Comparing the pharmacokinetic and pharmacodynamic qualities of current and future therapies for uterine fibroids.

INTRODUCTION: Uterine fibroids are the most common benign gynecological tumors affecting women of reproductive ages. Although surgery is the definitive treatment choice, several medical approaches have been investigated to control their symptoms. The main issue of currently employed drugs for uterine fibroids is the long-term safety and tolerability profile. Today, new emerging options represent hopeful alternatives that could potentially overcome these limitations. AREAS COVERED: This manuscript aims to give an updated overview of the pharmacodynamic and pharmacokinetic properties of current and new investigational medical drugs for the treatment of symptomatic uterine fibroids. The bibliographic research was conducted by searching alone or combined keywords on the following electronic databases: Medline, PubMed, Embase, Science Citation Index via Web of Science. EXPERT OPINION: The most recent therapeutic strategies for uterine fibroids are represented by gonadotropin-releasing hormone antagonists (GnRH-ants; elagolix and relugolix) and selective progesterone receptor modulators (SPRM; ulipristal acetate). After early promising results, studies on innovative drugs, such as linzagolix (GnRH-ant) and vilaprisan (SPRM) are demanding. In the near future, a deeper knowledge of biological mechanisms at the basis of the genesis and growth of uterine fibroids could pave the way for the development of innovative targeted therapies.

Prospective Evaluation of Outpatient Flexible Sigmoidoscopy in Patients With Deep Infiltrating Endometriosis.

INTRODUCTION: To study patients' acceptability of an outpatient flexible sigmoidoscopy (FS) protocol and to assess the diagnostic value of endoscopic assessment in patients with deep endometriosis (DE). METHODS: All patients with DE and suspected bowel involvement diagnosed were reviewed in the colorectal outpatient clinic before elective surgery following multidisciplinary team meeting discussion. Patients were consented for having the FS performed at the same time of the clinical consultation. Primary outcome was diagnostic value of the FS. RESULTS: Sixty patients were included. Fifty-eight (96.7%) patients consented for the outpatient FS, demonstrating a high rate of patients' acceptability. The sigmoidoscopy demonstrated no abnormalities in 48 patients (82.7%), diverticulosis in 5 patients (8.6%), polyps in 2 patients (3.4%) and mucosal endometriosis in 1 patient only (1.7%). CONCLUSIONS: Outpatient FS during the preoperative consultation with the colorectal surgeon is feasible in patients with DE affecting the bowel with a high rate of patients' acceptability but limited additional diagnostic value.

Performance of Circulating Placental Growth Factor as A Screening Marker for Diagnosis of Ovarian Endometriosis: A Pilot Study.

BACKGROUND: The aim of this study is to compare the circulating placental growth factor (PlGF) concentration in women with and without endometrioma to verify the performance of this marker to diagnose the disease. MATERIALS AND METHODS: In this case-control study, thirteen women with histological diagnosis of ovarian endometriosis were compared with women without endometriosis disease. PlGF plasma levels of endometriotic patients and controls were investigated using a fluorescence immunoassay technique. RESULTS: PlGF showed a direct correlation with body mass index (BMI) only in the control group (P=0.013). After adjustment for BMI values, PlGF median value in endometriosis group (14.7 pg/mL) resulted higher than in control group (13.8 pg/ mL, P=0.004). CONCLUSION: PlGF is a promising peripheral blood marker that can discriminate between patients with and without ovarian endometriosis.

Sexual function in women undergoing surgery for deep infiltrating endometriosis: a comparison with healthy women.

BACKGROUND: Endometriosis is a chronic and progressive condition of women of reproductive age. It is strongly associated with significant impairment of sexual function. AIM: To objectively evaluate the impact of laparoscopic excision of endometriosis on sexual function in patients with deep infiltrating endometriosis (DIE) compared to healthy women. SETTING AND DESIGN: Prospective study, including 250 patients with a diagnosis of DIE scheduled for laparoscopic surgery and 250 healthy women. METHODS: A sexual activity questionnaire, SHOW-Q (Sexual Health Outcomes in Women Questionnaire), was used to collect data pertaining to women's satisfaction, orgasm, desire and pelvic problem interference with sexual function. Women with DIE underwent complete excision of endometriotic lesions. All participants were asked to complete the SHOW-Q questionnaire before and after surgery. RESULTS: SHOW-Q scores in the endometriosis group before and 6 months after surgery were compared with the healthy group scores. A significant improvement was found between pre- and post-treatment in the scores of the satisfaction scale, desire scale and pelvic problem interference scale of SHOW-Q. The distribution of post-surgery SHOW-Q scores was comparable to healthy women's scores apart from the orgasm scale score, which was unchanged in the post-surgery group. CONCLUSIONS: The surgical approach to treatment has a positive impact not only on organ impairment but also on sexual function in women affected by DIE.

