First Australian estimates of incidence and prevalence of uterine fibroids: a data linkage cohort study 2000-2022.

STUDY QUESTION: What is the estimated prevalence and incidence of uterine fibroids diagnosed in Australian women of reproductive age? SUMMARY ANSWER: An estimated 7.3% of Australian women had a diagnosis of uterine fibroids by the age of 45-49 years, with age-specific incidence highest in women aged 40-44 years (5.0 cases per 1000 person-years). WHAT IS KNOWN ALREADY: Uterine fibroids are associated with a high symptom burden and may affect overall health and quality of life. Studies in different countries show a wide variation in both the prevalence (4.5-68%) and incidence (2.2-37.5 per 1000 person-years) of uterine fibroids, which may be partly explained by the type of investigation, method of case ascertainment, or the age range of the study population, necessitating the reporting of country-specific estimates. STUDY DESIGN, SIZE, DURATION: This observational prospective cohort study using self-report survey and linked administrative data (2000-2022) included 8066 women, born between 1973 and 1978, in the Australian Longitudinal Study on Women's Health. PARTICIPANTS/MATERIALS, SETTING, METHODS: A combination of self-report survey and linked administrative health data (hospital, emergency department, the Medicare Benefits Schedule, and the Pharmaceutical Benefits Scheme) were used to identify women with a report of a diagnosis of uterine fibroids between 2000 and 2022. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 8066 Australian women followed for 22 years, an estimated 7.3% of women (95% CI 6.9, 7.6) had a diagnosis of uterine fibroids by the age of 45-49 years. The incidence increased with age and was highest in women aged 40-44 years (5.0 cases per 1000 person-years, 95% CI 4.3, 5.7 cases per 1000 person-years). Women with uterine fibroids were more likely to experience heavy or painful periods. They were also more likely to report low iron levels, endometriosis, and poor self-rated health and to have two or more annual visits to their general practitioner. LIMITATIONS, REASONS FOR CAUTION: Our estimates are based on self-report of doctor diagnosis or treatment for fibroids and/or data linked to treatment and procedure administrative records. This predominantly captures women with symptomatic fibroids, but has the potential for misclassification of asymptomatic women and an underestimate of overall prevalence and incidence. In addition, questions on fibroids were only asked in surveys when women were 37-42 years of age to 43-48 years of age, so cases at younger ages may have been underestimated (particularly in women with less severe symptoms) as these were only ascertained through data linkage. WIDER IMPLICATIONS OF THE FINDINGS: These are the first population-based estimates of the prevalence and incidence of uterine fibroids in women of reproductive age in Australia. Establishing these first estimates will help inform health policy and health care provision in the Australian context. STUDY FUNDING/COMPETING INTEREST(S): The ALSWH is funded by the Australian Government Department of Health and Aged Care. L.FW. was supported by an Australian National Health and Medical Research Council (NHMRC) Centres for Research Excellence grant (APP1153420) and G.D.M. was supported by an NHMRC Leadership Fellowship (APP2009577). The funding bodies played no role in the design, the collection, analysis or interpretation of data, the writing of the manuscript, or the decision to submit the manuscript for publication. There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Top 10 priorities for future infertility research: an international consensus development study.

STUDY QUESTION: Can the priorities for future research in infertility be identified? SUMMARY ANSWER: The top 10 research priorities for the four areas of male infertility, female and unexplained infertility, medically assisted reproduction, and ethics, access, and organization of care for people with fertility problems were identified. WHAT IS KNOWN ALREADY: Many fundamental questions regarding the prevention, management, and consequences of infertility remain unanswered. This is a barrier to improving the care received by those people with fertility problems. STUDY DESIGN, SIZE, DURATION: Potential research questions were collated from an initial international survey, a systematic review of clinical practice guidelines, and Cochrane systematic reviews. A rationalized list of confirmed research uncertainties was prioritized in an interim international survey. Prioritized research uncertainties were discussed during a consensus development meeting. Using a formal consensus development method, the modified nominal group technique, diverse stakeholders identified the top 10 research priorities for each of the categories male infertility, female and unexplained infertility, medically assisted reproduction, and ethics, access, and organization of care. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, people with fertility problems, and others (healthcare funders, healthcare providers, healthcare regulators, research funding bodies and researchers) were brought together in an open and transparent process using formal consensus methods advocated by the James Lind Alliance. MAIN RESULTS AND THE ROLE OF CHANCE: The initial survey was completed by 388 participants from 40 countries, and 423 potential research questions were submitted. Fourteen clinical practice guidelines and 162 Cochrane systematic reviews identified a further 236 potential research questions. A rationalized list of 231 confirmed research uncertainties were entered into an interim prioritization survey completed by 317 respondents from 43 countries. The top 10 research priorities for each of the four categories male infertility, female and unexplained infertility (including age-related infertility, ovarian cysts, uterine cavity abnormalities, and tubal factor infertility), medically assisted reproduction (including ovarian stimulation, IUI, and IVF), and ethics, access, and organization of care, were identified during a consensus development meeting involving 41 participants from 11 countries. These research priorities were diverse and seek answers to questions regarding prevention, treatment, and the longer-term impact of infertility. They highlight the importance of pursuing research which has often been overlooked, including addressing the emotional and psychological impact of infertility, improving access to fertility treatment, particularly in lower resource settings, and securing appropriate regulation. Addressing these priorities will require diverse research methodologies, including laboratory-based science, qualitative and quantitative research, and population science. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods, which have inherent limitations, including the representativeness of the participant sample, methodological decisions informed by professional judgement, and arbitrary consensus definitions. WIDER IMPLICATIONS OF THE FINDINGS: We anticipate that identified research priorities, developed to specifically highlight the most pressing clinical needs as perceived by healthcare professionals, people with fertility problems, and others, will help research funding organizations and researchers to develop their future research agenda. STUDY FUNDING/ COMPETING INTEREST(S): The study was funded by the Auckland Medical Research Foundation, Catalyst Fund, Royal Society of New Zealand, and Maurice and Phyllis Paykel Trust. Geoffrey Adamson reports research sponsorship from Abbott, personal fees from Abbott and LabCorp, a financial interest in Advanced Reproductive Care, committee membership of the FIGO Committee on Reproductive Medicine, International Committee for Monitoring Assisted Reproductive Technologies, International Federation of Fertility Societies, and World Endometriosis Research Foundation, and research sponsorship of the International Committee for Monitoring Assisted Reproductive Technologies from Abbott and Ferring. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and editor for the Cochrane Gynaecology and Fertility Group. Hans Evers reports being the Editor Emeritus of Human Reproduction. Andrew Horne reports research sponsorship from the Chief Scientist's Office, Ferring, Medical Research Council, National Institute for Health Research, and Wellbeing of Women and consultancy fees from Abbvie, Ferring, Nordic Pharma, and Roche Diagnostics. M. Louise Hull reports grants from Merck, grants from Myovant, grants from Bayer, outside the submitted work and ownership in Embrace Fertility, a private fertility company. Neil Johnson reports research sponsorship from Abb-Vie and Myovant Sciences and consultancy fees from Guerbet, Myovant Sciences, Roche Diagnostics, and Vifor Pharma. José Knijnenburg reports research sponsorship from Ferring and Theramex. Richard Legro reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. Ben Mol reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. Ernest Ng reports research sponsorship from Merck. Craig Niederberger reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. Jane Stewart reports being employed by a National Health Service fertility clinic, consultancy fees from Merck for educational events, sponsorship to attend a fertility conference from Ferring, and being a clinical subeditor of Human Fertility. Annika Strandell reports consultancy fees from Guerbet. Jack Wilkinson reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. Andy Vail reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and of the journal Reproduction. His employing institution has received payment from HFEA for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. Lan Vuong reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the present work. All authors have completed the disclosure form. TRIAL REGISTRATION NUMBER: Not applicable.

