Estrogen-dependent gallbladder carcinogenesis in LXRβ?/? female mice

Gallbladder cancer is a highly aggressive disease with poor prognosis that is two to six times more frequent in women than men. The development of gallbladder cancer occurs over a long time (more than 15 y) and evolves from chronic inflammation to dysplasia/metaplasia, carcinoma in situ, and invasive carcinoma. In the present study we found that, in female mice in which the oxysterol receptor liver X receptor–β (LXRβ) has been inactivated, preneoplastic lesions of the gallbladder developed and evolved to cancer in old animals. LXRβ is a nuclear receptor involved in the control of lipid homeostasis, glucose metabolism, inflammation, proliferation, and CNS development. LXRβ^−/− female gallbladders were severely inflamed, with regions of dysplasia and high cell density, hyperchromasia, metaplasia, and adenomas. No abnormalities were evident in male mice, nor in LXRα^−/− or LXRα^−/−β^−/− animals of either sex. Interestingly, the elimination of estrogens with ovariectomy prevented development of preneoplastic lesions in LXRβ^−/− mice. The etiopathological mechanism seems to involve TGF-β signaling, as the precancerous lesions were characterized by strong nuclear reactivity of phospho-SMAD-2 and SMAD-4 and loss of E-cadherin expression. Upon ovariectomy, E-cadherin was reexpressed on the cell membranes and immunoreactivity of pSMAD-2 in the nuclei was reduced. These findings suggest that LXRβ in a complex interplay with estrogens and TGF-β could play a crucial role in the malignant transformation of the gallbladder epithelium.     

Long-term progestin therapy for female chronic respiratory insufficiency?

End-stage chronic obstructive pulmonary disease often leads to hypercapnic respiratory failure. Oxygen supplementation therapy may further aggravate hypercapnia and not all patients are compliant with non-invasive ventilation. This case documents successful control of chronic respiratory failure with medroxyprogesterone in a postmenopausal woman during 1-year follow-up.     

β-Mannosidase deficiency in a female infant with epileptic encephalopathy

Summary We report a female infant with an isolated deficiency of-mannosidase activity. At nine months of age dysmorphism was absent except for brachecephaly. There was moderate developmental delay and a startle response to sound. At 12 months there was a sudden onset of tonic-clonic seizures which were unresponsive to drug therapy, requiring paralysis and mechanical ventilation for control. The child died suddenly aged 15 months.-mannosidase activity was markedly reduced in white cells and cultured skin fibroblasts whilst other lysosomal enzymes were normal. The disaccharide ManGlcNAc was excreted in urine but urinary mucopolysaccharides were normal.     

Rare forms of female pseudohermaphroditism: when to investigate?

The congenital adrenal hyperplasia is the commonest cause of ambiguity of the external genitalia at birth, due to classic forms of 21-hydroxylase and 11beta-hydroxylase deficiencies. 3beta-hydroxysteroid dehydrogenase (3betaHSD) is a rare disorder that affects both sexes and female patients may have ambiguous genitalia. Familial glucocorticoid resistance is characterized by increased cortisol secretion without clinical evidence of hypercortisolism, but with manifestations of androgen and mineralocorticoid excess, caused by glucocorticoid receptor gene mutation, and rarely can lead to female pseudohermaphroditism. Placental aromatase deficiency is a rare disease characterized by a masculinized female fetus and a virilized mother, which should be considered in the absence of fetal adrenal hyperplasia and maternal androgen-secreting tumours. Finally, mutations of P450 oxidoreductase causes disordered steroidogenesis with ambiguous genitalia. The investigation of abnormal sexual development requires an initial karyotype analysis and serum 17OH progesterone, 11 deoxycortisol, 17 pregnenolone, and androgen measurements to assess the diagnosis of different forms of congenital adrenal hyperplasia.     

Thyroid pathology and female fertility: Myth or reality?