Does laparoscopic shaving for deep infiltrating endometriosis alter intestinal function? A prospective study.

BACKGROUND: 5-12% of deep infiltrating endometriosis involves the digestive tract, especially the distal sigmoid colon and rectum. Bowel endometriosis surgery may be associated with neurological complications. AIM: The aim of this study was to objectively evaluate whether excision of rectosigmoid deep infiltrating endometriosis by shaving technique alters intestinal and defecatory function at 6-months post-surgery. MATERIALS AND METHODS: Nineteen women were enrolled in our tertiary care university hospital. They were affected by rectosigmoid endometriosis and underwent laparoscopic shaving excision of the nodule. Anorectal manometry was performed prior to and after surgery. The parameters studied were resting pressure, maximum squeezing pressure, pushing, rectoanal inhibitory reflex and rectal sensibility. The women completed a defecatory function questionnaire and ranked pain symptoms using a visual analogue scale. RESULTS: After surgery, no alteration of rectoanal inhibitory reflex was found. The tone of the internal anal sphincter was not significantly different before and after surgery. The defecatory function questionnaire revealed a significant improvement in constipation, urgency, bowel movements and anal eczema. No cases of incontinence were described. CONCLUSIONS: This report of the objective assessment of neurological intestinal alterations after rectal shaving of endometriotic nodules suggests the laparoscopic shaving technique preserves intestinal neurological activity.

Diagnosis and laparoscopic management of a rare endometriosis-related peritoneal mass with rapid growth in early pregnancy.

Herein is described the diagnosis, clinical management and laparoscopic removal of a rapid growing retro-uterine mass in a pregnant woman. After laparoscopic removal of the pelvic mass, diagnosis of peritoneal endometriotic cyst was made on histology. The patient was asymptomatic and no history of endometriosis was reported. The laparoscopic management of the peritoneal mass was safe and effective and to our knowledge this is the first case report describing a decidualized endometriotic lesion in the absence of a pre-pregnancy endometriosis diagnosis.

Sexual function in women undergoing surgery for deep infiltrating endometriosis: a comparison with healthy women.

BACKGROUND: Endometriosis is a chronic and progressive condition of women of reproductive age. It is strongly associated with significant impairment of sexual function. AIM: To objectively evaluate the impact of laparoscopic excision of endometriosis on sexual function in patients with deep infiltrating endometriosis (DIE) compared to healthy women. SETTING AND DESIGN: Prospective study, including 250 patients with a diagnosis of DIE scheduled for laparoscopic surgery and 250 healthy women. METHODS: A sexual activity questionnaire, SHOW-Q (Sexual Health Outcomes in Women Questionnaire), was used to collect data pertaining to women's satisfaction, orgasm, desire and pelvic problem interference with sexual function. Women with DIE underwent complete excision of endometriotic lesions. All participants were asked to complete the SHOW-Q questionnaire before and after surgery. RESULTS: SHOW-Q scores in the endometriosis group before and 6 months after surgery were compared with the healthy group scores. A significant improvement was found between pre- and post-treatment in the scores of the satisfaction scale, desire scale and pelvic problem interference scale of SHOW-Q. The distribution of post-surgery SHOW-Q scores was comparable to healthy women's scores apart from the orgasm scale score, which was unchanged in the post-surgery group. CONCLUSIONS: The surgical approach to treatment has a positive impact not only on organ impairment but also on sexual function in women affected by DIE.

Prevalence of adenomyosis in women undergoing surgery for endometriosis.

