Andrzej Starczewski

Effects of metformin treatment in women with polycystic ovary syndrome depends on insulin resistance

Polycystic ovary syndrome (PCOS) affects 5–10% of women at reproductive age, and is the most common reason for hyperandrogenism and chronic anovulation. Some patients with PCOS are insulin-resistant. Also, lowered sex hormone-binding globulin (SHBG) concentration is usually observed. As a consequence, the amount of free and biologically active androgens increases. This implies that, by improving insulin and carbohydrate metabolism, metformin administration in PCOS patients could indirectly contribute to increase SHBG concentration. The aim of the present study was to assess the effects of metformin treatment in PCOS patients both with and without insulin resistance. Thirty-six patients completed treatment. Body mass index (BMI) was considerably reduced after therapy. Statistically significant decreases were noted in luteinizing hormone (LH) and fasting insulin concentrations and the free androgen index (FAI), and significant increases in follicle-stimulating hormone (FSH)/LH ratio and SHBG concentration. In the insulin-resistant group, BMI and fasting insulin concentrations were reduced considerably after treatment, and SHBG increased slightly. In the group of patients without insulin resistance, BMI, LH and FAI showed significant reductions, and FSH/LH and SHBG considerable increases. Considering the favorable effects of metformin treatment in PCOS patients both with insulin resistance and without it, it is purposeful to use this drug in both groups of women.

The bone mass density in postmenopausal women using hormonal replacement therapy in relation to polymorphism in vitamin D receptor and estrogen receptor genes

The aims of the study were as follows: (1) To identify the differences in spinal body mass density (BMD) in relation to polymorphism in vitamin D receptor (VDR) and estrogen receptor-α (ERα) genes in untreated women with postmenopausal osteoporosis. (2) To assess the efficacy of treatment in women with postmenopausal osteoporosis in relation to polymorphism in VDR and ERα genes. (3) To find the estradiol concentration necessary to protect bone tissue in patients with a given polymorphism in VDR and ERα genes. Methods. The study included 44 postmenopausal women with primary osteoporosis who used cyclic hormonal replacement therapy (HRT) for a year. The polymorphism of ERα and VDR genes were evaluated. We also determined the age, body mass index and spinal BMD before and after 12 months of administration the HRT. Results. We found a significant spinal BMD increase, what is connected with ERα genotype and both VDR and ERα genes. There is no such a correlation observed in polymorphism of VDR gene. Conclusions. (1) There is no relationship between VDR and ERα genes polymorphism and the stage of osteoporosis related to the spinal BMD value before treatment. (2) The XX, PP or Bb markers or only X, P, B alleles are connected with a significant decrease of treatment efficacy. (3) Estradiol serum concentration before and during HRT is not dependent on the polymorphism of VDR and ERα genes.

Leptin concentrations in patients with polycystic ovary syndrome before and after met-formin treatment depending on insulin resistance, body mass index and androgen con-centrations--introductory report.

Polycystic ovary syndrome (PCOS) is an endocrinological and metabolic disorder which may concern about 3-8% of women. Some PCOS women have the increased leptin concentration in blood serum. Leptin concentration is higher in patients with high body mass index (BMI) and impaired tissue sensitivity to insulin. The aim of this study was to determine leptin concentrations in PCOS patients before and after metformin treatment depending on BMI, insulin resistance calculated on the basis of the Homeostasis Model Assessment (HOMA) index, as well as concentrations of androgens: testosterone and androstendion. Such values as BMI, insulin resistance according to the HOMA index, and concentrations of androstendion, testosterone and leptin were determined in 35 patients with PCOS before and after 3-month metformin treatment administered in daily doses of 2 x 850 mg. Increased leptin levels before the therapy were observed in 91.3% (21 out of 23) of obese patients, in 75% (9 out of 12) non-obese patients, in 100% (8 patients) insulin resistance women, in 81.5% (22 out of 27) insulin sensitive patients, in 94.7% (18 out of 19) women with elevated androstendion concentration and in 75% (12 out of 16) with normal androstendion concentration, in 93.7% (15 out of 16) patients with increased testosterone concentration and in 78.9% (15 out of 19) patients with testosterone concentrations within the normal range. After treatment statistically significant decrease in leptin concentration was obtained in the patients with BMI<or=25, insulin-sensitive patients (HOMA<3.8) and patients whose testosterone and androstendion concentrations stayed within normal limits. Increased leptin concentrations may be one of the elements of PCOS clinical picture. Metformin treatment considerably reduces leptin concentration, if it is employed in non-obese PCOS patients, patients with normal an-drogen concentrations and those who not have an impaired glucose tolerance.

