The serum steroid signature of PCOS hints at the involvement of novel pathways for excess androgen biosynthesis.

CONTEXT Polycystic ovary syndrome (PCOS) is defined by androgen excess and ovarian dysfunction in the absence of a specific physiological diagnosis. The best clinical marker of androgen excess is hirsutism, while the best biochemical parameter is still a matter of debate. Current consensus guidelines recommend, among other hormones, serum free testosterone as an important serum parameter to measure androgen excess. Recently, however, novel active androgens and androgen metabolic pathways have been discovered. OBJECTIVE To assess the contribution of novel androgens and related steroid biosynthetic pathways to the serum steroid pool in PCOS women in comparison to healthy controls. DESIGN This is a case control study, wherein PCOS was diagnosed according to the AE-PCOS 2009 criteria. Serum steroid profiling was performed by liquid chromatography high-resolution mass spectrometry. SETTING Yeditepe University and associated clinics in Istanbul, Turkey, together with Bern University Hospital Inselspital, Bern, Switzerland. PARTICIPANTS 42 PCOS women and 42 matched, healthy control women. MAIN OUTCOME MEASURES Assessment of 34 steroids compartmentalized in four androgen related pathways: the classic androgen pathway, the backdoor pathway, the C11-oxy backdoor pathway, and the C11-oxy (11β-hydroxyandrostenedione) pathway. RESULTS Metabolites of all four pathways were identified in healthy and PCOS women. Highest concentrations were found for progesterone in controls and androstenedione in PCOS. Lowest levels were found for 11-ketotestosterone in controls compared to PCOS, and for 20α-hydroxyprogesterone in PCOS compared to controls. PCOS also had higher serum testosterone levels compared to the controls. PCOS women had overall higher levels of steroid metabolites of all four androgen pathways compared to healthy controls. CONCLUSIONS Novel alternative pathways contribute to the androgen production in healthy and PCOS women. Hyperandrogenism in PCOS is characterized by an overall increase of serum androgens in the classic, backdoor and C11-oxy pathways. While monogenetic disorders of steroid biosynthesis can be recognized by a specific pattern in the steroid profile, no diagnostic pattern or classifier was found in the serum for PCOS

Experimental treatments of endometriosis

Endometriosis is defined as the presence of endometrial gland and stroma outside the uterine cavity. It is an estrogen-dependent disease and is associated with chronic pelvic pain, dysmenorrhea, dyspareunia and infertility. The treatment of endometriosis is conservative or radical surgery, medical therapies or their combination. All currently used hormonally active treatments are effective in the treatment of endometriosis; however, the adverse effects of these hormonal treatments limit their long-term use. Moreover, recurrence rates are high after cessation of therapy, and the treatments have no benefit in endometriosis-associated infertility. Therefore, researchers are working on new treatment modalities with improved side effects, mainly focusing on the molecular targets involved in etiopathogenesis of endometriosis. Here we summarized these novel treatments modalities

Use of hematopoietic stem cells in obstetrics and gynecology

Stem cells can be used in different areas of obstetrics and gynecology. Adult stem cells are specialized cells found within many tissues of the body where they function in tissue homeostasis and repair. In vitro they have been shown to differentiate into a wide variety of cell types. Hematopoietic stem cells (HSC) have been used to set up therapeutic strategies for the treatment of gynecological solid tumors such as ovarian cancer. Stem cells can be used for prenatal transplantation and in utero gene therapy. Also stem cells can be used in infertility and IVF for research and treatment. (C) 2008 Elsevier Ltd. All rights reserved

Experimental treatments of endometriosis.

Endometriosis is defined as the presence of endometrial gland and stroma outside the uterine cavity. It is an estrogen-dependent disease and is associated with chronic pelvic pain, dysmenorrhea, dyspareunia and infertility. The treatment of endometriosis is conservative or radical surgery, medical therapies or their combination. All currently used hormonally active treatments are effective in the treatment of endometriosis; however, the adverse effects of these hormonal treatments limit their long-term use. Moreover, recurrence rates are high after cessation of therapy, and the treatments have no benefit in endometriosis-associated infertility. Therefore, researchers are working on new treatment modalities with improved side effects, mainly focusing on the molecular targets involved in etiopathogenesis of endometriosis. Here we summarized these novel treatments modalities

Anticancer and Anti-Metastatic Role of Thymoquinone: Regulation of Oncogenic Signaling Cascades by Thymoquinone

Cancer is a life-threatening and multifaceted disease. Pioneering research works in the past three decades have mechanistically disentangled intertwined signaling networks which play contributory roles in carcinogenesis and metastasis. Phenomenal strides have been made in leveraging our scientific knowledge altogether to a new level of maturity. Rapidly accumulating wealth of information has underlined a myriad of transduction cascades which can be pharmaceutically exploited for cancer prevention/inhibition. Natural products serve as a treasure trove and compel interdisciplinary researchers to study the cancer chemopreventive roles of wide-ranging natural products in cell culture and preclinical studies. Experimental research related to thymoquinone has gradually gained momentum because of the extra-ordinary cancer chemopreventive multifunctionalities of thymoquinone. In this mini-review, we provide an overview of different cell signaling cascades reported to be regulated by thymoquinone for cancer chemoprevention. Essentially, thymoquinone efficacy has also been notably studied in animal models, which advocates for a rationale-based transition of thymoquinone from the pre-clinical pipeline to clinical trials

Association of interleukin 1beta gene (+3953) polymorphism and severity of endometriosis in Turkish women

Endometriosis is regarded as a complex trait, in which genetic and environmental factors contribute to the disease phenotype. We investigated whether the interleukin (IL) 1beta (+3953) polymorphism is associated with the severity of endometriosis. Diagnosis of endometriosis was made on the basis of laparoscopic findings. Stage of endometriosis was determined according to the Revised American Fertility Society classification. 118 women were enrolled in the study. 78 women didnot have endometriosis, 6 women had stage I, 3 had stage II, 13 had stage III and 18 had stage IV endometriosis. Polymerase Chain Reaction (PCR), Restriction Fragment Length Polymorphism (RFLP), and agarose gel electrophoresis techniques were used to determine the IL 1beta (+3953) genotype. Frequencies of the IL-1beta (+3953) genotypes in the control group were: CC, 0.397; TT, 0.115; CT, 0.487. Frequencies of the IL-1beta (+3953) genotypes in cases were: CC, 0.375; TT, 0.225; CT, 0.400. We found a 2.22 fold increase in TT genotype in the endometriosis group. However, the difference was not statistically significant (P > 0.05). We also observed an increase in the frequency of IL-1beta (+3953) T allele in the endometriosis group. However, the difference was not statistically significant. We also investigated the association between IL-1beta (+3953) polymorphism and the severity of endometriosis. The frequencies of CC+CT genotypes in stage I, III and IV endometriosis patients were 83.3, 84/6 and 72.2%, respectively; and TT genotypes were 16.7, 15.4 and 27.8%, respectively. We observed a statistically insignificant increase in TT genotype in stage IV endometriosis (P > 0.05). We suggest that IL-1beta (+3953) polymorphism is not associated with endometriosis in Turkish women