Júlio César Rosa e Silva

Differentially expressed genes in eutopic and ectopic endometrium of women with endometriosis

OBJECTIVE To elucidate the potential mechanisms involved in the physiopathology of endometriosis. We analyzed the differential gene expression profiles of eutopic and ectopic tissues from women with endometriosis. DESIGN Prospective laboratory study. SETTING University hospital. PATIENT(S) Seventeen patients in whom endometriosis was diagnosed and 11 healthy fertile women. INTERVENTION(S) Endometrial biopsy specimens from the endometrium of healthy women without endometriosis and from the eutopic and ectopic endometrium tissues of patients with endometriosis were obtained in the early proliferative phase of the menstrual cycle. MAIN OUTCOME MEASURE(S) Six paired samples of eutopic and ectopic tissue were analyzed by subtractive hybridization. To evaluate the expression of genes found by rapid subtraction hybridization methods, we measured CTGF, SPARC, MYC, MMP, and IGFBP1 genes by real-time polymerase chain reaction in all samples. RESULT(S) This study identified 291 deregulated genes in the endometriotic lesions. Significant expression differences were obtained for SPARC, MYC, and IGFBP1 in the peritoneal lesions and for MMP3 in the ovarian endometriomas. Additionally, significant differences were obtained for SPARC and IGFBP1 between the peritoneal and ovarian lesions. No significant differences were found for the studied genes between the control and the eutopic endometrium. CONCLUSION(S) This study identified 291 genes with differential expression in endometriotic lesions. The deregulation of the SPARC, MYC, MMP3, and IGFBPI genes may be responsible for the loss of cellular homeostasis in endometriotic lesions.

REVIEWS: The Effects of Hypoestrogenism on the Vaginal Wall: Interference with the Normal Sexual Response

INTRODUCTION The sexual response depends on the adequate function of all systems related to the genital and extra-genital organs. Physiological conditions such as menopause can interfere with sexual expression because of central and peripheral changes. Genital effects of estrogen include vaginal trophism, lubrication, and local pleasure sensation in the sexual arousal phase. Hypoestrogenism causes changes in the four layers of the vaginal wall that may result in dyspareunia and a loss in the quality of the genital arousal response. AIM The purpose of this review is to highlight the changes in the vaginal wall caused by hypoestrogenism, its possible relationship with dyspareunia, and its repercussions for genital arousal. Treatments for hypoestrogenism are also discussed. METHODS We evaluated the data available in PubMed (1982-2008) and surveyed the reference list for relevant studies. Two reviewers analyzed the data independently. A study was considered to be of high quality if it had all three of the following characteristics: (i) prospective design; (ii) valid data; and (iii) adequate sample size. Reviews and experimental animal studies were also considered. MAIN OUTCOME MEASURES Normal genital morphology, hypoestrogenism and hormone replacement therapy were the focus of the studies reviewed in this paper. RESULTS Atrophy of the vaginal wall may be associated with dyspareunia and genital sexual arousal disorder, but psychological and sociocultural aspects must also be considered. Regardless, however, local estrogen therapy is useful in improving vaginal wall trophism and, thus, in improving the sexual response. CONCLUSIONS There are many possible alterations in the structure of the vaginal wall that are related to estrogen deficiency that may require medical intervention beyond the usual strategies used to attain adequate sexual function. Physicians should attempt to treat these alterations, and more research is needed to elucidate the physiopathology of dyspareunia and genital sexual arousal physiology.

Importance of pelvic muscle tenderness evaluation in women with chronic pelvic pain.

OBJECTIVE To determine the prevalence of pelvic muscle tenderness in women with chronic pelvic pain (CPP) and to assess the importance of evaluating muscle tenderness in such women. DESIGN Observational study of 48 healthy female volunteers and 108 women with CPP, who were clinically evaluated for pelvic muscle tenderness by two researchers blinded to all clinical data. RESULTS The frequency of clinically detected pelvic muscle tenderness was significantly higher in women with CPP than in healthy volunteers (58.3% vs 4.2%, P < 0.001). Among women with CPP, those with pelvic muscle tenderness had higher Beck Depression Index scores (22 [6-42] vs 13 [3-39], P = 0.02) and higher rates of dyspareunia (63.5% [40/63] vs 28.9% [13/45], P < 0.004) and constipation (46.0% [29/63] vs 26.7% [12/45], P = 0.05) than those without pelvic muscle tenderness. CONCLUSION Tenderness of pelvic muscles was highly prevalent among women with CPP and was associated with higher BDI scores and higher rates of dyspareunia and constipation. Determination of pelvic muscle tenderness may help in identifying women who require more intense treatment for CPP.