Top 10 priorities for future infertility research: an international consensus development study† ‡.

STUDY QUESTION: Can the priorities for future research in infertility be identified? SUMMARY ANSWER: The top 10 research priorities for the four areas of male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care for people with fertility problems were identified. WHAT IS KNOWN ALREADY: Many fundamental questions regarding the prevention, management and consequences of infertility remain unanswered. This is a barrier to improving the care received by those people with fertility problems. STUDY DESIGN, SIZE, DURATION: Potential research questions were collated from an initial international survey, a systematic review of clinical practice guidelines and Cochrane systematic reviews. A rationalized list of confirmed research uncertainties was prioritized in an interim international survey. Prioritized research uncertainties were discussed during a consensus development meeting. Using a formal consensus development method, the modified nominal group technique, diverse stakeholders identified the top 10 research priorities for each of the categories male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, people with fertility problems and others (healthcare funders, healthcare providers, healthcare regulators, research funding bodies and researchers) were brought together in an open and transparent process using formal consensus methods advocated by the James Lind Alliance. MAIN RESULTS AND THE ROLE OF CHANCE: The initial survey was completed by 388 participants from 40 countries, and 423 potential research questions were submitted. Fourteen clinical practice guidelines and 162 Cochrane systematic reviews identified a further 236 potential research questions. A rationalized list of 231 confirmed research uncertainties was entered into an interim prioritization survey completed by 317 respondents from 43 countries. The top 10 research priorities for each of the four categories male infertility, female and unexplained infertility (including age-related infertility, ovarian cysts, uterine cavity abnormalities and tubal factor infertility), medically assisted reproduction (including ovarian stimulation, IUI and IVF) and ethics, access and organization of care were identified during a consensus development meeting involving 41 participants from 11 countries. These research priorities were diverse and seek answers to questions regarding prevention, treatment and the longer-term impact of infertility. They highlight the importance of pursuing research which has often been overlooked, including addressing the emotional and psychological impact of infertility, improving access to fertility treatment, particularly in lower resource settings and securing appropriate regulation. Addressing these priorities will require diverse research methodologies, including laboratory-based science, qualitative and quantitative research and population science. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods, which have inherent limitations, including the representativeness of the participant sample, methodological decisions informed by professional judgment and arbitrary consensus definitions. WIDER IMPLICATIONS OF THE FINDINGS: We anticipate that identified research priorities, developed to specifically highlight the most pressing clinical needs as perceived by healthcare professionals, people with fertility problems and others, will help research funding organizations and researchers to develop their future research agenda. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Auckland Medical Research Foundation, Catalyst Fund, Royal Society of New Zealand and Maurice and Phyllis Paykel Trust. G.D.A. reports research sponsorship from Abbott, personal fees from Abbott and LabCorp, a financial interest in Advanced Reproductive Care, committee membership of the FIGO Committee on Reproductive Medicine, International Committee for Monitoring Assisted Reproductive Technologies, International Federation of Fertility Societies and World Endometriosis Research Foundation, and research sponsorship of the International Committee for Monitoring Assisted Reproductive Technologies from Abbott and Ferring. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and editor for the Cochrane Gynaecology and Fertility Group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. A.W.H. reports research sponsorship from the Chief Scientist's Office, Ferring, Medical Research Council, National Institute for Health Research and Wellbeing of Women and consultancy fees from AbbVie, Ferring, Nordic Pharma and Roche Diagnostics. M.L.H. reports grants from Merck, grants from Myovant, grants from Bayer, outside the submitted work and ownership in Embrace Fertility, a private fertility company. N.P.J. reports research sponsorship from AbbVie and Myovant Sciences and consultancy fees from Guerbet, Myovant Sciences, Roche Diagnostics and Vifor Pharma. J.M.L.K. reports research sponsorship from Ferring and Theramex. R.S.L. reports consultancy fees from AbbVie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. E.H.Y.N. reports research sponsorship from Merck. C.N. reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring and retains a financial interest in NexHand. J.S. reports being employed by a National Health Service fertility clinic, consultancy fees from Merck for educational events, sponsorship to attend a fertility conference from Ferring and being a clinical subeditor of Human Fertility. A.S. reports consultancy fees from Guerbet. J.W. reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. A.V. reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and the journal Reproduction. His employing institution has received payment from Human Fertilisation and Embryology Authority for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the present work. All authors have completed the disclosure form. TRIAL REGISTRATION NUMBER: N/A.

A comparative analysis of assisted reproductive technology cycles in Australia and New Zealand 2004-2007.

