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 whether the systemic inflammation induced by chlamydial infections might be associated with symptoms of polycystic ovary syndrome (PCOS). Design Nested case-control study. ...Setting A questionnaire including questions about hirsutism and oligo-amenorrhea was distributed to a representative sample of women (at age 31) from the general population-based Northern Finland Birth Cohort. Those who reported both symptoms were defined as symptomatic (n = 81). Patient(s) A representative sample of women (at age 31) from the general population-based Northern Finland Birth Cohort. Intervention(s) None. Main Outcome Measure(s) To test the presence of serum antibodies to Chlamydia pneumoniae (IgG titers ≥32) and Chlamydia trachomatis (IgG titers ≥8) by microimmunofluorescence in symptomatic and control women. Result(s) Antibodies were investigated in 79 symptomatic and 1427 control women ( C. pneumoniae ) and in 79 symptomatic and 425 control women ( C trachomatis ). C. trachomatis antibodies (odds ratio OR, 2.4; 95% confidence interval CI, 1.3–4.6) and C. pneumoniae antibodies (OR, 1.5; 95% CI, 1.0–2.4) were more commonly present in symptomatic women, and the simultaneous presence of elevated highly sensitive C-reactive protein levels strengthened this association. Conclusion(s) Chronic inflammation, which is associated with chlamydial infections, could contribute to the pathogenetic processes that lead to the metabolic and hormonal disorders of PCOS.
Objective To study the roles of self-reported symptoms and/or prior diagnosis of polycystic ovary syndrome (PCOS) and other potential risk factors for gestational diabetes mellitus (GDM) and to ...clarify whether the screening of GDM in early pregnancy is beneficial for all women with PCOS. Design The FinnGeDi multicentre case-control study including 1146 women with singleton pregnancies diagnosed with GDM and 1066 non-diabetic pregnant women. There were 174 women with PCOS (symptoms and/or diagnosis self-reported by a questionnaire) and 1767 women without PCOS (data missing for 271). Methods The study population (N = 1941) was divided into four subgroups: GDM + PCOS (N = 105), GDM + non-PCOS (N = 909), non-GDM + PCOS (N = 69), and controls (N = 858). The participants’ characteristics and their parents’ medical histories were compared. Results The prevalence of PCOS was 10.4% among GDM women and 7.4% among non-diabetics (odds ratios (OR) 1.44, 95% CI: 1.05–1.97), but PCOS was not an independent risk for GDM after adjustments for participants’ age and pre-pregnancy BMI (OR 1.07, 95% CI: 0.74–1.54). In a multivariate logistic regression analysis, the most significant parameters associated with GDM were overweight, obesity, age ≥35 years, participant’s mother’s history of GDM, either parent’s history of type 2 diabetes (T2D) and participant’s own preterm birth. Conclusions The increased risk of GDM in women with PCOS was related to obesity and increased maternal age rather than to PCOS itself, suggesting that routine early screening of GDM in PCOS women without other risk factors should be reconsidered. Instead, family history of GDM/T2D and own preterm birth were independent risk factors for GDM.
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 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.
In a randomized, placebo-controlled study, we studied the effects of 4 months’ treatment with rosiglitazone on low-grade inflammation, liver function, lipid levels, and blood pressure in 30 ...overweight women with polycystic ovary syndrome. Rosiglitazone significantly decreased serum C-reactive protein levels, white blood cell count, and alanine aminotransferase enzyme activity but did not affect lipid or blood pressure levels. Placebo had no effect on any parameters.
Eur J Clin Invest 2012; 42 (3): 321–328
Background Polycystic ovary syndrome (PCOS) is the most common gynaecological endocrinopathy characterized by oligomenorrhea, amenorrhoea, clinical and/or ...biochemical hyperandrogenism and polycystic ovaries. Abdominal deposition of excess body fat and metabolic diseases like insulin resistance and compensatory hyperinsulinemia are commonly observed in PCOS subjects. It has been suggested that visfatin is an adipokine secreted from the abdominal fat influencing glucose metabolism and might therefore contribute to the metabolic disturbances in PCOS.