The relationship between thyroid state and female fertility is an area of particular interest for both clinicians and researchers worldwide. This is partially due to the increasing prevalence of infertility and to the understanding of its complex and multifactorial aetiology. Studies conducted in variable forms of female infertility (e.g., recurrent miscarriages or polycystic ovarian syndrome) together with the worldwide rising use of assisted reproduction technologies (ART) contributed the uncovering of the potential role of thyroid conditions in relation to ovarian function and fertility. However, as the title of this short review suggests, several aspects are yet to be elucidated and several questions are still awaiting an answer. This short review is mainly focusing on the distinct roles of thyroid dysfunction and thyroid autoimmunity in infertile women undergoing ART procedures.     

Is female predominance in irritable bowel syndrome related to fibromyalgia?

Irritable bowel syndrome (IBS) and fibromyalgia (FM) are common functional diseases in adult women. The aim of this study was to investigate whether female predominance in IBS is related to FM. Fifty patients with IBS and 50 healthy controls were enrolled. All participants answered questionnaires including personal and medical history. In addition, psychiatric interviews were conducted. Patients were divided into two groups according to the coexistence of FM ( IBS+FM or IBS only). The data obtained from patients with or without FM and the control group were compared. There was a significant female predominance in patients with IBS+FM (83.4%, F:M=5:1), but IBS-only patients consisted mainly of males (59.4%, F:M=2:3) (P<0.01). Comparison of IBS+FM and IBS-only patients showed no significant difference in depression and anxiety status. However, both anxiety and depression scores were found to be higher in female IBS patients than their male counterparts (P<0.01 and P<0.05, respectively). Our findings suggest that the female predominance in IBS patients may result from coexisting FM.     

Male breast cancer. Does the prognosis differ compared to female?

Due to the low incidence of breast cancer in males there are not many reports in the literature. In this study we analyzed results of treatment in 65 breast cancer males, who had been treated in one institution. Radical surgery was performed in 45 patients. Lymph node metastases were found in 25 patients (55.5%), the tumor was usually moderately differentiated (21 pts - 46.7%). Median survival after radical surgery was 73 months compared to 38 months for nonsurgical patients (p < 0.0001). In the group of males after radical surgery the results of 5-, 10- and 15-year survival rates were 69.8, 59.7 and 31.3% respectively. Comparable analysis of two subgroups of patients with favorable (T1 or T2, N0, grade I or II) and unfavorable (T3 or N+ or grade III) prognostic factors was also performed. In the first subgroup the 5-, 10- and 15-year survival rates were 90, 77.4 and 62%, compared to 61.8, 23.1 and 23. 1% for the second subgroup. The multivariate analysis showed grading and node status as the strongest parameters influencing survival. Relative risk of death was over 3 times higher for nodal metastases and near 3 times higher for high grade carcinomas (p < 0.01), compared to patients without metastases and low grade of tumor. Similar analysis was performed when 45 males were compared to 500 selected women, with similar clinical parameters (age, node status, grading). Again, data indicated grading and lymph node status as the strongest prognostic factors. It was not unlikely, that gender had some influence on prognosis, when relative risk of death for males was over 1.5 times higher than for females, but this result was not clearly significant (p < 0.1 ). The question, whether male breast cancer prognosis is worse then in female remains open. Multiinstitutional prospective studies are needed in this area.     

Effects of exercise on lipid metabolism and musculoskeletal fitness in female athletes

