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Robert J Norman

Publications and source records attributed to Robert J Norman.

At least 19 recordsLinked to original sources

Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline.

OBJECTIVE: The Androgen Excess Society (AES) charged a task force to review all available data and recommend an evidence-based definition for polycystic ovary syndrome (PCOS), whether already in use or not, to guide clinical diagnosis and future research. PARTICIPANTS: Participants included expert investigators in the field. EVIDENCE: Based on a systematic review of the published peer-reviewed medical literature, by querying MEDLINE databases, we tried to identify studies evaluating the epidemiology or phenotypic aspects of PCOS. CONSENSUS PROCESS: The task force drafted the initial report, following a consensus process via electronic communication, which was then reviewed and critiqued by the AES Board of Directors. No section was finalized until all members were satisfied with the contents and minority opinions noted. Statements that were not supported by peer-reviewed evidence were not included. CONCLUSIONS: Based on the available data, it is the view of the AES Task Force on the Phenotype of PCOS that there should be acceptance of the original 1990 National Institutes of Health criteria with some modifications, taking into consideration the concerns expressed in the proceedings of the 2003 Rotterdam conference. A principal conclusion was that PCOS should be first considered a disorder of androgen excess or hyperandrogenism, although a minority considered the possibility that there may be forms of PCOS without overt evidence of hyperandrogenism but recognized that more data are required before validating this supposition. Finally, the task force recognized, and fully expects, that the definition of this syndrome will evolve over time to incorporate new research findings.

Androgens↗

Influence of acupuncture stimulation on pregnancy rates for women undergoing embryo transfer.

OBJECTIVE: To evaluate the effects of acupuncture on clinical pregnancy rates for women undergoing ET. DESIGN: Single-blind, randomized controlled trial using a noninvasive sham acupuncture control. SETTING: Repromed, The Reproductive Medicine Unit of The University of Adelaide. PATIENT(S): Women undergoing IVF. INTERVENTION(S): Women were randomly allocated to acupuncture or noninvasive sham acupuncture with the placebo needle. All women received three sessions, the first undertaken on day 9 of stimulating injections, the second before ET, and the third immediately after ET. MAIN OUTCOME MEASURE(S): The primary outcome was pregnancy. Secondary outcomes were implantation, ongoing pregnancy rate at 18 weeks, adverse events, and health status. RESULT(S): Two hundred twenty-eight subjects were randomized. The pregnancy rate was 31% in the acupuncture group and 23% in the control group. For those subjects receiving acupuncture, the odds of achieving a pregnancy were 1.5 higher than for the control group, but the difference did not reach statistical significance. The ongoing pregnancy rate at 18 weeks was higher in the treatment group (28% vs. 18%), but the difference was not statistically significant. CONCLUSION(S): There was no significant difference in the pregnancy rate between groups; however, a smaller treatment effect can not be excluded. Our results suggest that acupuncture was safe for women undergoing ET.

Acupuncture Therapy↗

Reducing multiple pregnancy from assisted reproduction treatment: educating patients and medical staff.

Multiple pregnancy, with its adverse outcomes, is a significant problem in assisted reproductive technology. Single embryo transfer (SET) is the only feasible solution for reducing the rate of multiple pregnancy. Many patients and some clinicians remain to be convinced that SET is a better clinical option. Adequate education, based on available evidence, is one important way to promote the use of SET.

Adult↗

Effects of lifestyle modification in polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is a common endocrine condition with reproductive and metabolic consequences, including anovulation, infertility and an increased prevalence of diabetes mellitus. Obesity, central obesity and insulin resistance are strongly implicated in its aetiology. Dietary weight loss is recommended as the primary treatment strategy; however, effective means of achieving and maintaining weight loss and reproductive and metabolic improvements are unknown. Lifestyle modification programmes with an emphasis on behavioural management and dietary and exercise interventions have been successful in the general population in reducing the risk of diabetes and the metabolic syndrome, and have had some initial success in improving fertility outcomes in PCOS. However, the literature on effective diet and exercise programmes for PCOS has been sparse, and structured advice for implementing components of lifestyle modification programmes should be assessed in this population.

