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PubMed1999

Usefulness of a 12-month treatment with finasteride in idiophathic and polycystic ovary syndrome-associated hirsutism.

OBJECTIVE: Hirsutism is considered as a skin disease due to increased 5 alpha-reductase activity in the pilosebaceous unit and finasteride is a drug that inhibits this enzymatic activity. This study showed the effectiveness of a chronic treatment with a selective 5 alpha-reductase inhibitor, finasteride, in idiopathic and PCOS-associated hirsutism. METHODS: Finasteride was administered orally at a daily dose of 5 mg for a period of 12 months to 20 women with IH and 20 women with PCOS. MAIN OUTCOME MEASURES: Each group was submitted to clinical (with Ferriman-Gallwey method) and serum hormonal (FSH, LH, 17 beta-estradiol, total and free T, delta 4-androstenedione, DHEAS; dihydrotestosterone, 3 alpha-androstanediol glucuronide) studies at baseline and after 3, 6 and 12 months of treatment. RESULTS: After 3 months of finasteride treatment, a significant decrease in the average hirsutism scores was recorded both in IH (p < 0.0001) and PCOS patients (p < 0.0001). A progressive significant decrease of hirsutism score was observed in IH patients after 6 and 12 months (p < 0.002) and in PCOS patients after 6 but not 12 months. In fact, the maximal therapeutic effect on the hirsutism was obtained after 12 months in the IH and 6 months in PCOS group.

Adolescent↗

PubMed1998

[Role of hyperinsulinemia in pathogenesis of polycystic ovary syndrome and treatment by reduction of insulin secretion].

OBJECTIVE: To investigate the role of insulin in the polycystic ovary syndrome (PCOS) pathogenesis and application of Metformin in the treatment of PCOS. METHODS: Serum androgen, luteinizing hormone (LH) and sex hormone-binding globulin(SHBG) concentration during fasting and serum 17 alpha-hydroxyprogesterone (17-OHP), LH level in response to gonadotropin-releasing hormone agonist (GnRH-a) stimulation were determined. Oral glucose-tolerance tests(OGTT) before and after oral administration of metoformin for 8-12 weeks were performed in 12 obese and 11 lean women with PCOS. RESULTS: After oral administration of metformin for 8-12 weeks, fasting insulin concentration in obese group and area under curve (AUC) after OGTT in lean group decreased significantly. There were significant decrease in basal 17 alpha-hydroprogesterone, androstenedione, testosterone concentration, and increase in serum SHBG concentration in obese and lean groups. Basal LH and the response of serum 17-OHP, LH to GnRHa were not significantly changed. CONCLUSIONS: Hyperinsulinemia may play an important role in hyperandrogenism GnRH-a of PCOS, and metformin may be used in the treatment of PCOS.

Adult↗

PubMed2000

Association of metformin and pregnancy in the polycystic ovary syndrome. A report of three cases.

BACKGROUND: Infertility is a common manifestation of the polycystic ovary syndrome (PCOS), a condition characterized by chronic anovulation, hyperinsulinemia and hyperandrogenism. Hyperinsulinemia leads to increased ovarian androgen production, resulting in follicular atresia and anovulation. Metformin, a medication that improves insulin sensitivity and decreases serum insulin levels, restores menstrual cyclicity and ovulatory function and may improve fertility rates in women with PCOS. We present three consecutive cases from our clinic that support this premise. CASES: Three patients were seen in the reproductive endocrinology clinic with documented PCOS, long-standing infertility and clinically diagnosed insulin resistance. The first patient had hyperandrogenic, insulin-resistant acanthosis nigricans syndrome and had been resistant to multiple courses of clomiphene citrate; the second exhibited hypertension, hyperlipidemia and glucose intolerance along with anovulation; and the third presented with poorly controlled type 2 diabetes and a desire to conceive. Each patient received metformin, which led to restoration of menstrual cyclicity and conception in all three cases. CONCLUSION: These three patients reflect the heterogeneous nature of PCOS, and treating their underlying insulin resistance with metformin resulted in pregnancy. These findings suggest that metformin may be a useful adjunct for treatment of infertility in patients with PCOS.

Adult↗

PubMed2000

Searching for the polycystic ovary syndrome genes.

PCOS is a common disorder of unknown etiology. Studies of first-degree relatives of women diagnosed with PCOS suggest familial clustering of the disease. A prospective study of first-degree female relatives of women with PCOS conducted by NCPIR found that 46% of ascertainable sisters of women with PCOS were hyperandrogenemic. NCPIR has conducted linkage and association studies using affected sibling-pair analysis and the transmission/disequilibrium test to explore candidate PCOS genes. These studies point a finger at a region 1 MB centromeric to the insulin receptor gene on chromosome 19.

