High prevalence of polycystic ovary syndrome in women with mild hirsutism and no other significant clinical symptoms

OBJECTIVE: To verify the conclusions of the Endocrine Society Guidelines that patients with mild hirsutism and no other important clinical signs (menstrual irregularities, infertility, central obesity, acanthosis nigricans, rapid progression of the hirsutism, clitoromegaly) should not be further studied. DESIGN: Retrospective study in patients referred because of mild hirsutism and no other clinical signs. SETTING: Department of Clinical Medicine of the University of Palermo. PATIENT(S): One hundred fifty-two patients with mild hirsutism. INTERVENTION(S): Measurement of serum testosterone, dehydroepiandrosterone sulfate, 17-OH-Progesterone, assessment of ovulation by measurement of progesterone in 21 to 24 days and ovarian ultrasound. RESULT(S): In 72 (47%) patients a diagnosis of polycyctic ovarian syndrome (PCOS) was performed. Polycyctic ovarian syndrome patients included 56 patients with the mild ovulatory form (OV-PCOS) but also 16 patients with the anovulatory form (classic PCOS). Three (2%) patients had nonclassic adrenal hyperplasia. CONCLUSION(S): Because of the high prevalence of PCOS and the possibility of finding nonclassic 21-hydroxylase deficiency, patients with mild hirsutism need a diagnostic evaluation that should include 17-hydroxyprogesterone measurement plus assessment of ovulation and ovarian ultrasound

Influence of sociocultural factors on the ovulatory status of polycystic ovary syndrome.

OBJECTIVE: To evaluate the role of social and cultural differences inside the same ethnic group on the ovulatory status of women with polycystic ovary syndrome (PCOS). DESIGN: To correlate social and cultural status with the phenotypic expression (body weight and ovulation) and with androgen and insulin levels of PCOS. SETTING: University department of medicine. PATIENT(S): Two hundred and forty-four consecutive PCOS women. INTERVENTION(S): All studied patients completed a simple questionnaire to indicate their mean family income and their school education. MAIN OUTCOME MEASURE(S): Ovulation was assessed by measurement of serum progesterone on day 22 of a spontaneous or induced menstrual cycle. Levels of blood testosterone, sex hormone-binding globulin, insulin, and blood glucose were evaluated. RESULT(S): In the low to medium income group, 21% of patients had ovulatory PCOS, but the prevalence of the same PCOS phenotype was 43% in patients with high income. In patients with low education, only 12% presented with ovulatory PCOS compared with 47% of the patients with high education status. Mean family income negatively correlated with body mass index, waist circumference, insulin, and insulin resistance. Serum progesterone correlated negatively with insulin and insulin resistance. CONCLUSION(S): In an ethnically homogeneous PCOS population, high socioeconomic status was associated with a higher prevalence of the ovulatory phenotype. Differences in ovulatory status between the social classes seem to be related to differences in insulin levels and fat quantity and distribution

Hereditary ovarian cancer

Apoptosis is a form of cell death that permits the removal of damaged, senescent or unwanted cells in multicellular organisms, without damage to the cellular microenvironment. Defective apoptosis represents a major causative factor in the development and progression of cancer. The majority of chemotherapeutic agents, as well as radiation, utilize the apoptotic pathway to induce cancer cell death. Resistance to standard chemotherapeutic strategies also seems to be due to alterations in the apoptotic pathway of cancer cells. Recent knowledge on apoptosis has provided the basis for novel targeted therapies that exploit apoptosis to treat cancer. These new target include those acting in the extrinsic/intrinsic pathway, proteins that control the apoptosis machinery such as the p53 and proteosome pathway. Most of these forms of therapy are still in preclinical development because of their low specifity and susceptibility to drug resistance, but several of them have shown promising results. In particular, this review specifically aims at providing an update of certain molecular players that are already in use in order to target apoptosis (such as bortezomib) or which are still being clinically evaluated (such ONYX-015, survivin and exisulind/aptosyn) or which, following preclinical studies, might have the necessary requirements for becoming part of the anticancer drug programs (such as TRAIL/ Apo2L, apoptin/VP3). Key words: apoptosis, TRAIL/Apo2L, apoptin/VP3, ONYX015, Bortezomib, exisulind, survivi

