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At least 127 records · Page 7Linked to original sources

PubMed2003

The effect of metformin treatment to ovarian response in cases with PCOS.

OBJECTIVE: To examine the effect of metformin therapy on ovarian response in clomiphene-resistant PCOS patients. DESIGN: Randomized prospective study. SETTING: Zeynep Kamil Hospital IVF Center. PATIENTS: Thirty-two female PCOS patients with clomiphene citrate resistance. INTERVENTIONS: Test group A received 2x850 mg/day metformin therapy for 8 weeks, followed by gonadotropin induction. Only gonadotropin induction was applied to Control group B. MAIN OUTCOME MEASURES: Total gonadotropin dosage, duration of gonadotropin therapy, estradiol level on HCG-day, number of follicles with >or=16 mm diameter, number of cases with hyperstimulation development, number of cancelled cycles, endometrial thickness on HCG-day, pregnancy outcome, multiple pregnancy rate. RESULTS: The total gonadotropin doses given to metformin-study group was significantly lower than the control group. In addition, duration of therapy, HCG level, plasma estradiol level on HCG-day in the study group was significantly lower than in the control group. CONCLUSIONS: Metformin therapy has led to a higher pregnancy outcome, as well as to a decrease in hyperstimulation risk, cycle cancellations, and multiple pregnancy rates with a lower gonadotropin dosage.

Adult↗

PubMed2004

The pathophysiology of polycystic ovary syndrome: trying to understand PCOS and its endocrinology.

The pathophysiology of the polycystic ovary syndrome (PCOS) encompasses inherent ovarian dysfunction that is strongly influenced by external factors, such as disturbances of the hypothalamic-pituitary-ovarian axis and hyperinsulinaemia. Exaggerated gonadotrophin releasing hormone (GnRH) pulsatility results in hypersecretion of luteinising hormone (LH), which has effects both on ovarian androgen production and oocyte development. Disturbed ovarian-pituitary and hypothalamic feedback accentuates the 0gonadotrophin abnormalities. Hyperinsulinaemia is secondary both to insulin resistance at the periphery and to abnormal pancreatic beta cell function. PCOS runs in families and a number of genetic abnormalities appear to result in features of the syndrome and account for the heterogeneity of the symptoms. Environmental influences, such as nutrition and lifestyle, further influence expression of the syndrome.

Female↗

PubMed2002

Hyperandrogenism, postprandial hyperinsulinism and the risk of PCOS in a cross sectional study of women with epilepsy treated with valproate.

Among a sample of 43 women with epilepsy treated for at least 2 years with valproate (n=22) or other antiepileptic drugs (AEDs) (n=21), polycystic ovary syndrome (PCOS) was diagnosed in three women, two of them were treated with valproate. Although the rate of PCOS and of menstrual disturbances, weight body mass index (BMI) and waist to hip ratio as well as fasting blood glucose levels, fasting insulin, proinsulin and C-peptide values was similar in this small sample of women treated with valproate and other AEDs, valproate exposure was associated with higher androgen levels, higher postprandial (pp) insulin and proinsulin levels, as well as lower cholesterol and low density lipoprotein (LDL) cholesterol levels. The pronounced increase in pp insulin levels during VPA treatment may indicate an effect of the fatty acid derivate VPA on pancreatic islet cells.

Adult↗

PubMed2003

In vitro fertilization in the PCOS patient: clinical considerations.

Of all the patients undergoing in vitro fertilization, the patient with polycystic ovary syndrome (PCOS) is probably the most challenging. This is due to the fact that the majority of patients exhibit exaggerated responses to exogenous gonadotropins, frequently leading to an increased rate of cancellation of a treatment cycle. Even those who proceed to oocyte retrieval, and in spite of an increased number of oocytes retrieved, poor fertilization rates may be encountered, probably secondary to an increased rate of oocyte immaturity. To compound the problem further, even fertilized eggs in these patients, generally speaking, may show lower cleavage rates, and this leads to decreased implantation and pregnancy rates. In addition, these are patients who exhibit a much higher incidence of ovarian hyperstimulation syndrome, which puts the patient's health at great risk. Possibly, some of these problems may be inherent in the PCOS ovary. Nevertheless, it is possible that modifications of clinical protocols may improve outcome.

Embryo, Mammalian↗

PubMed2004

The effect of combination therapy with metformin and combined oral contraceptives (COC) versus COC alone on insulin sensitivity, hyperandrogenaemia, SHBG and lipids in PCOS patients.