Ovarian reserve evaluation: state of the art

PurposeRevise role of hormonal basal and dynamic tests, as well as ultrasonographic measures as ovarian reserve markers, in order to provide better counseling to subfertile couples.MethodsReview of publications on the topic, with an emphasis on recent well designed articles.ResultsCurrently available ovarian reserve tests do not provide sufficient evidence to be solely considered ideal, even for premature ovarian senescence patients who do not present subfertility complaints. However, these markers occupy important place in initial approach to treatment of subfertile couples, predicting unsatisfactory results that could be improved by differentiated induction schemes and reducing excessive psychological and financial burdens, and adverse effects.ConclusionsIn order to remedy the limitations due to the scarcity of strong evidence about this topic, future studies should try to clarify predictive value of markers in groups of specific diseases-related subfertility and pay special attention to propaedeutic multivariate models including anti-Müllerian hormone and antral follicle count.

Positive correlation between serum and peritoneal fluid CA-125 levels in women with pelvic endometriosis

CONTEXT AND OBJECTIVE One of the diagnostic markers of endometriosis is CA-125, and elevated levels of this are caused by high concentrations in the ectopic endometrium. The objective of this study was to correlate CA-125 levels in serum and peritoneal fluid from women with and without pelvic endometriosis. DESIGN AND SETTING This was a prospective, cross-sectional, controlled study of consecutive patients undergoing laparoscopy for infertility, pelvic pain or tubal ligation, during early follicular phase, at the university hospital of Faculdade de Medicina de Ribeirão Preto. METHODS Fifty-two patients were divided into two groups: endometriosis group, consisting of 35 patients with biopsy-confirmed pelvic endometriosis, and control group, consisting of 17 patients without endometriosis. CA-125 levels in serum samples and peritoneal fluid were determined by chemiluminescence. RESULTS CA-125 levels in serum and peritoneal fluid were higher in patients with advanced pelvic endometriosis (means of 39.1 +/- 45.8 U/ml versus 10.5 +/- 5.9 U/ml in serum, p < 0.005; 1,469.4 +/- 1,350.4 U/ml versus 888.7 +/- 784.3 U/ml in peritoneal fluid, p < 0.05), and showed a positive correlation between each other (correlation coefficient (r) = 0.4880). Women with more advanced degrees of endometriosis showed higher CA-125 levels in both serum and peritoneal fluid (p = 0.0001). CONCLUSION There is a positive correlation between serum and peritoneal fluid values of CA-125 in women with and without endometriosis, and their levels are higher in peritoneal fluid. Advanced endometriosis is related to higher levels in both serum and peritoneal fluid.

High prevalence of chronic pelvic pain in women in Ribeirão Preto, Brazil and direct association with abdominal surgery

INTRODUCTION: Chronic pelvic pain is a disease that directly affects the social and professional lives of women. OBJECTIVE: To estimate the prevalence of this clinical condition and to identify independent factors associated with it in women living in Ribeirão Preto, Brazil. METHODS: A one-year cross-sectional study was conducted in a population sample of 1,278 women over the age of 14 years. The target population was predominantly composed of women who are treated by the public health system. The questionnaire was administered by interviewers who were not linked to the city health care programs. The prevalence of the morbidity was estimated. First, we identified the significant variables associated with pelvic pain (p<0.10) and then we attributed values of 0 or 1 to the absence or presence of these variables. Logistic regression analysis was used to identify and estimate the simultaneous impact of the independent variables. The results were expressed by odds ratio and their 95% confidence interval with p<0.05. RESULTS: The disease was found in 11.5% (147/1,278) of the sample. The independent predictors were dyspareunia, previous abdominal surgery, depression, dysmenorrhea, anxiety, current sexual activity, low back pain, constipation, urinary symptoms, and low educational level. CONCLUSION: The prevalence of chronic pelvic pain in Ribeirão Preto is high and is associated with conditions that can usually be prevented, controlled, or resolved by improvement of public health policies and public education.

Increased capsaicin receptor TRPV1 in the peritoneum of women with chronic pelvic pain.

ObjectiveTo investigate the expression of capsaicin receptor [transient receptor potential vanilloid type-1 (TRPV1)] in the peritoneum of women with chronic pelvic pain (CPP). MethodsA case-control study was conducted on 25 women with CPP and 10 controls. Samples of the rectouterine excavation (2 cm2) were obtained by laparoscopy, fixed in 4% formaldehyde, and underwent immunohistochemistry analysis using rabbit anti-TRPV1 (1:400) polyclonal antibodies and anti-protein gene product 9.5 (PGP 9.5) (1:2000) as a neuronal marker. Ten sequential images of high magnification fields (×40) were captured from each slide and the area identified with the antibody was calculated with Kontron V2.0 software. ResultsImmunoreactivity to TRPV1 was sparsely detected in the nervous tissue and epithelium of endometriotic lesions. The percent area of immunoreactivity for TRPV1 [expressed as median (range)] was greater in specimens from women with CPP, 1.02% (0.54 to 2.93), than from women without the disease, 0.14% (0.07 to 1.12) (P<0.0001). This greater expression was not secondary to an increase in neuronal fibers because there was also a significant difference in the percent area TRPV1:PGP 9.5 ratio between women with CPP, 1.18 (0.26 to 4.63), and controls, 0.15 (0.06 to 0.95) (P=0.0003). DiscussionTRPV1 may play an important role in the maintenance and perpetuation of symptoms in women with CPP. In view of the immunoreactivity detected for TRPV1, the endometriotic lesion may have the ability to interfere with nociception or with the inflammatory peritoneal environment in women with CPP. Further studies are needed to elucidate the participation of TRPV1 in CPP and its association with endometriosis.