OBJECTIVE(S): To evaluate the prevalence of adenomyosis in patients undergoing surgery for endometriosis. STUDY DESIGN: Retrospective study including 1618 women with preoperative clinical and ultrasound diagnosis of endometriosis. As preoperative assessment, all patients underwent ultrasound to assess endometriosis and all features associated with adenomyosis (heterogeneous myometrial echotexture, globular-appearing uterus, asymmetrical thickness of anteroposterior wall of the myometrium, subendometrial myometrial cysts, subendometrial echogenic linear striations or poor definition of the endometrial-myometrial junction). RESULTS: Adenomyosis was present in 353/1618 (21.8%) women included in the study. Multivariate analysis showed that the prevalence of adenomyosis was significantly associated with deep infiltrating endometriosis, parity, dysmenorrhea intensity and women's age (P<0.0001). CONCLUSION(S): Adenomyosis is a common condition but its aetiology and natural history are still unknown. Our experience showed a 21.8% of prevalence of adenomyosis in patients affected by endometriosis and its association with parous women, increasing age, dysmenorrhea intensity and with the presence of deep infiltrating endometriosis.

How to evaluate adenomyosis in patients affected by endometriosis?

Objective. The aim of the study is to evaluate adenomyosis in patients undergoing surgery for different type of endometriosis. It is an observational study including women with preoperative ultrasound diagnosis of adenomyosis. Demographic data and symptoms were recorded (age, body mass index, parity, history of previous surgery, dysmenorrhea, dyspareunia, dyschezia, dysuria, and abnormal uterine bleeding). Moreover a particular endometrial shape "question mark sign" linked to the presence of adenomyosis was assessed. Results. From 217 patients with ultrasound diagnosis of adenomyosis, we found 73 with ovarian histological confirmation of endometriosis, 92 with deep infiltrating endometriosis, and 52 patients who underwent surgery for infertility. Women with adenomyosis alone represented the oldest group of patients (37.8 ± 5.18 years, P = 0.02). Deep endometriosis patients were nulliparous more frequently (P < 0.0001), had history of previous surgery (P = 0.004), and complained of more intense pain symptoms than other groups. Adenomyosis alone was significantly associated with abnormal uterine bleeding (P < 0.0001). The question mark sign was found to be strongly related to posterior deep infiltrating endometriosis (P = 0.01). Conclusion. Our study confirmed the strong relationship between adenomyosis and endometriosis and evaluated demographic aspects and symptoms in patients affected by different type of endometriosis.

Do women with endometriosis have to worry about sex?

OBJECTIVE(S): Sexual function is negatively influenced by endometriosis and women with endometriosis show less sexual and partnership satisfaction compared to patients with other gynaecological disorders. This study aims to compare sexual function between patients with deep infiltrating endometriosis (DIE) and healthy women using Sexual Health Outcomes in Women Questionnaire (SHOW-Q). STUDY DESIGN: Case-control study including 182 patients with histological diagnosis of DIE and 182 healthy women, who referred to our tertiary care university hospital from 2010 to 2012. SHOW-Q was used to collect data concerning satisfaction, orgasm, desire and pelvic problem interference with sex. The un-paired t-test was performed to compare the means of a continuous variable between groups when the data were normally distributed; otherwise the Mann-Whitney test was used to check t-test results. Pearson's χ(2) test and Z-test for proportions - independent groups were performed to investigate the difference among grouping variables. RESULTS: As described in a previous study, the prevalence of sexual dysfunction in women with endometriosis is around 61% and in women with other gynaecological disorders is 35%. Assuming 5% significance and 95% power, 106 women would be required for the study. Every area of sexual function investigated through the SHOW-Q questionnaire (satisfaction, desire, orgasm and pelvic problem interference) was significantly impaired compared to healthy women. Among patients with DIE, 58% (105/182) reported that pelvic pain severely affected sexual function, while only 1% (2/182) of healthy women (p<0.0001). Moreover, sexual desire was absent or less than one or two times per month in 45% (82/182) of women with DIE compared to 14% (26/182) of healthy women (p<0.0001). CONCLUSION(S): DIE severely affects sexual function. Endometriosis is a global disease, which affects patients physically, psychologically and sexually. The potential sexual consequences of this disease need to be considered.

The role of ovarian suspension in endometriosis surgery: a randomized controlled trial.

