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Endometriosis is a relatively common condition in women of reproductive age and is associated with considerable morbidity. Despite an extensive literature describing its multiple clinical manifestations, their management, and many aspects of the biology of endometriotic lesions, the pathophysiological mechanisms involved remain poorly understood. A genetic component in endometriosis is now recognized, and several groups have taken up the challenge of using genetic techniques to identify the aberrant molecular and cellular mechanisms in endometriosis with the intention of providing much-needed insights that might, in turn, lead to new therapies. The techniques that have been applied include expression profiling, tumor genetic studies, functional candidate gene studies, and linkage studies that can adopt a hypothesis-free approach. This review describes the current status of these studies and explores the prospects for new therapies.

This study investigated the attributional styles of men with and without sexual dysfunction for both positive and negative sexual and general events using a sex-specific version of the Attributional Style Questionnaire (Sex-ASQ), and ascertained the preliminary psychometric properties of the measure. The Sex-ASQ was created by embedding 8 hypothetical sexual events (4 positive, 4 negative) among the original 12 events in the Attributional Style Questionnaire (ASQ; C. Peterson, A. Semmel, C. von Baeyer, L. Y. Abramson, G. I. Metalsky, & M. E. Seligman, 1982). The Sex-ASQ was completed by 21 men with a principal DSM-IV diagnosis of Male Erectile Disorder (MED) and 32 male control participants. The psychometrics of the Sex-ASQ were satisfactory, but with the positive sexual event scales found to be less stable and internally consistent than the negative sexual event scales. Reasons for modest reliability of the positive event scales are discussed in terms of the original ASQ. As expected, men with MED did not differ significantly from men without sexual dysfunction in their causal attributions for general events, indicating that both groups exhibited an optimistic attributional style in general. Also as predicted, men with MED made more internal and stable causal attributions for negative sexual events than men without sexual dysfunction, and also rated negative sexual events as more important. For positive sexual events, the 2 groups did not differ in attributional style, with both groups making more external/unstable/specific causal attributions than for positive general events. Differences between explanatory style for sexual versus nonsexual events found in both sexually functional and dysfunctional men lend support for explanatory style models that propose both cross-situational consistency and situational specificity.

Psychology has recently identified itself as a health care profession and codified this change in the bylaws of the American Psychological Association. Although psychologists make a number of contributions to the nation's health--and mental health--the most identifiable activity focuses on treating physical or psychological pathology with psychological interventions. Recently, health care policymakers have established that evidence supporting the efficacy of these interventions is more than sufficient for their inclusion in health care systems around the world. To promote faster and more widespread dissemination of these interventions specifically targeting problems severe enough to be included in health care systems and to solidify the identification of psychology as a health care profession, perhaps it is time for a change in terminology. It is proposed that psychologists label these procedures psychological treatments so as to differentiate them from more generic psychotherapy, which is often used outside of the scope of health care systems., (((c) 2004 APA, all rights reserved).)

The many dimensions of the field of reproduction (clinical, scientific, social, ethical, legal) must be addressed by those with editorial responsibility for the major journals in the field. As the editorial team of the leading reproductive journal Human Reproduction, we have evolved processes that attempt to ensure a transparent but robust approach to complexities whose impact varies across international boundaries.

Men with and without sexual dysfunction present with varying patterns of agreement between subjective estimates of sexual arousal and more objective psychophysiological measures of the same construct. This relative accuracy seems to be associated with sexual function, with men who have sexual dysfunction presenting less accurate estimations (mostly reporting below measured arousal levels). The purpose of this study is to clarify the processes underlying sexual arousal and the accuracy of its self-estimation. We looked at potential predictors of sexual arousal (subjective and physiological) and accuracy in estimating objective sexual arousal in a sample of 60 sexually functional males. Predictors included pre-existing sexual attitudes (erotophobia), both trait and state positive and negative affect, self-focused attention, and interoceptive awareness. Results indicate that this sexually functional sample generally reported below their own erection level. Interestingly, trait negative affect was associated with somewhat lower levels of subjective arousal and higher levels of physiological arousal. On the other hand, state positive affect facilitated both subjective and objective arousal and increased somewhat the accuracy of estimates of erectile responding. Pre-existing sexual attitudes as well as variations in self-focused attention and interoceptive awareness evidenced little effect on sexual arousal or the accuracy of its estimation.

Olfactory panic attacks have not been systematically assessed in a psychiatric population by any previous studies. Among Cambodian refugees attending a psychiatric clinic, the present investigation determines the following: (a) 1-month current prevalence of olfactory-triggered panic attacks, (b) associated psychopathology (Hopkins Symptom Checklist and the Structured Clinical Interview for DSM-IV-diagnosed posttraumatic stress disorder [PTSD]), and (c) frequency in events of olfactory panic of catastrophic cognitions (Panic Attack Cognitions Scale [PACQ]) and flashbacks (Clinician-Administered PTSD flashback scale). Forty-five percent of 100 consecutive psychiatric patients were found to have suffered an olfactory-triggered panic attack in the previous month; having current olfactory panic attacks was highly correlated with psychopathology (e.g., to PTSD diagnosis: and chi(2)=50.0; df=1; p<.001); and during olfactory-triggered panic attacks, catastrophic cognitions and flashbacks were common. Possible mechanisms for generation of high rates of olfactory-triggered panic attacks in this population are discussed (the "traumatic memory/catastrophic cognitions/interoceptive conditioning/escalating arousal" or "TCIE" model of panic generation) as are treatment implications.

