Cindy Farquhar

3 The Cochrane Library

Summary In the current era of patients seeking better information, managers seeking cost-effective treatments, clinicians struggling to keep up with the expanding medical literature, and professional groups requiring continuing medical education, there is a clear need for up-to-date and relevant systematic reviews of the effectiveness of treatment within our specialty. Such reviews will play an increasing role in the education of health professionals and lay people, in the evolution of the health service and in the direction of future research. The Cochrane Collaboration provides the infrastructure for the development and dissemination of these reviews. The specialty of obstetrics and gynaecology will benefit from several related groups already working within the Cochrane Collaboration (Pregnancy and Childbirth, Subfertility, Menstrual Disorders and Incontinence). Other groups are in the process of, or likely to, register in the near future (Fertility Control, Gynaecological Cancer). However, the need and demand for a large number of systematic reviews exceeds the current capacity of those who have committed themselves to prepare and maintain such reviews, and substantial challenges remain. However, there is every reason to believe that a concerted effort over many years will be worth while. Earlier in this commentary, obstetrics and gynaecology was referred to as the specialty most deserving of the ‘wooden spoon’ for its lack of evidence-based practice. With the development of various gynaecological groups within the Collaboration, we hope that the ‘wooden spoon’ can be discarded from our ranks for good.

Ovarian Conservation at the Time of Hysterectomy and Long-Term Health Outcomes in the Nurses' Health Study

OBJECTIVE: To report long-term health outcomes and mortality after oophorectomy or ovarian conservation. METHODS: We conducted a prospective, observational study of 29,380 women participants of the Nurses’ Health Study who had a hysterectomy for benign disease; 16,345 (55.6%) had hysterectomy with bilateral oophorectomy, and 13,035 (44.4%) had hysterectomy with ovarian conservation. We evaluated incident events or death due to coronary heart disease (CHD), stroke, breast cancer, ovarian cancer, lung cancer, colorectal cancer, total cancers, hip fracture, pulmonary embolus, and death from all causes. RESULTS: Over 24 years of follow-up, for women with hysterectomy and bilateral oophorectomy compared with ovarian conservation, the multivariable hazard ratios (HRs) were 1.12 (95% confidence interval [CI] 1.03–1.21) for total mortality, 1.17 (95% CI 1.02–1.35) for fatal plus nonfatal CHD, and 1.14 (95% CI 0.98–1.33) for stroke. Although the risks of breast (HR 0.75, 95% CI 0.68–0.84), ovarian (HR 0.04, 95% CI 0.01–0.09, number needed to treat=220), and total cancers (HR 0.90, 95% CI 0.84–0.96) decreased after oophorectomy, lung cancer incidence (HR=1.26, 95% CI 1.02–1.56, number needed to harm=190), and total cancer mortality (HR=1.17, 95% CI 1.04–1.32) increased. For those never having used estrogen therapy, bilateral oophorectomy before age 50 years was associated with an increased risk of all-cause mortality, CHD, and stroke. With an approximate 35-year life span after surgery, one additional death would be expected for every nine oophorectomies performed. CONCLUSION: Compared with ovarian conservation, bilateral oophorectomy at the time of hysterectomy for benign disease is associated with a decreased risk of breast and ovarian cancer but an increased risk of all-cause mortality, fatal and nonfatal coronary heart disease, and lung cancer. In no analysis or age group was oophorectomy associated with increased survival. LEVEL OF EVIDENCE: II

Association between Polycystic Ovaries and Extent of Coronary Artery Disease in Women Having Cardiac Catheterization

