Pharmacologic therapy to induce weight loss in women who have obesity/overweight with polycystic ovary syndrome: a systematic review and network meta-analysis.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) are almost three times more likely to be obese than those without PCOS. However, we have no specific interventions to induce weight loss so far and rely on drugs used to treat other symptoms of the syndrome or obesity in the general population. OBJECTIVE: The objective of this study is to compare the effectiveness of metformin, inositol, liraglutide and orlistat to induce weight loss in women with PCOS and overweight/obesity. METHODS: A search was conducted using the MEDLINE, EMBASE, PubMed and CENTRAL databases. Individually randomized, parallel group trials that evaluated the effects of these pharmacological treatments among adults or adolescents with PCOS and overweight/obesity, compared with a placebo or metformin group, were considered eligible. Registration number: PROSPERO CRD 42017076625. RESULTS: Twenty-three trials reporting on 941 women were included in the network meta-analysis. The amount of weight lost differed significantly among the drugs (in descending order): liraglutide, orlistat and metformin. Liraglutide alone, liraglutide/metformin and metformin alone significantly reduced waist circumference, but no change was found with orlistat. Data for waist-to-hip ratio were only available for metformin, which had no significant effect. CONCLUSION: Liraglutide appears superior to the other drugs in reducing weight and waist circumference.

An exploration of the hypothesis that testosterone is implicated in the psychological functioning of women with polycystic ovary syndrome (PCOS).

One of the diagnostic features of polycystic ovary syndrome (PCOS) is elevation of the androgen, testosterone. It is known that women with PCOS are more likely to suffer from psychological problems, especially anxiety and depression, than other women. However, little is known of how much of this is due to testosterone, and if so, what the mechanism(s) might be. This study explores the hypothesis that testosterone impacts women with PCOS both directly and indirectly, via testosterone currently in the bloodstream and through prenatal exposure. It is hypothesised that direct effects occur when testosterone acts directly upon receptors; indirect effects occur where the impact of testosterone is mediated via another variable; activational effects are ephemeral and are caused by testosterone in the bloodstream; organizational effects occur prenatally and cause permanent changes. Four pathways are hypothesised in this paper: 1/ a direct and activational pathway which improves mental rotation ability; 2/ an indirect and activational pathway, whereby distress is caused when the physiological symptoms of testosterone are experienced as embarrassing or otherwise disturbing; 3/ an indirect and organizational effect on mood, where elevated prenatal testosterone predisposes women with PCOS to low blood sugar levels and thus low mood; 4/ and finally, it is suggested that the pathway from biology to psychology can be travelled in reverse, with a direct activational effect of relaxation training on the reduction of adrenal androgens. Testing these hypotheses has important implications for our understanding of PCOS, and our ability to treat this condition more effectively.

Prolactin and hostility in hospitalised patients and healthy women: A systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to assess any difference in the self-ratings of hostility in mentally healthy women with different levels of prolactin (PRL). Electronic databases (PubMed, MEDLINE, EMBASE and the Cochrane Library) were searched up to 2nd July 2012 for published literature comparing hostility levels in women with different levels of PRL. Keyword pairs ('prolactin' and 'aggression', 'prolactin' and 'hostil*', 'prolactin' and 'anger', and 'prolactin' and 'angry') were entered simultaneously. From 1065 resulting titles, and one unpublished study, 214 articles underwent full-text review by authors JB and EM. Studies were selected based on clinical relevance. Eight comparative studies consisting of 242 female patients with high PRL levels, 207 female patients with normal PRL levels and 127 healthy controls with normal PRL levels were included. Data were analysed using the inverse variance method with a random-effects model. Analysis revealed significantly higher hostility in patients with high PRL compared with that in healthy control women (Z = 1.94, p < 0.05; Hedges' g = 0.72; 95% confidence interval [CI]: -0.01-1.45), significantly higher hostility in patient controls compared with that in healthy controls (Z = 1.94, p < 0.05; Hedges' g = 0.47; 95% CI: 0.00-0.94) and non-significantly higher hostility levels in patients with high PRL compared with that in patients with normal PRL levels (Z = 1.45, p < 0.15; Hedges' g = 0.38; 95% CI: -0.13-0.89). In this meta-analysis, hostility appears to be accounted for partly by PRL levels and also partly by patient status, perhaps due to the stress of being a patient. Methodological considerations and implications for patient care are discussed.

Prolactin and aggression in women with fertility problems.

