Medical treatment of mild endometriosis in infertile women: analysis of a failure

The easy access to the pelvis of infertile women by laparoscopy favours early diagnosis of endometriosis in an increasing number of subjects with minimal and mild disease. These initial forms have been associated with and considered as the cause of infertility despite the absence of relevant scientific evidence. Various hormone therapies, some with severe side-effects and high costs, have been used by numerous authors. However, no study comparing medically treated with untreated women has ever shown any drug to be more effective than expectant management. The possible explanations of treatment failures are reviewed.     

Endometriosis: Serum-soluble CD23 in patients with endometriosis and the effect of treatment with danazol and leuprolide acetate depot injection

Activated B cells have recently been shown to produce solubleCD23 from their membranes. The serumsoluble CD23 concentrationin 21 patients with pelvic pain diagnosed as having endometriosisand confirmed by histology, and in 18 patients without pelvicpain, who had a normal pelvis during laparoscopic sterilization,was studied by chemiluminescent enzyme-linked immunosorbentassay. The endometriosis patients were randomized to 3 monthsof either danazol or leuprolide acetate injection. Serum wastaken before and after 3 months of therapy. The serum-solubleCD23 concentration was significantly elevated in patients withendometriosis when compared with the controls (P < 0.0001).There was no correlation between soluble CD23 concentrationsand the severity of endometriosis (r = 0.48, P > 0.05). Theserum concentration of soluble CD23 decreased significantlyon treatment with danazol but not leuprolide acetate (P <0.05). We conclude that the elevation of soluble CD23 in patientswith endometriosis suggests that there is activation of B cells,which respond to danazol but not leuprolide acetate injection.     

Endometriosis: Hormonal regulation of endometriosis and the rationales and effects of gonadotrophin-releasing hormone agonist treatment: a review

The knowledge about the role of oestrogen in the regulationof endometriosis growth and symptoms has been reviewed. Studieson oestrogen and progesterone metabolism and receptivity inendometriotic tissue and the impact on growth regulation andclinical symptoms of steroidal hormones are discussed. Theseinclude tissue sample assays, ex-vivo tissue culturing as wellas clinical studies concerning the effect of different hormonaltreatment. All studies published on steroid receptors in endometriotictissue have shown lower levels of oestrogen and progesteronereceptors in endometriotic tissue than in uterine endometrium.These data might, at least partly, explain the poor clinicalresponse to hormonal treatment experienced in some cases. However,in cases of hormone-sensitive endometriotic tissue, a completeovarian inactivation is not important, as comparable reducingeffects on lesions and symptoms are seen after various hormonaltreatments leading to a varying degree of ovarian inactivation.A less pronounced hypo-oestrogenism during treatment gives lesssevere consequences for the future, mainly concerning the bonemass and the circulation, and might allow a prolonged symptom-freeperiod on low-dose treatment when needed. Not all cases of endometriosisare receptive to hormonal treatment.     

Subcutaneous depot medroxyprogesterone acetate versus leuprolide acetate in the treatment of endometriosis-associated pain

BACKGROUND: A clinical study compared efficacy and safety of depot medroxyprogesterone acetate (DMPA) with leuprolide for endometriosis-associated pain. METHODS: This multicentre, 18 month, evaluator-blinded, comparator-controlled trial randomized 300 women with laparoscopically diagnosed endometriosis to 6 month treatment with subcutaneous injection of 104 mg/0.65 ml DMPA (DMPA-SC 104) every 3 months or leuprolide (3.75 mg monthly or 11.25 mg every 3 months), with 12 months post-treatment follow-up. Endpoints included patient response to treatment in five signs/symptoms (dysmenorrhoea, dyspareunia, pelvic pain, pelvic tenderness, induration) and changes in bone mineral density (BMD) and productivity at 6 and 18 months. RESULTS: DMPA-SC 104 and leuprolide produced equivalent (P < 0.02) reductions in at least four pain categories and significant (P < 0.001) improvements in composite score at months 6 and 18. At month 6, reductions in total hip and lumbar spine BMD were significantly less (P < 0.001) with DMPA-SC 104 versus leuprolide. BMD returned to pre-treatment levels 12 months post-treatment in the DMPA-SC 104 but not the leuprolide group. Total productivity also significantly (P < or = 0.05) improved in both groups at 6 and 18 months. CONCLUSIONS: DMPA-SC 104 reduces endometriosis-associated pain as effectively as leuprolide and improves productivity with significantly less BMD decline.     

