of DNA mismatch repair proteins in primary epithelial ovarian tumors.

Lu FI1Gilks CBMulligan AMRyan PAllo GSy KShaw PAPollett AClarke BA.

 

Abstract

Although different histologic subtypes of epithelial ovarian tumors have long been recognized, their molecular abnormalities have not been fully defined. We examined the prevalence of DNA mismatch repair (MMR) protein loss in these tumors. Tissue microarrays (TMA) of suspected ovarian carcinomas were stained for hMLH1, hMSH2, hMSH6, and hPMS2 and scored separately by 2 groups of investigators. Loss of staining (negative) or discrepant staining results on TMA were verified on whole-section slides. Intact (positive) staining results were also verified for an additional 25 randomly selected cases. Clinical data for cases demonstrating MMR protein loss were collected. A second set of TMA composed purely of mucinous tumors was also stained for antibodies to MMR proteins and scored by 1 group of investigators. TMA was an effective method for screening a large number of ovarian tumors for MMR protein expression, with a sensitivity of 100% for all 4 MMR proteins, and a specificity of 22.2%-53.8% for different MMR proteins. Of the primary epithelial tumors of the ovary, loss of expression of MMR proteins was significantly more common in the endometriosis-associated carcinomas (7/69; 10.1%) than in high-grade serous carcinomas (2/182; 1.1%): P=0.0021. The former group also showed more frequent loss of MMR proteins compared with mucinous intestinal-type carcinomas (0/32; P=0.0940). Cases within the group of endometriosis-associated carcinomas were endometrioid (2/29 cases), clear cell (1/27 cases), undifferentiated (1/8 cases), and mixed carcinomas with an endometrioid, clear cell, and/or undifferentiated component (3/5 cases). No loss of MMR protein expression was identified in epithelial tumors of other histologic subtypes. Our study demonstrated the loss of MMR protein expression in 10.1% of endometriosis-associated ovarian carcinomas. These results raise the possibility of selective screening for Lynch syndrome in patients with these types of ovarian carcinoma.

 

 

 

Hum Reprod. 2013 Jan;28(1):119-24. doi: 10.1093/humrep/des346. Epub 2012 Sep 27.

CD4 CD25 FOXP3 regulatory T cells in peripheral blood and peritoneal fluid of patients with endometriosis.

Olkowska-Truchanowicz J1Bocian KMaksym RBBiałoszewska AWłodarczyk DBaranowski WZąbek JKorczak-Kowalska GMalejczyk J.

 

Abstract

STUDY QUESTION:

Is endometriosis associated with changes in CD4⁺ CD25⁺ FOXP3⁺ regulatory T cells (Treg cells)?

SUMMARY ANSWER:

Endometriosis is associated with disturbed compartmentalization of CD25(high) FOXP3⁺ Treg cells.

WHAT IS KNOWN ALREADY:

Endometriosis is associated with an abrogated immune response and displays some features of an autoimmune disorder. Treg cells play a part in the development of autoimmune reactions; however, their role in pathogenesis of endometriosis is still poorly recognized.

STUDY DESIGN, SIZE AND DURATION:

Case-control study comparing 17 women with laparoscopically and histopathologically confirmed ovarian endometriosis with 15 control women without visible endometriosis foci, pelvic inflammation or related pathology who were subjected to laparoscopic surgery between 2010 and 2011.

PARTICIPANTS/MATERIALS, SETTING AND METHODS:

Peripheral blood and peritoneal fluid were collected during laparoscopy and T cell subpopulations were analysed by flow cytometry using specific monoclonal antibodies recognizing CD4⁺, CD25⁺ and FOXP3⁺ markers.

MAIN RESULTS:

The percentage of CD25(high) FOXP3⁺ Treg cells was significantly decreased in the peripheral blood of women with ovarian endometriosis compared with control women. On the other hand, the proportion of these cells was significantly increased in the peritoneal fluid of women with endometriosis.

LIMITATIONS, REASONS FOR CAUTION:

The present study is limited to patients with ovarian endometrioma and further investigations are needed, including patients with lower grade of endometriosis.

WIDER IMPLICATIONS OF THE FINDINGS:

The present results suggest that Treg cells may play a part in immunopathogenesis of endometriosis being responsible for abrogated local cellular immune responses and facilitation and development of autoimmune reactions. Treg cells may be thus a potential target in the treatment of endometriosis.

STUDY FUNDING/COMPETING INTEREST(S):

This study was supported by 1M15/N/2011 and NK1W grants from the I Faculty of Medicine, Warsaw Medical University. None of the authors has any competing interests to declare.

 

 

 

 

 

J Gynecol Surg. 2012 Oct;28(5):369-371.

