Irene Lambrinoudaki

Pathogenesis of endometriosis: the role of genetics, inflammation and oxidative stress

IntroductionEndometriosis is defined as the presence of endometrial tissue outside the uterine cavity.Materials and Methods The etiology of this multifactorial disease is still unresolved and an increasing number of studies suggest that genetic, hormonal, environmental, immunological and oxidative factors may all play an important role in the pathogenesis of this disorder.Conclusions In this literature review, inflammatory activity, oxidative stress as well as genetic abnormalities and mutations have been studied in an effort to identify factors predisposing to endometriosis.

Pathogenesis of endometriosis: The role of defective ‘immunosurveillance’

Objective To analyse the aetiopathogenesis and the role of defective ‘immunosurveillance’ in endometriosis. Method Review of studies on the pathogenesis of endometriosis, focusing particularly on novel molecules which express adhesive or proteolytic properties. Hypotheses addressing the role of oxidative stress in endometriosis were also reviewed. Results Endometriosis is a multifactorial disease associated with a general inflammatory response aiming to clear the peritoneal cavity from the ectopic endometriotic cells and tissue. Modern theories suggest that this inflammatory response creates an environment that may promote implantation and proliferation due to defective ‘immunosurveillance’. Conclusion The modern interpretation of the theory of reflux menstruation holds that women destined to develop endometriosis have a deficient immune system, which cannot defend against regurgitated endometrial cells. New findings on genetics, immune modulation, and secreted products of endometriotic lesions of affected women have given insight into the pathogenesis of this disorder and may serve as the background for new treatments of endometriosis-associated pain and infertility.

Circulating androgen levels are associated with subclinical atherosclerosis and arterial stiffness in healthy recently menopausal women

Although increasing evidence supports an association between endogenous sex hormones and cardiovascular disease, the results still remain controversial. This study aims to examine the association between endogenous sex hormones and indices of vascular function and structure. Serum follicle-stimulating hormone, luteinizing hormone, estradiol, testosterone, sex hormone-binding globulin, dehydroepiandrosterone sulfate (DHEAS), and Δ4-androstenedione were measured in 120 healthy postmenopausal women aged 41 to 60 years. Possible associations with surrogate markers of subclinical atherosclerosis, arterial stiffness, and endothelial function were investigated. Indices of arterial structure included carotid and femoral intima-media thickness and atheromatous plaques presence. Indices of arterial function included flow-mediated dilation of the brachial artery, carotid-femoral pulse wave velocity (PWV), and augmentation index. Total testosterone and free androgen index (FAI) were the most important predictors of common carotid artery intima-media thickness (β = 0.376 and β = 0.236, P < .001 and P = .014, respectively). Similarly, FAI was the only significant independent predictor of PWV (β = 0.254, P = .027) after adjusting for age, smoking, body mass index, homeostasis model assessment of insulin resistance, and blood lipids. Free estrogen index showed a positive association with PWV, independently of age, smoking, and body mass index, but not of homeostasis model assessment of insulin resistance and blood lipids. Age-adjusted levels of DHEAS exhibited a significant independent negative association with measures of augmentation index. Follicle-stimulating hormone, luteinizing hormone, estradiol, sex hormone-binding globulin, and Δ4-androstenedione were not associated with any of the vascular parameters independently of traditional cardiovascular risk factors. Higher serum testosterone and FAI are associated with subclinical atherosclerosis in healthy recently menopausal women. This association is independent of traditional cardiovascular risk factors or insulin resistance. On the contrary, serum DHEAS exhibits a negative association with arterial stiffness.

Mammographic changes associated with raloxifene and tibolone therapy in postmenopausal women : A prospective study