Post-operative GnRH analogue treatment after conservative surgery for symptomatic endometriosis stage III-IV: a randomized controlled trial.

BACKGROUND: In order to decrease endometriosis recurrence after surgical therapy, it has been proposed to use a post-surgical oestrogen-lowering medical treatment. Results from previous trials on this topic are contradictory. METHODS: A total of 89 women were randomized, by computer-generated list, after laparoscopic conservative surgery for symptomatic endometriosis stage III-IV to receive monthly i.m. injections of gonadotrophin-releasing hormone (GnRH) analogue, leuprolide acetate depot (3.75 mg) for 3 months (n = 44) or to an expectant management (n = 45). All patients were followed up every 6 months for evaluation of pain symptoms, fertility and objective disease recurrence. RESULTS: During the follow-up, which ranged from 6-36 months, five (33%) of the 15 women who wanted children and who were allocated the GnRH analogue and six (40%) of the 15 given no treatment became pregnant (not significant). Moderate/severe pelvic pain recurred during the follow-up in 10 (23%) of the women allocated the GnRH analogue and 11 (24%) of those allocated no treatment; the cumulative pain recurrence rates at 18 months were 23 and 29% respectively (not significant). Four women (9%) treated with GnRH analogue and four women (9%) who received no treatment had objective disease recurrence as demonstrated by gynaecological examination and/or pelvic ultrasonography. CONCLUSIONS: This study does not support the routine post-operative use of a 3 month course of GnRH analogue in women with symptomatic endometriosis stage III-IV.     

Laparoscopic excision of posterior vaginal fornix in the treatment of patients with deep endometriosis without rectum involvement: surgical treatment and long-term follow-up

BACKGROUND: The objective of the study is to evaluate the short- and long-term efficacy of complete laparoscopic excision of deep endometriosis, without rectum involvement, with the opening and partial excision of the posterior vaginal fornix. METHODS: Thirty-one patients were included in the study with symptomatic extensive disease including involvement of the cul-de-sac, rectovaginal space and posterior vaginal fornix without rectum involvement. Endoscopic surgery was performed with complete separation of rectovaginal space and in-block resection of the diseased tissue, opening and partial excision of the posterior vaginal fornix and vaginal closure either by laparoscopic or by vaginal route. Patients filled in questionnaires on pain before and 12, 24, 36, 48 and 60 months after surgical treatment. RESULTS: No intraoperative complications were observed; 65% were free of analgesic on post-operative day 2, 38% had total remission of chronic pain and 22% were improved; 38% had total remission of dysmenorrhoea and 22% were improved; 45% had total remission of dyspareunia and 25% were improved. Follow-up improvement of symptoms was statistically significant and was maintained for 5 years without recurrence of the disease or repeated surgery (P < 0.001). CONCLUSION: Complete surgical resection of deep infiltrative endometriosis with excision of the adjacent tissue of the posterior vaginal fornix improves quality of life with persistence of results for long time in patients not responsive to medical treatment.     

The effects and effectiveness of laparoscopic excision of endometriosis: a prospective study with 2-5 year follow-up

