George Creatsas

Increased levels of serum advanced glycation end-products in women with polycystic ovary syndrome

objective  Women with polycystic ovary syndrome (PCOS) carry a number of cardiovascular risk factors and are considered to be at increased risk for atherosclerosis. Elevated concentrations of advanced glycation end‐products (AGE), which exert their effects through interaction with specific receptors (RAGE), have been implicated in the cellular and tissue damage during atherosclerotic processes.

Androgen and lipid profiles in adolescents with polycystic ovary syndrome who were treated with two forms of combined oral contraceptives

OBJECTIVE To compare the effects of cyproterone acetate and desogestrel, as part of combined oral contraceptives, on lipid metabolism and hirsutism of adolescents with polycystic ovary syndrome (PCOS). DESIGN Prospective randomized clinical trial. SETTING Outpatient gynecology clinic (referral center) of a university. PATIENT(S) Twenty-eight adolescent girls with clinical and biological hyperandrogenism and six or less menses during the past 12 months. INTERVENTION(S) Group A (n = 14) received 0.15 mg of desogestrel plus 0.030 mg of ethinyl estradiol daily. Group B (n = 14) received 2 mg of cyproterone acetate plus 0.035 mg of ethinyl estradiol daily. Treatment was given for 21 days followed by a 7-day rest for a period of 12 months. MAIN OUTCOME MEASURE(S) Hirsutism and lipid profile were evaluated before initiation and at 3, 6, 9, and 12 months of treatment. Androgen profile was evaluated before and at 12 months of treatment. RESULT(S) A significant decline of the Ferriman-Gallway hirsutism score was observed from the sixth month of therapy in both groups. During therapy, the levels of testosterone, free testosterone, Delta(4)-androstenedione, and 17OH-progesterone decreased significantly, whereas sex hormone-binding globulin (SHBG) increased significantly in both groups. The level of total cholesterol and low density lipoprotein (LDL) cholesterol increased significantly, whereas high density lipoprotein (HDL) cholesterol and apolipoprotein A-I increased significantly from the third month of therapy in both groups. Total cholesterol/HDL cholesterol and LDL cholesterol/HDL cholesterol ratios remained unchanged. The levels of triglycerides increased significantly in the cyproterone acetate-treated group after the third month. CONCLUSION(S) Treatment of adolescent girls with PCOS with the two studied formulations is comparably effective in decreasing hirsutism and androgen levels. Both combined oral contraceptives are associated with an increase of total cholesterol, LDL cholesterol, and HDL cholesterol levels and no change of the total cholesterol/HDL cholesterol and LDL cholesterol/HDL cholesterol ratios. Treatment with the cyproterone acetate combined oral contraceptive is associated with a tendency toward increasing the levels of triglycerides.

Creation of a neovagina following Williams vaginoplasty and the Creatsas modification in 111 patients with Mayer- Rokitansky-Kuster-Hauser syndrome

OBJECTIVE Evaluation of the Creatsas modification of Williams vaginoplasty for the creation of neovagina in patients with Mayer-Rokitansky-Küster-Hauser syndrome (MRKH syndrome). DESIGN Record of perioperative and postoperative results and complications. Follow-up evaluations of patients yearly after the operation. SETTING Division of Pediatric-Adolescent Gynecology and Gynecologic Corrective Surgery, University of Athens (tertiary referral center). PATIENT(S) One hundred eleven patients with MRKH syndrome. INTERVENTION(S) Surgical creation of neovagina using the Williams vaginoplasty technique (group A: 10 patients) or the Creatsas modification of the previous method (group B: 101 patients). MAIN OUTCOME MEASURE(S) Length and width of the neovagina, and the quality of sexual life postoperatively. RESULT(S) A functioning vagina of 10 to 12 cm depth and 5 cm width was created in eight of the patients in group A (80%) and in 98 of those in group B (97.02%). A vagina of 7 to 9 cm depth and 2 to 3 cm width was created in the rest of the patients in both groups. In group A, two wound openings were reported (20%); in two of the patients hemorrhage occurred during the first intercourse, compared to none in group B. A satisfactory sexual life was reported from 94.4% of the patients and an adequate one from 4.16% of them. CONCLUSION(S) The Creatsas modification of Williams vaginoplasty is a simple and effective technique for the creation of a functioning neovagina in young women with vaginal aplasia.

Oral Contraceptives and Reproductive System Cancer

Abstract: Extensive research during the last 20 years has shown that oral contraceptives are safe. Several recent epidemiological studies have confirmed that combined oral contraceptives (COCs) provide substantial protection against endometrial and ovarian cancer, and this protection is long‐lasting and may persist for 15 or more years after termination of OC use. In many studies COCs have been associated with an increased risk of cervical abnormalities and cervical cancer, but there might be alternative explanations for these epidemiological associations (COC users can start having sexual intercourse at an earlier age, they have more sexual partners, and they rarely use barrier methods of contraception), so OCs act as a promoter for HPV‐induced carcinogenesis. Finally, women who are currently using COCs or have used them in the past 10 years are at a slightly increased risk of having breast cancer during the next 10 years, although the additional cancers diagnosed tend to be localized to the breast and they are less advanced clinically than the cancers diagnosed in those who have never used COCs.