This study tested the hypothesis that women with higher prolactin feel more hostility, anger and aggression. A total of 66 women with moderate fertility problems were grouped into the 50% who had the highest and the 50% who had the lowest levels of prolactin. Levels of hostility, aggression and anger were compared. Women with higher prolactin levels did not report significantly increased hostility. After Bonferroni correction, women with lower prolactin showed non-significantly increased scores on two measures of state anger, and on a measure of trait temper. When comparing those with the highest and lowest 20% of prolactin levels, those with lower prolactin had non-significantly higher scores on trait temper and outward expression of anger, and non-significantly lower scores for control of anger. Although non-significant, these findings run counter to those of earlier studies on this topic. Implications for future research and patient care are discussed.

Visual-spatial cognition in women with polycystic ovarian syndrome: the role of androgens.

STUDY QUESTION: Are women with polycystic ovary syndrome (PCOS) better at three-dimensional mental rotation than other women? SUMMARY ANSWER: Women with PCOS scored significantly higher on a mental rotation task than a female control group. WHAT IS KNOWN ALREADY: PCOS is a condition characterized by elevated testosterone levels. Some researches have found that three-dimensional mental rotation task performance is positively correlated with testosterone levels. STUDY DESIGN, SIZE, DURATION: This cross-sectional study was conducted between June 2006 and January 2009. The participants were 69 women with PCOS and 41 controls recruited from five gynaecology clinics in London. The control group consisted of non-PCOS women of comparable subfertility to PCOS group. These groups sizes gave roughly 80% power to detect moderate effect sizes for the main statistical test. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were recruited at London gynaecology clinics. The women were aged between 18 and 43. PCOS was diagnosed based on the Rotterdam criteria. Controls were women who experienced some degree of subfertility. Blood samples from participants were frozen for up to 4 months until being assayed by direct electrochemiluminescence. The mental rotation task was undertaken electronically. Some questionnaires and other tasks were completed as control measures. MAIN RESULTS AND THE ROLE OF CHANCE: Women with PCOS scored significantly higher than controls: median (range) 3.00 (0-9) and 2.00 (0-8), respectively (U = 1147.500, N1 = 69, N2 = 41, P < 0.047). Within the PCOS group, circulating levels of testosterone were significantly positively correlated with three-dimensional scoring (rs = 0.376, n = 56, P < 0.002), whereas estradiol was significantly negatively correlated with three-dimensional scoring (rs = -0.473, n = 29, P < 0.010). In the control group, the relationship between sex hormones and mental rotation was non-significant. Other factors, including general intelligence and social class, did not account for these findings. A subgroup analysis comparing hyperandrogenic PCOS cases, non-hyperandrogenic PCOS cases and controls, in which age and body mass index were controlled for using ANCOVA, found a non-significant difference in three-dimensional scoring between the three groups (F = 1.062, d.f. = 1, 73, P < 0.351). LIMITATIONS, REASONS FOR CAUTION: The small number of women in the control group meant that correlations were underpowered in this group. WIDER IMPLICATIONS OF THE FINDINGS: This study is the first to find a benefit of PCOS in visuospatial cognition, and the first to find a link between visuospatial cognition and sex hormones in PCOS. The fact that the correlations went in the opposite direction in the PCOS group compared with the controls might suggest the influence of increased prenatal exposure to androgen in PCOS. STUDY FUNDING/COMPETING INTEREST(S): The assays for this study were funded by the Department of Psychology, City University London. All authors report no conflicts of interest.

Meta-analysis of sex difference in testosterone levels in umbilical cord blood.

This meta-analysis reviewed published literature comparing human male and female umbilical cord total testosterone (T) levels. A total of 18 studies using 1,229 samples from 602 male and 627 female newborns were analysed using the RevMan 5 statistical package. Analysis using the inverse variance method based on a random-effects model revealed significantly higher cord T in boys than girls at a moderate effect size (Hedges' g = 0.57). There was significant heterogeneity between the 18 studies, although the five studies using direct assays showed no heterogeneity. For studies using extraction and chromatography, those that combined T from arterial and venous cord blood found a larger sex difference than those using only cord venous samples (Hedges' g = 0.94 vs 0.32); this suggests umbilical cord venous T is of maternal/placental origin and arterial T is of fetal origin. The wide range of T values between studies suggests high cross-reactivity in the assay methods reviewed.

Anxiety and depression in polycystic ovary syndrome: a systematic review and meta-analysis.