BACKGROUND: This study investigates the outcomes for women up to 5 years after laparoscopic excision of endometriosis. METHODS: In this prospective observational cohort study, 254 women with chronic pelvic pain were referred to two units specializing in minimal access surgical management of endometriosis. Of these, 216 women underwent surgical assessment and 176 were confirmed to have endometriosis. Questionnaires and visual analogue scale (VAS) scores for dysmenorrhoea, non-menstrual pelvic pain, dyspareunia and dyschesia as well as quality of life instruments; the EQ-5Dindex and EQ-5Dvas, Short-Form 12 (SF-12) and sexual activity questionnaires were completed pre-operatively. Intra-operative details of revised American Fertility Society (rAFS) stage, site of disease, associated tests, duration of surgery and complications were noted. Follow-up was performed by postal questionnaire and chart review. For women who had further surgery, rAFS stage, site of disease, other procedures and histology were all recorded. RESULTS: Pain scores were all significantly reduced at 2-5 years for dysmenorrhoea (median VAS baseline versus follow-up 2-5 years); 9 versus 3.3 (P < 0.0001), non-menstrual pelvic pain 8 versus 3 (P < 0.0001), dyspareunia 7 versus 0 (P < 0.0001) and dyschesia 7 versus 2 (P < 0.0001). Quality of life was improved for the EQ-5Dindex (P = 0.008 and the EQ-5Qvas (P = 0.03) and for sexual function with pleasure (P = 0.001) and habit (P = 0.012) being improved and discomfort being decreased (P = 0.001). The chance of requiring further surgery as determined by the Kaplan-Meier survival curve was 36%. A rAFS score of >70 was predictive of requiring further surgery (P = 0.03). Of women who had further surgery, endometriosis was found histologically in 68%. CONCLUSIONS: Laparoscopic excision of endometriosis significantly reduces pain and improves quality of life for up to 5 years. The probability of requiring further surgery is 36%. Return of pain following laparoscopic excision is not always associated with clinical evidence of recurrence.     

Evaluation of a new questionnaire for the presurgical diagnosis of bladder endometriosis

BACKGROUND: The main objective was to evaluate the diagnostic accuracy of a new questionnaire for the presurgical diagnosis of bladder endometriosis in patients with a high suspicion index for this disease. METHODS: We included all patients of age <40 years undergoing laparoscopy or laparotomy for chronic pelvic pain. We partially modified the American Urologic Association Symptom Index with the aim of identifying bladder endometriosis among 157 women undergoing surgery for chronic pelvic pain. All patients underwent preoperative ultrasonography; selected patients, with suspected bladder endometriosis, underwent computed tomography and cystoscopy. The physicians performing both the preoperative evaluation and surgery were blinded to the questionnaires' results. RESULTS: A total of 127 (81%) patients had pelvic endometriosis, 14 (8.9%) had bladder endometriosis. The questionnaires' score for patients with and without bladder endometriosis was 21 +/- 8.7 and 4.6 +/- 5.7, respectively (P < 0.0001). The area under the receiver operating characteristic curve was 0.951. With a cut-off of 9, sensitivity was 93% and specificity 88%. CONCLUSIONS: The questionnaire proved to be effective in identifying bladder endometriosis, allowing a proper diagnostic work-up and surgical treatment, and minimizing the risk of recurrence. In this primary referral centre for endometriosis the prevalence of the disease was high-therefore it may achieve a lower diagnostic accuracy when evaluated on a population of women with a lower prevalence of bladder endometriosis.     

Randomized clinical trial of a levonorgestrel-releasing intrauterine system and a depot GnRH analogue for the treatment of chronic pelvic pain in women with endometriosis

BACKGROUND: The objective of this multicentre randomized, controlled clinical trial was to compare the efficacy of a levonorgestrel-releasing intrauterine system (LNG-IUS) and a depot-GnRH-analogue in the control of endometriosis-related pain over a period of six months. METHODS: Eighty-two women, 18 to 40 years of age (mean 30 years), with endometriosis, dysmenorrhoea and/or CPP, were randomized using a computer-generated system of sealed envelopes into either LNG-IUS (n = 39) or GnRH analogue (n = 43) treatment groups at three university centres. Daily scores of endometriosis-associated CPP were evaluated using the Visual Analogue Scale (VAS), daily bleeding score was calculated from bleeding calendars, and improvement in quality of life was evaluated using the Psychological General Well-Being Index Questionnaire (PGWBI). The pain score diary was based on the VAS in which women recorded the occurrence and intensity of pain on a daily basis. A monthly score was calculated from the result of the sum of the daily scores divided by the number of days in each observation period. RESULTS: CPP decreased significantly from the first month throughout the six months of therapy with both forms of treatment and there was no difference between the groups (P > 0.999). In both treatment groups, women with stage III and IV endometriosis showed a more rapid improvement in the VAS pain score than women with stage I and II of the disease (P < 0.002). LNG-IUS users had a higher bleeding score than GnRH-analogue users at all time points of observation with 34% and 71% of patients in the LNG-IUS and GnRH-analogue groups, respectively, reporting no bleeding during the first treatment month, and 70% and 98% reporting no bleeding during the sixth month. No difference was observed between groups with reference to improvement in quality of life. CONCLUSIONS: Both, the LNG-IUS and the GnRH-analogue were effective in the treatment of CPP-associated endometriosis, although no differences were observed between the two treatments. Among the additional advantages of the LNG-IUS is the fact that it does not provoke hypoestrogenism and that it requires only one medical intervention for its introduction every 5 years. This device could therefore become the treatment of choice for CPP-associated endometriosis in women who do not wish to conceive.     