Objective: Placebo effects in treatment of three anxiety disorders were compared., Method: Treatment response and patients' treatment expectancy were examined by using data from 70 patients with obsessive-compulsive disorder, social phobia, or panic disorder who received placebo in three randomized, controlled trials comparing cognitive behavior therapy, medication, and their combination to placebo., Results: Patients with obsessive-compulsive disorder were less likely to respond to placebo than patients with generalized social phobia or panic disorder. Differential expectancy did not account for these findings., Conclusions: Further examination of the placebo effect across the anxiety disorders may elucidate maintenance mechanisms of these disorders and have implications for development of more effective treatments.

Substantial advances in our understanding of the etiology and treatment of performance anxiety have occurred during the past decade. It has become clear that the development of efficient and effective treatments cannot be divorced from knowledge of the specific form of psychopathology being treated and that treatments must be tailored to this psychopathology. After describing a current model of the etiology of performance anxiety and social phobia, this commentary notes the common factors present across the rich and diverse set of articles in this issue describing treatments from different approaches and different theoretical orientations. To the extent that these common factors are important mechanisms of action, it is possible that the future will introduce more unified and more effective, efficient, and theoretically informed treatment for performance anxiety as well as the potential for preventive techniques., (Copyright 2004 Wiley Periodicals, Inc.)

Objective: Endometriosis is inherited as a complex trait, which means that multiple susceptibility genes interact with each other and the environment to produce the phenotype. Previous studies have implicated p53, a tumor suppressor gene, as a factor in the development of the disease. In a Japanese population, we investigated the frequency of the p53 polymorphism in women affected with endometriosis., Methods: We compared the distribution of the p53 codon 72 polymorphism in endometriosis cases (n = 111) and population controls consisting of female neonates (n = 180) by using polymerase chain reaction restriction fragment-length polymorphism analysis in a Japanese population., Results: The frequencies of the three p53 genotypes, Arginine (Arg)/Arg, Arg/Proline (Pro), and Pro/Pro in controls were 39.4%, 41.7%, and 18.9 %, respectively. The crude genotype frequencies in the endometriosis cases were similar to those of the controls (35.2%, 48.6%, and 16.2%, respectively). Using the Arg/Arg genotype as the reference, the odds ratios of the Arg/Pro and Pro/Pro genotypes were 1.30 (95% confidence interval [CI] 0.72-1.86, P =.33) and 0.96 (95% CI 0.47-1.94, P =.91), respectively. Thus, there were no significant differences in the frequency of the p53 codon 72 polymorphism between endometriosis cases and controls in this population. The endometriosis cases with severe disease only were also evaluated, but no significant difference was observed in the frequency of the polymorphism between this subgroup and the controls., Conclusion: Our findings suggest that the p53 codon 72 polymorphism is unlikely to be associated with endometriosis in Japanese women.

The purpose of this study was to examine independent evaluators' (IEs) blindness to treatment condition during a Multicenter Comparative Treatment Study of Panic Disorder. IEs were 15 doctoral- and masters-level clinicians in psychology, social work, and medicine. They conducted three post-treatment assessments with each patient. Immediately after each assessment interview, IEs completed a form indicating which of the five possible treatments they believed the patient had received and any specific information that provided IEs with information about a patient's treatment condition. These forms were completed for 170 patients. Analyses were conducted to determine the accuracy of guesses about treatment condition by IEs during post-treatment assessments, the relationship between accuracy of IE guessing and actual treatment assignment, the relationship between accurate guessing and outcome ratings, and contributors to the breaking of the blind. A significant relationship was found between IE guesses and actual treatment at all three assessment points, across individual IEs, treatment sites, and IE professional affiliations. IEs were no more accurate in their guessing about patients taking medication than those receiving behavior therapy. Patients and project staff inadvertently provided information to IEs that enhanced the rates of accurate guessing. Implications of these findings on interpretation of the treatment study are discussed, and recommendations are made for improving blindness procedures.

This study employs a release of proactive interference technique to explore encoding-related processes in social phobia. Twenty-six individuals with social phobia and 24 individuals with panic disorder participated in the memory task. Significant release of proactive interference was found when neutral and threat dimensions were encoded, but not when social and physical threat dimensions, or when positive and threat dimensions were presented. Threat was therefore differently encoded depending on the active encoding context in which semantic processing occurred. Individuals with social phobia or panic disorder did not differ in the release of proactive interference. The present experiment consequently yields little support for the specificity hypothesis in memory of anxious individuals. Instead, the findings generally demonstrate that threat encoding is similar for people with social phobia and those with panic disorder.

