Christos Vosnakis

Pravastatin improves pregnancy outcomes in obstetric antiphospholipid syndrome refractory to antithrombotic therapy

BACKGROUND Administration of conventional antithrombotic treatment (low-dose aspirin plus low-molecular weight heparin [LDA+LMWH]) for obstetric antiphospholipid syndrome (APS) does not prevent life-threatening placenta insufficiency-associated complications such as preeclampsia (PE) and intrauterine growth restriction (IUGR) in 20% of patients. Statins have been linked to improved pregnancy outcomes in mouse models of PE and APS, possibly due to their protective effects on endothelium. Here, we investigated the use of pravastatin in LDA+LMWH-refractory APS in patients at an increased risk of adverse pregnancy outcomes. METHODS We studied 21 pregnant women with APS who developed PE and/or IUGR during treatment with LDA+LMWH. A control group of 10 patients received only LDA+LMWH. Eleven patients received pravastatin (20 mg/d) in addition to LDA+LMWH at the onset of PE and/or IUGR. Uteroplacental blood hemodynamics, progression of PE features (hypertension and proteinuria), and fetal/neonatal outcomes were evaluated. RESULTS In the control group, all deliveries occurred preterm and only 6 of 11 neonates survived. Of the 6 surviving neonates, 3 showed abnormal development. Patients who received both pravastatin and LDA+LMWH exhibited increased placental blood flow and improvements in PE features. These beneficial effects were observed as early as 10 days after pravastatin treatment onset. Pravastatin treatment combined with LDA+LMWH was also associated with live births that occurred close to full term in all patients. CONCLUSION The present study suggests that pravastatin may improve pregnancy outcomes in women with refractory obstetric APS when taken at the onset of PE or IUGR until the end of pregnancy.

Lifestyle intervention and anti-obesity therapies in the polycystic ovary syndrome: impact on metabolism and fertility

Obesity is frequently present in patients with polycystic ovary syndrome (PCOS) and plays an important role in the pathogenesis of the metabolic, endocrine, and reproductive abnormalities associated with this syndrome. We aimed to summarize the effects of lifestyle changes and anti-obesity pharmacotherapy in patients with PCOS. We reviewed the literature regarding the effects of lifestyle changes and anti-obesity agents on the metabolic and endocrine abnormalities of PCOS. Lifestyle changes, including diet, exercise, and behavioral modification, appear to improve the metabolic and reproductive abnormalities of overweight and obese patients with PCOS. Therefore, lifestyle changes appear to represent the first-line management for all overweight and obese patients with PCOS. However, the optimal composition of diet and the optimal type of exercise in these patients are unknown. Anti-obesity agents that have been studied in PCOS include orlistat, sibutramine, and rimonabant. However, the latter two agents have been withdrawn from the market because of side effects. Long-term studies with orlistat in overweight and obese diabetic patients showed greater weight loss and metabolic and cardiovascular benefits than those achieved with lifestyle changes alone. However, there are limited data on the efficacy of orlistat in women with PCOS. In conclusion, lifestyle changes (diet, exercise and behavioral modification), particularly when combined with anti-obesity agents, exert beneficial effects on the endocrine abnormalities of obese patients with PCOS and improve metabolic parameters.

Clinical Improvement and Successful Pregnancy in a Preeclamptic Patient With Antiphospholipid Syndrome Treated With Pravastatin

The clinical hallmarks of the antiphospholipid syndrome (APS) are thrombosis and adverse obstetric outcomes. Women with APS have a higher incidence of preeclampsia.1 Currently, treatment of APS focuses on anticoagulation therapy, treatment mostly given empirically and often ineffective. Similarly, treatment for preeclampsia remains symptomatic and also ineffective. Studies in animal models support the hypothesis that pravastatin may be an effective therapy to prevent pregnancy complications in APS and in preeclampsia.2–5 Here, we describe a patient, with a previous history of preeclampsia, thrombosis, and APS, presenting with preeclampsia at 23 weeks’ gestation in her second pregnancy that was treated with pravastatin, which resulted in marked clinical improvement and successful pregnancy outcome. A 30-year-old woman with no previous medical history had a first pregnancy complicated with early preeclampsia with bilateral notching (22 weeks and 0 days) and hypertension and edema at 24 weeks, leading to a still birth at week 26. She developed deep vein thrombosis 2 days postpartum. Based on her history of deep vein thrombosis, early preeclampsia, and twice positive lupus anticoagulant, with an interval of 3 months between the tests, the patient was diagnosed with APS. The patient received therapeutic doses of low-molecular-weight heparin for 3 months and prophylactic doses while trying to conceive again. Her blood pressure and proteinuria remained normal. Ten months later, she got pregnant and was started on intermediate doses of enoxaparin (0.6 OD) and aspirin (100 mg OD). Blood pressure …