Luteal phase support in in-vitro fertilization using gonadotrophin releasing hormone analogue before ovarian stimulation: a prospective randomized study of human chorionic gonadotrophin versus intramuscular progesterone.

This study was conducted to compare the endocrine milieu and pregnancy rates in an in-vitro fertilization and embryo transfer (IVF-ET) programme employing a gonadotrophin-releasing hormone agonist (GnRHa) and human menopausal gonadotrophin (HMG) when either human chorionic gonadotrophin (HCG) or progesterone were used for luteal phase support. A total of 121 IVF-ET treatment cycles were prospectively studied. All patients started leuprolide acetate in the midluteal phase and it was continued for at least 10 days. When oestradiol levels were less than 150 pmol/l, HMG was started. When at least three follicles were greater than or equal to 17 mm in diameter, HCG 5000 IU i.m. was given. Oocytes were retrieved using transvaginal ultrasound and embryos were transferred 48 h later. The patients' cycles were prospectively randomized to receive HCG (72 cycles) or progesterone (49 cycles) luteal support. The HCG group received 1500 IU i.m. on days 3, 6 and 9 after the initial trigger. The progesterone group received 12.5 mg i.m. q.d. starting from the day after the HCG trigger. The dose of progesterone was increased to 25 mg i.m. q.d. starting on the day of embryo transfer and continued for 17-21 days. If the patient became pregnant, this dose of progesterone was continued until fetal heart activity was visualized by ultrasound. Mean ages, number of eggs retrieved, embryos transferred, oestradiol levels on the day of the HCG trigger, oestradiol and progesterone at the time of embryo transfer were the same in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

One year comparison between two add-back therapies in patients treated with a GnRH agonist for symptomatic endometriosis: a randomized double-blind trial

BACKGROUND: It has been proposed that hormonal supplementationduring prolonged GnRH agonist therapy prevents hypoestrogenicside effects, including bone loss. The optimal combination forlong-term treatments with safe metabolic profile remains questionable.A norprogesterone derivative, promegestone, was assessed forthe first time in a double-blind trial. METHODS: Seventy-eightpatients with endometriosis with rAFS (Revised American Societyfor Reproductive Medicine) scores of III–IV were randomlyassigned to monthly leuprorelin 3.75 mg (1 year) which,after the third injection was used in combination with promegestone0.5 mg (P) plus either estradiol placebo (PL) or estradiol2 mg (E) per day. Bone mineral density (BMD) was determinedat baseline, 6 and 12 months, and biological and clinical quarterlyassessments were performed. Analysis was by the intention totreat method. RESULTS: At month 12, BMD changes from baselinewere –6.1 ± 3.7 and –4.9 ± 4.0%in the PL-P group, at the spine and hip, respectively. Thisbone loss was prevented in the E-P group: –1.9 ± 3.1and –1.4 ± 2.3%, respectively (P < 0.0001inter-group comparisons). The BMD decrease in the E-P groupwas explained by the changes occurring during the first 6 monthsof treatment. There was no deleterious change in lipid parameters.Clinical improvement was observed without an inter-group difference.CONCLUSIONS: Estradiol 2 mg and promegestone 0.5 mgper day is an effective and safe add-back therapy, which canbe proposed for prolonged leuprorelin treatment over 6 monthsin severe endometriosis.     