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.

Concentrations of angiogenic factors in follicular fluid and oocyte-cumulus complex culture medium from women undergoing in vitro fertilization: association with oocyte maturity and fertilization

OBJECTIVE To determine the concentration of angiogenic factors (vascular endothelial growth factor [VEGF], basic fibroblast growth factor [bFGF], and angiogenin) in the follicular fluid (FF) and oocyte-cumulus complex culture medium (CM) of women undergoing IVF and to investigate the association of the concentrations with the maturity and fertilization of the oocyte. DESIGN Prospective study. SETTING Academic tertiary-care institution. PATIENT(S) IVF patients with unexplained or tubal factor infertility. INTERVENTION(S) Analysis of VEGF, bFGF, and angiogenin FF and CM concentrations. MAIN OUTCOME MEASURE(S) Oocyte maturity and fertilization and FF and CM angiogenic factor concentrations. RESULT(S) VEGF, bFGF, and angiogenin were determined in FF and CM. FF angiogenin concentrations were significantly higher when the oocyte was mature versus immature. CM VEGF concentrations were significantly higher when the oocyte was nonfertilized versus fertilized. Positive correlations were observed between angiogenic factors in CM. CONCLUSION(S) VEGF, bFGF, and angiogenin (determined for the first time) are secreted in the FF and CM. Elevated CM VEGF concentrations, probably implying oocyte-cumulus complex hypoxia, are negatively associated with oocyte fertilization. Elevated FF angiogenin concentrations are positively associated with oocyte maturity, possibly indicating angiogenins biological role beyond neovascularization.

Anxiety and depression in adolescents with polycystic ovary syndrome and Mayer-Rokitansky-Küster-Hauser syndrome

Purpose. The purpose of this study was to assess self-reported depressive and anxiety symptoms in adolescents with polycystic ovary syndrome (PCOS) and those with the rare Mayer-Rokitansky-Küster-Hauser Syndrome (MRKHS), compared with healthy adolescents. Material and methods. The participants were 49 adolescent girls, of whom 27 were patients with confirmed menstrual disorder, 22 with PCOS and 5 with MRKHS; and 22 were healthy eumenorrheic adolescents (control group) matched by age and school grade. The Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI-Gr) were used to measure depression and anxiety, respectively. Results. The results showed that it was 1.08 times more likely for the PCOS group (p = 0.043) and 1.12 times more likely for the MRKHS group (p = 0.039) to have higher scores than healthy adolescents on the anxiety scale. The MRKHS group was 1.40 times more likely to have a higher number of depressive symptoms (p = 0.040) than the control group. Conclusions. These findings, although based on a small sample, suggest a relationship between PCOS and MRKHS and the presence of psychological problems, such as anxiety and depressive symptoms in adolescents. This study is among the first to examine psychological difficulties in adolescents with such a rare menstrual syndrome as MRKHS.

General Practice as a career choice among undergraduate medical students in Greece

BackgroundAlthough General Practice (GP) was recognized as a medical specialty in Greece in 1986, the number of GPs is insufficient to cover needs and only few medical graduates choose GP as a career option. In the present study we investigated the profile of medical students in terms of their decisions regarding specialization and the possible association of career choices different from GP with the status of undergraduate training regarding GP.MethodsThe sample consisted of final year students in the Medical School of the University of Athens, Greece. Students filled in a self-reported questionnaire focusing on medical specialization, and GP in particular.ResultsResponse rate was 82.5% with 1021 questionnaires collected, out of 1237 eligible medical students. Only 44 out of the 1021 (4.3%) respondents stated that GP is -or could be- among their choices for specialty. The most popular medical specialty was General Surgery (10.9%), followed by Cardiology (9.6%), Endocrinology (8.7%) and Obstetrics-Gynaecology (8.3%). The most common criterion for choosing GP was the guaranteed employment on completion of the residency (54.6%) while a 56.6% of total respondents were positive to the introduction of GP/FM as a curriculum course during University studies.ConclusionDespite the great needs, GP specialty is currently not a career option among undergraduate students of the greater Medical University in Greece and is still held in low esteem. A university department responsible for undergraduate teaching, promotion and research in GP (where not available) is essential; the status of undergraduate training in general practice/family medicine seems to be one of the most important factors that influence physician career choices regarding primary care specialties.

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.

Fetal growth restriction and postnatal development.

Abstract:  The interaction between genetic constitution and in utero environment determines fetal growth and development and influences the susceptibility to certain disorders in adulthood. Data from both animal and human studies indicate that prenatal and early postnatal malnutrition can program the hypothalamus‐pituitary‐adrenal axis (HPA axis), altering neuroendocrine response to stressors throughout lifetime. Impaired uteroplacental perfusion results in fetal growth restriction (FGR). In FGR there is evidence of chronic hypoxemia and alterations in metabolic, endocrine, and hematological parameters, compatible with starvation. Furthermore, FGR is associated with increased perinatal mortality and in the survivors there is increased susceptibility to diabetes and cardiovascular disease in adulthood. There is evidence that early postnatal growth acceleration, which would normally be considered desirable, may exacerbate metabolic dysfunction in later life.