Appetite↗

Short-term meal replacements followed by dietary macronutrient restriction enhance weight loss in polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS), a common condition in women, improves with weight loss. Meal replacements in short-term weight loss and strategies for weight maintenance have not been investigated in PCOS. OBJECTIVE: We compared in overweight women with PCOS the effects of meal replacements in short-term weight-loss and longer-term carbohydrate- or fat-restriction strategies on weight maintenance and improvements in reproductive and metabolic variables. DESIGN: Overweight women with PCOS (n = 43; x +/- SD age: 32.1 +/- 5.2 y; weight: 96.1 +/- 18.4 kg) followed an 8-wk weight-loss regimen (2 meal replacements/d, 4904.4 +/- 127 kJ; phase 1) and then a 6-mo weight-maintenance carbohydrate- (<120 g/d) or fat- (<50 g/d) restriction regimen (phase 2). RESULTS: Thirty-four women completed phase 1, and 23 women completed phase 2; the proportion of dropouts was similar in the 2 groups. During phase 1, significant (P < 0.05) reductions in weight (5.6 +/- 2.4 kg), waist circumference (6.1 +/- 2.5 cm), body fat (4.1 +/- 2.2 kg), insulin (2.8 +/- 1.1 mU/L), total testosterone (0.3 +/- 0.7 nmol/L), and free androgen index (3.1 +/- 4.6) occurred; these changes were sustained during phase 2. No significant differences between diet groups were seen for any variables. At 6 mo, both approaches resulted in a net weight loss of 4.7 +/- 4.6 kg. Improvements in menstrual cyclicity occurred for 16 (57.1%) of 28 subjects. CONCLUSIONS: Meal replacements are an effective strategy for the short-term management of PCOS. Advice on moderate fat or carbohydrate restriction was equally effective in maintaining weight reduction and improving reproductive and metabolic variables.

Adult↗

Troglitazone regulates peroxisome proliferator-activated receptors and inducible nitric oxide synthase in murine ovarian macrophages.

Peroxisome proliferator-activated receptor-gamma (PPARG) and PPAR-alpha (PPARA) control metabolic processes in many cell types and act as anti-inflammatory regulators in macrophages. PPAR-activating ligands include thiazolidinediones (TZDs), such as troglitazone, once frequently used to treat insulin resistance as well as symptoms of polycystic ovary syndrome (PCOS). Since macrophages within the ovary mediate optimal follicle development, TZD actions to improve PCOS symptoms are likely to be partly mediated through these specifically localized immune cells. In mouse ovary, PPARG protein was expressed in granulosa cells and in isolated cells localized to theca, stroma, and corpora lutea, consistent with EMR1+ macrophages. Isolation of immune cells (EMR1+ or H2+) showed that Pparg and Ppara were expressed in ovarian macrophages at much higher levels than in peritoneal macrophages. Ovulatory human chorionic gonadotropin downregulated expression of Pparg and Ppara in EMR1+ ovarian macrophages, but no hormonal responsiveness was observed in H2+ cells. Downstream anti-inflammatory effects of PPARG activation were analyzed by in vitro treatment of isolated macrophages with troglitazone. Interleukin-1 beta (Il1b) expression was not altered, and tumor necrosis factor-alpha (Tnf) expression was affected in peritoneal macrophages only. In ovarian macrophages, inducible nitric oxide synthase (Nos2), an important proinflammatory enzyme that regulates ovulation, was significantly reduced by troglitazone treatment, an effect that was restricted to cells from the preovulatory ovary. Thus, expression of PPARs within ovarian macrophages is hormonally regulated, reflecting the changing roles of these cells during the ovulatory cycle. Additionally, ovarian macrophages respond directly to troglitazone to downregulate expression of proinflammatory Nos2, providing mechanistic information about ovarian effects of TZD treatment.

Animals↗

Towards less confusing terminology in reproductive medicine: clarifying medical ambiguities to the benefit of all.