Female↗

PubMed2001

[Study on the mode of inheritance for familial polycystic ovary syndrome].

OBJECTIVE: To investigate the mode of inheritance of polycystic ovary syndrome(PCOS). METHODS: The first female relatives with irregular cycle and the first male relatives with premature balding in each nuclear family were designated the affected. Their prevalence rates in families were respectively calculated. Analyses of segregation ratio were carried out among 139 nuclear families with PCOS by the methods of simple segregation and complex segregation of genetic epidemiology, respectively. RESULTS: The prevalence rates of irregular cycle among mothers and sisters with PCOS were 37.4% and 33.1% respectively, and the prevalence rates of premature balding among fathers and brothers of patients were 19.4% and 6.5%, respectively. The simple segregation analysis indicated that the segregation ratio of PCOS trait in siblings was 0.3023, the complex segregation analysis indicated that it fitted in with the inheritance model of co-dominant disorder with full penetrance and sporadic cases. The frequency of homozygote of disease gene in population was 0.046. CONCLUSION: PCOS presents the mode of co-dominant inheritance with complete penetrance.

Female↗

PubMed1999

[Expression of apoptosis regulatory protein bcl-2 and bax in endometrium of polycystic ovary syndrome].

OBJECTIVE: To study the expression and implication of apoptosis regulatory protein bcl-2 and bax in endometrium of polycystic ovary syndrome (PCOS). METHODS: The apoptosis regulatory protein expression of bcl-2 and bax protein in endometrium were investigated by immunohistochemical method in 18 PCOS and 27 normal subjects proliferative phase 10 and secretory phase 17. RESULTS: Bcl-2 expression was higher in PCOS than that both in control proliferative phase (P < 0.05) and secretory phase (P < 0.001). Bax expression was not significantly different between PCOS and controls (P > 0.05). CONCLUSIONS: The higher bcl-2 protein expression inhibits the endometrium apoptosis and plays an important role in the abnormal proliferative changes of endometrium in PCOS.

Adult↗

PubMed2001

[Polycystic ovary syndrome: the importance of establishing diagnosis].

Polycystic ovary syndrome (PCOS) is a very common disorder that occurs up to 10% of premenopausal women. Although PCOS is known to be associated with a higher reproductive morbility and increased risk of hormone dependent-cancer, its diagnosis is particularly important because PCOS is strongly linked to insulin resistance. This involves a major risk of early metabolic and cardiovascular complications. On the other hand, the prevalence of metabolic disorders associated with insulin resistance is higher in family members of patients with PCOS than in those of normal women, which suggests that the treatment of this syndrome should be preventive rather than symptomatic. For that reason, PCOS might be considered a signal of a family disorder, a route to diabetes and a public health problem.

Female↗

PubMed2001

[Can hormonal contraceptives affect plasma levels of IGF-1 and IGFBP-1 in slim women with polycystic ovary syndrome?].

BACKGROUND: Polycystic ovary syndrome (PCOS) represents a frequent endocrinopathy among fertile women. Ethiopathogenesis of the syndrome is multifactorial and it is a subject of scientific discussions. Considered is the possibility of intraovarial IGF system disorder affecting maturation of ovarial folicles. The aim of our work was to determine effects of peroral contraceptives with low-androgen progestin on IGF system in PCOS patients and healthy woman controls. METHODS AND RESULTS: 14 patients fulfilling diagnostic criteria of PCOS and 7 healthy controls were included into the study. All persons were examined before and after six months lasting administration of monophasic estrogen-progesteron contraceptive therapy with 35 micrograms of ethinylestradiol per day and 250 micrograms of low-androgen progestin norgestimate per day. In PCOS patients low increase of basal insulinemia levels occurred (16.3 +/- 4.8 vs. 20.8 +/- 4.8 mU.l-1, p < 0.05). IGF-1 serum levels were not influenced (230 +/- 70 vs. 235 +/- 112 pg.ml-1, n.s.), IGFBP-1 serum concentration significantly increased (46.3 +/- 24.1 vs. 75.6 +/- 24.0 pg.ml-1, p < 0.001). Insulinemia in healthy women also slightly increased (15.9 +/- 4.0 vs. 18.4 +/- 4.0 pg.ml-1, p < 0.05). IGF-1 serum concentration significantly increased (140 +/- 65 vs. 241 +/- 89 pg.ml-1, p < 0.001). IGFBP-1 was also higher (45.0 +/- 19.19 vs. 80.0 +/- 15.6 pg.ml-1, p < 0.001). Influence of the hormonal contraception on the followed parameters was estimated using Wilcoxon's test. While BP-1 increase was significant in both groups, the increase of IGF-1 was significant only in healthy controls. CONCLUSIONS: Increased levels of IGFBP-1 were found in both studied groups of women. Women with PCOS had higher serum levels of IGF-1 before the therapy and the treatment did not influence it. Contrary to it, in healthy women the increased value was observed. Explanation of that finding will become the aim of our next study.

