This clinical trial aims to compare hormonal and metabolic changes after a 9-week continuous use of oral or vaginal combined hormonal contraceptives (CHCs) in women with polycystic ovary syndrome ...(PCOS). We recruited 24 women with PCOS and randomized them to use either combined oral (COC,
= 13) or vaginal (CVC,
= 11) contraception. At baseline and 9 weeks, blood samples were collected and a 2 h glucose tolerance test (OGTT) was performed to evaluate hormonal and metabolic outcomes. After treatment, serum sex hormone binding globulin (SHBG) levels increased (
< 0.001 for both groups) and the free androgen index (FAI) decreased in both study groups (COC
< 0.001; CVC
= 0.007). OGTT glucose levels at 60 min (
= 0.011) and AUCglucose (
= 0.018) increased in the CVC group. Fasting insulin levels (
= 0.037) increased in the COC group, and insulin levels at 120 min increased in both groups (COC
= 0.004; CVC
= 0.042). There was a significant increase in triglyceride (
< 0.001) and hs-CRP (
= 0.032) levels in the CVC group. Both oral and vaginal CHCs decreased androgenicity and tended to promote insulin resistance in PCOS women. Larger and longer studies are needed to compare the metabolic effects of different administration routes of CHCs on women with PCOS.
IntroductionGestational diabetes mellitus (GDM) is a common disorder of pregnancy and contributes to adverse pregnancy outcomes. Metformin is often used for the prevention and management of GDM; ...however, its use in pregnancy continues to be debated. The Metformin in Pregnancy Study aims to use individual patient data (IPD) meta-analysis to clarify the efficacy and safety of metformin use in pregnancy and to identify relevant knowledge gaps.Methods and analysisMEDLINE, EMBASE and all Evidence-Based Medicine will be systematically searched for randomised controlled trials (RCT) testing the efficacy of metformin compared with placebo, usual care or other interventions in pregnant women. Two independent reviewers will assess eligibility using prespecified criteria and will conduct data extraction and quality appraisal of eligible studies. Authors of included trials will be contacted and asked to contribute IPD. Primary outcomes include maternal glycaemic parameters and GDM, as well as neonatal hypoglycaemia, anthropometry and gestational age at delivery. Other adverse maternal, birth and neonatal outcomes will be assessed as secondary outcomes. IPD from these RCTs will be harmonised and a two-step meta-analytic approach will be used to determine the efficacy and safety of metformin in pregnancy, with a priori adjustment for covariates and subgroups to examine effect moderators of treatment outcomes. Sensitivity analyses will assess heterogeneity, risk of bias and the impact of trials which have not provided IPD.Ethics and disseminationAll IPD will be deidentified and studies contributing IPD will have ethical approval from their respective local ethics committees. This study will provide robust evidence regarding the efficacy and safety of metformin use in pregnancy, and may identify subgroups of patients who may benefit most from this treatment modality. Findings will be published in peer-reviewed journals and disseminated at scientific meetings, providing much needed evidence to inform clinical and public health actions in this area.
Objective Obesity is considered to be the strongest predictive factor for cardio-metabolic risk in women with polycystic ovary syndrome (PCOS). The aim of the study was to compare blood pressure (BP) ...in normal weight women with PCOS and controls matched for age and BMI. Methods From a Nordic cross-sectional base of 2615 individuals of Nordic ethnicity, we studied a sub cohort of 793 normal weight women with BMI < 25 kg/m2 (512 women with PCOS according to Rotterdam criteria and 281 age and BMI-matched controls). Participants underwent measurement of BP and body composition (BMI, waist-hip ratio), lipid status, and fasting BG. Data were presented as median (quartiles). Results The median age for women with PCOS were 28 (25, 32) years and median BMI was 22.2 (20.7, 23.4) kg/m2. Systolic BP was 118 (109, 128) mmHg in women with PCOS compared to 110 (105, 120) mmHg in controls and diastolic BP was 74 (67, 81) vs 70 (64, 75) mmHg, both P < 0.001. The prevalence of women with BP ≥ 140/90 mmHg was 11.1% (57/512) in women with PCOS vs 1.8% (5/281) in controls, P < 0.001. In women ≥ 35 years the prevalence of BP ≥ 140/90 mmHg was comparable in women with PCOS and controls (12.7% vs 9.8%, P = 0.6). Using multiple regression analyses, the strongest association with BP was found for age, waist circumference, and total cholesterol in women with PCOS. Conclusions Normal weight women with PCOS have higher BP than controls. BP and metabolic screening are relevant also in young normal weight women with PCOS.