It has been argued that terminology in reproductive medicine related to reproductive success is ambiguous, confusing and misleading. A proposed solution is the conditional use of the term 'fertility' which is qualified according to statements concerning description, diagnosis and prognosis, and for which a grading system is proposed. We argue that there already exists (from 1989) a well-articulated conceptualization of fertility that does not appear to have been well disseminated within reproductive medicine. Within this conceptualization there is an important place for separate terms that clearly distinguish aetiology from outcome. We therefore see a central role for maintaining and articulating the terms fecundity and fertility. It is also suggested that one source of confusion within reproductive medicine stems from the conflation of interests for clinicians and patients when discussing infertility as both a cause and an outcome. Unpacking the meaning of the term 'infertility' reveals a complex of interdependent concepts that are both social and biological in origin.

Female↗

Effect of a synthetic progestin on the exercise status of sedentary young women.

CONTEXT: The impact of progestins on exercise performance in women has not been previously studied. OBJECTIVE: The objective of this study was to examine the effect of a synthetic progestin on aspects of exercise status in young women. DESIGN, PATIENTS, SETTING: Twenty-three young, healthy, habitually sedentary women participated in a single-blind, randomized, counterbalanced, cross-over study in a university-based laboratory setting. INTERVENTION: Two monophasic oral contraceptive pills (OCPs) were administered in which the dose of the synthetic progestin, norethisterone, was 2-fold different but the dose of the synthetic estrogen, ethinyl estradiol, was constant. During each month of OCP aspects of exercise status were assessed during incremental exercise to exhaustion and steady-state submaximal exercise and with a performance test. MAIN OUTCOME MEASURES: The main outcome measures were peak oxygen uptake (VO(2peak)), respiratory exchange ratio (RER), time to exhaustion, lactate concentrations, and total work done. RESULTS: Peak heart rates were approximately 95% of age-predicted values with both OCP preparations, whereas VO(2peak) was approximately 30% above age-predicted values. Peak postincremental exercise plasma lactate concentrations exceeded those reported for males and females, whereas the RER was below expected values throughout both incremental and steady-state exercise. The effects on VO(2peak) and RER were increased with the higher dose progestin OCP, as were exercise time to exhaustion and total work done. CONCLUSION: Synthetic progestins in OCP formulations can have a significant effect on the exercise status of young, sedentary women, possibly through an effect on stroke volume and a shift in the principal energy substrate used during exercise from carbohydrate to lipid.

Adult↗

Polycystic ovarian syndrome: marked differences between endocrinologists and gynaecologists in diagnosis and management.

BACKGROUND: Women with polycystic ovarian syndrome (PCOS) commonly consult endocrinologists or gynaecologists and it is not known whether these specialty groups differ in their approach to management. OBJECTIVE: To compare the investigation, diagnosis and treatment practices of endocrinologists and gynaecologists who treat PCOS. DESIGN AND SETTING: A mailed questionnaire containing a hypothetical patient's case history with varying presentations--oligomenorrhoea, hirsutism, infertility and obesity--was sent to Australian clinical endocrinologists and gynaecologists in teaching hospitals and private practice. RESULTS: Evaluable responses were obtained from 138 endocrinologists and 172 gynaecologists. The two specialty groups differed in their choice of essential diagnostic criteria and investigations. Endocrinologists regarded androgenization (81%) and menstrual irregularity (70%) as essential diagnostic criteria, whereas gynaecologists required polycystic ovaries (61%), androgenization (59%), menstrual irregularity (47%) and an elevated LH/FSH ratio (47%) (all P-values < 0.001). In investigation, gynaecologists were more likely to request ovarian ultrasound (91%vs. 44%, P < 0.001) and endocrinologists more likely to measure adrenal androgens (80%vs. 58%, P < 0.001) and lipids (67%vs. 34%, P < 0.001). Gynaecologists were less likely to assess glucose homeostasis but more likely to use a glucose tolerance test to do so. Diet and exercise were chosen by most respondents as first-line treatment for all presentations. However, endocrinologists were more likely to use insulin sensitizers, particularly metformin, for these indications. In particular, for infertility, endocrinologists favoured metformin treatment whereas gynaecologists recommended clomiphene. CONCLUSIONS: There is a lack of consensus between endocrinologists and gynaecologists in the definition, diagnosis and treatment of PCOS. As a consequence, women may receive a different diagnosis or treatment depending on the type of specialist consulted.