Cognitions are hypothesized to play a central role in panic disorder (PD). Previous studies have used questionnaires to assess cognitive content, focusing on prototypical cognitions associated with PD; however, few studies have qualitatively examined cognitions associated with the feared consequences of panic attacks. The purpose of this study was to conduct a qualitative and quantitative analysis of feared consequences of panic attacks. The initial, qualitative analysis resulted in the development of 32 categories of feared consequences. The categories were derived from participant responses to a standardized, semi-structured question (n = 207). Five expert-derived categories were then utilized to quantitatively examine the relationship between cognitions and indicators of PD severity. Cognitions did not predict PD severity; however, correlational analyses indicated some predictive validity to the expert-derived categories. The qualitative analysis identified additional areas of patient-reported concern not included in previous research that may be important in the assessment and treatment of PD.

Traditionally, therapeutic preparations of gonadotrophins are quantified with a rat in-vivo bioassay in biological international units (IU). This method was developed to cope with variability of production batch quality. The bioassay, however, presents some limitations, and differences in clinical responses when using different batches of urine-derived gonadotrophins have been reported. The production of human FSH by recombinant technology now allows the use of advanced physicochemical methods for quantifying FSH, which can be measured in microg of FSH proteins (in mass). The study reported here was designed and conducted to assess the clinical relevance of this new method for quantifying therapeutic preparation of FSH. Four bulk lots of recombinant human FSH (r-hFSH) were used to prepare batches filled by IU (FbIU) and four batches filled by mass (FbM). These eight batches were compared in a double-blind, randomized study in patients undergoing assisted reproductive technology. One hundred and thirty-one patients were enrolled in this study and met protocol criteria (66 in the FbM group and 65 in the FbIU group). The starting dose of recombinant human FSH (r-hFSH) was either 150 IU or 11 microg/day. Both preparations induced multiple follicular development and all patients underwent oocyte retrieval. The number of follicles >/= 11mm was 14.85 and 14.91, serum oestradiol concentration on day of human chorionic gonadotrophin (HCG) administration was 6524 and 6350 pmol/l, number of oocytes retrieved was 10.76 and 11.28, number of two-pronuclear (2 PN) oocytes was 5.2 and 5.00, number of viable embryos (replaced or cryopreserved) was 4.15 and 3.72, and clinical pregnancy rate was 30.3 and 26.2% respectively in the FbM and FbIU groups. Overall, the patients' response consistency was found to be superior with FbM (P = 0.039), and in particular for clinical pregnancy rates (P < 0.001). This new method for quantifying r-hFSH delivers an improved consistency in clinical outcome.

The interleukin-11 (IL-11) receptor alpha has an important function in decidualization of mouse endometrial stroma but the function of IL-11 and its receptor in the human endometrium remains unknown. The mRNA for IL-11 and its receptor alpha in human endometrial tissue samples were analysed by semi-quantitative RT-PCR and RNase protection assays respectively. The proteins were detected in frozen endometrial tissue samples by immunofluorescence. The effect of heparin-binding epidermal growth factor (HB-EGF) on secretion of IL-11 by cultured endometrial stromal cells was assessed by enzyme-linked immunosorbent assay. The proliferative potential of IL-11 in endometrial stromal cells was assessed by [(3)H]thymidine uptake. IL-11 and its receptor alpha mRNAs and proteins were detected in the endometrium throughout the cycle. Distinct patterns of localization of the ligand and receptor were observed. HB-EGF induced IL-11 secretion by cultured stromal cells, and IL-11 induced [(3)H]thymidine uptake by these cells. Our data suggest that IL-11-receptor interactions may perform different functions in the human endometrium at different stages of the cycle, and that secretion of IL-11 is modulated by local growth factors.

A large number of studies suggest that individual characteristics of psychotherapists affect the outcome of psychosocial treatments for psychiatric illness, but little work has been done to see if this is also the case for pharmacotherapy. In the context of a multicenter study that compared psychosocial and medication treatments for panic disorder, we assessed whether such characteristics as age of the psychiatrist, number of years of experience, and gender influence the outcome of treatment with the antipanic drug imipramine. Data were examined by multiple and logistic regression analyses for eight psychiatrists who treated a total of 57 patients with panic disorder. More physician experience, measured as years since completing residency, was associated with better response to imipramine on one of two main dichotomous measures (the Clinical Global Impression-Improvement Scale) and on six of nine continuous measure rating scales. Associations between psychiatrist age and outcome and between psychiatrist gender and outcome were also present but on fewer measures. Although these are post-hoc analyses that were not planned when the multicenter study was originally designed and therefore there are limitations in the information available about the psychiatrists' characteristics, the findings suggest that even in the context of a clinical trial that employs a specific protocol and single medication, physician experience may influence patient outcome. Depression and Anxiety 17:88-93, 2003., (Copyright 2003 Wiley-Liss, Inc.)