Monoclonal antibodies and antibody fragments: state of the art and future perspectives in the treatment of non-haematological tumors

Introduction: The use of monoclonal antibodies is one of the strategies for targeting the specific key points of the main pathways of cancer growth and survival, but only a few antibodies have offered a clear clinical benefit in the treatment of non-haematological malignancies. Areas covered: This review summarizes the general properties of monoclonal antibodies, including structure, nomenclature and production techniques. The antibodies approved for use in clinical practice for the treatment of non-haematological tumors and those antibodies still being developed in this setting are briefly described. The types of antibody fragments are also reported. Expert opinion: Monoclonal antibodies were initially developed in order to avoid the cytotoxic effects of chemotherapy on healthy tissues. However antibodies have not yet replaced chemotherapy agents, since the combination of both kinds of drugs have usually appeared to achieve higher benefit compared with chemotherapy alone. The research for the development of new monoclonal antibodies aims to identify further targets and to provide innovative antibody constructs

Osteodystrophy in chronic liver diseases.

Osteoporosis and osteomalacy are, to date, among the most common metabolic disease in the world. Recently, association between metabolic bone diseases and chronic liver diseases has been increasingly reported, inducing many authors to create a new nosographic entity known as "hepatic osteodystrophy". The importance of such a condition is, moreover, further increased by morbidity of these two diseases, which greatly reduce patients quality of life because of frequent fractures, especially vertebral and femoral neck ones. For this, early identification of high-risk patients should be routinely performed by measuring Bone Mass Density. The explanation for the association between bone diseases and chronic liver disease is still uncertain, and involves many factors: from hypogonadism to use of corticosteroid drugs, from genetic factors to interferon therapy. To date, few studies have been conducted, and all with a small number of patients, in order to establish definitive conclusions about the possible treatment, but some evidences are beginning to emerge about the safety and efficacy of bisphosphonates

Milder forms of atherogenic dyslipidemia in ovulatory versus anovulatory polycystic ovary syndrome phenotype

BACKGROUND Dyslipidemia is common in women with polycystic ovary syndrome (PCOS) but its prevalence in different PCOS phenotypes is still largely unknown. METHODS We measured plasma lipids and lipoproteins in 35 anovulatory PCOS (age: 25 ± 6 years, BMI: 28 ± 6 kg/m2), 15 ovulatory PCOS (age: 30 ± 6 years, BMI: 25 ± 3 kg/m2) and 27 healthy women (controls) age- and BMI-matched with ovulatory PCOS. PCOS was diagnosed by the presence of clinical or biologic hyperandrogenism associated with chronic anovulation and/or polycystic ovaries at ultrasound. In women with normal menses chronic anovulation was indicated by low serum progesterone levels (<9.54 nmol/l) during midluteal phase (days 21-24) in two consecutive menstrual cycles. RESULTS Total cholesterol, triglycerides and low-density lipoprotein (LDL)-cholesterol levels increased and high-density lipoprotein (HDL)-cholesterol decreased from controls to ovulatory and then to anovulatory PCOS (all P < 0.05). Levels of lipoprotein(a) (Lp(a)) and small, dense LDL increased (P < 0.0001 for both) and LDL size reduced (P < 0.005) between groups. Insulin resistance (by HOMA) showed a positive correlation with triglycerides and small, dense LDL and an inverse correlation with HDL-cholesterol and LDL size (P < 0.05 for all) in both PCOS phenotypes. No significant correlations were found with testosterone levels. At multivariate analysis, insulin resistance was independently associated with HDL-cholesterol and small, dense LDL in both PCOS phenotypes and with triglyceride concentrations in ovulatory PCOS only. CONCLUSIONS Women with ovulatory PCOS showed milder forms of atherogenic dyslipidemia than anovulatory PCOS and this seemed to be related to the extent of insulin resistance. Future prospective studies are needed to assess the relative contribution of such alterations on cardiovascular ris