Diet, physical exercise and Orlistat administration increase serum Anti-Müllerian Hormone (AMH) levels in women with polycystic ovary syndrome (PCOS)

The present study investigates the combined effect of diet, physical exercise and Orlistat for 24 weeks, on serum Anti-Müllerian Hormone (AMH) levels in overweight and obese women with polycystic ovary syndrome (PCOS) and in overweight and obese controls. Sixty-one (61) selected women with PCOS and 20 overweight and obese controls followed an energy-restricted diet, physical exercise plus Orlistat administration (120 mg, 3 times per day) for 24 weeks. At baseline, week 12 and week 24, serum levels of AMH, FSH, LH, PRL, androgens, sex hormone–binding globulin (SHBG), glucose, and insulin were measured and Free Androgen Index (FAI) and Insulin Resistance (IR) indices were calculated. In PCOS women, serum AMH levels increased after 12 and 24 weeks of treatment. After 12 weeks LH and SHBG were increased, while Testosterone decreased. After 12 and 24 weeks, FAI was decreased and all indices of IR were significantly improved. We concluded that in overweight and obese women with PCOS Orlistat administration, combined with diet and physical exercise, for 24 weeks, resulted in significant weight loss, improvement of hyperandrogenism and insulin sensitivity, and increased serum AMH levels.

Weight loss significantly reduces serum lipocalin-2 levels in overweight and obese women with polycystic ovary syndrome.

Serum lipocalin-2 levels are elevated in obese patients. We assessed serum lipocalin-2 levels in polycystic ovary syndrome (PCOS) and the effects of weight loss or metformin on these levels. Forty-seven overweight/obese patients with PCOS [body mass index (BMI) >27 kg/m2] were instructed to follow a low-calorie diet, to exercise and were given orlistat or sibutramine for 6 months. Twenty-five normal weight patients with PCOS (BMI <25 kg/m2) were treated with metformin for 6 months. Twenty-five normal weight and 25 overweight/obese healthy female volunteers comprised the control groups. Serum lipocalin-2 levels did not differ between overweight/obese patients with PCOS and overweight/obese controls (p = 0.258), or between normal weight patients with PCOS and normal weight controls (p = 0.878). Lipocalin-2 levels were higher in overweight/obese patients with PCOS than in normal weight patients with PCOS (p < 0.001). In overweight/obese patients with PCOS, weight loss resulted in a fall in lipocalin-2 levels (p < 0.001). In normal weight patients with PCOS, treatment with metformin did not affect lipocalin-2 levels (p = 0.484). In conclusion, PCOS per se is not associated with elevated lipocalin-2 levels. Weight loss induces a significant reduction in lipocalin-2 levels in overweight/obese patients with PCOS.

The clinical significance and primary determinants of hirsutism in patients with polycystic ovary syndrome

OBJECTIVE Hirsutism is frequently present in patients with polycystic ovary syndrome (PCOS) and is a major sign of hyperandrogenism. However, other disorders frequently present in PCOS, particularly abdominal obesity and insulin resistance (IR), have also been implicated in the development of hirsutism in this population but relevant data are limited. We aimed to define the determinants of the presence of hirsutism in PCOS. DESIGN Observational study. METHODS We studied 1297 patients with PCOS (age 24.3±5.8 years, BMI 26.8±6.9 kg/m(2)). Hirsutism was defined as a modified Ferriman-Gallwey score ≥8. RESULTS Women with hirsutism were younger, had greater BMI, and had higher levels of circulating androgens than women without hirsutism; markers of IR did not differ between the two groups after adjustment for age and BMI. The prevalence of hirsutism progressively declined with age, was lower in normal-weight women than in overweight and obese women, and was comparably prevalent in the hyperandrogenemic phenotypes of PCOS. In binary logistic regression analysis, independent predictors of the presence of hirsutism were younger age, larger waist circumference (W), and higher serum testosterone levels. In stepwise linear regression analysis, the Ferriman-Gallwey score independently correlated with age, W, free androgen index, and serum Δ4-androstenedione and DHEAS levels. CONCLUSIONS Besides hyperandrogenemia, abdominal obesity, and young age are independently associated with the presence of hirsutism. In contrast, the relationship between IR and hirsutism appears to be mediated by the more severe obesity of insulin-resistant patients with PCOS.