STUDY OBJECTIVE: A very high percentage of patients with severe pelvic endometriosis develop adhesions after laparoscopic surgery. The objective of this trial was to evaluate the role of ovarian suspension performed during surgery for severe endometriosis on ovarian adhesions and postoperative pelvic pain. DESIGN: A randomized controlled trial (Canadian Task Force classification I). SETTING: The tertiary care University Hospital of Bologna, Bologna, Italy. PATIENTS: Eighty patients with ovarian and posterior deep infiltrating endometriosis were included in the study. INTERVENTIONS: Patients underwent laparoscopic surgery for endometriosis and were randomized sequentially into 2 groups: transient ovarian suspension was performed in the treatment group (n = 40), whereas in the control group (n = 40) ovaries were left free in the pelvis. Symptom intensity (dysmenorrhea, chronic pelvic pain, dyspareunia, dyschezia, and dysuria) were ranked using a visual analog scale. Postsurgical ovarian adhesions were evaluated using transvaginal ultrasonographic scans performed by an ultrasound operator who was blinded to the details of the operative procedure and women's randomization allocation. Complications, lesion localization, endometrioma diameter, and surgery time were recorded. MEASUREMENTS AND MAIN RESULTS: At follow-up, a significantly lower rate of ultrasound-detectable ovarian adhesions with the uterus and the bowel was observed in the treatment group, respectively (46.7% vs 77.3%, p = .003 and 26.7% vs 68.2%, p < .0005). Patients in the control group showed a higher percentage of fixed ovaries with moderate and severe adhesions than the treatment group, respectively (56.8% vs 28.9%, p = .003 and 20.5% vs 8.9%, p = .110). No differences between the 2 groups were found regarding complications and pelvic pain. CONCLUSION: Ovarian suspension seems to be an additional effective surgical procedure associated with an increased ovarian mobility in women treated for severe endometriosis. Moreover, it is feasible, safe, simple, and fast. Hence, it should be routinely used during laparoscopic surgery for endometriosis.

Do women with deep infiltrating endometriosis have more tubal alterations? Objective evaluation of 473 patients.

OBJECTIVE: To evaluate whether deep infiltrating endometriosis (DIE) is associated with tubal alterations. STUDY DESIGN: This was a retrospective study. Our study included 335 women with ovarian endometriosis (Group A), 66 women with DIE (Group B), and 72 women presenting with both conditions (Group C). We evaluated tubal morphology and patency during laparoscopic excision of endometriosis. Tubal patency was assessed by tubal dye test. Tubal morphology was determined using the tubal morphology score (TMS), obtained by a total grade of 4 parameters: tubal caliber, course, surface and fimbrial morphology. RESULTS: There was no significant difference in the 3 groups regarding the presence of tubal occlusion (p = 0.23). Total TMS was not significantly different in the 3 groups (p = 0.13). A history of surgical treatment for endometriosis was associated with higher rate of tubal occlusion (p < 0.0005) and more severe morphological alterations (p < 0.0005). There was a positive correlation between number of previous surgical interventions and worse TMS (rho = 0.197, p < 0.0005). CONCLUSION: Alterations in tubal patency and morphology were not significantly different in patients with DIE as compared to women with ovarian endometriosis. History of surgical interventions for endometriosis was related with the presence of tubal alterations.

Women with deep infiltrating endometriosis: sexual satisfaction, desire, orgasm, and pelvic problem interference with sex.