Australia↗

Periovulatory expression of intercellular adhesion molecule-1 in the rat ovary.

Leukocytes, especially neutrophils and macrophages, traditional cellular regulators of the immune system, reside within the tissue architecture of the rodent and human ovary and dramatically increase in number, in response to gonadotropin, in the theca of preovulatory follicles. Evidence strongly suggests a modulatory role for leukocytes in ovarian tissue remodeling events, such as ovulation, luteinization, and luteolysis. The present study investigates the ovarian localization and potential gonadotropin regulation of intercellular adhesion molecule-1 (ICAM-1), an important factor in neutrophil and monocyte attachment to endothelium. Reverse transcription-polymerase chain reaction and immunohistochemical detection and quantification of ICAM-1 mRNA and protein were carried out in ovaries of immature and eCG/hCG-primed rats during the periovulatory period (0, 6, 12, and 24 h post-hCG). While whole ovarian ICAM-1 mRNA levels did not vary significantly during the preovulatory period, ovarian follicles exhibited ICAM-1 mRNA and protein specifically within the thecal region, where mRNA expression increased 5-fold and protein expression increased 6-fold when comparing pre-hCG levels with those at the estimated time of ovulation (12 h post-hCG). Thecal ICAM-1 was most prevalent in highly vascularized regions as evidenced by serial staining with an endothelium-specific antibody. Granulosa layer ICAM-1 immunoactivity was acquired only during/after follicle rupture. These results show ICAM-1 is localized within the ovarian theca and its expression is associated with follicular development in periovulatory follicles, peaking in expression at the time of rupture. Additionally, ICAM-1 is expressed among granulosa-lutein cells of the ovulating follicle and developing corpus luteum. Taken together, these findings suggest rat ovarian ICAM-1 may be instrumental in the active recruitment of leukocytes into the preovulatory ovary and may have a role in corpus luteum formation.

Animals↗

What is the most relevant standard of success in assisted reproduction? Assessing the BESST index for reproduction treatment.

It has been proposed that use of performance indicators for assisted reproduction treatment (ART) should be revised to better reflect the burden of treatment endured by a couple, and to place greater emphasis on the desired outcome of healthy babies. Recently, the BESST (birth emphasizing a successful singleton at term) score as a routine measurement for use in ART has been suggested. We applied the BESST index to a sample of ART patients and found that the BESST score was sensitive to the effects of patient age and extremes in the number of embryos transferred. However, the statistical properties of the index placed great weight on the effective implantation rate, which when applied to a time series in which implantation rates were improving, showed BESST scores to increase simultaneously with multiple pregnancy rates. This limits the completeness of the summary score as an expression of benefits compared to risks. A modified BESST index, not including cycles of initiated treatment as a denominator, indicated that the ART births contained a substantially lower proportion of BESST babies when compared to the entire population of births.

Adult↗

4: Polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common condition characterised by menstrual abnormalities and clinical or biochemical features of hyperandrogenism. Features of PCOS may manifest at any age, ranging from childhood (premature puberty), teenage years (hirsutism, menstrual abnormalities), early adulthood and middle life (infertility, glucose intolerance) to later life (diabetes mellitus and cardiovascular disease). While pelvic ultrasound examination is useful, many women without PCOS have polycystic ovaries; ultrasound evidence is not necessary for the diagnosis. Testing for glucose intolerance and hyperlipidaemia is wise, especially in obese women, as diabetes mellitus is common in PCOS. Lifestyle changes as recommended in diabetes are fundamental for treatment; addition of insulin-sensitising agents (eg, metformin) may be valuable in circumstances such as anovulatory infertility. Infertility can be treated successfully in most women by diet and exercise, clomiphene citrate with or without metformin, ovarian drilling, or ovulation induction with gonadotrophins; in-vitro fertilisation should be avoided unless there are other indications.