Coronary artery disease is the most common cause of death among women in developed countries. Established risk factors for coronary disease in women include smoking [1], high serum cholesterol levels [2], low high-density lipoprotein (HDL) cholesterol levels [3], diabetes, and hypertension [2]. Premenopausal women have a lower risk for heart disease than do postmenopausal women [4]. Polycystic ovaries are seen in 22% of women [5, 6] and are associated with hirsutism, infertility, and menstrual disturbances [7]. Insulin resistance [8], higher serum triglyceride levels, and lower HDL cholesterol levels [9] commonly occur in women with polycystic ovaries; these factors may be associated with a higher incidence of coronary artery disease [10, 11]. The metabolic syndrome of hypertension, diabetes, and central obesity (the Stein-Leventhal syndrome) is also associated with polycystic ovaries [12]. We sought to determine whether women with 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 extensive coronary disease. Methods All women 60 years of age or younger who had had coronary angiography in Auckland, New Zealand, in the preceding 2 years were invited to participate in this study. Women who had had bilateral oophorectomy were excluded. The local ethics committee approved the study. Women who were menstruating were studied between days 5 and 9 of the menstrual cycle. Data were collected on infertility (failure to conceive within 1 year), menstrual cycle irregularity (>a 4-day variation), hypercholesterolemia (requiring medication), hypertension (requiring medication), and a family history of heart disease in a first-degree female relative younger than 60 years of age or in a first-degree male relative younger than 55 years of age. Hirsutism was assessed on the Ferriman-Gallwey scale [13]. Ultrasonography was done prospectively, without knowledge of the coronary angiography results. In consenting patients (71.3%), a transvaginal ultrasound was also done. Polycystic ovaries were defined by modified Adams criteria [14] as eight or more cysts that were between 2 and 8 mm in diameter and were associated with an increase in ovarian stroma. Chest pain (96% of women) or valvular disease (4% of women) was assessed by angiography after administration of nitroglycerin spray. Quantitative angiography was done using a computerized automatic analysis system (Cardiovascular Measurement Systems, Neunen, the Netherlands). The extent of coronary artery disease was evaluated by adding the number of segments containing stenoses of more than 50% diameter according to the Coronary Artery Surgery Study scoring system [15]. A secondary end point was severity of coronary artery disease. Patients were given a score on the basis of luminal diameter narrowing according to the following scale: 25% luminal diameter narrowing, 1 point; 26% to 50%, 2 points; 51% to 75%, 4 points; 76% to 90%, 8 points; 91% to 99%, 16 points; and 100%, 32 points. Each stenosis was multiplied by the appropriate score. Functional significance was evaluated by the Coronary Artery Surgery Study [15] weighting system, which accounts for the severity and location of stenoses. Continuous variables were analyzed using one-way analysis of variance. Discrete variables were analyzed using chi-square tests. Multiple logistic regression analysis was done using the presence or absence of polycystic ovaries as the outcome variable. Explanatory variables include those listed in Table 1 and Table 2 and the extent of coronary artery disease. Explanatory variables were entered into the model in a stepwise fashion if they had a P value of 0.15. These variables included age, extent of coronary artery disease, total cholesterol level, HDL cholesterol level, presence of diabetes, family history of heart disease, and history of smoking. Table 1. Characteristics of Women with Normal Ovaries and Women with Polycystic Ovaries* Table 2. Laboratory Findings in Women with Normal Ovaries and Women with Polycystic Ovaries* Results Of 207 women, 143 (69%) agreed to participate. One or more ovaries were visualized in 99.3% of the study women either by transabdominal (77.6%) or transvaginal (94%) ultrasonography. Neither ovary was visualized in one woman, and her results were excluded. Clinical characteristics are shown in Table 1. Polycystic ovaries were diagnosed by ultrasonography in 42.3% of women. There was no difference in the prevalence of polycystic ovaries between premenopausal women and postmenopausal women (25 of 48 women and 35 of 94 women, respectively; P = 0.13). The differences in ovaries seen by ultrasonography were present in both premenopausal (follicle-stimulating hormone level < 20 IU/L) and postmenopausal (follicle-stimulating hormone level > 20 IU/L) women [16]. One woman had previously received a diagnosis of the polycystic ovary (Stein-Leventhal) syndrome. Compared with women with normal ovaries, women with polycystic ovaries had higher triglyceride levels (P < 0.01) and lower HDL cholesterol levels (P < 0.05), although more women with polycystic ovaries were receiving lipid-lowering medications (P = 0.01). Compared with women who had normal ovaries, women with polycystic ovaries had higher free testosterone levels (P < 0.001) and a trend for increased C-peptide levels (P = 0.06) (Table 2). These differences all persisted when the data were stratified according to whether the women were premenopausal or postmenopausal [16]. Women with polycystic ovaries had more coronary artery segments with greater than 50% diameter loss (1.7 segments [95% CI, 1.1 to 2.3 segments]) than did women with normal ovaries (0.82 segments [CI, 0.54 to 1.1 segments]) (P < 0.01). Women with polycystic ovaries had a higher functional significance score (1767 [CI, 1123 to 2412]) than did women with normal ovaries (1029 [CI, 709 to 1349]) (P = 0.05) and had a trend toward a higher severity score (39.5 [CI, 29.3 to 49.7] and 28.7 [CI, 22.2 to 35.2], respectively; P = 0.06). Forty-nine women with normal ovaries (59.8%) and 32 women with polycystic ovaries (53.3%) did not have coronary artery stenoses of 50% or more (P > 0.2). By multivariate logistic regression analysis, the extent of coronary artery disease was found to be independently associated with the presence of polycystic ovaries (P = 0.032), as was family history of heart disease (P = 0.022). If the extent score increased by 1, the odds ratio increased by approximately 26%. Discussion Our study has three important findings. First, in women having coronary angiography, those with more extensive coronary artery disease were more likely to have polycystic ovaries appearing on sonography than were women with less extensive coronary disease. Second, polycystic ovaries were identified in postmenopausal women. Third, the diagnosis of polycystic ovaries seen on ultrasonography was associated with specific metabolic and endocrine abnormalities. Women with polycystic ovaries have been shown to have risk factors for coronary disease [8-11]. However, a direct association between polycystic ovaries and angiographic coronary artery disease has not been previously reported. Diagnosis of polycystic ovaries in postmenopausal women by ultrasonography has only recently been described [16]. Our finding of a high incidence of polycystic ovaries relates to the patients studied, all of whom had had coronary angiography. The women with polycystic ovaries had high testosterone and triglyceride levels, low HDL cholesterol levels, and some insulin resistance. Women with polycystic ovaries seen on ultrasonography often do not have the clinical features of the polycystic ovarian syndrome. The disorder probably exists on a continuum ranging from no symptoms to the fully developed syndrome. Why should polycystic ovaries appear on ultrasonography more frequently in women with more extensive coronary artery disease than in women with less extensive disease? Polycystic ovaries are the most common cause of anovulation with reduced production of estradiol. Decreased estradiol levels may be associated with coronary artery disease, shown by the reduced incidence of heart disease in postmenopausal women receiving estrogen replacement therapy [17]. Although estrone levels are elevated in women with polycystic ovaries, estrone is less potent than estradiol and may not be cardioprotective. Insulin resistance could be the link between polycystic ovaries and coronary artery disease. We found that C-peptide levels, a stable indicator of insulin production, were higher in women with polycystic ovaries than in women with normal ovaries. Abnormal lipid levels may also account for the increase in significant coronary artery disease. In addition, women with increased testosterone production may have a risk for adverse cardiac events similar to that of men. Hirsutism has also been reported as a risk factor for coronary artery disease in women [18]. What are the implications of our findings? Young women with polycystic ovaries often present with hirsutism, acne, infertility, or menstrual irregularity. Once the diagnosis of polycystic ovaries has been made, lifestyle modifications may be indicated to decrease cardiovascular risk. Further research must be done to investigate the natural history and to determine whether any of the current treatments for polycystic ovaries, such as the oral contraceptive pill, antiandrogens, ovulatory agents, or laparoscopic ovarian surgery, are beneficial. From National Womens Hospital, University of Auckland, and Green Lane Hospital, Auckland, New Zealand. Dr. Farquhar: National Womens Hospital, Epsom, Auckland 1003, New Zealand. Dr. White: Cardiology Department, Green Lane Hospital, Epsom, Auckland 1003, New Zealand.