BACKGROUND: There are different funding arrangements for fertility treatments between New Zealand (NZ) and Australia. In NZ, there are two options for patients accessing treatment: either meeting specified criteria for age, no smoking and BMI for publicly funding or funding their own treatment. This differs from Australia, which has no explicit eligibility criteria restricting access to fertility treatment. An analysis of assisted reproductive technology (ART) in Australia and NZ was undertaken to consider the impact of these different funding approaches. METHODS: Data were extracted from the Australian and New Zealand Assisted Reproduction Database between 2004 and 2007. A total of 116 111 autologous fresh cycles were included. RESULTS: In Australia, more cycles were in women aged 40 years or older compared with those in NZ (23.5 versus 16.0%, P < 0.01). Single embryo transfer was more common in NZ than that in Australia, in women < 35 years of age (75.1 versus 59.6%, P < 0.01). In women <35 years, the crude rates of clinical pregnancy (37.5 versus 31.2%, P < 0.01) and live delivery (31.6 versus 26%, P < 0.01) following fresh ART cycles were significantly higher in NZ than that in Australia. These differences in outcomes persisted in older age groups. CONCLUSIONS: The purpose of the criteria used in NZ to access public funding for fertility treatments is to optimize pregnancy outcomes. This approach has resulted in a healthier population of women undergoing treatment and may explain the improved pregnancy outcomes seen in NZ couples who undergo fertility treatments.

PCOSMIC: a multi-centre randomized trial in women with PolyCystic Ovary Syndrome evaluating Metformin for Infertility with Clomiphene.

BACKGROUND: Ovulation induction treatment with metformin, either alone or in combination with clomiphene citrate (CC), remains controversial even though previous randomized trials have examined this. METHODS: A double blinded multi-centre randomized trial was undertaken including 171 women with anovulatory or oligo-ovulatory polycystic ovary syndrome. Women with high body mass index (BMI) > 32 kg/m(2) received placebo ('standard care') or metformin; women with BMI < or = 32 kg/m(2) received CC ('standard care'), metformin or both. Treatment continued for 6 months or until pregnancy was confirmed. Primary outcomes were clinical pregnancy and live birth. RESULTS: For women with BMI > 32 kg/m(2), clinical pregnancy and live birth rates were 22% (7/32) and 16% (5/32) with metformin, 15% (5/33) and 6% (2/33) with placebo. For women with BMI < or = 32 kg/m(2), clinical pregnancy and live birth rates were 40% (14/35) and 29% (10/35) with metformin, 39% (14/36) and 36% (13/36) with CC, 54% (19/35) and 43% (15/35) with combination metformin plus CC. CONCLUSIONS: There is no evidence that adding metformin to 'standard care' is beneficial. Pregnancy and live birth rates are low in women with BMI > 32 kg/m(2) whatever treatment is used, with no evidence of benefit of metformin over placebo. For women with BMI < or = 32 kg/m(2) there is no evidence of significant differences in outcomes whether treated with metformin, CC or both. ClinicalTrials.gov number NCT00795808; trial protocol accepted for publication November 2005: Johnson, Aust N Z Journal Obstet Gynaecol 2006;46:141-145.

Epigenetic regulation of endometrium during the menstrual cycle.

The endometrium undergoes morphological and functional changes during the menstrual cycle which are essential for uterine receptivity. These changes are driven by estrogen and progesterone and involve the fine control of many different genes-several of which have been identified as being epigenetically regulated. Epigenetic modification may therefore influence the functional changes in the endometrium required for successful implantation. There is, however, only limited information on epigenetic regulation in endometrium. We review the potential role of epigenetic regulation of key processes during the menstrual cycle and present our own findings following a preliminary study into global acetylation levels in the human endometrium. A changing epigenetic state is associated with the differentiation of stem cells into different lineages and thus may be involved in endometrial regeneration. Histone acetylation is implicated in the vascular endothelial growth factor pathway during angiogenesis, and studies using histone deacetylase inhibitors suggest an involvement in endometrial proliferation and differentiation. The processes of decidualization and implantation are also associated with epigenetic change and epigenetic modulators show variable expression across the menstrual cycle. Our own studies found that endometrial global histone acetylation, as determined by western blotting, changed throughout the menstrual cycle and correlated well with expected transcription activity during the different phases. This suggests that epigenetics may be involved in the regulation of endometrial gene expression during the menstrual cycle and that abnormal epigenetic modifications may therefore be associated with implantation failure and early pregnancy loss as well as with other endometrial pathologies.

The impact of body mass index on semen parameters and reproductive hormones in human males: a systematic review with meta-analysis.

BACKGROUND: It has been suggested that body mass index (BMI), especially obesity, is associated with subfertility in men. Semen parameters are central to male fertility and reproductive hormones also play a role in spermatogenesis. This review aimed to investigate the association of BMI with semen parameters and reproductive hormones in men of reproductive age. METHODS: MEDLINE, EMBASE, Biological Abstracts, PsycINFO and CINAHL databases and references from relevant articles were searched in January and February 2009. Outcomes included for semen parameters were sperm concentration, total sperm count, semen volume, motility and morphology. Reproductive hormones included were testosterone, free testosterone, estradiol, FSH, LH, inhibin B and sex hormone binding globulin (SHBG). A meta-analysis was conducted to investigate sperm concentration and total sperm count. RESULTS: In total, 31 studies were included. Five studies were suitable for pooling and the meta-analysis found no evidence for a relationship between BMI and sperm concentration or total sperm count. Overall review of all studies similarly revealed little evidence for a relationship with semen parameters and increased BMI. There was strong evidence of a negative relationship for testosterone, SHBG and free testosterone with increased BMI. CONCLUSIONS: This systematic review with meta-analysis has not found evidence of an association between increased BMI and semen parameters. The main limitation of this review is that data from most studies could not be aggregated for meta-analysis. Population-based studies with larger sample sizes and longitudinal studies are required.

Surgical interruption of pelvic nerve pathways in dysmenorrhea: a systematic review of effectiveness.

