Ethinylestradiol30µg-drospirenone and metformin: could this combination improve endothelial dysfunction in polycystic ovary syndrome?

BACKGROUND: We are hereby investigating for the first time the effect of the association ethinylestradiol30µg-drospirenone 3mg (DRP/EE30µg) plus metformin and weight loss on endothelial status and C-reactive protein (hsCRP) levels in polycystic ovary syndrome (PCOS). METHODS: 25 young women with PCOS (mean age 22.76 ± 0.83 years, body mass index (BMI): 28.44 ± 6.23) who completed the study were prospectively evaluated. The oral contraceptive- DRP/EE30µg (21 days/month) and metformin (1700 mg daily) were administered for 6 months to the PCOS group. Additionally, the 15 overweight and obese patients (BMI > 25 kg/m2) were instructed in a diet of no more than 1500 cal daily. Primary outcome measures were surrogate markers of cardiovascular disease and included endothelial function, i.e. flow-mediated dilatation (FMD) on the brachial artery and endothelin-1 levels, as well as hsCRP concentrations, body composition (measured by whole-body dual-energy X-ray-absorptiometry) and insulin resistance. Variables were assessed at baseline, as well as after our medical intervention. RESULTS: The combination between DRP/EE30µg plus metformin combined with weight loss triggered a significant improvement in the FMD values (FMD-PCOSbasal 3.48 ± 1.00 vs FMD-PCOS6 months7.43 ± 1.04, p = 0.033), as well as body composition and insulin insensitivity (p < 0.05). Regarding hsCRP levels, there was no significant intragroup (PCOS6months - PCOSbasal) difference. CONCLUSION: A 6-month course of metformin- DRP/EE30µg (associated with weight loss) improves the endothelial dysfunction in PCOS and shows neutral effects on hsCRP concentrations as an inflammation marker. These data demand for reevaluation of the medical therapy in PCOS, particularly in women with additional metabolic and cardiovascular risk factors (ClinicalTrials.gov Identifier: NCT01459445).

Soluble platelet/endothelial cell adhesion molecule (sPECAM)-1 is increased in polycystic ovary syndrome and related to endothelial dysfunction.

Striking evidence indicates endothelial impairment in polycystic ovary syndrome (PCOS) but the mechanisms linking PCOS status to cardiovascular risk remain elusive. Platelet/endothelial cell adhesion molecule (PECAM)-1 is a soluble (s) signaling molecule involved in inflammation and angiogenesis with predictive value for endothelial dysfunction in patients at risk. In a prospective, controlled study, sPECAM-1 levels and the relationships to metabolic, inflammatory and vascular PCOS traits were evaluated in 26 patients and 29-age- and body mass index-matched controls. To assess endothelial injury, carotid artery intimae-media thickness (CIMT) and brachial artery flow-mediated vasodilatation (FMD) were employed. Of the 26 women with PCOS, 25 completed a six-month metformin combined with ethinylestradiol 0.3 mg/drospirenone 3 mg therapy. Soluble PECAM-1 levels were increased in PCOS (p = 0.018 vs. Controls) and significantly decreased at follow-up (p = 0.0002). Smoking and weight had no effect on sPECAM-1 dynamics. In both univariate and multivariate analysis, basal sPECAM-1 was inversely related to FMD (r = -0.311, p = 0.021) but not CIMT. To conclude, sPECAM-1 is increased in PCOS, an effect reversed by combined metformin and anti-androgenic contraceptive therapy. Elevated sPECAM-1 contributes to endothelial dysfunction however further studies are inquired to assess its relevance as biomarker and potential therapeutic target in PCOS.

Circulating osteoprotegerin and soluble receptor activator of nuclear factor κB ligand in polycystic ovary syndrome: relationships to insulin resistance and endothelial dysfunction.

OBJECTIVE: There is plenty of evidence that osteoprotegerin (OPG) is linked to subclinical vascular damage and predicts cardiovascular disease in high-risk populations. Our aim is to investigate the relationships of OPG/free soluble receptor activator of nuclear factor κB ligand (sRANKL) to insulin resistance, brachial artery flow-mediated vasodilation (FMD), and the carotid artery intima-media thickness (CIMT) in polycystic ovary syndrome (PCOS), a disorder characterized by hyperandrogenism, impaired glucose control, and endothelial injury. DESIGN: A cross-sectional, observational study. METHODS: Hormonal and metabolic profiles, FMD, CIMT, serum OPG, and ampli-sRANKL were assessed in 64 young PCOS patients and 20 controls of similar age. Body composition was measured by dual energy X-ray absorptiometry. RESULTS: OPG was significantly lower in PCOS and related negatively to free testosterone and positively to estradiol (E(2)) levels. In multivariate analysis, OPG but not ampli-sRANKL correlated positively to fasting insulin, insulin sensitivity indices, and FMD. Neither OPG nor ampli-sRANKL was associated with CIMT. Significantly lower adjusted FMD values were demonstrated in women in the upper OPG quartile group (>2.65 pmol/l) compared with all other quartile groups together (P=0.012). In PCOS, multiple regression analysis retained E(2)/sex hormone-binding globulin ratio, fat mass, and homeostasis model assessment of insulin resistance as independent predictors of OPG. CONCLUSIONS: In PCOS, circulating OPG is related to both endothelial dysfunction and insulin resistance, independent of obesity and androgen excess, suggesting OPG as a useful biomarker of these effects. Further studies are needed to evaluate OPG in relation to cardiovascular events and cardiovascular mortality in PCOS.

Primary pituitary abscess followed by empty sella syndrome in an adolescent girl.

Primary pituitary abscess is a rare pituitary pathology, particularly at a young age and is characterized by atypical clinical features making the diagnosis difficult. Correct diagnosis and therapy are mandatory due to the potentially lethal outcome of pituitary infection. We report the case of an adolescent girl presenting with headache, diabetes insipidus and central thyro-gonadic insufficiency with no history of infection, in whom the intra-operative diagnosis of primary pituitary abscess was made. Bacterial cultures indicated infection with Streptococcus spp. One year after neurosurgery and antibiotic therapy, recovery of diabetes insipidus and pituitary insufficiency was documented except for persistence of subnormal growth hormone secretion. Post-surgery, pituitary magnetic resonance imaging revealed an empty sella syndrome.