Heparin-binding epidermal growth factor (HB-EGF), a member of the epidermal growth factor (EGF) family, is implicated in a variety of biological processes, including reproduction. Previous studies describe increased levels of HB-EGF in the human endometrium during the midsecretory stage of the menstrual cycle, suggesting a function for HB-EGF in implantation of the human blastocyst. Here we have investigated the expression and function of the soluble and transmembrane forms of HB-EGF in the human endometrium. We show that the expression of the transmembrane form of HB-EGF in the human endometrium is modulated according to the stage of the menstrual cycle. We present data demonstrating that both the soluble and transmembrane forms of HB-EGF induce DNA synthesis in human endometrial stromal cells. Furthermore, TNFalpha has a cooperative effect on HB-EGF, EGF, TGFalpha, and betacellulin-induced DNA synthesis in stromal cells, suggesting roles for the EGF family and TNFalpha in regeneration and maturation of human endometrium. Induction of DNA synthesis by HB-EGF and its modulation by TNFalpha in endometrial stromal cells are mediated by the EGF receptor and not the HB-EGF receptor ErbB4. Our data suggest key functions for HB-EGF, TNFalpha, and the EGF receptor in endometrial maturation, via autocrine/paracrine and juxtacrine pathways, in preparation for embryo implantation.

The mechanisms that mediate implantation of the human embryo remain poorly understood and represent a fundamental problem in reproductive biology. Candidate molecules that mediate and facilitate implantation have been identified in animal studies, and include heparin binding epidermal growth factor. Here we demonstrate a potential function for the transmembrane form of heparin-binding epidermal growth factor in mediating blastocyst attachment to the endometrium, in two different novel in vitro models for human implantation. Furthermore, we demonstrate specific localisation of the heparin-binding epidermal growth factor receptor ErbB4, on the surface of the trophectoderm in peri-implantation human blastocysts. Our data lead the way for further dissection of the molecular mechanisms of implantation of the human embryo, and have implications for infertility, in vitro fertilization and contraception.

Background: Approximately one in six couples experiences problems with their fertility at some point in their reproductive lives. The economic implications of the use of assisted reproductive techniques require consideration. Herein, the health economics research in this area are critically appraised., Methods: Multiple strategies were used to identify relevant studies. Each title and abstract was independently reviewed by two members of the study team and categorized according to perceived relevance. The selected papers were then assessed for quality and data were extracted, converted to UK pounds sterling at 1999/2000 prices, tabulated and critically appraised., Results: A total of 2547 papers was identified through the searches; this resulted in 30 economic evaluations, 22 cost studies and five economic benefit studies that met the selection criteria. The quality of these studies was mixed; many failed to disaggregate costs, discount future costs or conduct sensitivity analyses. Consistent findings included the following: initiating treatment with intrauterine insemination appeared to be more cost-effective than IVF; vasectomy reversal appeared to be more cost-effective than ICSI; factors associated with poor prognosis decreased the cost-effectiveness of interventions., Conclusions: The cost-effectiveness of different interventions should be considered when making decisions about treatment. Future economic appraisals of assisted reproductive techniques would benefit from more robust methodology than is evident in much of the published literature to date.

Objective: The aim of the International Endogene Study is to discover genes that influence susceptibility to endometriosis., Design: The study brings together two research groups based in Australia and the United Kingdom that independently have been collecting families for linkage analysis and candidate gene studies. Both groups used similar methods to recruit families, obtain clinical notes, assign disease status based on the operative records and available histology, and collect common clinical data including age at onset of symptoms, age at diagnosis, and symptoms experienced., Setting: Recruitment has been mainly from Australia, the United Kingdom, and the United States., Patient(s): All affected participants have surgically confirmed disease., Intervention(s): None., Main Outcome Measure(s): Clinical and epidemiological data., Result(s): To date, >1,100 families with affected sisters have been recruited, and >1,200 triads (affected women and both parents), for case-control studies., Conclusion(s): We have created the largest resource yet assembled of clinical data and DNA for linkage and association studies in endometriosis. The increase in power to detect susceptibility genes vindicates the decision to merge the two studies and demonstrates the value of large-scale international collaboration.

Background: The objective of this study was to confirm the source and study the acute changes and relationship between inhibins and FSH at surgical menopause., Methods: Regularly cycling women (42-47 years; n = 10) undergoing bilateral oophorectomy for non-ovarian pathology were recruited for this study. One blood sample was taken before surgery and after removal of the ovaries, samples were taken every 15 min up to 1 h, hourly up to 6 h, after 12 h and daily during the hospital admission (3 days)., Results: There were five women in the follicular phase and five women in the luteal phase of the cycle. For women in both phases, levels of inhibin A, inhibin B, estradiol (E(2)) and progesterone decreased after the removal of the ovaries. Serum FSH levels started to rise after 12 h in both follicular and luteal phase women after the surgical menopause. Correlation analysis showed that inhibin A and E(2) were significantly negatively correlated in both phases with FSH concentration. Inhibin B had a negative correlation in the follicular phase and progesterone had a negative correlation in the luteal phase., Conclusions: This study showed that ovarian inhibin A and B were cleared from the circulation within 12 h of oophorectomy, whereas E(2) and progesterone remain in the circulation for longer. Negative correlation between FSH, inhibin A and inhibin B suggests that inhibins may contribute to the observed early rise in FSH after the surgical menopause.