OBJECTIVES: To assess the effectiveness of surgical interruption of pelvic nerve pathways in primary and secondary dysmenorrhea. Data sources. The Cochrane Menstrual Disorders and Subfertility Group Trials Register (9 June 2004), CENTRAL (The Cochrane Library, Issue 2, 2004), MEDLINE (1966 to Nov. 2003), EMBASE (1980 to Nov. 2003), CINAHL (1982 to Oct. 2003), MetaRegister of Controlled Trials, the citation lists of review articles and included trials, and contact with the corresponding author of each included trial. REVIEW METHODS: The inclusion criteria were randomized controlled trials of uterosacral nerve ablation or presacral neurectomy (both open and laparoscopic procedures) for the treatment of dysmenorrhea. The main outcome measures were pain relief and adverse effects. Two reviewers extracted data on characteristics of the study quality and the population, intervention, and outcome independently. RESULTS: Nine randomized controlled trials were included in the systematic review. There were two trials with open presacral neurectomy; all other trials used laparoscopic techniques. For the treatment of primary dysmenorrhea, laparoscopic uterosacral nerve ablation at 12 months was better when compared to a control or no treatment (OR 6.12; 95% CI 1.78-21.03). The comparison of laparoscopic uterosacral nerve ablation with presacral neurectomy for primary dysmenorrhea showed that at 12 months follow-up, presacral neurectomy was more effective (OR 0.10; 95% CI 0.03-0.32). In secondary dysmenorrhea, along with laparoscopic surgical treatment of endometriosis, the addition of laparoscopic uterosacral nerve ablation did not improve the pain relief (OR 0.77; 95% CI 0.43-1.39), while presacral neurectomy did (OR 3.14; 95% CI 1.59-6.21). Adverse events were more common for presacral neurectomy than procedures without presacral neurectomy (OR 14.6; 95% CI 5-42.5). CONCLUSION: The evidence for nerve interruption in the management of dysmenorrhea is limited. Methodologically sound and sufficiently powered randomized controlled trials are needed.

Levonorgestrel-releasing intrauterine device (LNG-IUD) for symptomatic endometriosis following surgery.

BACKGROUND: Various options exist for treating endometriosis, including ovarian suppression therapy, surgical treatment or a combination of these strategies. Surgical treatment of endometriosis sets out to remove visible areas of endometriosis and restore anatomy by division of adhesions. The aim of medical therapy is to inhibit growth of endometriotic implants by suppression of ovarian steroids and induction of a hypo-estrogenic state. Postoperative treatment with a hormone-releasing intrauterine system, using levonorgestrel (LNG-IUS), has been suggested. OBJECTIVES: To determine if postoperative use of an LNG-IUS in women with endometriosis improves pain symptoms associated with menstruation and reduces recurrence compared with treatment with surgery only, placebo or systemic hormones. SEARCH STRATEGY: The following databases were searched: (1) Cochrane Menstrual Disorders and Subfertility Group Specialised Register of controlled trials; (2) Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2006, Issue 1); (3) MEDLINE (1966 to January 2006) and EMBASE (1980 to January 2006); (4) National Research Register (NRR). (5) The citation lists of relevant publications, review articles, abstracts of scientific meetings and included studies were also searched. SELECTION CRITERIA: Trials were included if they compared women undergoing any type of surgical treatment for endometriosis with uterine preservation then randomized to LNG-IUS insertion within two to three months versus no treatment, placebo (inert IUD) or systemic treatment. Diagnostic laparoscopy alone was excluded. DATA COLLECTION AND ANALYSIS: Two review authors (AM Abou-Setta and HG Al-Inany) independently selected studies for inclusion and extracted data. Statistical analysis was performed in accordance with the statistical guidelines developed by the Cochrane Menstrual Disorders and Subfertility Group. Data extracted from the trials was analyzed on an intention-to-treat basis. For binary data, the overall common odds ratio (OR) (that is, the odds of having clinical symptoms) and the risk difference with 95% confidence interval (CI) were calculated using the Mantel-Haenszel fixed-effect method. MAIN RESULTS: In one small randomized controlled trial (RCT) there was a statistically significant reduction in the recurrence of painful periods in the LNG-IUS group compared with the control group receiving a gonadotrophin-releasing hormone (GnRH) agonist (OR 0.14, 95% CI = 0.02 to 0.75). The proportion of women who were satisfied with their treatment was higher in the LNG-IUS group than in the control group but this difference did not reach statistical difference (OR 3.00, 0.79 to 11.44). AUTHORS' CONCLUSIONS: One small study has shown that postoperative use of the LNG-IUS reduces the recurrence of painful periods in women who have had surgery for endometriosis. There is a need for further well-designed RCTs of this approach.

Surgical interruption of pelvic nerve pathways for primary and secondary dysmenorrhoea.

BACKGROUND: Dysmenorrhoea is the occurrence of painful menstrual cramps of uterine origin and is a very common gynaecological complaint with negative effect on a sufferer's quality of life. Medical therapy for dysmenorrhoea includes oral contraceptive pills (OCP) and nonsteroidal anti-inflammatory drugs (NSAIDs) which both act by suppressing prostaglandin levels. While these treatments are very successful there is still a 20 to 25% failure rate and surgery has been an option for such cases. Uterine nerve ablation (UNA) and presacral neurectomy (PSN) are two surgical treatments that have become increasingly utilised in recent years due to advances in laparoscopic procedures. These procedures both interrupt the majority of the cervical sensory pain nerve fibres. Observational studies have supported the use of these procedures for primary dysmenorrhoea. However, both operations only partially interrupt the cervical sensory nerve fibres in the pelvic area and, therefore, this type of surgery may not always benefit women with dysmenorrhoea. OBJECTIVES: To assess the effectiveness of surgical interruption of pelvic nerve pathways as treatment for primary and secondary dysmenorrhoea, and to determine the most effective surgical treatment. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched 9 June 2004), CENTRAL (The Cochrane Library Issue 2, 2004), MEDLINE (1966 to Nov 2003), EMBASE (1980 to Nov 2003), and CINAHL (1982 to Oct 2003). Attempts were also made to identify trials from the metaRegister of Controlled Trials and the citation lists of review articles and included trials. In most cases the first or corresponding author of each included trial was contacted for additional information. SELECTION CRITERIA: The inclusion criteria were randomised comparisons of surgical techniques of interruption of the pelvic nerve pathways (using both open and laparoscopic procedures) for the treatment of primary and secondary dysmenorrhoea. The main outcome measures were pain relief and adverse effects. DATA COLLECTION AND ANALYSIS: Eleven randomised controlled trials (RCTs) were identified that initially appeared to fulfil the inclusion criteria for this review. Two trials were subsequently excluded (Garcia Leon 2003; Sutton 1991). Of the remaining nine trials, eight were included in the meta-analysis. The results of one trial were included in the text of the review for discussion because the data were not available in a form that allowed them to be combined in the meta-analysis. Five trials investigated laparoscopic uterine nerve ablation (LUNA), two trials laparoscopic presacral neurectomy (LPSN) and two open presacral neurectomy (PSN). MAIN RESULTS: For the treatment of primary dysmenorrhoea there was some evidence of the effectiveness of laparoscopic uterine nerve ablation (LUNA) when compared to a control or no treatment. The comparison between LUNA and laparoscopic presacral neurectomy (LPSN) for primary dysmenorrhoea showed no significant difference in pain relief in the short term; however, long-term LPSN was shown to be significantly more effective than LUNA. For the treatment of secondary dysmenorrhoea six identified RCTs addressed endometriosis and one included women with uterine myomas. The treatment of LUNA combined with surgical treatment of endometrial implants versus surgical treatment of endometriosis alone showed that the addition of LUNA did not aid pain relief. For PSN combined with endometriosis treatment versus endometriosis treatment alone there was an overall difference in pain relief although the data suggests this may be specific to laparoscopy and for midline abdominal pain only. Adverse events were significantly more common for presacral neurectomy; however, the majority were complications such as constipation, which may spontaneously improve. AUTHORS' CONCLUSIONS: There is insufficient evidence to recommend the use of nerve interruption in the management of dysmenorrhoea, regardless of cause. Future methodologically sound and sufficiently powered RCTs should be undertaken.