Objective The prolonged use of estrogen therapy is associated with a slightly increased risk of breast cancer. Alternative therapies that are effective in the prevention of menopause, having associated morbidities but no unwanted effects, are of primary interest in the pharmacologic research. The aim of this study was to evaluate the effect of two alternative to estrogens drugs, the selective estrogen receptor modulator raloxifene and the tissue-specific tibolone, on the mammographic appearance of the breast. Design The study group comprised 131 postmenopausal women aged 41 to 67 years. The women were at least 2 years postmenopausal, free of climacteric symptoms, and at the time of entry to the study had not had therapy for at least 9 months. Women with risk factors for osteoporosis or cardiovascular disease were allocated either to tibolone (n = 56) or raloxifene (n = 48) therapy. Women with no risk factors and women who either did not qualify for or denied treatment (n = 27) served as controls. The study duration was 12 months. Women received a baseline mammogram before commencing therapy and a repeat mammogram at the end of the study period. Mammogram findings were classified according to the modified Wolfe criteria by two expert radiologists. Results No difference was identified between groups with respect to baseline characteristics associated with breast cancer risk. Similarly, no difference was detected between groups concerning the modified Wolfe classification of baseline mammographic findings. In the tibolone group, 10.7% of the women showed an increase in breast density in the 12-month reevaluation. The respective figure in the raloxifene group was 6.3%, whereas no woman in the control group showed an increase in breast density. Differences in the increase in breast density between groups did not, however, reach statistical significance. Accordingly, 10.7% of women in the tibolone group and 18.8% of women in the raloxifene group exhibited involutionary changes in the repeat mammogram, whereas 25.9% of women in the control group revealed a decrease in breast density in the 12-month examination. The percentages were not significantly different between groups. Conclusions Breast density as shown by mammography was stable in a majority of patients and changed in a minority of cases for both tibolone and raloxifene. In most patients, these drugs are not likely to interfere with mammogram interpretation. Larger long-term studies are needed to confirm the impact of prolonged tibolone or raloxifene administration on mammography.

Cross-sectional long-term micronutrient deficiencies after sleeve gastrectomy versus Roux-en-Y gastric bypass: A pilot study

BACKGROUND Nutritional deficiencies are highly prevalent in obese patients. Bariatric surgery has been associated with adverse effects on homeostasis of significant vitamins and micronutrients, mainly after gastric bypass. The aim of the present study was to compare the extent of long-term postsurgical nutritional deficiencies between Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). METHODS This cross-sectional, pilot study included 95 patients who underwent RYGB or SG surgery with a mean follow-up of 4 years. Demographic, anthropometric, and biochemical parameters were compared according to the type of surgery. RESULTS Both types of surgery were associated with significant nutritional deficiencies. Vitamin B12 deficiency was significantly higher in patients with RYGB compared with SG (42.1% versus 5%, P = .003). The type of surgery was associated neither with anemia nor with iron or folate deficiency (SG versus RYGB: anemia, 54.2% versus 64.3%, P = .418; folate deficiency, 20% versus 18.4%, P = .884; iron deficiency, 30% versus 36.4%, P = .635). CONCLUSION During a mean follow up period of 4 years postRYGB or SG, patients were identified with several micronutrient deficiencies, including vitamin D, folate, and vitamin B12. SG may have a more favorable effect on the metabolism of vitamin B12 compared with RYGB, being associated with less malabsorption. Adherence to supplemental iron and vitamin intake is of primary significance in all cases of bariatric surgery.

Thoracic Endometriosis Syndrome

Endometriosis is defined as the presence of endometrial glands and stroma outside the uterine cavity and is usually confined to the pelvis. Thoracic endometriosis syndrome (TES) is a rare disorder characterized by the presence of functioning endometrial tissue in the pleura, the lung parenchyma and the airways. TES may present with hemoptysis, due to the shedding of endometrial tissue in the bronchial tree, or spontaneous pneumothorax or hemothorax if the endometrial tissue is localized peripherally. Patients are of reproductive age, often nulliparous, with long-standing symptoms. The crucial issue for establishing the diagnosis is the cyclicity of the symptoms which occur along with the menstrual cycle. TES is virtually a diagnosis of exclusion, established on clinical grounds, since neither CT nor endoscopy are specific for TES. Treatment consists of gonadotropin-releasing hormone analogues, aiming to suppress the hypophyseal-gonadal axis, so as to ensure a regression of the endometrial implants. If medical treatment fails, surgical resection of the endometriomas is suggested, although relapse rate may be high.

Previous Gestational Diabetes Mellitus and Markers of Cardiovascular Risk

The prevalence of gestational diabetes mellitus (GDM) in the developed world has increased at an alarming rate over the last few decades. GDM has been shown to be associated with postpartum diabetes, insulin resistance, hypertension, and dyslipidemia. A history of previous GDM (pGDM), associated or not with any of these metabolic abnormalities, can increase the risk of developing not only type 2 diabetes mellitus but also cardiovascular disease (CVD) independent of a diagnosis of type 2 diabetes later in life. In this paper we discuss the relationship among inflammatory markers, metabolic abnormalities, and vascular dysfunction in women with pGDM. We also review the current knowledge on metabolic modifications occurring in normal pregnancy and the link between alterations of a normal metabolic state with the long-term maternal complications that may result in increased CVD risk. Our review of studies on pGDM prompts us to recommend that these women be considered a population at risk for later CVD events, which however could be avoided via the use of specially designed follow-up programs in the future.