Visible and non-visible endometriosis at laparoscopy in fertile and infertile women and in patients with chronic pelvic pain: a prospective study

In 100 consecutive patients who were undergoing laparoscopyfor infertility (group 1, n = 52), chronic pelvic pain (group2, n = 18) or tubal sterilization (group 3, n = 30, asymptomaticfertile women), peritoneal biopsies were taken from areas ofvisually normal peritoneum of uterosacral ligaments. Twenty-sixpatients in group 1 (50%), eight patients in group 2 (44.4%)and 13 patients in group 3 (43.3%), were found to have laparoscopicevidence of endometriosis elsewhere in the pelvis. The majorityof women (80.7% in group 1, 87.5% in group 2, and 100% in group3) had stage I disease. The incidence of the distinctive appearancesof the lesions was similar in the three groups of patients and7% of all women or 15% (7/47) of those patients having endometriosisat laparoscopy had only subtle (non-‘typical’) endometrioticperitoneal lesions. Uterosacral biopsies showed the presenceof endometriotic tissue in three cases (5.7%), two cases (11%)and three cases (10%) in groups 1, 2, and 3 respectively. Oneof the two patients in group 2 and two of the three patientsin group 3 had no evidence of endometriosis at laparoscopy;thus histological study revealed the presence of endometriosisin normal peritoneum hi 11 % (5/47) of patients having macroscopicendometriosis and hi 6% (3/53) of patients without endometriosisat laparoscopy. Previous oral contraceptive users were significantlyhigher among women having macroscopic and/or microscopic endometriosisthan among women without the condition. In conclusion, our prospectivestudy shows a high prevalence (45–50%) of endometriosis(including microscopic forms) in both patients with chronicpelvic pain and asymptomatic women (fertile and infertile),thus supporting the modern concept that in many women endometriosismay be a paraphysiological condition while probably only hisome patients small amounts of endometriosis are an ‘annoyance’with implications to their reproductive health and may producesymptoms (eg. pelvic pain) and therefore should be defined asa ‘dis-ease’. Previous use of oral contraceptivesmay increase the risk of developing endometriosis.     

Endometriosis: Immunohistochemical study of c-erb B-2 protein expression in endometriosis

Using immunohistochemical techniques, we studied the expressionof c-erb B-2 in normal human endometrial tissue (n = 8), endometriosisinterna (adenomyosis) (n = 8) and endometriosis externa (endometrioticcyst of the ovary) (n = 6). The glandular epithelium of normalendometrial tissue specimens in the proliferative phase stainedpositively. Most of the cases of endometriosis studied showedno expression of c-erb B-2 in glandular epithelium. No expressionwas detected in either the normal or endometriotic stromal cells.Results suggest that c-erb B-2 is not significantly involvedin the pathogenesis of endometriosis.     

Endometriosis: The bubble test: a new tool to improve the diagnosis of endometriosis

The objective of this study was to determine the clinical sensitivityand specificity of a bubbling phenomenon, including peritonealsurfaces, as a diagnostic test for endometriosis during laparoscopy.A prospectively controlled study of women with infertility ofat least 1 year duration, who underwent laparoscopy, was conductedat a medical school-affiliated private infertility centre andresearch foundation. The study included 48 prospectively enrolledfemale infertility patients who underwent laparoscopy. Of these,32 were found to suffer from endometriosis (group A) and 16control patients did not show any evidence of disease (groupB). The study involved the irrigation of the posterior cul-de-sacwith short bursts of either saline or lactated Ringer‘ssolution, utilizing a standard laparoscopic aspiration/irrigationsystem, and the subsequent observation for an excessive soap-likebubbling phenomenon (positive bubble test) in association withendometriosis. All 32 endometriosis patients (group A) demonstrateda positive bubble test. In contrast, only two of the 16 controlpatients (group B) were positive (P = 0.00242, Fisher's exacttest; odds ratio, 8.000). A positive bubble test during laparoscopywas thus 100% sensitive and 88% specific for the diagnosis ofendometriosis by laparoscopy, resulting in positive and negativepredictive values of 94 and 100% respectively. Since the literatureprovides considerable evidence that the diagnosis of endometriosisduring laparoscopy is frequently missed, a positive bubble testduring laparoscopy therefore may be considered a reason to searchfurther (possibly with biopsies) for endometriosis in the absenceof obviously visible disease. If confirmed, a positive bubbletest could then become an even more accurate single diagnostictest for endometriosis than laparoscopy.     