Pulmonary Benign Metastasizing Leiomyoma from the Uterine Leiomyoma: A Case Report

Summary Background Benign metastasizing leiomyoma (BML) is a rare condition described as multiple well-differentiated leiomyomas at sites distant from the uterus. Apart from lungs it has also been reported in lymph nodes, heart, brain, bone, skin, eye and spinal cord. We present a case of pulmonary benign metastasizing leiomyoma in a female patient admitted to our hospital with suspicion of left adnexal tumor. Case Report A 45-year-old woman was referred to our hospital with suspicion of left adnexal tumor. The control transvaginal ultrasound examination performed at admission to the Gynecological Department excluded adnexal neoplasm. However, a large amount of fluid within the Douglas pouch raised the oncological concern. The patient underwent myomectomy in 2005. In the same year she was diagnosed with multiple lung nodules and underwent pulmonary wedge resection with the diagnosis of pulmonary benign metastasizing leiomyoma being stated. The decision of reevaluation of the specimen, control CT and puncture of the Douglas pouch fluid was made. Computed tomography performed at the Department of Diagnostic Imaging and Interventional Radiology of the Pomeranian Medical University Hospital revealed multiple, bilateral nodules. The microscopic examination of the samples confirmed the initial diagnosis of benign metastasizing leiomyoma with no evidence of neoplastic cells within the fluid. Conclusions Pulmonary benign metastasizing leiomyoma is a rare entity. However, it should be always taken into consideration in women with a previous or coincident history of uterine leiomyoma, especially when no evidence of other malignancy is present.

Effect of IGF-I and TNF-α on intensification of steroid pathways in women with PCOS phenotypes are not identical. Enhancement of progesterone pathway in women with PCOS increases the concentration of TNF-α.

Abstract Objective: The aim of this study was to determine the correlations between the concentration of tumor necrosis factor (TNF-α) and insulin-like growth factor I (IGF-I) in each woman with polycystic ovary syndrome (PCOS) phenotypes based on the levels of androgen. Methods: Two groups of women with PCOS differing in their levels of androgens. The test group composed of 39 women with PCOS according to the Rotterdam criteria in their reproductive age. The hormonal levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid stimulating hormone (TSH), prolactin (PRL), androstenedione, testosterone (T), estradiol (E2) and sex hormone binding globulin (SHBG) were measured. Correlations analysis were performed calculating Spearman’s rank correlation coefficient of hormones with relation to TNF-α and IGF-I. Results: There was a medium positive correlation of IGF-1 with LH levels (p < 0.05) and negative medium correlation of TNF-α with of dehydroepiandrosterone (DHEA)-SO4 levels (p < 0.05) only in group of PCOS women with elevated androgens. Conclusion: Analysis of TNF-α showed that women with high testosterone negative correlation between level of TNF-α and the concentration of DHEA-SO4. Inflammatory state involving TNF-α in women with PCOS and high concentration of androgens is caused by intensified Δ4 (progesterone) pathway and omitted or limited Δ5 (dehydroepiandrosterone) pathway of testosterone biosynthesis.

Cardiovascular system diseases in patients with polycystic ovary syndrome – the role of inflammation process in this pathology and possibility of early diagnosis and prevention

Polycystic ovary syndrome is a disorder which affects 5-10% of women in reproductive age. PCOS is a cause of hyperandrogenism, menstrual disorders and infertility. The most common clinical symptoms are hirsutism, acne and obesity. Patients often suffer from metabolic disorders: insulin resistance, hyperinsulinemia, dislipidemia, leading to atherosclerosis and others irregularities of the metabolic syndrome. Patients are in the high risk group for cardiovascular diseases (CVD) development because of the metabolic abnormalities. Obesity is observed in 35-60% of women with PCOS. Lean women with PCOS are also exposed to a greater risk of glucose intolerance development and abnormalities in lipid profile than women without PCOS with comparable BMI. Adipocytes are the source of many compounds of the paracrine and endocrine activity. Some of them are also markers and mediators of inflammation. Increased levels of proinflammatory cytokines in blood can promote atherosclerosis and cardiovascular disease. Markers: IL-18, TNF, IL-6 and hs-CRP are often elevated in patients with polycystic ovary syndrome. An increase in inflammatory markers may be an early indicator of the risk of developing insulin resistance and atherosclerosis, and may become a useful prognostic and therapeutic tool for monitoring patients with PCOS: lean and those with overweight and obesity. Assessment of the concentrations of inflammatory markers may become a very useful test in evaluating the risk of developing atherosclerosis and cardiovascular disease, long before their clinical manifestation. It will also allow for the appropriate prophylaxis.

Serum Mg and Zn levels in postmenopausal women

Approximately 30% of a womans life is spent in the postmenopausal period. This is when steroid hormone deficiency is often accompanied by mineral homeostasis perturbations and deficiencies that could be related to the intensity of any clinical symptoms. The aim of this study was to assess how serum Mg and Zn levels in postmenopausal women correlate with climacteric symptoms, body mass index (BMI), and the time interval since the final menstruation. The study involved 171 healthy, postmenopausal women, who had had their final menstruation at least one year prior to the study and who did not use menopausal hormone therapy. Both hypomagnesaemia and hypozincaemia were detected in the postmenopausal women involved in this study. The analysis revealed statistically significant differences between serum Mg levels, depending on the time interval since the final menstruation (p<0.05). No statistically significant differences were found in serum Mg and Zn levels between women as regards the severity of the climacteric symptoms or BMI (p>0.05). In conclusion, serum Mg and Zn concentrations in postmenopausal women, not using MHT, were low. The average serum Mg levels decreased considerably with the time since the final menstruation. No correlation between BMI and worsening of climacteric symptoms and serum Mg and Zn concentrations in postmenopausal women, not using MHT was found.