Hysteroscopic Removal of Cervical Ectopic Pregnancy Following Failed Intramuscular/Intra-Sac Methotrexate: A Case Report.

Kofinas JD1Purisch SE1Brandt JS1Montes M2.

 

Abstract

Background: Cervical pregnancy is a diagnosis associated with significant morbidity, specifically life-threatening hemorrhage that potentially requires hysterectomy to prevent maternal death. Conservative and fertility-sparing management strategies are poorly described in the literature, and there is no clear standard of care. Case: The patient was a 34-year-old gravida 1, para 0 who had conceived spontaneously after laparoscopic treatment of endometriosis, and was found to have cervical pregnancy. She received both intramuscular and intra-sac methotrexate, with no resolution of the ectopic pregnancy. The pregnancy was removed hysteroscopically. Results: Subsequently, the patient was able to achieve a normal clinical pregnancy with ovulation induction/intrauterine insemination. This pregnancy was carried to term. Conclusions: Although cervical pregnancy is particularly hazardous and potentially fatal, conservative/fertility-sparing management of these pregnancies can be successful.

 

 

Fertil Steril. 2013 Jan;99(1):219-26. doi: 10.1016/j.fertnstert.2012.08.055. Epub 2012 Sep 29.

Interleukin-19 and interleukin-22 serum levels are decreased in patients with ovarian endometrioma.

Santulli P1Borghese BChouzenoux SStreuli IBorderie Dde Ziegler DWeill BChapron CBatteux F.

 

Abstract

OBJECTIVE:

To determine the serum levels of interleukin (IL)-10 family ILs in women with ovarian endometriosisand investigate the correlation of these levels with disease activity.

DESIGN:

A case-control laboratory study.

SETTING:

Tertiary-care university hospital.

PATIENT(S):

Two hundred nineteen women, with (n = 112) and without (n = 107) endometriosis.

INTERVENTION(S):

Complete surgical excision with pathological analysis.

MAIN OUTCOME MEASURE(S):

Blood samples were obtained during surgical procedures. IL-10, -19, -20, and -22 were assayed by ELISA in sera, and the concentrations correlated with the extent and the severity of the disease.

RESULT(S):

IL-19 was detectable in 18.3% and IL-22 in 47.9% of sera samples from all 219 women studied. Serum IL-19 was lower in women with endometriosis (median, 292.7 pg/mL; range, 32.2-1,339.3) than in endometriosis-free women (median, 1,035.8 pg/mL; range, 32.2-2,000.0). In addition, serum IL-22 levels were decreased in women affected by endometriosis (median, 352.0 pg/mL; range, 31.2-1,392.2) as compared with endometriosis-free women (median, 709.2 pg/mL; range, 73.3-2,012.0). We found significant correlations between serum IL-22 concentrations and intensity of deep dyspareunia (r = -0.303) and noncyclic chronic pelvic pain (r = -0.212). IL-19 was correlated with the intensity of deep dyspareunia (r = -0.749).

CONCLUSION(S):

Serum IL-19 and IL-22 are decreased in women with ovarian endometrioma. IL-10 family ILs may be involved in the pathogenesis of endometriosis.

 

 

PLoS One. 2012;7(9):e45223. doi: 10.1371/journal.pone.0045223. Epub 2012 Sep 18.

Pigment epithelium derived factor inhibits the growth of human endometrial implants in nude mice and of ovarian endometriotic stromal cells in vitro.

Sun Y1Che XZhu LZhao MFu GHuang XXu HHu FZhang X.

 

Abstract

Angiogenesis is a prerequisite for the formation and development of endometriosis. Pigment epithelium derived factor (PEDF) is a natural inhibitor of angiogenesis. We previously demonstrated a reduction of PEDF in the peritoneal fluid, serum and endometriotic lesions from women with endometriosis compared with women without endometriosis. Here, we aim to investigate the inhibitory effect of PEDF on human endometriotic cells in vivo and in vitro. We found that PEDF markedly inhibited the growth of human endometrial implants in nude mice and of ovarian endometriotic stromal cells in vitro by up-regulating PEDF expression and down-regulating vascular endothelial growth factor (VEGF) expression. Moreover, apoptotic index was significantly increased in endometriotic lesions in vivo and endometriotic stromal cells in vitro when treated with PEDF. In mice treated with PEDF, decreased microvessel density labeled by Von Willebrand factor but not by α-Smooth Muscle Actin was observed in endometriotic lesions. And it showed no increase in PEDF expression of the ovary and uterus tissues. These findings suggest that PEDF gene therapy may be a new treatment for endometriosis.

 

PLoS One. 2012;7(9):e45529. doi: 10.1371/journal.pone.0045529. Epub 2012 Sep 19.

Puerarin suppresses proliferation of endometriotic stromal cells partly via the MAPK signaling pathway induced by 17ß-estradiol-BSA.