Body Mass Index↗

PubMed2001

The polycystic ovary syndrome--a medical condition but also an important psychosocial problem.

PCOS, the leading cause of anovulatory infertility that affects up to one fifth of the female population, is a complex chronic disease of genetic as well as environmental determination, but still unclear etiology. Besides of infertility, PCOS leads to menstrual dysfunctions, hirsutism and obesity--symptoms that are known to cause profound psychosocial distress. The present paper review the problematic of etiology and symptom expression of PCOS, which is not only a disease needing medical treatment but also a psychosocial problem for the affected women. PCOS may not only coinduced by psychosocial factors, the main symptoms of PCOS such as infertility, menstrual dysfunctions, hirsutism and obesity cause by themselves increased psychosocial stress.

Adaptation, Psychological↗

PubMed2002

Polycystic ovary syndrome. Long term sequelae and management.

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in women and is defined by hyperandrogenic chronic anovulation with the exclusion of secondary causes, such as congenital adrenal hyperplasia or an androgen secreting tumor. PCOS women are uniquely insulin resistant. It is estimated that 5% of the female population is affected. The underlying genetic defect in insulin action is unknown. Obesity aggravates the underlying predisposition to insulin resistance. Diagnostic criteria which focus on menstrual irregularity are more likely to identify insulin resistant women. About 40% of PCOS women display glucose intolerance (either impaired glucose tolerance or type 2 diabetes) in response to an oral glucose challenge. Additionally women display multiple other risk factors for cardiovascular disease including dyslipidemia and elevated circulating inflammatory markers. The lack of a clear etiologic mechanism to the syndrome has led in the past to a multitude of symptom-oriented treatments with few therapies improving all aspects of the endocrine syndrome of PCOS. Recently treatments resulting in improved insulin sensitivity, either through weight loss/exercise programs or pharmaceutical, have been shown to improve both the endocrine and metabolic abnormalities in the syndrome. Anti-diabetic agents in PCOS have been examined in a number of randomized studies which have shown a treatment benefit. Further indications for these agents such as the prevention of pregnancy loss or the conversion to type 2 diabetes still need to be investigated in properly designed studies.

Adult↗

PubMed2002

Pfiesteria complex organisms and human illness.

BACKGROUND: Pfiesteria piscicida and look-alike dinoflagellates are collectively known as Pfiesteria complex organisms (PCOs). The purposes of this paper are to evaluate the threat that PCOs pose to human health and to clarify some common misconceptions concerning these organisms. METHODS: References about P piscicida and PCOs were identified and reviewed using MEDLINE, Sea Grant databases, and other sources obtained from various Internet sites. RESULTS: Researchers exposed to aerosols of water containing P piscicida in a laboratory setting exhibited a variety of symptoms, including reversible cognitive impairment and loss of short-term memory. This led to multiple biologic, animal model, and epidemiologic studies that are reviewed and discussed. CONCLUSIONS: Exposure to P piscicida and possibly other PCOs can cause human illness. Until further isolation and purification of toxins from PCOs allows for development of tests to detect these toxins, predicting and documenting toxic PCO fish kills as well as potential PCO-related illness will be difficult.

Animals↗

PubMedDate not supplied

Evaluation of tumor necrosis factor alpha production in ex vivo short term cultured whole blood from women with polycystic ovary syndrome.

In mammals, the pleiotropic biological functions of tumor necrosis factor alpha (TNF-alpha) may include important effects on human reproductive physiology. Thus, chronic anovulation, oligo or amenorrhea, infertility, hyperandrogenism, obesity, insulin resistance and increased TNFalpha serum levels have been observed in women affected by polycystic ovary syndrome (PCOS). Whole blood short - term cell cultures (WBSC) are simple systems where the capacity to produce TNF-alpha by circulating leukocytes, mainly of the macrophage/monocyte lineage, can be accurately quantified. Given the relevance of monocytes/macrophages in the production of TNF-alpha, in this study, in a control-case approach, WBSC from women with PCOS were analyzed in their basal and lipolysaccharide (LPS)- stimulated capacity to produce the cytokine. These measurements did not correlate with the increased serum levels of the cytokine and the normal levels of cortisol, found in PCOS women. Increased serum TNF-alpha levels in PCOS women correlated positively with body mass index and negatively with insulin sensitivity. In spite of the increased serum TNF-alpha levels in PCOS women, basal and LPS stimulated production of the cytokine, by the ex vivo WBSC from these patients, were within normal values.