Materials and methods We measured circulating full‐length visfatin levels with a specific enzyme immunoassay (AdipoGen Inc, Incheon, South‐Korea) in 57 women with self‐reported symptoms of PCOS (hirsutism and/or oligomenorrhea) and ultrasound confirmed polycystic ovaries, and in 57 controls from the Northern Finland 1966 Birth Cohort and explored its association with metabolic and inflammatory parameters.
Results Polycystic ovary syndrome cases had higher body mass index (BMI) (25·7 vs. 24·1 kg/m2) and waist circumference (83·2 vs. 78·8 cm) compared to controls, yet there was no difference in plasma visfatin levels between them. In contrast, visfatin significantly correlated with C‐reactive protein (CRP) in the control group and with white blood cell count (WBC) in both groups. In linear regression analysis, adjusted for PCOS, smoking, socioeconomic status, BMI or waist circumference, serum lipids and markers of glucose metabolism and hormone status, only WBC remained significantly associated with plasma visfatin levels.
Conclusion Our results suggest that circulating visfatin levels correlate with WBC and CRP but are not associated with PCOS, obesity or metabolic markers, suggesting that visfatin may act as a proinflammatory cytokine.
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.
To study the effects of metformin treatment on bone turnover in women with polycystic ovary syndrome (PCOS), as measured by serum concentrations of bone turnover markers.
Post hoc study of a ...previously conducted prospective multicenter, placebo-controlled, randomized study.
University clinic.
The study cohort consisted of 74 non-obese women (body mass index < 27 kg/m2) and 44 obese women (body mass index ≥ 27 kg/m2) diagnosed with PCOS, with a mean age of 27.6 ± 4.0 (SD) years.
Randomization to receive metformin or placebo for 3 months.
Serum levels of bone formation marker procollagen type I amino-terminal propeptide (PINP) and bone resorption marker carboxy-terminal cross-linking telopeptide of type I collagen (CTX) at baseline and after metformin/placebo treatment.
Serum levels of PINP and CTX were similar between the metformin and placebo groups at baseline in the whole study population. Obese women, when compared with non-obese, had lower baseline levels of PINP and CTX. Levels of PINP and CTX were significantly reduced in the whole study population, as well as in both non-obese and obese women after 3 months of metformin treatment, whereas no significant changes were observed in the placebo group.
Metformin treatment, when compared with placebo, was associated with reduced bone turnover, as suggested by reductions in markers of bone formation and resorption, leading to slower bone remodeling in premenopausal women with PCOS.
NCT00994812.
La metformina disminuye marcadores de recambio óseo en el síndrome de ovario poliquístico: un estudio post hoc
Estudiar los efectos del tratamiento con metformina sobre el recambio óseo en mujeres con síndrome de ovario poliquístico (PCOS), medido por concentraciones séricas de marcadores de recambio óseo.
Estudio post hoc de un estudio prospectivo, aleatorizado, controlado con placebo, multicéntrico realizado previamente.
Clínica universitaria.
La cohorte en estudio consistió de 74 mujeres no obesas (índice de masa corporal < 27 Kg/m2) y 44 mujeres obesas (índice de masa corporal > 27 Kg/m2) diagnosticadas con PCOS, con una edad media de 27.6 ± 4.0 (SD) años.
Aleatorización a recibir metformina o placebo durante 3 meses.
Niveles séricos del marcador de formación ósea propéptido amino-terminal del procolágeno tipo I (PINP) y del marcador de resorción ósea telopéptido isomerizado carboxi-terminal del colágeno tipo I (CTX) al inicio y tras el tratamiento con metformina/placebo.
Los niveles séricos de PINP y CTX fueron similares entre los grupos con metformina y placebo al inicio en toda la población de estudio. Las mujeres obesas, comparadas con no obesas, tuvieron niveles basales más bajos de PINP y CTX. Los niveles de PINP y CTX estuvieron reducidos significativamente en toda la población en estudio, tanto en mujeres no obesas como obesas tras 3 meses de tratamiento con metformina, mientras que no se observaron cambios significativos en el grupo placebo.
El tratamiento con metformina, comparado con placebo, se asoció con una reducción del recambio óseo, como sugiere la reducción en marcadores de formación y resorción ósea, llevando a una remodelación ósea más lenta en mujeres premenopáusicas con PCOS.