Cheng W1Chen LYang SHan JZhai DNi JYu CCai Z.

 

Abstract

BACKGROUND:

Puerarin is a major isoflavonoid compound extracted from Radix puerariae. It has a weak estrogenic action by binding to estrogen receptors (ERs). In our early clinical practice to treat endometriosis, a better therapeutic effect was achieved if the formula of traditional Chinese medicine included Radix puerariae. The genomic and non-genomic effects of puerarin were studied in our Lab. This study aims to investigate the ability of puerarin to bind competitively to ERs in human endometriotic stromal cells (ESCs), determine whether and how puerarin may influence phosphorylation of the non-genomic signaling pathway induced by 17ß-estradiol conjugated to BSA (E(2)-BSA).

METHODOLOGY:

ESCs were successfully established. Binding of puerarin to ERs was assessed by a radioactive competitive binding assay in ESCs. Activation of the signaling pathway was screened by human phospho-kinase array, and was further confirmed by western blot. Cell proliferation was analyzed according to the protocol of CCK-8. The mRNA and protein levels of cyclin D1, Cox-2 and Cyp19 were determined by real-time PCR and western blotting. Inhibitor of MEK1/2 or ER antagonist was used to confirm the involved signal pathway.

PRINCIPAL FINDINGS:

Our data demonstrated that the total binding ability of puerarin to ERs on viable cells is around 1/3 that of 17ß-estradiol (E(2)). E(2)-BSA was able to trigger a rapid, non-genomic, membrane-mediated activation of ERK1/2 in ESCs and this phenomenon was associated with an increased proliferation of ESCs. Treating ESCs with puerarin abrogated the phosphorylation of ERK and significantly decreased cell proliferation, as well as related gene expression levels enhanced by E(2)-BSA.

CONCLUSIONS/SIGNIFICANCE:

Puerarin suppresses proliferation of ESCs induced by E(2)-BSA partly via impeding a rapid, non-genomic, membrane-initiated ERK pathway, and down-regulation of Cyclin D1, Cox-2 and Cyp19 are involved in the process. Our data further show that puerarin may be a new candidate to treat endometriosis.

 

 

Urologia. 2012 Jul;79(3):171-3. doi: 10.5301/RU.2012.9683. Epub 2012 Sep 21. Italian.

Urinary tract endometriosis.

Antonelli A1.

 

Abstract

Urinary endometriosis is a rare diagnosis which is becoming much more common at referral centres. The bladder and the pelvic ureter are the sites that can be affected, each posing to the urologist and gynecologist some specific diagnostic and therapeutic difficulties. Bladder endometriosis, indeed, usually causes lower urinary tract symptoms, has a typical appearance at imaging and can be an isolated presentation; ureteral location, at the contrary, often presents with a vague or aspecific symptomatology and is often associated to other pelvic locations, so that a careful evaluation of the urinary tract, preferably with NMR, is mandatory for severe pelvic endometriosis, also in the absence of symptoms. The treatment of bladder presentation is partial cystectomy, preferably via a laparoscopic approach, while ureteral endometriosis can require different surgical solutions, from ureterolysis to ureteral reimplantation, open, laparoscopic or robot-assisted, basing on its extent and on the need of additional procedures for other locations.

 

 

Urologia. 2012 Jul;79(3):171-3. doi: 10.5301/RU.2012.9689. Epub 2012 Sep 21. Italian.

Urinary tract endometriosis: anatomopathology features.

Pedruzzi E1Tardanico R.

 

Abstract

Endometriosis is a pathological entity characterized by the presence of endometrial glands and stroma in ectopic side, out of the uterus and the histological analysis represents the basic examination to a definitive diagnosis. The macroscopic and microscopic features to urological level are similar to those in the others sides and include not only the “usual” aspects of the pathology but also hyperplastic and metaplastic changes both in the glandular and stromal components.

 

 

Indian J Pathol Microbiol. 2012 Jul-Sep;55(3):326-32. doi: 10.4103/0377-4929.101738.

Clinicopathological spectrum of 19 adenosarcomas of female genital tract, including uncommon clinical associations and immunohistochemical profile, reviewed at a single institution.

Rekhi B1Deodhar KKMaheshwari AMenon SKerkar RBajpai JGhosh JGupta SEngineer RShrivastava SK.

 

Abstract

BACKGROUND:

Adenosarcomas of the female genital tract have been rarely documented as case series from our continent.

MATERIALS AND METHODS:

Over a seven-year period, 19 adenosarcomas were critically reviewed.