Adolescent↗

PubMed2002

[Effect of insulin in polycystic ovary syndrome].

BACKGROUND: Polycystic ovary syndrome (PCOS) has been accompanied by insulin resistance. The aim of this study was to compare the insulin action between thin and obese women with PCOS and to analyse its relationship to serum concentration of selected hormones. METHODS AND RESULTS: Total number of 32 women with PCOS between them there were 22 thin and 10 obese subjects was examined in this study. Control group consisted of 21 nonobese healthy women. The insulin action was determined by euglycemic hyperinsulinemic clamp. Normal insulin action found in the group of thin women with PCOS was comparable with that in healthy controls whereas insulin resistance was observed in obese ones. An inverse relationship was found between insulin action and body mass index (r = 0.62, p < 0.01). By using HOMA index this relationship to BMI was on the borderline significance. No correlation was observed between insulin action and serum hormone concentrations (testosterone, androstendione, LH, FSH) but sex hormone binding globulin (SHBG) positively correlated with parameters of insulin action (r = 0.50-0.54). CONCLUSIONS: The insulin action may be normal in thin women with PCOS whereas obesity and other not yet disclosed factors influence development of insulin resistance in women with polycystic ovary syndrome.

Adult↗

PubMedDate not supplied

[Remission of polycystic ovary syndrome associated with valproic acid in an epileptic female].

INTRODUCTION: In the epileptic female there is an increase in the number of disorders affecting the reproductive function, which on some occasions can be related to a polycystic ovary syndrome (PCOS). The Finnish school showed an increase in the number of cases of PCOS among females receiving antiepileptic therapy with valproic acid over a long period of time, which can affect up to 43% of the patients being treated. Such a high incidence has not been confirmed in other European series and it is likely that specific ethnic characteristics exert an influence on the results. We examine the possibility that PCOS constitutes a secondary chronic side effect of using valproic acid (VPA) and, as such, is reversible if the antiepileptic therapy is modified following its detection. CASE REPORT: Female, aged 21, who developed PCOS during the course of therapy with VPA, which remitted after changing the treatment to lamotrigine. The clinical signs that have to act as a warning of the possible presence of PCOS in epileptic patients are the appearance of menstrual disorders or signs of virilisation, such as hirsutism and android obesity.

Adolescent↗

PubMed2003

Elevated serum TNF-alpha levels in normal-weight women with polycystic ovaries or the polycystic ovary syndrome.

OBJECTIVE: To compare the serum tumor necrosis factor-alpha (TNF-alpha) levels in nonobese women with those in women with polycystic ovaries (PCO) and polycystic ovary syndrome (PCOS) and healthy controls. STUDY DESIGN: Twenty-one sonographically and biochemically diagnosed women with PCOS, 19 with PCO and 14 healthy women were recruited for the study. Serum TNF-alpha levels were measured in all three groups. Insulin and glucose serum concentrations were analyzed before and after a 75-g oral glucose tolerance test in all samples. The serum TNF-alpha, glucose and insulin levels were compared in PCOS, PCO and controls. RESULTS: Serum TNF-alpha levels were similar in the PCOS and PCO groups (23.67 +/- 5.58 and 13.58 +/- 1.34 pg/mL, respectively) and significantly higher than in the control group. Serum TNF-alpha levels did not significantly correlated with body mass index, serum total testosterone, LH, DHEAS, fasting glucose and fasting insulin levels or glucose and insulin area under the curve values in the three groups. CONCLUSION: We found similar TNF-alpha levels in patients with PCOS and with PCO; however, there was no correlation between the TNF-alpha and insulin, glucose and androgen levels in the study.

Adolescent↗

PubMed1992

11 beta-hydroxyandrostenedione in plasma, follicular fluid, and granulosa cells of women with normal and polycystic ovaries.