Metformin, a biguanide antihyperglycemic drug, has been shown to improve ovarian function and glucose metabolism in women with polycystic ovary syndrome (PCOS), but results concerning its effects on ...insulin sensitivity are controversial. Oral contraceptive pills are commonly used in the treatment of PCOS; but, like metformin, their influence on insulin sensitivity is not well known. We randomized 32 obese (body mass index > 27 kg/m2) women with PCOS, either to metformin (500 mg x 2 daily for 3 months, then 1,000 mg x 2 daily for 3 months) or to ethinyl estradiol (35 microg)-cyproterone acetate (2 mg) oral contraceptive pills (Diane Nova) for 6 months. Metformin significantly decreased the waist-to-hip ratio, serum testosterone, fasting free fatty acid, and insulin concentrations and improved oxidative glucose utilization and menstrual cyclicity, with slight (but nonsignificant) improvements in insulin hepatic extraction and insulin sensitivity. Diane Nova significantly decreased serum testosterone and increased serum sex hormone-binding globulin concentrations and glucose area under the curve during oral glucose tolerance test. It is concluded that metformin, probably by way of its effect on adipose tissue, leads to reduction of hyperinsulinemia and concomitant improvement in the menstrual pattern; and therefore, it offers a useful alternative treatment for obese, anovulatory women with PCOS. Despite slight worsening of glucose tolerance, Diane Nova is an efficient treatment for women with hyperandrogenism and hirsutism.
To study the contributions of body mass, body fat distribution and family history of type 2 diabetes mellitus to hyperinsulinaemia, insulin secretion and resistance in polycystic ovarian syndrome ...(PCOS), 17 lean (LC) and 17 obese (OC) healthy control subjects, and 15 lean (LPCOS) and 28 obese (OPCOS) women with PCOS were investigated. Waist:hip ratio (WHR), serum concentrations of sex steroids, glucose and insulin during a 75 g oral glucose tolerance test (OGTT), and insulin and C-peptide early phase secretion, and insulin sensitivity index using a euglycaemic hyperinsulinaemic clamp were assessed. The PCOS subjects had a higher mean WHR than the controls. A trend towards hyperinsulinaemia and impairment of insulin sensitivity (including the rates of both glucose oxidation and non-oxidation) was observed in LPCOS subjects, but only in OPCOS subjects were these changes significant. Early phase insulin secretion but not the early phase C-peptide secretion was increased in PCOS subjects compared to controls, suggesting that peripheral hyperinsulinaemia in PCOS women was mainly due to the observed lowered hepatic insulin extraction and insulin resistance in skeletal muscle. Moreover, the presence of a family history of type 2 diabetes did not affect early phase insulin or C-peptide secretion in the PCOS group. These results confirm and strengthen earlier contentions, that insulin resistance is a characteristic defect in PCOS and is worsened particularly by abdominal obesity.
Objective To investigate oxidative stress and angiogenetic factors in polycystic ovary syndrome (PCOS). Design Prospective cohort study. Setting University outpatient clinic. Subjects Fifty women ...with PCOS were divided into two groups: body mass index (BMI) >27 kg/m2 (n = 25) and BMI <27 kg/m2 (n = 25). The control group consisted of 20 age- and BMI-matched healthy women. Intervention(s) None. Main Outcome Measure(s) Enzyme-linked immunosorbent assays were used to measure serum levels of 8-hydroxydeoxyguanosine (8-OHdG), angiopoietin-2, and vascular endothelial growth factor (VEGF). Result(s) Women with PCOS had significantly lower serum 8-OHdG levels (mean 137.8 pg/mL, range 53.4–282.9 pg/mL) compared with the control subjects (mean 219.78 pg/mL, 124.6–372.4 pg/mL). This difference was obvious in both lean (BMI <27 kg/m2 ) and obese (BMI >27 kg/m2 ) subjects. Concentrations of VEGF were higher among obese subjects with PCOS. Conclusion(s) Serum 8-OHdG levels are significantly lower in women with PCOS than in healthy controls. The clinical significance of this finding is discussed.