The presence and role of progesterone receptor in the ovaries of postmenopausal women who have not applied hormone replacement therapy.

At present, not much is known about progesterone receptor (PR) expression and localization in postmenopausal women ovaries. In the ovaries of reproductive age women, PR is localized in internal theca and granulosa cells, corpus luteum, ovary surface epithelium (OSE) and in stroma. PR expression depends on the serum concentration of progesterone, estrogen, gonadotropin and androgen. The goal of the conducted studies was to examine PR localization and expression in the ovaries of postmenopausal women who have not applied hormone replacement therapy so far. Also, the correlation was examined between PR expression and localization in the ovaries, steroid and gonadotropin hormone serum concentrations, and influence of the time from the last menstruation. The material came from 50 postmenopausal women who had their ovaries removed due to non-neoplastic diseases. The women were divided into 3 groups (A, B, C) depending on the time from the last menstruation. The follitropin (FSH), luteotropin (LH), estradiol (E2), testosterone (T), androstendione (A) and dehydroepiandrosterone sulphate (DHEAS) concentrations in blood plasma were measured. Monoclonal mouse anti-human PR antibody was used for immunohistochemical detection (examination involved 50 postmenopausal ovaries). Between particular groups, E2 serum concentrations did not differ, but FSH, LH, T, A, DHEAS serum concentrations were significantly different. Immunohistochemical nuclear localization of PR in postmenopausal women ovaries was observed. PR expression was similar in all three groups (A, B, C). PR expression was observed in OSE nuclei and invaginations cysts deriving from the isolation of invaginated epithelium and metaplastic columnar epithelium and in stroma. In the ovaries of postmenopausal women who have not applied hormone replacement therapy so far, PR was detected in all three groups. Its expression did not depend on the time from menopause and was similar in all examined groups. FSH, LH, T, A, DHEAS serum concentrations did not influence PR expression.

Health behaviors of postmenopausal women

Introduction Health status and health-related quality of life of postmenopausal women are issues, which nowadays pose a serious challenge to many domains of science. Climacteric symptoms which occur at this stage of life, lower its quality and make a negative contribution to self-reported health status, are mostly observed in a particular group of women. Evaluation of health behaviors performed using a standardized questionnaire, the Health Behavior Inventory (HBI), may help establish a comprehensive diagnosis of womens health, and thus select effective interventions. A systemic approach to menopause assumes that full fitness of women and good quality of their lives can be maintained not only by means of pharmacotherapy but also other forms of action, especially health education oriented towards changes in the lifestyle and promotion of healthy behaviors. The aim of this study Aim of the study is to perform a HBI-based assessment of womens health behaviors in such categories as healthy eating habits (HEH), preventive behaviors (PB), positive mental attitudes (PMA), and health practices (HP). Material and methods The study involved 151 healthy postmenopausal women. A research tool was a standardized questionnaire, the Health Behavior Inventory (HBI). Results The surveyed women obtained 70% of the maximum score on average, which suggests a medium level of health behaviors in this group. The levels of health behaviors in the categories of positive mental attitudes and health practices significantly differed between older women and their younger counterparts (higher levels were observed among older respondents). There were also significant differences in the levels of healthy behaviors between women with secondary and higher education (those better educated declared healthy behaviors more often). There was no correlation between the level of health behaviors and the BMI of the surveyed women. Conclusions Older women attached greater importance to positive mental attitudes, and so they avoided tension, stress and depressing situations. They also attached more weight to health practices (HP), i.e. the number of hours devoted to sleeping, resting and physical activity. The main determinant of a healthy lifestyle was higher education.

Hormone concentrations in the homogenates of ovarian tissue and blood serum in postmenopausal women not using hormone therapy

Ovaries in postmenopausal women synthesize steroids, mostly androgens. Removal of the ovaries after menopause may be reflected by menopausal symptoms and arterial hypertension observed during postoperative period, along with a significantly increased risk of death due to cardiovascular complications. It is not understood if the clinical consequences of gonad removal at different time points after menopause are similar. The aim of this study was to evaluate ovarian steroidogenesis and consequently to define the role of the ovaries in postmenopausal women depending on the time after menopause. Concentrations of hormones were determined in ovarian homogenates and serum of postmenopausal women. This study included 207 postmenopausal women. They were divided into groups depending on the time after menopause. All participants had laparotomic removal of the ovaries. Concentrations of estradiol, testosterone and androstenedione were measured in ovarian homogenate and serum. The study revealed that ovarian homogenate and serum concentrations of estradiol, testosterone and androstenedione were the highest in women up to 5 years after menopause and since then significantly decreased. This study showed that testosterone, androstenedione and estradiol are synthesized in the postmenopausal ovaries. The peak synthesis of these hormones occurs up to 5 years after menopause and significantly decreases thereafter.