OBJECTIVE: To investigate the role of 11 beta-hydroxylase/11 beta-hydroxyandrostenedione (11-OHA) in the ovarian metabolism of androgens in women with polycystic ovaries (PCO) and its associated syndrome (PCOS). DESIGN: Prospective observational study examining the plasma and follicular fluid (FF) concentrations of 11-OHA, testosterone (T), androstenedione (A), and cortisol from women with PCOS and normal women in spontaneous and stimulated cycles. SETTING: The study was carried out in an infertility department and an endocrine research laboratory of a university hospital. PATIENTS: Five groups of women were studied. Blood was taken from 53 women with PCOS and 13 normal controls. Follicular fluid and blood was obtained from 51 women with stimulated cycles undergoing in vitro fertilization embryo-transfer (IVF-ET), 27 of whom had PCO and 24 had normal ovaries. Follicular fluid alone was also taken from 13 women with normal ovaries undergoing laparoscopies. INTERVENTIONS: Clear FF was obtained for analysis during oocyte collection. Granulosa cells (GCs) were obtained from seven women with PCO undergoing IVF-ET and were incubated with radiolabeled substrates. RESULTS: Circulating concentrations of T and 11-OHA were higher in women with PCOS compared with women with normal ovaries. In women with PCO receiving exogenous gonadotropin, only 11-OHA concentrations were higher. Concentrations of all steroids measured were higher in FF than plasma, with plasma 11-OHA concentrations 4 to 12 times higher in FF. Significantly lower concentrations of 11-OHA were found in the FF of women with PCO compared with women with normal ovaries. There was no evidence of 11 beta-hydroxylation of A by GCs. CONCLUSIONS: Although the raised plasma concentrations of 11-OHA may reflect hyperandrogenism in PCOS and lower 11-OHA concentrations in FF in women with PCO suggest abnormal androgen metabolism, neither can be regarded as a marker for this syndrome.

Androstenedione↗

PubMed2003

Polycystic ovary syndrome and ovulation induction.

Polycystic ovary syndrome (PCOS) is likely the most common cause of anovulatory infertility. Although many options are available for ovulation induction in these patients, there is currently no evidence-based algorithm to guide the initial and subsequent choices of ovulation induction methods. In obese women with PCOS, mild to moderate weight loss results in improvement of ovulatory dysfunction, and should be advocated at the onset of the evaluation. Clomiphene citrate is currently the 1st line medical therapy for ovulation induction. Glucocorticoids do not result in consistent ovulation and have significant side effects. Exogenous pulsatile GnRH treatment has low ovulation and pregnancy rates with a high risk of miscarriage. The most commonly used medical agents for ovulation induction in clomiphene-resistant women with PCOS are parenteral gonadotropins. Various gonadotropin preparations and different protocols are available; however the risk of multiple pregnancy and ovarian hyperstimulation is high with gonadotropin therapy. The frequent association between PCOS and insulin resistance has prompted recent studies on the effect of insulin-sensitizing agents on spontaneous and as an adjuvant to conventional ovulation induction therapies. Overall, the improvement in ovulation with insulin sensitizing drugs is modest, and unresolved issues such as variability in ovarian response remain to be addressed in future studies. Nevertheless, these agents may be beneficial in a subset of PCOS patients. Surgical ovulation induction methods such as ovarian diathermy have been reported to be moderately effective. However, due to the inherent associated risks and unknown effect on long-term reproductive potential, this modality should be reserved for patients who are clomiphene-resistant and unable or unwilling to proceed to gonadotropin therapy.

Female↗

PubMed2004

The treatment of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women in reproductive age. As for the treatment of this disease the lack of a clear etiology for PCOS has led to a symptom-orientated treatment. However, the overall aims of treatment are to induce ovulation for women desiring conception, to reduce androgen levels, to reduce body weight and to reduce long-term health risks of diabetes mellitus and cardiovascular disease. Clomiphene citrate (CC) is recommended as first line treatment for induction of ovulation in patients with PCOS by virtue of its efficacy, safety, and ease of administration. Alternatives for CC-resistant patients include gonadotrophin therapy (better with low-dose step-up protocol) and laparoscopic ovarian diathermy. Recently, recombinant FSH (rFSH) has been introduced in clinical practice and it seems more effective than urinary FSH as demonstrated by a significantly higher number of follicles recruited and embryos obtained with a shorter treatment period. The addition of GnRH-agonist to the stimulation protocol for women affected by PCOS could reduce premature luteinization and increase cycle fecundity. Other drugs under investigation are metformin and cabergoline. Hirsutism is the manifestation of hyperandrogenemia in PCOS. The primary goal of the treatment of hirsutim is central or peripheral androgen suppression using 3 groups of drugs: inhibitors of androgen production (oral contraceptives, GnRH analogues), peripheral androgen blockers (cyproterone acetate, flutamide, finasteride and spironolactone), and insulin-sensitizing agents (metformin). Weight reduction and exercise could also improve not only menstrual disturbances and infertility, but also insulin resistance and its adverse metabolic con-sequences.

Adult↗