Great strides have been made in developing psychosocial interventions for the treatment of depression and bipolar disorder over the last three decades, but more remains to be done. The National Institute of Mental Health Psychosocial Intervention Development Workgroup recommends three priorities for future innovation: 1) development of new and more effective interventions that address both symptom change and functional capacity, 2) development of interventions that prevent onset and recurrence of clinical episodes in at-risk populations, and 3) development of user-friendly interventions and nontraditional delivery methods to increase access to evidence-based interventions. In each of these areas, the Workgroup recommends systematic study of the mediating mechanisms that drive the process of change and the moderators that influence their effects. This information will highlight the elements of psychosocial interventions that most contribute to the prevention and treatment of mood disorders across diagnostic groups, populations served, and community settings. The process of developing innovative interventions should have as its goal a mental health service delivery system that prevents the onset and recurrence of the mood disorders, furnishes increasingly effective treatment for those who seek it, and provides access to evidence-based psychosocial interventions via all feasible means.

Objective: To determine effects of five years of treatment with an oral continuous combined regimen of 2 mg 17beta-oestradiol and 1 mg norethisterone acetate on endometrial histology in postmenopausal women., Design: Follow up study in postmenopausal women., Setting: 31 menopause clinics in the United Kingdom., Participants: 534 postmenopausal women, all with an intact uterus, who had completed nine months of treatment with oral continuous combined 2 mg 17beta-oestradiol and 1 mg norethisterone acetate agreed to take part in a long term follow up study. Women were assigned to different groups on the basis of the treatment status immediately before entering the original study: 360 women had taken sequential oestrogen-progestogen hormone replacement therapy, 164 had taken no hormone replacement therapy, and 10 had taken unopposed oestrogen therapy., Methods: Endometrial aspiration specimens were taken before the women started the continuous combined regimen, after 9 and 24-36 months, and at the end of the five year treatment period or on withdrawal from the study., Main Outcome Measure: Results of endometrial histology., Results: The duration of treatment with continuous combined hormone replacement therapy was 4.4 (range 1.1-5.9) years. Data on endometrial specimens were available for 526 women after nine months of treatment, 465 women after 24-36 months of treatment, and 398 women who completed the five years treatment (345 women) or were withdrawn between the two latter visits for biopsies (53 women). No cases of endometrial hyperplasia or malignancy were detected at biopsy; 69% of women had an endometrium classified as atrophic or unassessable on completion of the study or withdrawal from it. Before the continuous combined therapy was started, complex hyperplasia was detected in 21 women who had taken sequential hormone replacement therapy before the study and in one who had taken unopposed oestrogen. All of these women had normal results on histological examination of endometrial tissue after nine months of treatment with continuous combined hormone replacement therapy, and hyperplasia did not recur after up to five years of treatment., Conclusions: Long term treatment (for up to five years) with continuous combined hormone replacement therapy containing oestradiol 2 mg and norethisterone 1 mg daily was associated with neither endometrial hyperplasia nor malignancy. In women who had complex hyperplasia during previous sequential or unopposed regimens, the endometrium returned to normal during treatment with continuous combined hormone replacement therapy. These findings provide reassurance about the long term safety of this continuous combined regimen in terms of the endometrium.

Seventy-three patients (ages 18 to 66) with specific phobias from one of four DSM-IV subtypes (animal, situational, blood-injection-injury, and natural environment) were assessed by experienced clinicians using a semistructured diagnostic interview. All patients were free of lifetime anxiety comorbidity. Subtype groups were compared on age of onset, mode of onset, presence of unexpected panic attacks, and focus of fear. Consistent with earlier findings, participants with situational phobia had a later age of onset and more unexpected panic attacks. No differences were found across subtypes in mode of onset. Contrary to previous findings, natural environment and situational phobias were most frequently associated with a focus on danger or harm rather than other foci such as internal sensations associated with panic attacks. Implications for the usefulness of current subtype categories are discussed.

Objective: This study was designed to assess the ovarian response in the same patient in consecutive IVF cycles., Design: Retrospective study., Setting: Assisted reproductive unit at a university hospital., Patient(s): One hundred ninety women who underwent three consecutive cycles of IVF., Intervention(s): All women used a combination of pituitary desensitization and gonadotropin stimulation protocol and underwent oocyte retrieval., Main Outcome Measure(s): Number of follicles produced and number of oocytes retrieved., Result(s): There were no significant differences in the number of follicles produced, number of oocytes retrieved, and number of embryos created by the same woman among the three cycles of treatment., Conclusion(s): Consistent ovarian response can be achieved during the first three consecutive IVF cycles.