Low-dose danazol after combined surgical and medical therapy reduces the incidence of pelvic pain in women with moderate and severe endometriosis.

The most effective therapy for endometriosis is a matter for debate. The aim of the present randomized study was to evaluate the efficacy of low doses of danazol on recurrence of pelvic pain in patients with moderate or severe endometriosis, who had undergone laparoscopic surgery and 6 months of gonadotrophin-releasing hormone analogue (GnRHa) therapy. After surgery, 28 patients with moderate or severe endometriosis underwent therapy for 6 months with GnRHa i. m. every 4 weeks. They were then randomized into two groups: group A (14 subjects) was treated with 100 mg/day danazol for 6 months; group B (14 subjects, control) did not receive any type of therapy. After 12 months of treatment, group A had a significantly (P < 0.01) lower pain score than group B. There was no significant difference between the groups in oestrogen concentrations, bone mineral density or side-effects. The results suggest that low-dose danazol therapy reduces recurrence of pelvic pain in patients with moderate or severe endometriosis, treated surgically, and has few or no metabolic side-effects.     

Endometriosis: Electrocauterization in rats of experimentally induced endometriosis at a low temperature

Endometriosis was induced in 40 mature female rats by meansof transplantation of endometrium on the peritoneum near theovary. Three weeks later, all the rats were laparotomized andthey were randomized into four groups according to treatment;an untreated group and three groups with electrocauterizationat different temperatures. Three weeks after these treatments,they were again subjected to laparotomy and the implants wereexamined for their size, histology and lactate dehydrogenase(LDH) activity. In the untreated group, the size of the implantswas increased significantly. Electrocauterization at a hightemperature (about 300°C) was enough to destroy all theendometriosis and no LDH activity was observed. Electrocauterizationat a low temperature (70 or 85°C) with newly developed bipolarforceps also revealed complete remission of endometriosis andthere was no LDH activity in all the transplantation sites examined.These results indicate that the electrocauterization of endometriosisat a low temperature is safe and as effective as that at a hightemperature.     

Ultrasonic transvaginal aspiration of endometriotic cysts: an optional line of treatment in selected cases of endometriosis.

Transvaginal ultrasonically guided aspiration of pelvic endometriotic cysts was performed on 21 patients with recurrent endometriosis after previous surgical treatment. Their main complaint was pelvic pain and infertility. Further conservative surgery was considered a contraindication. The symptoms improved markedly following aspiration. During a 12 month follow-up, reaccumulation occurred in only six cases (28.5%) and the improvement in symptoms persisted in the majority of cases. The technique is simple, safe and effective in the treatment of selected cases of endometriosis.     

Comparative stimulatory effect of gonadotrophin releasing hormone (GnRH) and GnRH agonist upon pulsatile human chorionic gonadotrophin secretion in superfused placental explants: reversible inhibition by a GnRH antagonist.

The roles of gonadotrophin releasing hormone (GnRH) and a GnRH agonist (GnRHa) (D-Ala6-Met-Leu7-Pro-N-ethyl-amide) in controlling pulsatile human chorionic gonadotrophin (HCG) secretion by superfused placental explants in the first trimester were examined. One minute pulses of both GnRH and GnRHa had a biphasic effect upon pulsatile HCG secretion. GnRHa was maximally effective at 10(-10) M concentration, at 10(-11) M the effect was mild while at 10(-8) M, no effect was noted. GnRH exerted a maximal stimulatory effect at 10(-8) M; at 10(-10) M no effect was seen, while at 10(-7) M the effect was mildly stimulatory. This was evaluated by carrying out both a between and within channel type of analysis. The effect of a GnRH antagonist GnRH(ant) upon GnRH and GnRHa-induced HCG secretion was examined. Explants were incubated overnight with 10(-8) M GnRH(ant), which was also continuously administered during superfusion. The addition of 1-min pulses of GnRH and GnRHa during the exposure to GnRH(ant) failed to stimulate pulsatile HCG secretion. This effect was reversible since the response to GnRH was restored within 10 min after stopping GnRH(ant) administration. In addition, by the third cycle, co-administration of GnRH(ant) for 2 min together with 10(-10) M GnRHa for 1 min completely blocked the GnRHa-induced effect. Continuous administration of 10(-8) M GnRH(ant) decreased spontaneous HCG pulse amplitude and the area under the curve but failed to modify pulse frequency. In conclusion, GnRH appears to exert a receptor-dependent stimulatory effect upon pulsatile HCG secretion in superfusion in the first trimester placenta.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endometriosis: Prevalence and anatomical distribution of endometriosis in women with selected gynaecological conditions: results from a multicentric Italian study