INTRODUCTION: Endometriosis is a chronic and progressive condition of women of reproductive age. It is strongly associated with a significant reduction of quality of life (QOL) and sexual function. AIMS: This study aims to objectively evaluate sexual function in women with deep infiltrating endometriosis (DIE) and to study the impact of endometriosis symptoms and type of lesion on patient's sexual function. METHODS: This is a cross-sectional study in a tertiary care university hospital. It included 182 patients with preoperative clinical and ultrasound diagnosis of DIE who were referred to our center from 2008 to 2011. MAIN OUTCOME MEASURES: A sexual activity questionnaire, the Sexual Health Outcomes in Women Questionnaire (SHOW-Q) was used to collect data pertaining to satisfaction, orgasm, desire, and pelvic problem interference with sex. Short Form 36 (SF-36) was used to evaluate QOL. Demographic and clinical characteristics were assessed: age, body mass index, parity, ethnicity, postsecondary education, employment, smoking, history of surgical treatment, and hormonal contraception. Patients were asked about pain symptoms (dysmenorrhea, dyspareunia, dyschezia, chronic pelvic pain, and dysuria) using a visual analog scale. RESULTS: The mean values obtained on the different scales of the SHOW-Q showed poor sexual function (mean SHOW-Q total score 56.38 ± 22.74). Satisfaction was the dimension most affected (mean satisfaction score 55.66 ± 34.55), followed by orgasm (mean orgasm score 56.90 ± 33.77). We found a significant correlation between the SF-36 scores and the SHOW-Q scores (P < 0.0001). Sexual dysfunction and deterioration of QOL seem to be correlated. Analyzing the impact of symptoms and lesions on sexual function, we found that dyspareunia and vaginal DIE nodules significantly affect sexual activity (P < 0.05). CONCLUSION: The results of this study demonstrated that women with DIE have a sexual function impairment, correlated with the overall well-being decrease. Moreover, the presence of dyspareunia and vaginal endometriotic lesions seems to be involved in sexual dysfunction.

Cervical length and risk of antepartum hemorrhage in presence of low-lying placenta.

OBJECTIVES: To evaluate whether transvaginal ultrasound cervical length (TVU CL) can predict antepartum bleeding (APB) in women with low-lying placenta. STUDY DESIGN: A retrospective study was performed including pregnancies with low-lying placenta for which third trimester TVU CL was available. Multiple pregnancies were excluded. Short cervix was defined as TVU CL ≤25 mm. Outcomes of interest were compared with respect to the TVU CL. RESULTS: Forty three cases of singleton pregnancies complicated by low-lying placenta in third trimester were identified. Short cervix was reported in 8 cases (19%). APB (75% vs. 31 %, p = 0.02), blood transfusions (25% vs. 3%, p = 0.02), lower birth weight (2246 vs. 2985 g, p = 0.02), and neonatal intensive care unit (NICU) admissions (50% vs. 17%, p = 0.04) were more frequent in the women with short cervix. Rate of unplanned cesarean delivery for APB was similar between both the groups (25% vs. 28%, p = 0.83). CONCLUSIONS: In women with low-lying placenta persisting into third trimester, short cervical length can be used as a predictor for APB.

What is the impact on sexual function of laparoscopic treatment and subsequent combined oral contraceptive therapy in women with deep infiltrating endometriosis?

INTRODUCTION: Deep infiltrating endometriosis (DIE) is a form of endometriosis in which the lesion penetrates for more than 5 mm under the peritoneal surface. It is a chronic disease which can impair women's sexual function. There is a growing body of evidence supporting combined surgical/medical treatment in the management of DIE. AIMS: The aims of this article are to evaluate the impact of the laparoscopic full excision of endometriosis and postoperative combined oral contraceptives (COC) administration on sexual function in patients with DIE and to compare sexual function outcomes of women submitted to intestinal resection and nodule excision. METHODS: It is a prospective cohort study in a tertiary care university hospital on 106 sexually active women, with histologically confirmed DIE, managed by laparoscopy and subsequent COC therapy for 6 months. Patients filled preoperatively and 6-month postoperatively a quality of sexual life questionnaire, the Sexual Health Outcomes in Women Questionnaire (SHOW-Q) and they ranked their symptom intensity using a 10-point visual analogue scale (VAS). MAIN OUTCOME MEASURES: Sexual function was measured through the SHOW-Q scores and pain symptoms through VAS scores. Intraoperative details, type of intervention and perioperative complications were noted. RESULTS: Six months after surgery and postoperative COC treatment, a significant improvement was observed in the SHOW-Q domains of pelvic problem interference, sexual satisfaction and desire (P<0.05). Laparoscopic management of DIE did not change significantly the orgasm area of the sexual functioning (P=0.7). No significant difference was found in SHOW-Q scores between patients submitted to intestinal resection and patients submitted to intestinal nodule excision (P>0.05). CONCLUSIONS: Sexual desire, satisfaction with sex and pelvic problem interference with intercourse are significantly improved after 6 months from laparoscopic excision of DIE combined with postoperative COC therapy. No difference in sexual outcomes was detected between patients submitted to intestinal resection and nodule excision.

Does colorectal endometriosis alter intestinal functions? A prospective manometric and questionnaire-based study.