Background: Endometriosis is the presence of endometrial glands or stroma in sites other than the uterine cavity. It is variable in both its surgical appearance and clinical manifestation often with poor correlation between the two. Surgical treatment of endometriosis aims to remove visible areas of endometriosis and restore anatomy by division of adhesions., Objectives: To assess the efficacy of laparoscopic surgery in the treatment of subfertility associated with endometriosis. The review aims to compare outcomes of laparoscopic surgical interventions compared to no treatment or medical treatment with regard to improved fertility., Search Strategy: We searched the Cochrane Menstrual Disorders and Subfertility Group's specialised register of trials (searched Feb 2000), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 2, 2000), MEDLINE (1966-July 2001), EMBASE (1980-July 2001), the National Research Register (Issue 1, 2000) and reference lists of articles., Selection Criteria: Trials were selected if they were randomised and compared the effectiveness of laparoscopic surgery in the treatment of subfertility associated with endometriosis versus other treatment modalities or placebo., Data Collection and Analysis: Two studies had data appropriate for inclusion within the review. These studies compared laparoscopic surgical treatment of minimal and mild endometriosis compared with diagnostic laparoscopy only. The recorded outcomes included live birth, pregnancy, fetal losses and complications of surgery., Main Results: Meta-analysis of the two randomised trials show improvement in infertility associated with endometriosis with laparoscopic surgery. The largest trial (Marcoux 1997) clearly supports this outcome with an increased chance of pregnancy (OR 2.03, 95% CI 1.28 to 3.24) and ongoing pregnancy rate after 20 weeks (OR 1.95, 95% CI 1.18 to 3.22) but the smaller trial (Gruppo Italiano 1999) does not show benefit (pregnancy OR 0.76, 95% CI 0.31 to 1.88; livebirth OR 0.85, 95% CI 0.32 to 2.28). Combining ongoing pregnancy and live birth rates there was a statistically significant increase with surgery (OR 1.64, 95% CI 1.05 to 2.57)., Reviewer's Conclusions: The use of laparoscopic surgery in the treatment of minimal and mild endometriosis may improve success rates. The relevant trials have some methodological problems and further research in this area is needed.

An association between endometriosis and the glutathione S-transferase (GST) M1 null mutation has been reported in French and Slavic populations. We aimed to replicate this association of endometriosis in a UK population, and to test for association with the GSTT1 null mutation or the cytochrome P450 (CYP) 1A1 MspI polymorphism. We genotyped 148 women each with endometriosis (sporadic cases, n = 91; familial cases, n = 57), a population control of 95 male blood donors, and a control group of 53 women with a normal pelvis at hysterectomy. No significant differences were found between cases and controls in the frequencies of the GSTM1 and GSTT1 null mutations, or the CYP1A1 MspI polymorphism. However, the combination of the GSTM1 null genotype and the CYP1A1 MspI polymorphism was associated with a small increased risk of endometriosis, and this warrants further investigation. We also tested for linkage to the chromosome 1p13 region, to which GSTM1 has been mapped, in 52 sister-pairs with stage III-IV disease using three highly polymorphic microsatellite markers. However, there was no evidence of linkage, suggesting that this region may not be implicated in disease susceptibility.

The relationship between therapists and treatment outcome was examined in 14 highly trained therapists who participated in the Multicenter Collaborative Study for the Treatment of Panic Disorder. Overall, therapists yielded positive outcomes in their caseloads; yet, therapists significantly differed in the magnitude of change among caseloads. Effect sizes for therapist impact on outcome measures varied from 0% to 18%. Overall experience in conducting psychotherapy was related to outcome on some measures, whereas age, gender, gender match, and experience with cognitive-behavioral therapy (CBT) were not. Therapists with above- and below-average outcomes were rated similarly on measures of adherence and competency. The results suggest that therapists make a contribution to outcome in CBT for panic disorder, even when patients are relatively uniform, treatment is structured, and outcome is positive. Implications for future clinical outcome studies and for training clinicians are discussed.

Anxiety sensitivity (AS) has been defined as the fear of anxiety and anxiety-related sensations, and evidence suggests that AS plays an important role in the psychopathology of panic. It is entirely unclear whether the relation between AS and panic should be attributed to one (or more) of the AS group factors, the general AS factor, or to factors at both levels of the AS hierarchy. The authors reanalyzed data presented earlier by R. M. Rapee, T. A. Brown, M. A. Antony, and D. H. Barlow (1992) to tease apart the contributions of the different levels of the AS hierarchy to fear responses to hyperventilation and 5.5% carbon dioxide challenges. The results demonstrated that AS-Physical Concerns is the only one of the three AS group factors that contributes to relations with fear responses to these two challenges. However, AS-Mental Incapacitation Concerns had a stronger positive linear association with depressed mood than did AS-Physical Concerns.

Background: Chronic pelvic pain has often been described as a major women's health issue, but no information exists on the extent of the problem in the United Kingdom., Aim: To investigate the community prevalence of chronic pelvic pain and its effect on the lives of consulting and non-consulting women., Design of Study: Postal questionnaire survey., Setting: Women aged 18 to 49 (n = 3916) randomly selected from the Oxfordshire Health Authority Register., Method: The questionnaire response rate (adjusted for non-deliveries) was 74% (2304/3106). Chronic pelvic pain was defined as recurrent or constant pelvic pain of at least six months' duration, unrelated to periods, intercourse, or pregnancy. Case subgroups comprised recent consulters, past consulters, and non-consulters. Women who reported dysmenorrhoea alone formed a comparison group., Results: The three-month prevalence of chronic pelvic pain was 24.0% (95% CI = 22.1% to 25.8%). One-third of women reported pain that started more than five years ago. Recent consulters (32% of cases) were most affected by their symptoms in terms of pain severity, use of health care, physical and mental health scores, sleep quality, and pain-related absence from work. Non-consulters (41% of cases) did not differ from women with dysmenorrhoea in terms of symptom-related impairment. Irrespective of consulting behaviour, a high rate of symptom-related anxiety was found in women with chronic pelvic pain (31%) compared with women with dysmenorrhoea (7%)., Conclusions: This study showed a high community prevalence of chronic pelvic pain in women of reproductive age. Cases varied substantially in the degree to which they were affected by their symptoms. The high symptom-related anxiety in these women emphasises the need for more information about chronic pelvic pain and its possible causes.