The syndrome, characterised by hyperandrogenism and chronic oligo-anovulation, is also the cause of female infertiliity in up to 30% of cases.1,2 In addition, excess weight is a common feature of ...PCOS, with approximately 60–70% of women with the syndrome being obese or overweight in adulthood, with the percentage varying by geographical region and ethnicity.3,4 Weight loss of as little as 5% of existing bodyweight has been shown to improve menstrual regularity and fertility in women with PCOS.1,5 However, most patients are unable to maintain weight loss in the long term;5 therefore, the use of pharmacotherapy is recommended in the international evidence-based guidelines for the assessment and management of PCOS.6 Bariatric surgery is a successful management strategy for morbid obesity.7,8 The most recent systematic review and meta-analysis9 has revealed that women with PCOS have similar improvements in anthropometric, hormonal, and metabolic outcomes after bariatric surgery compared with those without PCOS; however, existing research is mostly retrospective, limited, and of low quality with high risk of bias, particularly regarding a comparison with existing PCOS treatments9 There is therefore a clear need for a large-scale, multicentre, high-quality trial of bariatric surgery in PCOS.9 The multicentre, open-label randomised controlled trial (RCT), the BAMBINI trial, by Suhaniya Samarasinghe and colleagues10 partially fills this gap; it is the first ever RCT in this field. 80 women (mean age 32 SD 6·0 years; medical group: 80% White, 7·5% Black, and 10% Asian; surgical group: 77·5% White, 12·5% Black, and 7·5% Asian) with PCOS, obesity, and oligomenorrhoea were assigned in a 1:1 ratio to either vertical sleeve gastrectomy or behavioural interventions and medical therapy (metformin or orlistat) and followed up for 52 weeks.10 As expected, bariatric surgery was more effective than medical care, as women in the surgical group had 2·5 times more spontaneous biochemically confirmed ovulations (the primary endpoint) and restoration of spontaneous menses over 52 weeks, thereby suggesting an improvement in spontaneous fertility in these women. There was a significant reduction in waist circumference, HbA1c, and HOMA-IR, as well as a greater improvement in most metabolic parameters and significant reduction in the free androgen index and anti-müllerian hormone levels at 52 weeks in the surgical group, but not in the medical group. ...quality of life endpoints significantly improved in the surgery group, but not in the medical group. The weight loss induced by these new anti-obesity drugs is substantially greater than that with traditional pharmaceutical interventions and is associated with a significant improvement in ovulation and in the metabolic and hormonal disorders associated with PCOS.11 Thus far, these potent medications are contraindicated during pregnancy, but with the explosion of their use worldwide and the emergence of even more efficient preparations, their role in the treatment of infertility disorders in PCOS needs to be further investigated.
The maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A) were reduced in hormonally stimulated pregnancies in the in vitro fertilization and intracytoplasmic sperm injection groups ...(N = 176; PAPP-A: 0.82) and in the entire assisted reproduction group (N = 282; PAPP-A: 0.83) as compared with controls (N = 24,783; PAPP-A: 0.94). However, the false-positive rate of first-trimester combined screenings was not statistically significantly increased in assisted reproduction pregnancies after adjustment for maternal age.
STUDY QUESTION
Is it necessary to monitor lipid profiles in all young women with polycystic ovary syndrome (PCOS)?
SUMMARY ANSWER
Lipid profiling is required when women with PCOS develop type 2 ...diabetes (T2D) or hypertension, but rarely changes clinical care before the age of 35 years.
WHAT IS KNOWN ALREADY
PCOS consensus statements and guidelines recommend that women with PCOS should be screened for dyslipidaemia every second year or annually.
STUDY DESIGN, SIZE, DURATION
Women from Denmark, Norway, Finland and Sweden, who had participated in research projects or clinical trials or in whom lipid profiles had been determined routinely as part of clinical care since 2000 were included.
PARTICIPANTS/MATERIALS, SETTING, METHODS
One thousand three hundred and twenty-seven women with PCOS (Rotterdam criteria) were included. Based on individual cardiovascular risk score and lipid levels, treatment level was guided by the European Society of Cardiology and the European Atherosclerosis Society Task Force for the management of dyslipidaemias. Change in clinical care was defined as need to (i) immediately start statin treatment or (ii) consider statin treatment if life-style intervention fails.
MAIN RESULTS AND THE ROLE OF CHANCE
All in all, 74 (5.6%) women with PCOS should immediately start statin treatment, and statin treatment should be considered in 33 women (2.5%). Among women with T2D, 27/28 (96.4%) should initiate statin treatment and the corresponding number for women with hypertension was 42/57 (73.7%). In PCOS women who had not yet developed T2D or hypertension, lipid profiling only changed clinical care in 28 (2.3%). This number was further reduced to 12 (1.2%) in women below the age of 35 years, and to zero in normal-weight women below the age of 35 years.
LIMITATIONS, REASONS FOR CAUTION
Findings can only be generalized to countries with low cardiovascular mortality rates.
WIDER IMPLICATIONS OF THE FINDINGS
Lipid profiling is required when women with PCOS develop T2D or hypertension. However, lipid profiling rarely changes the clinical care of low risk PCOS patients before the age of 35, especially in the normal-weight women.
STUDY FUNDING/COMPETING INTEREST(S)
The Academy of Finland, Sigrid Juselius Foundation and the Nordic Federation of Obstetrics and Gynecology. There are no conflicts of interest to be declared.
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