Adolescent↗

The potential danger of COX-2 inhibitors.

Cyclooxygenase (COX)-2 inhibitors have a major effect on ovulation and may impair fertilization, decidualization, implantation, and parturition, as well as female fertility. Women attempting to become pregnant need to pay more attention to their use of COX-2 inhibitors.

Animals↗

Risk factors for the deterioration of glucose metabolism in polycystic ovary syndrome.

Women with polycystic ovary syndrome (PCOS) have a high risk of abnormal glucose metabolism, which deteriorates gradually over time. This study was designed to assess contributing factors to the rate of deterioration of glucose metabolism over the 4- to 7-year follow-up period. The study group included 67 PCOS women who had normal glucose tolerance in the initial test in 1990-1992. There was a significant increase in both fasting and 2-h glucose concentrations, and body weight, over the follow-up period. The initial obesity, expressed as waist:hip ratio and BMI, was significantly related to the increase of glucose concentrations, while weight gain was not a significant factor. The overweight/obese PCOS women have a faster deterioration of glucose metabolism over the follow-up period than the non-obese ones. Moderate weight gain has no significant detrimental effect on the rate of deterioration of glucose metabolism.

Adult↗

Incidence of spontaneous abortion among pregnancies produced by assisted reproductive technology.

BACKGROUND: There has been increasing number of pregnancies following assisted reproductive technology treatment and their survival is understandably a matter of interest. The relative risk of spontaneous abortion in these pregnancies remains unclear. The objectives of this study were to quantify the relative risk in assisted reproductive technology pregnancies in relation to two cohorts of naturally conceived pregnancies and to assess the possible risk factors for spontaneous abortion among assisted reproductive technology pregnancies. METHODS: Three cohorts of pregnancies, 1945 pregnancies conceived following assisted reproductive technology treatment in a tertiary infertility clinic, 549 natural pregnancies in a prospective study of lifestyle and pregnancy (the Ford cohort), and 4265 pregnancies from another cohort (the Treloar cohort), were used in the study. RESULTS: After adjusting for age, the relative risk of spontaneous abortion was 1.20 (95% CI 1.03-1.46) in the assisted reproductive technology cohort in comparison with the Ford cohort. Within the assisted reproductive technology cohort, a history of spontaneous abortion predicted increased risk, while a low level of ovarian stimulation seemed to be related to a reduced risk. CONCLUSIONS: The study showed that the risk of spontaneous abortion was slightly increased in the assisted reproductive technology pregnancies after adjusting for maternal age and previous spontaneous abortion. Within the assisted reproductive technology cohort, several variables, including the level of stimulation, appeared to be linked with the risk of spontaneous abortion.

Abortion, Spontaneous↗

Should we continue or stop insulin sensitizing drugs during pregnancy?

PURPOSE OF REVIEW: The use of insulin sensitizing drugs such as metformin in polycystic ovary syndrome has been increasingly popular and validated by systematic reviews. There has also been an interest in the use of metformin for gestational diabetes. However, administration of metformin to prevent miscarriage is controversial and widespread use of this drug in early pregnancy requires investigation. RECENT FINDINGS: There are claims that miscarriage and gestational diabetes are more common in polycystic ovary syndrome and that use of insulin sensitizers improves outcomes dramatically. This review suggests there is no evidence for increased risk of miscarriage solely due to polycystic ovary syndrome and that there are insufficient data for promoting therapy with metformin. There is some reason for use of metformin in mid-pregnancy for gestational diabetes but better evidence from randomized controlled trials is urgently needed. SUMMARY: The use of metformin in early pregnancy for reducing the risk of miscarriage should be avoided outside of the context of properly designed prospective randomized trials. Safety in early pregnancy appears to be reassuring but not completely proven. The use of metformin in mid-pregnancy for gestational diabetes appears more logical but also needs adequate trials before general use is advocated.

Abortion, Spontaneous↗