Long term hormone therapy for perimenopausal and postmenopausal women.

BACKGROUND: Hormone therapy (HT) is widely used for controlling menopausal symptoms. It has also been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women but the evidence supporting its use for these indications is largely observational. OBJECTIVES: To assess the effect of long-term HT on mortality, heart disease, venous thromboembolism, stroke, transient ischaemic attacks, breast cancer, colorectal cancer, ovarian cancer, endometrial cancer, gallbladder disease, cognitive function, dementia, fractures and quality of life. SEARCH STRATEGY: We searched the following databases up to November 2004: the Cochrane Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Biological Abstracts. Relevant non-indexed journals and conference abstracts were also searched. SELECTION CRITERIA: Randomised double-blind trials of HT (oestrogens with or without progestogens) versus placebo, taken for at least one year by perimenopausal or postmenopausal women. DATA COLLECTION AND ANALYSIS: Fifteen RCTs were included. Trials were assessed for quality and two review authors extracted data independently. They calculated risk ratios for dichotomous outcomes and weighted mean differences for continuous outcomes. Clinical heterogeneity precluded meta-analysis for most outcomes. MAIN RESULTS: All the statistically significant results were derived from the two biggest trials. In relatively healthy women, combined continuous HT significantly increased the risk of venous thromboembolism or coronary event (after one year's use), stroke (after 3 years), breast cancer (after 5 years) and gallbladder disease. Long-term oestrogen-only HT also significantly increased the risk of stroke and gallbladder disease. Overall, the only statistically significant benefits of HT were a decreased incidence of fractures and colon cancer with long-term use. Among relatively healthy women over 65 years taking continuous combined HT, there was a statistically significant increase in the incidence of dementia. Among women with cardiovascular disease, long-term use of combined continuous HT significantly increased the risk of venous thromboembolism. No trials focussed specifically on younger women. However, one trial analysed subgroups of 2839 relatively healthy 50 to 59 year-old women taking combined continuous HT and 1637 taking oestrogen-only HT, versus similar-sized placebo groups. The only significantly increased risk reported was for venous thromboembolism in women taking combined continuous HT; their absolute risk remained very low. AUTHORS' CONCLUSIONS: HT is not indicated for the routine management of chronic disease. We need more evidence on the safety of HT for menopausal symptom control, though short-term use appears to be relatively safe for healthy younger women.

A double-blind randomised controlled trial of laparoscopic uterine nerve ablation for women with chronic pelvic pain.

OBJECTIVE: To determine the effectiveness of laparoscopic uterine nerve ablation (LUNA) for chronic pelvic pain in women with endometriosis and women with no laparoscopic evidence of endometriosis. DESIGN: A prospective double-blind randomised controlled trial (RCT). SETTING: Single-centre, secondary-level gynaecology outpatient service and tertiary-level pelvic pain and endometriosis outpatient service in Auckland, New Zealand. POPULATION: One hundred and twenty-three women undergoing laparoscopy for investigation and management of chronic pelvic pain, 56 with no laparoscopic evidence of endometriosis and 67 with endometriosis. METHODS: Women were randomised from the two populations, firstly those with no evidence of endometriosis and secondly those undergoing laparoscopic surgical treatment for endometriosis, to receive LUNA or no LUNA. Participant and assessor blinding was employed. Follow up for pain outcomes was undertaken at 24 hours, 3 months and 12 months. MAIN OUTCOME MEASURES: Changes in non-menstrual pelvic pain, dysmenorrhoea, deep dyspareunia and dyschezia were assessed primarily by whether there was a decrease in visual analogue score for these types of pain of 50% or more from baseline and additionally whether there was a significantly different change in median visual analogue score. The numbers requiring further surgery or starting a new medical treatment for pelvic pain and complications were also measured. RESULTS: There was a significant reduction in dysmenorrhoea at 12 month follow up in women with chronic pelvic pain in the absence of endometriosis who underwent LUNA (median change in visual analogue scale (VAS) from baseline -4.8 versus-0.8 (P= 0.039), 42.1%versus 14.3% experiencing a successful treatment defined as a 50% or greater reduction in visual analogue pain scale for dysmenorrhoea (P= 0.045). There was no significant difference in non-menstrual pelvic pain, deep dyspareunia or dyschezia in women with no endometriosis undergoing LUNA versus no LUNA. The addition of LUNA to laparoscopic surgical treatment of endometriosis was not associated with a significant difference in any pain outcomes. CONCLUSIONS: LUNA is effective for dysmenorrhoea in the absence of endometriosis, although there is no evidence of effectiveness of LUNA for non-dysmenorrhoeic chronic pelvic pain or for any type of chronic pelvic pain related to endometriosis.

Hormone replacement therapy in postmenopausal women: endometrial hyperplasia and irregular bleeding.