RESULTS:

Nineteen tumors occurred in the age range of 21-65 years (mean: 43), in the endometrium (8), endometrium and cervix (4), cervix (4), and ovary (3). Four cases displayed coexisting leiomyomas; two, adenomyosis; two on background endometriosis; and one in post-treated cervix carcinoma. Histopathologically, the tumors were low grade (10; 52.6%) and high grade (9; 47.3%), the latter with sarcomatous overgrowth (SO) (7/9 cases). Dedifferentiation (8, 42.1%) and conspicuous decidualization (2) were noted. Immunohistochemically, the tumors focally expressed CD10 (4/6), smooth muscle actin (SMA) (3/8), desmin (8/11); diffuse vimentin (7/7), and estrogen receptor/progesterone receptor (ER/PR) (2/4). Ki-67 (6 cases) varied 5-20%. Seventeen patients underwent surgery and four received adjuvant treatment (3/4 high-grade tumors). Five tumors recurred (4 high-grade tumors with SO) and one metastasized. Among 11 patients, five were alive with disease (AWD) (mean: 29.4 months) and six, free of disease (FOD) (mean: 15 months), the latter mostly with low-grade type tumors (83.3% cases).

CONCLUSIONS:

Diverse clinicopathological spectrum was noted within adenosarcomas. Low-grade tumors were less aggressive than high-grade ones, with SO. Immunohistochemically, lower CD10 and ER/PR positivity was noted in high-grade tumors. Surgery formed the mainstay of treatment. Adjuvant treatment was offered in high-grade subtypes, including in tumors with SO.

 

 

 

Magn Reson Med Sci. 2012;11(3):201-4.

MR imaging of polypoid endometriosis of the ovary.

Kozawa E1Inoue KIwasa NFujiwara KYasuda MTanaka JKimura F.

 

Abstract

We report a case of polypoid endometriosis of the ovary and correlate magnetic resonance (MR) and pathological findings. The endometriosis appeared as multiple polypoid areas along the wall of the ovarian cystic lesion with hyperintensity on T₂-weighted images and slight hyperintensity on diffusion-weighted images. However, the polypoid areas did not yield low apparent diffusion coefficient (ADC) values on ADC map images. These MR findings were similar to the signal intensity of the uterine endometrium, reflecting the presence of abundant endometrial glands.

 

 

Urologia. 2012 Jul;79(3):160-6. doi: 10.5301/RU.2012.9391. Italian.

Endometriosis: the gynecologist’s opinion.

Marana R1Lecca ABiscione AMuzii L.

 

 

Abstract

Endometriosis is defined as the presence of endometrial glands and stroma outside the uterine cavity. Endometriosis affects 7-10% of women of reproductive age, 60% of women with pelvic pain, and up to 50% of women with infertility. Etiology and pathogenesis of the disease are still unclear, with the theory of retrograde menstruation, and possibly associated cofactors, as the most important. The definitive method to diagnose endometriosis is visualization at surgery, preferably at laparoscopy, with histology confirmation of disease. The revised classification of the American Society for Reproductive Medicine is used to stage the disease and determine the patient’s prognosis. The treatment of the disease depends on the patient’s age, associated symptoms, and disease stage. Medical or surgical therapy may be used in case of pain associated with endometriosis, whereas surgery is the mainstay of treatment in case of endometriosis-associated infertility.

 

 

Contraception. 2013 Mar;87(3):273-9. doi: 10.1016/j.contraception.2012.08.039. Epub 2012 Oct 4

Added health benefits of the levonorgestrel contraceptive intrauterine system and other hormonal contraceptive delivery systems.

Fraser IS1.

 

Abstract

BACKGROUND:

It has been recognized for well over half a century that hormonal preparations designed as contraceptives are also capable of offering health benefits through the treatment and prevention of benign gynecological disease and even some systemic conditions. Increasing attention is now being paid to the extent and detail of such added health benefits, and it is becoming clear that the long-acting, low-dose, hormonal contraceptive delivery systems may offer particular advantages in this regard.

METHODS:

Conventional databases were thoroughly searched, especially for publications from 2006 to 2012, which addressed non-contraceptive-related indications for therapy and prevention.

RESULTS:

A considerable literature now exists to demonstrate the multiple and substantial noncontraceptive health benefits of long-acting progestogen-releasing systems, especially the levonorgestrel-releasing intrauterine system. These benefits mainly relate to disturbances of menstruation and related symptoms, such as heavy menstrual bleeding (due to many causes); iron deficiency; pelvic pain, especially around endometriosis; and endometrial hyperplasia. The long-acting estrogen-progestogen systems may carry similar added health benefits to those of the combined oral contraceptives, but data are still lacking.

CONCLUSION:

Added health benefits are now becoming an important part of the contraceptive choice equation, and the long-acting delivery systems are recognized as suitable primary therapies for a range of gynecological disorders.

 

 

 

 

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