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.

The Prevalence of Polycystic Ovaries on Ultrasound Scanning in a Population of Randomly Selected Women

Summary: Polycystic ovaries (PCO) diagnosed by ultrasound have been commonly reported amongst healthy women. The study aimed to determine the prevalence of PCO in a population of women from the community, and to relate it to clinical and endocrinological data. Twelve hundred women chosen randomly from electoral rolls were invited to take part in the study. Two hundred and fifty five women (21%) who met eligibility criteria agreed to participate and 183 women (16%) finally completed the study. Seventy two women did not attend. An ultrasound scan and blood tests were taken on day 5–9 of their menstrual cycles. Data about their menstrual periods and reproductive history was collected. The prevalence of PCO was 21% (39 of 183). No differences existed between women with PCO and normal ovaries with respect to uterine size, body mass index, luteinizing hormone levels, serum hormone binding globulin levels and fertility status. Hirsutism (Ferriman Gallwey score >7), elevated testosterone levels and irregular menstrual cycles were significantly more frequent amongst women with PCO. Mean ovarian volume was larger in women with PCO irrespective of the use of hormonal contraception. Fifty nine per cent of women with PCO had irregular menstrual cycles or elevated Ferriman Gallwey scores or both. There was no detectable effect of PCO on parity or miscarriage although only 70% of women with PCO had evidence of an adequate ovulation compared to 95% of women with normal ovaries.