Objectives: This study was undertaken to investigate the overlap between chronic pelvic pain, dysmenorrhea, dyspareunia, irritable bowel syndrome, and genitourinary symptoms in the community and also to examine associated investigations and diagnoses., Study Design: A postal questionnaire was used to survey 3916 women aged 18 through 49 randomly selected from the Oxfordshire Health Authority Register. The number of responders was 2304 (74% of 3106 questionnaire recipients). Chronic pelvic pain was described as recurrent or constant pelvic pain of > or =6 months' duration unrelated to periods, intercourse, or pregnancy. Case patients (n = 483) were subgrouped as follows: (1) chronic pelvic pain only, (2) chronic pelvic pain and irritable bowel syndrome, (3) chronic pelvic pain and genitourinary symptoms, and (4) chronic pelvic pain, genitourinary symptoms, and irritable bowel syndrome., Results: Half the women with chronic pelvic pain also had either genitourinary symptoms or irritable bowel syndrome, or both. Prevalences of dysmenorrhea and dyspareunia were higher among women with chronic pelvic pain (81% and 41%, respectively) than among women without chronic pelvic pain (58% and 14%, respectively); rates did not differ among the chronic pelvic pain subgroups. Irritable bowel syndrome and stress were the most common diagnoses received by patients with chronic pelvic pain, but 50% had never received a diagnosis., Conclusions: There is substantial overlap between chronic pelvic pain and other abdominal symptoms in the community. Despite a high prevalence of chronic pelvic pain, many women have never had the condition diagnosed.

After viewing 2 sexually explicit films, 52 sexually functional participants were given bogus feedback indicating a low erectile response. The men were given either an external, fluctuating attribution (i.e., poor films) or an internal, stable attribution (i.e., problematic thoughts about sex) for the low arousal. As hypothesized, participants in the external, fluctuating group evidenced greater erectile response and subjective arousal during a 3rd film than did participants given the internal, stable attribution. This may indicate that after an occasion of erectile difficulty, the cause to which the difficulty is attributed plays an important role in future sexual functioning.

In the past, many studies attempting to compare pharmacological and psychosocial treatments for mood and anxiety disorders have been conducted by partisans of either approach. More recently, rigorously conducted, unbiased comparative studies have begun to appear. Here we reviewed our own experience in designing and conducting a multicenter study comparing medication and cognitive behavioral therapy and their combination for the treatment of panic disorder.

Several theories of the development of panic disorder (PD) with or without agoraphobia have emerged in the last 2 decades. Early theories that proposed a role for classical conditioning were criticized on several grounds. However, each criticism can be met and rejected when one considers current perspectives on conditioning and associative learning. The authors propose that PD develops because exposure to panic attacks causes the conditioning of anxiety (and sometimes panic) to exteroceptive and interoceptive cues. This process is reflected in a variety of cognitive and behavioral phenomena but fundamentally involves emotional learning that is best accounted for by conditioning principles. Anxiety, an anticipatory emotional state that functions to prepare the individual for the next panic, is different from panic, an emotional state designed to deal with a traumatic event that is already in progress. However, the presence of conditioned anxiety potentiates the next panic, which begins the individual's spiral into PD. Several biological and psychological factors create vulnerabilities by influencing the individual's susceptibility to conditioning. The relationship between the present view and other views, particularly those that emphasize the role of catastrophic misinterpretation of somatic sensations, is discussed.

The current investigation explores possible reasons for the poor overall success rates of medical techniques used in the treatment of erectile dysfunction. This is the first study to compare directly the psychological impact of a mechanically produced versus an erotically produced erection. Subjective and objective parameters of sexual arousal were used to compare the experience of a mechanically attained erection versus an erotically stimulated erection. Twenty-eight (28) men without sexual dysfunction were asked to reach a full erection during each of the following two conditions: (a) by using an ErecAid System and (b) by self-stimulating while watching an erotic video. The results of this study suggest that the penile vacuum device was a successful method for attaining penile tumescence; however, the presence of penile tumescence was not accompanied by a subjective state of physical or mental sexual arousal. Thus, the mere physical presence of an erection does not seem to evoke bodily or mental feelings of sexual arousal. It is important to note that these findings suggest that attention to the psychosexual components of the individual's sexual experience are critical to the subjective experience of sexual arousal and reflect once again the multimodal response systems involved in sexual arousal. These results suggest that more effective treatment approaches would be based on a clinical strategy that provides instruction both on the technical use of a mechanical device as well as on the importance of creating an appropriate psychosexual environment.