BACKGROUND: The decline in circulating oestrogen around the time of the menopause often induces unacceptable symptoms that affect the health and well being of women. Hormone replacement therapy (both unopposed oestrogen and oestrogen and progestogen combinations) is an effective treatment for these symptoms. In women with an intact uterus, unopposed oestrogen may induce endometrial stimulation and increase the risk of endometrial hyperplasia and carcinoma. The addition of progestogen reduces this risk but may cause unacceptable symptoms, bleeding and spotting which can affect adherence to therapy. OBJECTIVES: The objective of this review is to assess which hormone replacement therapy regimens provide effective protection against the development of endometrial hyperplasia and/or carcinoma with a low rate of abnormal vaginal bleeding. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (searched January 2003), The Cochrane Library (Issue 2, 2003), MEDLINE (1966 to January 2003), EMBASE (1980 to January 2003), Current Contents (1993 to January 2003), Biological Abstracts (1969 to 2002), Social Sciences Index (1980 to January 2003), PsycINFO (1972 to February 2003) and CINAHL (1982 to January 2003). The search strategy was developed by the Cochrane Menstrual Disorder and Subfertility Group. Attempts were also made to identify trials from citation lists of review articles and drug companies were contacted for unpublished data. In most cases, the corresponding author of each included trial was contacted for additional information. SELECTION CRITERIA: The inclusion criteria were randomised comparisons of unopposed oestrogen therapy, combined continuous oestrogen-progestogen therapy and sequential oestrogen-progestogen therapy with each other and placebo administered over a minimum treatment period of six months. Trials had to assess which regimen was the most protective against the development of endometrial hyperplasia/carcinoma and/or caused the lowest rate of irregular bleeding. DATA COLLECTION AND ANALYSIS: Sixty RCTs were identified. Of these 23 were excluded and seven remain awaiting assessment. The reviewers assessed the thirty included studies for quality, extracted the data independently and odds ratios for dichotomous outcomes were estimated. Outcomes analysed included frequency of endometrial hyperplasia or carcinoma, frequency of irregular bleeding and unscheduled biopsies or dilation and curettage, and adherence to therapy. MAIN RESULTS: Unopposed moderate or high dose oestrogen therapy when compared to placebo was associated with a significant increase in rates of endometrial hyperplasia with increasing rates at longer duration of treatment and follow up. Odds ratios ranged from (1 RCT; OR 5.4, 95% CI 1.4 to 20.9) for 6 months of treatment to (4 RCTs; OR 9.6, 95% CI 5.9 to 15.5) for 24 months treatment and (1 RCT; OR 15.0, 95% CI 9.3 to 27.5) for 36 months of treatment with moderate dose oestrogen (in the PEPI trial, 62% of those who took moderate dose oestrogen had some form of hyperplasia at 36 months compared to 2% of those who took placebo). Irregular bleeding and non adherence to treatment were also significantly more likely under these unopposed oestrogen regimens that increased bleeding with higher dose therapy. Although not statistically significant, there was a 3% incidence (2 RCTs) of hyperplasia in women who took low dose oestrogen compared to no incidence of hyperplasia in the placebo group. The addition of progestogens, either in continuous combined or sequential regimens, helped to reduce the risk of endometrial hyperplasia and improved adherence to therapy. At longer duration of treatment, continuous therapy was more effective than sequential therapy in reducing the risk of endometrial hyperplasia. There was evidence of a higher incidence of hyperplasia under long cycle sequential therapy (progestogen given every three months) compared to monthly sequential therapy (progestogen given every month). No increase in endometrial cancer was seen in any of t in any of the treatment groups during the duration (maximum of six years) of these trials. During the first year of therapy irregular bleeding and spotting was more likely in continuous combined therapy than sequential therapy. However, during the second year of therapy bleeding and spotting was more likely under sequential regimens. REVIEWERS' CONCLUSIONS: There is strong and consistent evidence in this review that unopposed oestrogen therapy, at moderate and high doses, is associated with increased rates of endometrial hyperplasia, irregular bleeding and consequent non adherence to therapy. The addition of oral progestogens administered either sequentially or continuously is associated with reduced rates of hyperplasia and improved adherence to therapy. Irregular bleeding is less likely under sequential than continuous therapy during the first year of therapy but there is a suggestion that continuous therapy over long duration is more protective than sequential therapy in the prevention of endometrial hyperplasia. Hyperplasia is more likely when progestogen is given every three months in a sequential regimen compared to a monthly progestogen sequential regimen.

A six-year audit of the management of ectopic pregnancy.

OBJECTIVE: To audit the management of ectopic pregnancy at National Women's Hospital over a six-year period to monitor changes in practice and assess adherence to hospital protocols. STUDY DESIGN: A retrospective audit of the management of women with a discharge diagnosis of ectopic pregnancy from 1996-2001 at National Women's Hospital, Auckland, New Zealand. Information was collected regarding the demographics, risk factors for ectopic pregnancy, delay in diagnosis, management undertaken and failure and complications of initial treatment. RESULTS: Over a six-year period a total of 673 women had a discharge diagnosis of ectopic pregnancy. Surgery was the most frequent method of management but there was increasing utilisation of systemic methotrexate. The proportion of women who met the criteria for methotrexate varied from 27-54% over the six year period although the highest proportion who received methotrexate in any given year was only 24% (2001). The proportion of women who met the criteria for receiving methotrexate and had the option of methotrexate discussed with them increased from 12% in 1996 to 91% in 2001. Over the six year period 74 women received methotrexate and 14 (18.9%) failed and required surgical management. Surgical management was performed in 537 women and 30 (5.6%) required either further surgery or methotrexate or a combination of both. A laparoscopic procedure was performed in 86.5% (465/533) and 10.9% (51/465) converted to laparotomy CONCLUSIONS: Although there is evidence that methotrexate is an effective and safe option for a proportion of women with ectopic pregnancy, the majority of women still undergo surgical management.

A randomised trial comparing single dose systemic methotrexate and laparoscopic surgery for the treatment of unruptured tubal pregnancy.