OBJECTIVE: To objectively evaluate using anorectal manometry whether endometriotic nodules influence intestinal function and to reveal subjective intestinal dysfunctions in patients with rectosigmoid deep infiltrating endometriosis. DESIGN: Prospective study. SETTING: Tertiary care university hospital. PATIENT(S): Patients (n = 25) with a preoperative diagnosis of rectosigmoid endometriosis. INTERVENTION(S): Patients underwent anorectal manometry; after that, they filled a questionnaire about defecatory functions and ranked their pain symptoms. MAIN OUTCOME MEASURE(S): The parameters studied were resting pressure, maximum squeezing pressure, pushing, rectoanal inhibitory reflex, and rectal sensibility. We analyzed the responses to the defecatory function questionnaire and the scored the endometriosis pain symptoms using a Visual Analogue Scale. RESULT(S): No alterations of the rectoanal inhibitory reflex were found. Hypertone of the internal anal sphincter was found in 20 of 25 patients. Almost half of the patients had an increase of the threshold of desire to defecate, and 7 patients had a reduction of the anal sphincter squeeze pressure. According to the responses to the defecatory function questionnaire, incomplete evacuation was the most common symptom. CONCLUSION(S): We did not find marked motility or sensitive dysfunctions at the anorectal manometry, whereas subjectively patients reported some defecatory disorders. We revealed the presence of hypertone of the internal anal sphincter in most of the patients. CLINICAL TRIAL REGISTRATION NUMBER: 74/2010/O/Sper.

Preoperative ultrasound diagnosis of deep endometriosis: importance of the examiner's expertise and lesion size.

Objectives: To evaluate the accuracy of transvaginal sonography (TVS) in the diagnosis of deep infiltrating endometriosis (DIE) of the posterior compartment (rectovaginal septum, uterosacral ligaments, rectosigmoid colon, vagina) when undertaken by physicians of varying experience and to investigate if size of the nodule is relevant in influencing diagnostic accuracy. Methods: 381 patients who were operated on between January 2007 and December 2010 for suspected pelvic endometriosis were prospectively recruited. Clinical, surgical and histopathologic data were collected and a preoperative TVS was carried out. Comparison was made between the diagnostic accuracy of TVS performed by two groups of physicians of different expertise. Results: One hundred and thirty-six patients underwent removal of deep endometriotic lesions of the posterior compartment. Sensitivity, specificity, positive and negative predictive value and the overall diagnostic accuracy of the expert operators were 77%, 95%, 90%, 87% and 88% respectively. Corresponding values for first-level operators were: 45%, 98%, 92%, 79% and 81%. In patients with positive findings at TVS, the mean diameter of the endometriotic nodule was of 4.7 ± 3.4 cm while, in cases with negative findings, the average diameter was 2.6 ± 1.1 cm (P < 0.05). Conclusions: TVS is accurate in detecting the presence of DIE. Accuracy is dependent on the experience of the physician and the size of the nodule.

Does laparoscopic management of deep infiltrating endometriosis improve quality of life? A prospective study.

BACKGROUND: Deep infiltrating endometriosis (DIE) can affect importantly patients' quality of life (QOL). The aim of this study is to evaluate the impact of the laparoscopic management of DIE on QOL after six months from treatment. METHODS: It is a prospective cohort study. In a tertiary care university hospital, between April 2008 and December 2009, 100 patients underwent laparoscopic management of DIE and completed preoperatively and 6-months postoperatively a QOL questionnaire, the short form 36 (SF-36).Quality of life was measured through the SF-36 scores. Intra-operative details of disease site, number of lesions, type of intervention, period of hospital stay and peri-operative complications were noted. RESULTS: Six months postoperatively all the women had a significant improvement in every scale of the SF-36 (p < 0,0005). Among patients with intestinal DIE, significant differences in postoperative scores of SF-36 were not detected between patients submitted to nodule shaving and segmental resection (p > 0.05). There was no significant difference in the SF-36 scores at 6 months from surgery between patients who received postoperative medical treatment and patients who did not (p > 0.05). CONCLUSIONS: Laparoscopic excision of DIE lesions significantly improves general health and psycho-emotional status at six months from surgery without differences between patients submitted to intestinal segmental resection or intestinal nodule shaving.