AIM:This study investigated the effects of intense trainingon lipid metabolism,bone metabolism and bone mineraldensity (BMD) in female athletes.METHODS:Sixty-six female subjects participated in this study,age ranging from 18 to 55 years.The sample group includedthirty-six athletic subjects and the control group comprisedthirty non-athletic individuals.Five athletes competed withnational level (5/36) and nine non-athletic subjects (9/30) werepostmenopausal women.The assessment items included bodycomposition,radius BMD,calcaneus BMD,lung function,muscular endurance,renal and liver function,bone markerassay and hormone status.All data were analysed,using SPSS10.0 software,and were presented as mean rank statisticaldifference,using the Kurskal-Wallis (K-W) test.After that thenon-parameter statistics were used.Either Kvalue or Pvaluebelow 0.05 was considered significant.RESULTS:Urine deoxypyridinoline/creatinine (Dpd/Cre) levelsincreased significantly (5.93±2.31 vs 6.85±1.43,K<0.01),sit-reach (29.30±9.48 cm vs 41.31±9.43 cm,K<0.001,P<0.001),1 minute sit-ups with bended knees (1 min sit-ups) (17.60±9.34 count vs 30.00±10.38 count,K<0.001,P<0.001),and vertical jump (25.27±6.63cm vs34±69±7.99cm,K<0.001,P<0.001) improved significantly in the athletesgroup.The athletes group also had a significantly increasedlevel of estriol (E_3) (0.14±0.13 pg/mL vs0.07±0.04 pg/mL,K<0.01,P<0.01),radius BMD (1.37±0.49 gm/cm~2 vs 1.19±0.40gm/cm~2,K<0.05) and calcaneus BMD (0.57±0.17 gm/cm~2vs-0.20±0.17 gm/cm~2,K<0.01,P<0.05) compared withthose of the controls.The high density lipoprotein (HDL)(65.00±14.02 mg/dL vs52.26±4.84 mg/dL,K<0.05,P<0.05)was significantly lower in postmenopausal inactive athletes(5/36) than premenopausal active athletes (31/36).On theother hand,low-density lipoprotein (LDL) (98.35±23.84 mg/dLvs 131.00±21.63 mg/dL,K<0.05,P<0.01),cholesterol (CHO)(164.03±27.01 mg/dL vs 193.00±23.48 mg/dL,K<0.05,P<0.05),triglyceride (TG) (63.00±26.39 mg/dL vs 147.00±87.21 mg/dL,K<0.01),body fat % (BF%) (28.16±4.90% vs34.84±4.44%,K<0.05,P<0.001) and body mass index (BMI)(21.98±2.98 kg/m~2 vs26.42±5.01 kg/m~2,K<0.05,P<0.001)were significantly higher in postmenopausal inactive athletes(5/36) than premenopausal active athletes (31/36).TG(90.22±39.82 mg/dL vs 147.00±87.21 mg/dL),CHO (186.44±24.90 mg/dL vs 193.00±23.48 mg/dL) were higher,but the HDL was significantly lower (62.18±10.68 mg/dLvs 52.26±4.84 mg/dL,P<0.05)in postmenopausal athletes(5/36) group than in postmenopausal control group (9/30).CONCLUSION:Postmenopausal athletes (5/36) who nolonger took competing exercises had reduced levels ofphysical activity,faced increased risk of cardiovasculardisease compared to active athletes (31/36) and thepostmenopausal controls (9/30).We may thus concludedthat long term exercise effectively improves musculoskeletalfitness and prevents BMD loss in female athletes.     

Anderson–Fabry disease: Clinical manifestations of disease in female heterozygotes

Anderson–Fabry disease is a rare, X-chromosomal lipid storage disorder caused by a deficiency of lysosomal -galactosidase A. Clinical manifestations of Anderson–Fabry disease include excruciating pain in the extremities (acroparaesthesia), skin vessel ectasia (angiokeratoma), corneal and lenticular opacity, cardiovascular disease, stroke and renal failure, only renal failure being a frequent cause of death. Heterozygote female carriers have often been reported as being asymptomatic or having an attenuated form of the disease. To evaluate the spectrum of clinical signs in heterozygotes, a comprehensive clinical examination was performed on 20 carriers of Anderson–Fabry disease. This revealed that, in addition to the skin manifestation, various other clinical manifestations of the disease are present, including acroparaesthesia, kidney dysfunction, cerebrovascular disease, and gastrointestinal and heart problems. It therefore appears that Anderson–Fabry disease affects both hemizygotes and heterozyotes and therefore should be considered to be an X-linked dominant disease.     

Inhibins and activins in blood: predictors of female reproductive health?

Inhibins A and B are gonadal factors which are important in fertility. Their use as predictors of female reproductive health has centred on their application to ovarian cancer, Anorexia Nervosa, Down Syndrome and preeclampsia. Inhibin B also provides an index of the endocrine feedback relationship between the ovary and pituitary particularly when the ovarian follicle reserve is low. These applications are relevant in monitoring the onset of the menopause transition, ovarian recovery following chemotherapy and disturbances in pubertal development. Currently, these applications have only found widespread use in Down Syndrome and ovarian cancer. Activins, on the other hand, appear to have a limited application.