OBJECTIVE: To compare single dose systemic methotrexate (50 mg/m2) with laparoscopic surgery for the treatment of unruptured tubal pregnancy. DESIGN: An open, pragmatic, prospective randomised trial. SETTING: Departments of obstetrics and gynaecology at three hospitals in Auckland, New Zealand. PARTICIPANTS: Clinically stable women with an unruptured tubal pregnancy diagnosed by transvaginal ultrasound and quantitative serum beta-hCG measurement. Inclusion criteria included a serum beta-hCG concentration < 5,000 IU/L, and a tubal pregnancy of < 3.5 cm diameter. MAIN OUTCOME MEASURES: Treatment success, physical and psychological functioning, side effects, and subsequent ipsilateral tubal patency. RESULTS: Two hundred and eighteen women with ectopic pregnancies were seen at the three hospitals. 79 women (36% eligibility rate) were eligible for trial entry and 62 women (78% recruitment rate) were recruited. Twenty-six of the 28 women (93%) randomised to laparoscopic surgery required no further treatment, compared with 22 of the 34 women (65%) randomised to methotrexate (95% CI of difference in success rate 10 - 47%; P < 0.01). Two women (7%) in the laparoscopic surgery group had persistent trophoblast. Nine women (26%) in the methotrexate group required more than one dose of methotrexate and five women (15%) underwent laparoscopy during follow up. In the laparoscopy group three women (11%) had negative laparoscopies and two women (7%) had were found to have a ruptured fallopian tube at the time of surgery. Women treated with methotrexate had significantly better objective physical functioning scores but there were no differences in any other psychological outcomes. Women treated with methotrexate experienced greater and more prolonged vaginal bleeding. The likelihood of methotrexate treatment failure was greater at higher serum beta-hCG concentrations. Ipsilateral tubal patency rates were similar in each group. CONCLUSION: This trial shows that in the treatment of tubal pregnancy single dose systemic methotrexate is a less effective treatment than laparoscopic salpingotomy. It is well tolerated, but should only be offered as an alternative to surgery to women who have mild symptoms and present at low serum beta-hCG concentrations. In our population this likely to be no more than a quarter of women presenting with a tubal pregnancy.

An economic evaluation of single dose systemic methotrexate and laparoscopic surgery for the treatment of unruptured ectopic pregnancy.

OBJECTIVE: To compare the direct and indirect costs of single dose systemic methotrexate with laparoscopic surgery for the treatment of unruptured ectopic pregnancy. DESIGN: A cost minimisation study undertaken alongside a randomised trial. SETTING: Departments of Obstetrics and Gynaecology in three hospitals in Auckland, New Zealand. PARTICIPANTS: Sixty-two women with an ectopic pregnancy randomised to treatment with either a single dose of methotrexate (50 mg/m2) or laparoscopic surgery. MAIN OUTCOME MEASURES: Direct and indirect costs based on the results of the randomised trial. RESULTS: Direct costs per case were significantly lower in the methotrexate group (mean $NZ 1,470) than in the laparoscopy group (mean $NZ 3,083) with a mean difference of $NZ 1,613 (95% CI $NZ 1,166 - $NZ 2,061). These significant differences existed under a wide range of alternative assumptions about unit costs. The difference in direct costs in favour of methotrexate was greatest for women presenting with low pretreatment serum beta-hCG concentrations. Mean indirect costs were also significantly lower in the methotrexate group (mean $NZ 1,141) than in the laparoscopy group (mean $NZ 1899) with a mean difference of $NZ 758 (95% CI $NZ 277 - $NZ 1,240). For women presenting with pretreatment serum beta-hCG concentrations of over 1,500 IU/ L this difference in indirect costs is lost due to the prolonged follow up required and a higher rate of surgical intervention in women receiving methotrexate. CONCLUSION: This economic evaluation shows that treating suitable women with an ectopic pregnancy using systemic methotrexate therapy results in a significant reduction in direct costs. The indirect costs borne by the woman and her carers are only likely to be reduced in women with pretreatment serum beta-hCG concentrations under 1,500 IU/L.

Surgical interruption of pelvic nerve pathways for primary and secondary dysmenorrhoea.

BACKGROUND: Dysmenorrhoea is the occurrence of painful menstrual cramps of uterine origin and is a very common gynaecological complaint. Medical therapy for dysmenorrhoea includes oral contraceptive pills (OCP) and nonsteroidal anti-inflammatory drugs (NSAIDS) which both act by suppressing prostaglandin levels. While these treatments are very successful there is still a 20-25% failure rate and surgery has been an option for cases of dysmenorrhoea that fail to respond to medical therapy. Uterine nerve ablation (UNA) and presacral neurectomy (PSN) are two surgical treatments that have become increasingly utilised in recent years. These procedures both interrupt the majority of the cervical sensory nerve fibres, thus diminishing uterine pain. Uncontrolled studies have supported the use of these procedures for primary dysmenorrhoea however both operations only partially interrupt some of the cervical sensory nerve fibres in the pelvic area; therefore dysmenorrhoea associated with additional pelvic pathology may not always benefit from this type of surgery. OBJECTIVES: To assess the effectiveness of surgical interruption of pelvic nerve pathways as treatment for primary and secondary dysmenorrhoea, and to determine the most effective surgical treatment. SEARCH STRATEGY: Electronic searches of the Cochrane Menstrual Disorders and Subfertility Group Register of controlled trials, MEDLINE, and EMBASE were performed to identify relevant randomised controlled trials (RCTs). Attempts were also made to identify trials from citation lists of review articles and handsearching. In most cases, the first or corresponding author of each included trial was contacted for additional information. SELECTION CRITERIA: The inclusion criteria were randomised comparisons of surgical techniques of interruption of the pelvic nerve pathways (both open and laparoscopic procedures) for the treatment of primary and secondary dysmenorrhoea. The main outcome measures were pain relief and adverse effects. DATA COLLECTION AND ANALYSIS: Seven RCTs were identified that fulfilled the inclusion criteria for this review. One trial (Sutton 1994) was excluded because another treatment was given in combination with destruction of pelvic nerve pathways and the effects of these two treatments could not be separated. Of the remaining six trials, three were included in the meta-analysis (Chen 1996, Candiani 1992, Lichten 1987). The results of the other three trials (Dover 1999, Tjaden 1990, Vercellini 1997) were included in the text of the review for discussion because the data were not available in a form that allowed them to be combined in a meta-analysis. MAIN RESULTS: For the treatment of primary dysmenorrhoea there is some evidence of the effectiveness of uterine nerve ablation (UNA) when compared to a control of no treatment. The comparison between UNA with presacral neurectomy (PSN) for primary dysmenorrhoea showed no significant difference in pain relief in the short term, however long term PSN was shown to be significantly more effective. For the treatment of secondary dysmenorrhoea the identified RCTs addressed only endometriosis. The treatment of UNA combined with surgical treatment of endometrial implants versus surgical treatment of endometriosis alone showed that the addition of UNA did not aid pain relief. For PSN combined with endometriosis treatment versus endometriosis treatment alone there was also no overall difference in pain relief, although the data suggests a significant difference in relief of midline abdominal pain. Adverse events were significantly more common for presacral neurectomy, however the majority were complications such as constipation, which may spontaneously improve. REVIEWER'S CONCLUSIONS: There is insufficient evidence to recommend the use of nerve interruption in the management of dysmenorrhoea, regardless of cause. Future RCTs should be undertaken.