BACKGROUND: Our aim was to assess differences in anxiety and depression between women with and without (controls) polycystic ovary syndrome (PCOS). METHODS: We conducted a systematic review and meta-analysis of published literature comparing women with PCOS to control groups on anxiety and depression. Electronic databases were searched up to 17 December 2010. The inverse variance method based, as appropriate, on a random- or fixed-effects model in Review Manager, Version 5 was used to analyse the data. RESULTS: Twelve comparative studies were included; all studies assessed depression (910 women with PCOS and 1347 controls) and six also assessed anxiety (208 women with PCOS and 169 controls). Analysis revealed higher depression (Z = 17.92, P < 0.00001; Hedges' g = 0.82; 95% CI 0.73-0.92) and anxiety (Z = 5.03, P < 0.00001; Hedges' g = 0.54; 95% CI 0.33-0.75) scores in the participants with, than without, PCOS. Studies controlling for BMI showed a smaller difference between women with PCOS and controls on anxiety and depression scores than studies not controlling for BMI. CONCLUSIONS: Women with PCOS on average tend to experience mildly elevated anxiety and depression, significantly more than women without PCOS. Women with PCOS with lower BMI tended to have slightly lower anxiety and depression scores, suggesting that having a lower BMI reduces anxiety and depression. Future studies might consider (i) controlling for BMI, (ii) stratifying by medication use in order to control for any anti-androgenic effects of medication and (iii) excluding women with polycystic ovaries from control groups.

Symmetric dimethylarginine (SDMA) is raised in women with polycystic ovary syndrome: a pilot study.

Polycystic ovary syndrome (PCOS) is associated with endothelial dysfunction, which may be caused by elevated levels of asymmetric dimethylarginine (ADMA). ADMA reduces nitric oxide production in diabetes mellitus, hypertension and renal failure. Symmetric dimethylarginine (SDMA) is a stereoisomer produced alongside ADMA, and has recently been described as a risk factor for cardiovascular events. In this cross-sectional study based in a teaching hospital, 16 women with PCOS were recruited alongside 15 healthy controls, and fasting venous blood samples were obtained. Renal function was measured, and ADMA and SDMA were analysed using a high-performance liquid chromatography method. After controlling for BMI, mean ADMA and SDMA levels in women with PCOS were higher than in controls (p = 0.036 and p = 0.030, respectively). Renal function was not different between the two groups (p = 0.152). Women with PCOS have raised levels of SDMA, a molecule implicated in endothelial dysfunction and long-term cardiovascular risk.

Umbilical vein testosterone in female infants born to mothers with polycystic ovary syndrome is elevated to male levels.

The aetiology of polycystic ovary syndrome (PCOS) is poorly understood, but an intrauterine hyperandrogenic environment has been implicated. This study was designed to assess whether the female offspring of mothers with PCOS are exposed to raised levels of testosterone (T) in utero. In this case-control study, three groups of pregnant women were recruited from the labour ward: PCOS women with a female baby (n = 10, PCOS girls); control women with a female baby (n = 20, control girls) and control women with a male baby (n = 10, control boys). Maternal and umbilical vein (UV) blood was assayed for T levels. UV T in PCOS girls was significantly raised, compared with control girls (p < 0.012). The difference in UV T between PCOS girls and control boys was not significant (p < 0.254). This is the first demonstration of a hyperandrogenic in utero environment in PCOS pregnancies; UV T in female infants is raised to male levels.

Could epithelial ovarian cancer be associated with chlamydial infection?

PURPOSE OF INVESTIGATION: Epithelial ovarian cancer (EOC) is the leading cause of death from gynaecological malignancy in the UK. The pathogenesis of this disease is poorly understood. Our hypothesis was that chlamydial infection might play a role in the pathogenesis of EOC. METHODS: 122 serum samples of patients undergoing surgery for benign or malignant gynaecological conditions were analysed. There was a total of 41 patients with EOC (33.6%), 27 with benign cystadenomas (22.1%) and 54 with normal ovaries (44.3%). RESULTS: There was a higher incidence of IgA seropositivity and lower incidence of IgG seropositivity in the EOC group compared with the other groups; however, this was not statistically significant. There was no statistical difference in the serum IgM antibodies to chlamydia in the three different groups. CONCLUSION: Although chronic infection and persistent inflammation may contribute to the pathogenesis of EOC, and chlamydia is a common genital tract pathogen, our study did not find an association between chlamydia and EOC.

Ovarian epithelial dysplasia in relation to ovulation induction and nulliparity.