Objectives: To assess the efficacy of laparoscopic surgery in the treatment of pelvic pain associated with endometriosis. The review aims to compare the effectiveness of any laparoscopic procedure versus any other treatment modality, including expectant management., Search Strategy: The search strategy of the Menstrual Disorders and Subfertility Review Group was used to identify all publications that described or might have described randomised trials of laparoscopic surgery in the treatment of symptomatic endometriosis. For a full description of the Review Group strategy see the Review Group details., Selection Criteria: Trials were selected if they were randomised and compared the effectiveness of laparoscopic surgery in the treatment of pelvic pain associated with endometriosis, with other treatment modalities or placebo., Data Collection and Analysis: One study had data appropriate for inclusion within the review. This study compared laparoscopic laser surgery with diagnostic laparoscopy. Pain relief was the primary outcome measure. The data was extracted independently by two reviewers., Main Results: In comparison to expectant treatment there is a significant degree of pain relief at six months after surgery with laser laparoscopic surgery for minimal, mild and moderate endometriosis. Odds Ratio (OR) 4.97, 95% Confidence Interval (CI) 1.85,13.39, Reviewer's Conclusions: The combined surgical approach of laparoscopic laser ablation, adhesiolysis and uterine nerve ablation is likely to be a beneficial treatment for pelvic pain associated with minimal, mild and moderate endometriosis. As only one trial is included in the analysis, this conclusion should be interpreted with caution.

The ascendance of emotion theory, recent advances in cognitive science and neuroscience, and increasingly important findings from developmental psychology and learning make possible an integrative account of the nature and etiology of anxiety and its disorders. This model specifies an integrated set of triple vulnerabilities: a generalized biological (heritable) vulnerability, a generalized psychological vulnerability based on early experiences in developing a sense of control over salient events, and a more specific psychological vulnerability in which one learns to focus anxiety on specific objects or situations. The author recounts the development of anxiety and related disorders based on these triple vulnerabilities and discusses implications for the classification of emotional disorders.

Objectives: 1. To determine the prevalence of endometrial hyperplasia in postmenopausal women taking standard proprietary regimens of sequential oestrogen/progestogen; 2. to determine the effects of nine months treatment with an oral continuous combined regimen of 2 mg 17beta-oestradiol and 1 mg norethisterone acetate (Kliofem [Kliogest outside the UK]; Novo Nordisk, Denmark) on endometrial histology in postmenopausal women., Design: An open, prospective study in postmenopausal women., Setting: Fifty-four menopause clinics in the UK., Participants: 2028 postmenopausal women: 1312 (Group A) taking sequential oestrogen-progestogen hormone replacement therapy (HRT), and 716 (Group B) not taking HRT, were recruited. In Group A, 388 women took preparations containing 10 days of progestogen, 921 had 12 days, and 3 had 13 days per cycle., Methods: Endometrial aspiration biopsies were taken towards the end of a three-month run-in period (Group A) or at study entry (Group B), before administration of the continuous combined HRT regimen. Biopsies were repeated at the end of the nine month treatment period., Main Outcome Measure: Endometrial histology., Results: Initial endometrial biopsy data were available for 1106 women in Group A, who by the time of endometrial investigation had been taking HRT for a median duration of 2.56 years (5th to 95th centiles: 0.77 to 8.49 years). Data were available for 661 untreated women, who had no bleeding and had not taken HRT within the last year (Group B). Complex hyperplasia was found in 59 women (5.3%), and atypical hyperplasia in a further eight (0.7%) in Group A. In Group B there were no cases with complex hyperplasia, but one woman showed atypical hyperplasia (0.2%). At the end of the nine months of continuous combined therapy there was no case of hyperplasia among 1196 biopsies (upper 95% confidence limit of risk 0.31%) in women completing the study. Within this Group all of the women with complex hyperplasia arising during previous sequential HRT and who completed the study (n = 38) reverted to normal endometrial patterns. There was no case of endometrial carcinoma during the study., Conclusions: Despite taking standard regimens of sequential HRT containing at least 10 days of progestogen, there was a 5.3% prevalence of complex endometrial hyperplasia, and a 0.7% prevalence of atypical hyperplasia. However, continuous combined HRT (Kliofem) containing daily progestogen is not associated with an increased risk of hyperplasia and will convert the endometrium to normal in those with complex hyperplasia arising during previous sequential HRT.

An overview is given of the current knowledge of the epidemiology of chronic pelvic pain (CPP) in terms of prevalence, incidence, and associated risk factors. However, the lack of a consensus on the definition of CPP greatly hinders epidemiological studies. Although data are limited, the prevalence of CPP in the general population appears to be high. A single study found a 3-month prevalence (pelvic pain of at least 6 months' duration) of 15% in women aged 18-50 in the general US population. In the UK, an annual prevalence in primary care of 38/1000 was found in women aged 15-73, a rate comparable to that of asthma (37/1000) and back pain (41/1000). The monthly incidence in primary care was 1.6/1000. No incidence figures exist for the general population. Analysis of risk factors for CPP is highly complicated owing to its multifactorial aetiology. At present, it is only of some value using women with CPP identified at community level, since those in primary, secondary or tertiary care are likely to constitute highly selected sub-groups.