EMAS position statement: management of uterine fibroids.

INTRODUCTION Uterine fibroids (also termed leiomyomas or myomas) are the most common tumors of the female reproductive tract. AIM The aim of this position statement is to provide and critically appraise evidence on the management of women with uterine fibroids. METHODS Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS Many uterine fibroids are asymptomatic and require no intervention, although it is advisable to follow up patients to document stability in size and growth. Fibroid-associated symptoms include heavy menstrual bleeding and pain or pelvic discomfort. The association between infertility and fibroids increases with age. Fibroids do not increase the risk of malignant uterine disease and leiomyosarcomas are extremely rare (less than one in 1000). It is unknown at present whether leiomyosarcoma represents de novo growth or malignant transformation from benign uterine fibroids. Treatment options for symptomatic fibroids include pharmacologic, surgical and radiologically guided interventions. The range of medical treatments allows flexible management of fibroid-related symptoms; the options include tranexamic acid, non-steroidal anti-inflammatory drugs, contraceptive steroids, gonadotropin-releasing hormone analogs, antiprogesterone, and selective progesterone receptor modulators. However, these medical options do not remove the tumors and symptoms may return when treatment is stopped. Surgical and radiologically guided procedures may be tailored to age, general health, and individual patient wishes. Hysterectomy is the most effective treatment, although in some cases myomectomy may be sufficient to control symptoms. Alternatives to surgery include uterine artery embolization, myolysis and ablation by high-intensity focused ultrasound (guided with magnetic resonance imaging or ultrasound). The choice of treatment depends on fibroid size, the underlying symptoms and their severity and the womans desire for subsequent fertility and pregnancy, as well as efficacy and need for repeated interventions.

EMAS clinical guide: Low-dose vaginal estrogens for postmenopausal vaginal atrophy

Vaginal atrophy is common in postmenopausal women. This clinical guide provides the evidence for the clinical use of vaginal estrogens for this condition focussing on publications since the 2006 Cochrane systematic review. Use after breast cancer, before assessment of cervical cytology and prolapse surgery is also discussed.

Polycystic Ovary Syndrome in Adolescents

Polycystic ovary syndrome (PCOS) is a very common disorder affecting 5–10% of women of reproductive age. The pivotal endocrine abnormalities of this syndrome are insulin resistance and ovarian and, to a lesser degree, adrenal hypersensitivity to hormonal stimulation. PCOS may manifest itself as early as the first decade of life by premature pubarche or menarche. Oligoamenorrhea in the first postpubarchal years, although very common, may be an early symptom of PCOS, especially in overweight girls with hirsutism or acne. Girls with low birth weight as well as a family history of diabetes mellitus or premature cardiovascular disease are at high risk for developing PCOS. Circulating bioavailable testosterone levels are usually elevated, while total testosterone may be normal due to low levels of sex hormone-binding globulin. The typical sonographic appearance of PCOS ovaries consists of high ovarian volume (>10mL) and the presence of 12 or more follicles in each ovary measuring 2–9mm in diameter. However, this finding is not specific, since it may occur in >20% of healthy girls.The therapeutic goals in adolescents with PCOS is first to restore bodyweight and menses and to reduce the signs of hyperandrogenism. The reduction of bodyweight in this young age group may require the collaboration of the pediatrician, dietitian, and psychotherapist. The adolescent should be urged to adopt a healthy lifestyle with the aim to maintain a normal body mass index throughout adolescence and adult life. The choice of medical therapy depends on the clinical presentation. Oral contraceptives are a good option when acne and hirsutism are the principal complaints. Adolescents with isolated cycle irregularity may be placed on a cyclical progestin regimen to induce withdrawal bleeding. Metformin, by decreasing insulin resistance, alleviates many of the hormonal disturbances and restores menses in a considerable proportion of patients. It may be used alone or in combination with oral contraceptives. Independently of medical treatment, restoration and maintenance of bodyweight within normal range is of paramount importance.