OBJECTIVE: The goal of this study was to assess the relationship between ovulation induction, nulliparity, and ovarian epithelial dysplasia. METHODS: This retrospective cohort study was performed in one teaching and one district general hospital in London. The subjects, 83 women who had undergone hysterectomy and bilateral oophorectomy and whose ovaries were reported as "normal," were divided into three groups: ovulation induction (13), nulliparity (20), and fertile controls (50). These ovaries were independently reviewed by two pathologists who assigned a score of 0, 1, or 2 to nine epithelial cytological and architectural features. The main outcome measure was the total dysplasia score, which was used to quantify the degree of ovarian epithelial abnormality in the three groups. RESULTS: The mean dysplasia score was significantly higher in the women who had undergone ovulation induction than in the fertile controls (7.92 vs 5.70, P = 0.012). The magnitude of the difference between the ovulation induction group and controls remained similar after adjusting for age, parity, and duration of oral contraceptive use (2.17, 95% CI: -0.11-4.44). However, the statistical significance of this difference was reduced (P = 0.062). We did not find any evidence of a difference in dysplasia score between nulliparous women and controls, neither before (P = 0.85) nor after adjusting for age and duration of oral contraceptive use (P = 0.87). CONCLUSIONS: These results suggest a possible association between ovarian epithelial dysplasia and ovulation induction therapy, in accord with previous reports of increased risk of ovarian cancer in women with a history of fertility treatment. The higher dysplasia score could be attributable to the drugs used to induce ovulation or to a genetic susceptibility to ovarian cancer.

Sacrospinous vault suspension and abdominal colposacropexy: success rates and complications.

OBJECTIVE: Our purpose was to compare success rates and complications of sacrospinous vault suspension and abdominal colposacropexy. STUDY DESIGN: A case series is presented of 130 attempted sacrospinous vault suspensions with the Miya hook and 80 cases of abdominal colposacropexy, done in conjunction with other procedures. Patients were assessed 6 weeks and 6 and 12 months after surgery and yearly thereafter. RESULTS: Sacrospinous vault suspension was completed in 125 women (5 abandoned because of technical difficulty). Abdominal colposacropexy was completed in all 80 women. There was only one intraoperative complication-hemorrhage from the presacral veins during abdominal colposacroplexy. The incidence of postoperative febrile morbidity was 10% after sacrospinous vault suspension and 6% after abdominal colposacropexy. Follow-up ranged from 6 months to 5 years. The incidence of recurrent vault prolapse was 2.4% with sacrospinous vault suspension and 1.3% with abdominal colposacropexy. Demonstrable stress urinary incontinence occurred in one woman after abdominal colposacropexy and in none after sacrospinous vault suspension. CONCLUSION: Sacrospinous vault suspension and abdominal colposacropexy are associated with a low incidence of intraoperative and postoperative complications and recurrent vault prolapse. Latent stress urinary incontinence may be unmasked, particularly with abdominal colposacropexy, and preoperative urodynamic evaluation is therefore recommended.

Limb exsanguination. II. The leg: effect of angle of elevation.

Although limb exsanguination prior to tourniquet inflation is usually accomplished using mechanical devices, elevation alone may still be employed under circumstances where mechanical means are contraindicated. The rather confusing advice within the literature as to duration of elevation, stimulated a study in the arm which revealed the optimal duration of elevation to be 5 min, a period somewhat longer than generally advised. Because the pattern of venous drainage within the leg is slightly different to that of the arm, we undertook a similar study to ascertain if our findings for the arm also held true for the leg. Volume changes in the calves of seven male volunteers during elevation at 45 degrees and 90 degrees were assessed using strain gauge plethysmography. To achieve maximal exsanguination it is recommended that the leg should be elevated at an angle of 45 degrees for 5 min. Higher angles of elevation produce slower and less complete exsanguination.

Limb exsanguination. I. The arm: effect of angle of elevation and arterial compression.

Limb exsanguination before tourniquet inflation is usually accomplished using mechanical devices although, where their use is contraindicated, exsanguination by elevation alone may be employed. Advice regarding duration of elevation within the literature is a little confusing with recommendations ranging from 20 s to 5 min. Volume changes, during elevation at 45 degrees and 90 degrees, were measured using strain gauge plethysmography in seven male volunteers. In addition, the superimposed effect of brachial arterial compression on elevation at 90 degrees was investigated. To achieve maximal exsanguination it is recommended that the arm should be elevated for 5 min at 90 degrees before tourniquet inflation. Supplementary brachial arterial compression is not recommended as this tends to attenuate changes in volume.