Extracts from the "clinical evidence". Endometriosis.

DEFINITION: Endometriosis is characterised by ectopic endometrial tissue, which can cause dysmenorrhoea, dyspareunia, non-cyclical pelvic pain, and subfertility. Diagnosis is made by laparoscopy. Most endometrial deposits are found in the pelvis (ovaries, peritoneum, uterosacral ligaments, pouch of Douglas, and rectovaginal septum). Extrapelvic deposits, including those in the umbilicus and diaphragm, are rare. Endometriomas are cysts of endometriosis within the ovary. INCIDENCE/PREVALENCE: In asymptomatic women, the prevalence ranges from 2% to 22%, depending on the diagnostic criteria used and the populations studied. In women with dysmenorrhoea, the incidence of endometriosis ranges from 40% to 60%, and in women with subfertility it ranges from 20% to 30%. The severity of symptoms and the probability of diagnosis increase with age. Incidence peaks at about age 40. Symptoms and laparoscopic appearance do not always correlate. AETIOLOGY: The cause is unknown. Risk factors include early menarche and late menopause. Embryonic cells may give rise to deposits in the umbilicus, while retrograde menstruation may deposit endometrial cells in the diaphragm. Oral contraceptives reduce the risk of endometriosis, and this protective effect persists for up to a year after their discontinuation. PROGNOSIS: We found one small randomised controlled trial (RCT) in which repeat laparoscopy was performed in the women treated with placebo. Over 12 months, endometrial deposits resolved spontaneously in a quarter, deteriorated in nearly half, and were unchanged in the remainder. AIMS: To relieve pain (dysmenorrhoea, dyspareunia, and other pelvic pain) and to improve fertility, with minimal adverse effects. OUTCOMES: American Fertility Society scores for size and number of deposits; recurrence rates; time between stopping treatment and recurrence; rate of adverse effects of treatment. In women with pain: relief of pain, assessed by visual analogue scale and subjective improvement. In women with subfertility: cumulative pregnancy rate, live birth rate. In women undergoing surgery: ease of surgical intervention (rated as easy, average, difficult, or very difficult).

An evaluation of risk factors for endometrial hyperplasia in premenopausal women with abnormal menstrual bleeding.

OBJECTIVE: We sought to determine the clinical risk factors for endometrial hyperplasia in premenopausal women with abnormal bleeding. STUDY DESIGN: A laboratory database was searched to identify all endometrial samples taken in 1033 premenopausal women over a 30-month period from January 1995 to July 1997. Clinical data were extracted from the patients' clinical records retrospectively, and univariate and multivariate analyses were performed. The setting was the gynecologic service of a large teaching hospital. RESULTS: There were 46 cases of endometrial hyperplasia and 5 cases of endometrial cancer diagnosed. The following factors were independently associated with increased risk of endometrial hyperplasia or the presence of carcinoma: age >/=45 years (odds ratio, 3.1; 95% confidence interval, 1.5-6.1), weight >/=90 kg (odds ratio, 5.5; 95% confidence interval, 2.9-10.6), history of infertility (odds ratio, 3.6; 95% confidence interval, 1.3-9.9), family history of colonic carcinoma (odds ratio, 5.0; 95% confidence interval, 1.3-19.1), and nulliparity (odds ratio, 2.8; 95% confidence interval, 1.1-7.2). There was no increased association of endometrial hyperplasia on the basis of irregularity of menstrual cycle or duration of menstrual bleeding. CONCLUSIONS: The following are risk factors for endometrial hyperplasia in premenopausal women with abnormal menstrual bleeding: body weight >/=90 kg, age >/=45 years, infertility, family history of colonic carcinoma, and nulliparity. Current guidelines may need to be reconsidered.

Association between polycystic ovaries and extent of coronary artery disease in women having cardiac catheterization.

BACKGROUND: Women with polycystic ovaries have associated risk factors for coronary artery disease. It is unknown whether women with more extensive coronary artery disease are more likely to have polycystic ovaries. OBJECTIVE: To determine whether women who have more extensive coronary artery disease as seen on coronary angiography are more likely to have polycystic ovaries appearing on ultrasonography than are women with less severe coronary disease. DESIGN: Prevalence study of women who had had coronary angiography. SETTING: Women referred for coronary angiography for assessment of chest pain or valvular disease in Auckland, New Zealand, during a 2-year period. PATIENTS: 143 women 60 years of age or younger who had had coronary angiography. Women who had previously had bilateral oophorectomy were excluded. MEASUREMENTS: The extent of coronary artery disease assessed by quantitative angiography was compared with the presence or absence of polycystic ovaries. Pelvic ultrasonography was done without knowledge of the extent of coronary artery disease. Assessment of angiograms was blinded. Insulin resistance and gonadotropin, testosterone, and serum lipid levels were also measured. RESULTS: Polycystic ovaries were found in 42% of women and were associated with hirsutism; previous hysterectomy; higher free testosterone, triglyceride, and C-peptide levels; and lower high-density lipoprotein cholesterol levels. Women with polycystic ovaries had more extensive coronary artery disease than women with normal ovaries (number of segments with > 50% stenosis, 1.7 [95% CI, 1.1 to 2.3] compared with 0.82 [CI, 0.54 to 1.1]; P < 0.01). On logistic regression analysis, the extent of coronary artery disease (P = 0.032) and family history of heart disease (P = 0.022) were predictors of the presence of polycystic ovaries. CONCLUSIONS: In women having coronary angiography, those with more extensive coronary artery disease were more likely to have polycystic ovaries on ultrasonography than were those with less extensive disease. Visualization of polycystic ovaries by sonography was associated with distinct metabolic and endocrine abnormalities. Further study is required to evaluate whether surgery or hormone replacement therapy can modify the risk.