Ovarian conservation at the time of hysterectomy for benign disease

Objective: Prophylactic oophorectomy is often recommended concurrent with hysterectomy for benign disease. The optimal age for this recommendation in women at average risk for ovarian cancer has not been determined. Methods: Using published age-specific data for absolute and relative risk, both with and without oophorectomy, for ovarian cancer, coronary heart disease, hip fracture, breast cancer, and stroke, a Markov decision analysis model was used to estimate the optimal strategy for maximizing survival for women at average risk of ovarian cancer. For each 5-year age group from 40 to 80 years, 4 strategies were compared: ovarian conservation or oophorectomy, and use of estrogen therapy or nonuse. Outcomes, as proportion of women alive at age 80 years, were measured. Sensitivity analyses were performed, varying both relative and absolute risk estimates across the range of reported values. Results: Ovarian conservation until age 65 benefits long-term survival for women undergoing hysterectomy for benign disease. Women with oophorectomy before age 55 have 8.58% excess mortality by age 80, and those with oophorectomy before age 59 have 3.92% excess mortality. There is sustained, but decreasing, benefit until the age of 75, when excess mortality for oophorectomy is less than 1%. These results were unchanged following multiple sensitivity analyses and were most sensitive to the risk of coronary heart disease. Conclusion: Ovarian conservation until at least age 65 benefits long-term survival for women at average risk of ovarian cancer when undergoing hysterectomy for benign disease.

Diagnosis and management of dysmenorrhoea

The prevalence of dysmenorrhoea (painful menstrual cramps of uterine origin) is difficult to determine because of different definitions of the condition—prevalence estimates vary from 45% to 95%. However, dysmenorrhoea seems to be the most common gynaecological condition in women regardless of age and nationality.1 2 Absenteeism from work and school as a result of dysmenorrhoea is common (13% to 51% women have been absent at least once and 5% to 14% are often absent owing to the severity of symptoms).3 Dysmenorrhoea, especially when it is severe, is associated with a restriction of activity and absence from school or work. Yet despite this substantial effect on their quality of life and general wellbeing, few women with dysmenorrhoea seek treatment as they believe it would not help.w1 We used Medline (1966 to March 2006) to conduct a literature search of the Cochrane Database of Systematic Reviews on the Cochrane Library, issue 1, 2006, and we searched citation lists of relevant publications, including studies for randomised controlled trials (RCTs) and review articles. We used the following subject headings and keywords: dysmenorrhoea, dysmenorrhea, menstrual pain, period pain, and pelvic pain. Dysmenorrhoea is commonly divided into two categories based on pathophysiology (table). Primary dysmenorrhoea is menstrual pain without organic disease, and secondary dysmenorrhoea is menstrual pain associated with an identifiable disease. Common causes of secondary dysmenorrhoea include endometriosis, fibroids (myomas), adenomyosis, endometrial polyps, pelvic inflammatory disease, and the use of an intrauterine contraceptive device. View this table: Differential diagnosis of primary and secondary dysmenorrhoea Until recently, many medical and gynaecological texts ascribed the source of dysmenorrhoea to emotional or psychological problems—for example, anxiety, emotional instability, a faulty outlook on sex and menstruation, and imitation of the mothers feelings about menstruation.w2 However, experimental and clinical research has identified a physiological reason for dysmenorrhoea—the production of …

The association of hysterectomy and menopause: a prospective cohort study

Objective  To determine whether or not hysterectomy leads to an earlier onset of the menopause.

A systematic review of transvaginal ultrasonography, sonohysterography and hysteroscopy for the investigation of abnormal uterine bleeding in premenopausal women

Background.  To determine the accuracy of transvaginal ultrasonography, sonohysterography and diagnostic hysteroscopy for the investigation of abnormal uterine bleeding in premenopausal women.

Stillbirths: recall to action in high-income countries

Variation in stillbirth rates across high-income countries and large equity gaps within high-income countries persist. If all high-income countries achieved stillbirth rates equal to the best performing countries, 19,439 late gestation (28 weeks or more) stillbirths could have been avoided in 2015. The proportion of unexplained stillbirths is high and can be addressed through improvements in data collection, investigation, and classification, and with a better understanding of causal pathways. Substandard care contributes to 20-30% of all stillbirths and the contribution is even higher for late gestation intrapartum stillbirths. National perinatal mortality audit programmes need to be implemented in all high-income countries. The need to reduce stigma and fatalism related to stillbirth and to improve bereavement care are also clear, persisting priorities for action. In high-income countries, a woman living under adverse socioeconomic circumstances has twice the risk of having a stillborn child when compared to her more advantaged counterparts. Programmes at community and country level need to improve health in disadvantaged families to address these inequities.