Sibutramine administration decreases serum anti-Mullerian hormone (AMH) levels in women with polycystic ovary syndrome

OBJECTIVE To investigate the effect of diet, physical exercise and sibutramine administration on serum anti-Müllerian hormone (AMH) levels, hormonal and metabolic parameters in overweight and obese patients with polycystic ovary syndrome (PCOS). STUDY DESIGN Prospective clinical study, in an outpatient clinic setting, of 76 overweight and obese women with PCOS. All patients were placed on a hypocaloric diet, physical exercise plus sibutramine (10 mg per day) for the first month and then on either a hypocaloric diet, physical exercise plus sibutramine (10 mg per day) or a hypocaloric diet and physical exercise for the subsequent 6 months. Serum AMH levels, body composition, hormonal and metabolic features and insulin sensitivity indices were evaluated at baseline and at 4 and 7 months of treatment. RESULTS Body weight reduction was greater in the sibutramine group. Moreover, serum FSH and testosterone levels decreased, and SHBG, free androgen index and all indices of insulin resistance significantly improved at 4 and 7 months. Serum AMH levels decreased only in PCOS women who received sibutramine, at both 4 and 7 months of treatment. CONCLUSION A hypocaloric diet and a diet plus sibutramine both resulted in significant weight loss in overweight and obese women with PCOS. Patients who received sibutramine showed greater weight loss and improvement in hyperandrogenemia and insulin sensitivity after 7 months of treatment. Serum AMH levels significantly decreased at both 4 and 7 months of treatment only in PCOS women who received sibutramine, indicating a possible direct, gonadotropin independent effect of sibutramine on the ovarian production of AMH.

Case of prenatally diagnosed non‐mosaic trisomy 20 with minor abnormalities

Non‐mosaic trisomy 20 is a rare trisomy and almost all affected fetuses do not survive past the first trimester of the pregnancy. Severe abnormalities are frequently present in these embryos. We report the case of prenatally diagnosed non‐mosaic trisomy 20 with only minor anomalies in the fetus. At external examination of the fetus we detected only low‐set ears and no other abnormalities. Internally, all organs appeared normal macroscopically.

Uneventful cesarean delivery with administration of factor XI concentrate in a patient with severe factor XI deficiency

Factor XI (FXI) is a procoagulant factor and antifibrinolytic agent, and its absence causes a bleeding tendency. FXI deficiency is autosomal in inheritance, with severe FXI deficiency in homozygotes and partial deficiency in heterozygotes. A 24-year-old primigravida with an uneventful pregnancy and no history of bleeding manifestations was admitted to our department at 38 weeks of gestation. Her blood count and serum biochemistry findings were normal except for a coagulation screen, which revealed a prolonged activated partial thromboplastin time (APTT) of 63 seconds (normal range, 24-35 seconds). The measured FXI coagulant activity of 8 IU/dL (reference range, 70-150 IU/dL) established a diagnosis of severe FXI deficiency. The breech presentation of the fetus prompted the decision for cesarean delivery under general anesthesia. We administered a single dose of FXI concentrate (15 IU/kg), which corrected the APTT to 34 seconds. The cesarean delivery was uncomplicated, and postpartum recovery of the mother and her baby was uneventful with no bleeding complications. The finding of an isolated prolonged APTT should prompt obstetricians to consider FXI deficiency. The appropriate use of factor FXI concentrate in managing obstetric patients with FXI deficiency can minimize potential bleeding complications and ensure an optimal outcome for both mother and neonate.

Uneventful delivery with caesarean section in a woman with a history of endovascular management of an intracranial aneurysm

Introduction Intracranial aneurysms are present in 1 – 5% of the adult population and their rupture accounts for 5 – 15% of stroke cases (Brisman et al. 2006). Endovascular management is the treatment of choice of ruptured intracranial aneurysms, as it is associated with a lower risk of dependency or death than surgical management (Molyneux et al. 2005). However, the management of women who have undergone endovascular management of intracranial aneurysms and become pregnant is unclear. Pregnancy increases the risk for aneurysm rupture (Nelson 2005; Selo-Ojeme et al. 2004; Stoodley et al. 1998). In addition, there appears to be a greater risk of late bleeding of intracranial aneurysms aft er endovascular management (Molyneux et al. 2005). Arteriovenous malformations, which are the cause of one-quarter of cases of intracranial haemorrhage during pregnancy, might diff er from intracranial aneurysms in the risk of rupture and in their management during pregnancy (Dias and Sekhar 1990). We report the case of a woman who had undergone endovascular management of an intracranial aneurysm and became pregnant 2 years aft erwards. Caesarean section was elected and was uneventful for both the mother and the neonate. Th erefore, caesarean section could be considered in pregnant women with this medical history.