Sexuality during the climacteric period.

BACKGROUND Cultural, social, physiological and psychological factors may alter the course of sexual function in climacteric women. OBJECTIVE The objective of the present literature review is to survey the prevalence of sexual dysfunctions in the climacteric and to establish the association between the organic and psychic changes that occur during this phase and sexual dysfunction. We also discuss potential treatments. METHODS We evaluated the data available in PubMed (1982-2008). For each original article, two reviewers analyzed the data independently and considered a study to be of high quality if it had all three of the following characteristics: prospective design, valid data and adequate sample size. Both reviewers extracted data from each of the 99 studies selected: 34 cross-sectional studies, 25 cohort studies, 9 trials, 31 reviews related to sexuality in pre- and post-menopausal women. RESULTS Sexual dysfunction among climacteric women is widespread and is associated with bio-psychosocial factors. However, there is not enough evidence to correlate sexual dysfunction with a decrease in estrogen levels and biological aging. A strong association exists between climacteric genital symptoms and coital pain. There is, however, sufficient evidence demonstrating the benefits of local estrogen therapy for patients with genital symptoms. CONCLUSION A significant decline in sexual function occurs in climacteric women, although it is still unclear whether this is associated with the known decrease in estrogen levels or with aging, or both. Relational factors may interfere with sexual function during this phase. The climacteric genital symptoms improve with estrogen replacement therapy, and positively influence sexual function. Further studies are needed to establish the actual impact of the decrease in estrogen levels and of aging on the sex life of climacteric women.

TRPV1 Expression on Peritoneal Endometriosis Foci is Associated With Chronic Pelvic Pain

Objective: To investigate the expression of capsaicin receptor (transient receptor potential vanilloid type 1 [TRPV1]) in the peritoneal endometriosis foci of women with and without chronic pelvic pain (CPP). Methods: A case−control study was conducted on 49 women with endometriosis who underwent laparoscopy, 28 of whom had CPP and 21 without CPP. Samples from peritoneum of the rectouterine excavation (2 cm2) were obtained by laparoscopy, fixed in 4% formaldehyde, and underwent immunohistochemistry analysis using rabbit anti-TRPV1 (1:400) polyclonal antibody. Results: Image analysis revealed that the immunoreactivity for TRPV1 was more frequent in specimens (endometriosis foci) from women with CPP (n = 15 of 28, 53.6%), compared to samples from the endometriosis foci of women without CPP (n = 6 of 21, 28.6%; P = .04). There was no correlation with duration, intensity of pain, or stage of the disease (endometriosis). Discussion: The present study shows that TRPV1 expression in peritoneal endometriosis foci is related to CPP in women. However, this association is not related to the endometriosis stage. In view of the immunoreactivity for TRPV1 observed here, we believe that some endometriotic lesions may provide a scenario for TRPV1 to be tonically active and this activity may contribute to the underlying pathology of CPP.

Glycodelin expression in the endometrium of healthy women and in the eutopic and ectopic endometrium of women with endometriosis.

OBJECTIVE To analyze the expression of the glycodelin gene to better understand the molecular environment of endometriotic lesions and to elucidate the potential mechanisms that underlie the complex physiopathology of endometriosis. DESIGN Prospective laboratory study. SETTING University hospital. PATIENT(S) Eleven healthy fertile women and 17 patients with endometriosis in the early proliferative phase of the menstrual cycle. INTERVENTION(S) Endometrial biopsy specimens were obtained from the endometrium of healthy women without endometriosis (controls) and from eutopic and ectopic endometrium tissues (pelvic and ovarian endometriotic implants) of endometriosis patients. MAIN OUTCOME MEASURE(S) The glycodelin relative expression level by real-time polymerase chain reaction (PCR) analysis. RESULT(S) The glycodelin down-regulation found in the endometriotic lesions was 332.26 and 123.17-fold lower, respectively, when compared with the eutopic tissue and the control endometrium. CONCLUSION(S) Glycodelin may be one of the molecules that contributes to the loss of cellular homeostasis in endometriotic lesions.