We have evaluated the prevalence of endometriosis in selectedgynaecological conditions requiring surgery. Eligible for thestudy were women with primary or secondary sterility, chronicpelvic pain, fibroids or benign ovarian cysts requiring laparoscopyor laparotomy consecutively observed during the study periodin 23 obstetrics and gynaecology departments in Italy betweenMay 1991 and July 1992. Women with a previous diagnosis of endometriosiswere specifically excluded. A total of 3684 subjects enteredthe study. Of these, 660 (mean age 31 years) were included forsterility, 409 (mean age 32) for chronic pelvic pain, 1880 (meanage 42) for fibroids and 735 (mean age 33) for benign ovariancysts. During the surgical procedure surgeons were asked toexamine the pelvis carefully to identify endometriosis. Outof the 660 women included for sterility, 195 [30%, 95% confidenceinterval (CI) 26–35] had endometriosis; the correspondingfigures were 185 out of 409 (45%, 95% CI 39–52) for pelvicpain, 219 out of 1880 (12%, 95% CI 10–14) for fibroidsand 257 out of 735 (35%, 95% CI 31–40) for ovarian cysts;these differences were significant (x²₃ heterogeneity, absenceversus presence = 323.9, P < 0.001). Among women with endometriosiswho entered the study for sterility, 51% were at stage 1, 22%at stage 2, 20% at stage 3 and 7% at stage 4. The correspondingfigures for pelvic pain and fibroids were largely similar: 37%,24%, 30%, 10% for women with pelvic pain, 36%, 11%, 45% and8% for those with fibroids, but among cases with ovarian cystsstage 3 was over-represented (62% of cases). The most commonsites of endometriosis were, in order of frequency, the ovariesconsidered together, the posterior cul de sac and uterosacralligaments. Endometriotic implants were more common on the uterosacralligaments and the posterior cul de sac among women with sterilityand pelvic pain than in those with fibroids and ovarian cysts.The frequency of endometriosis was not directly related to ageat surgery, but decreased with increasing parity in all thefour criteria for entry groups.     

Time elapsed from onset of symptoms to diagnosis of endometriosis in a cohort study of Brazilian women

BACKGROUND: The study aim was to assess the time elapsed between onset of symptoms and diagnosis of endometriosis, and to identify the factors associated with diagnostic delay in a group of Brazilian women. METHODS: In this retrospective cohort study, 200 women with surgically confirmed endometriosis were interviewed at an endometriosis outpatient clinic. RESULTS: The median (interquartile range) time elapsed from onset of symptoms until diagnosis of endometriosis was 7.0 (range 3.5-12.1) years. The younger the women at onset of symptoms, the longer the period for diagnosis to be made: the median delay was 12.1 (range 8.0-17.2) years in women aged < or =19 years, and 3.3 (range 2.0-5.5) years in women aged > or =30 years. The median time period between onset of symptoms and diagnosis was 4.0 (2.0-6.0) years for women whose main complaint was infertility, but 7.4 (3.6-13.0) years for those with pelvic pain. CONCLUSIONS: The delay in diagnosis of endometriosis was considered to be long, and especially so for young women with pelvic pain. More information relating to endometriosis should be offered to general physicians and gynaecologists in order to reduce the time taken to diagnose this condition.