BACKGROUND: Neither oral contraceptives (COC) nor metformin are an optimal modality for the long-term treatment of polycystic ovary syndrome (PCOS). The aim of this study was to evaluate whether a combination of both is beneficial over COC monotherapy. METHODS: Altogether, 30 women were included in the study and 28 finished the protocol. The patients were randomly assigned to two groups treated with either COC (COC group) or COC and metformin (1500 mg/day) (METOC group) for 6 months. Anthropometric parameters, androgens, lipids, fasting insulin, glucose and sex hormone binding globulin (SHBG) concentrations were measured before and at the end of the sixth cycle of treatment. The insulin sensitivity index was evaluated using the euglycaemic clamp. RESULTS: There were no significant changes in anthropometric parameters, fasting glucose or insulin sensitivity in either group. Total testosterone, free androgen index, androstenedione and dehydroepiandrosterone decreased and SHBG increased significantly in both groups. When comparing the effect of both treatments, only a more pronounced decrease in free androgen index was found in the METOC group. CONCLUSIONS: Adding metformin slightly modified the treatment effect of COC, causing a more significant decrease in the free androgen index but having no additional positive impact on lipids, insulin sensitivity, SHBG or testosterone. The available data do not offer enough evidence to advocate the standard use of combined treatment in PCOS. Whether the combination might be beneficial for specific subgroups of patients is of further interest.

Adult↗

PubMed2006

Follow-up study of two sisters with type A syndrome of severe insulin resistance gives a new insight into PCOS pathogenesis in relation to puberty and pregnancy outcome: a case report.

We report two sisters with profound insulin resistance associated with a novel heterozygous missense mutation in exon 19 (His1130Arg) of the insulin receptor gene. The eldest was seen after puberty at age 15 and she presented a severe form of polycystic ovary syndrome (PCOS) with biological hyperandrogenism (HA) mimicking a virilizing tumour. However, she has been able to ovulate under clomiphene citrate (CC) and to achieve two uneventful pregnancies. The patient had no glucose tolerance abnormality during pregnancies. The outcome of pregnancy was good except for a low birthweight. The youngest sister was seen earlier in life (at age 11) before puberty. First, she developed polycystic ovaries (PCO), seen under ultrasound scan, and later also developed full PCOS. This second finding gave us the opportunity to observe that PCO developed before and at the beginning of puberty despite low LH levels. We postulate that the development of PCO was the consequence of an LH-independent intra-ovarian HA likely induced by the severe hyperinsulinism in the context of genetic abnormalities.

Adolescent↗

PubMedDate not supplied

Long-term health consequences of PCOS.

The prevalence of cardiovascular risk factors, insulin resistance/diabetes and/or uterine pathology appears to be increased in women with polycystic ovarian syndrome (PCOS), although more outcome studies are necessary to determine incidence. Data pertaining to some of the potential long-term health consequences associated with PCOS are summarized. Medline, Current Contents and PubMed were searched for studies from the time of our original interest in this issue in 1980 to the present. The review is limited to published human data. The current literature indicate that women with this syndrome cluster risk factors for premature morbidity and mortality. Large multi-site co-operative studies are necessary to evaluate the long-term health outcomes.

Diabetes Mellitus↗

PubMed2003

Update: The pathogenesis and treatment of PCOS.

Irregular menstrual cycles, acne, and hirsutism often cause women to present to a primary care setting. This article demonstrates how to take a careful history, perform a physical examination, and order the laboratory tests necessary to diagnose polycystic ovary syndrome (PCOS). Managing PCOS complaints and maintaining important health issues are also addressed, as well as when to refer to a specialist.

Acne Vulgaris↗

PubMed2005

Reproductive function and risk for PCOS in women treated for bipolar disorder.

INTRODUCTION: This study examined the reproductive function and prevalence of polycystic ovary syndrome (PCOS) in women with bipolar disorder taking antimanic medications. METHOD: Women aged 18-45 treated for bipolar disorder and not taking steroid contraceptives were recruited to complete questionnaires about their menstrual cycle and to provide blood samples for measurement of a range of reproductive endocrine and metabolic hormone levels. Eighty women participated in completing the questionnaires and 72 of them provided blood samples. RESULTS: Fifty-two of the 80 women (65%) reported current menstrual abnormalities, 40 of which (50%) reported one or more menstrual abnormalities that preceded the diagnosis of bipolar disorder. Fifteen women (38%) reported developing menstrual abnormalities since treatment for bipolar disorder, 14 of which developed abnormalities since treatment with valproate (p = 0.04). Of the 15 patients reporting menstrual abnormalities since starting medication, 12 (80%) reported changes in menstrual flow (heavy or prolonged bleeding) and five (33%) reported changes in cycle frequency. No significant differences were observed between women receiving or not receiving valproate in mean levels of free or total serum testosterone levels. This was true for the total sample and for the sub-group without preexisting menstrual problems. However, within the valproate group, duration of use was significantly correlated with free testosterone levels (r = 0.33, p = 0.02). Three of the 50 women (6%) taking VPA, and 0% of the 22 taking other antimanic medications, met criteria for PCOS (p = 0.20). Other reproductive and metabolic values outside the normal range across treatment groups included elevated 17 alpha-OH progesterone levels, luteinizing hormone: follicle-stimulating hormone ratios, homeostatic model assessment (HOMA) values, and low estrogen and dehydroepiandrosterone sulfate (DHEAS) levels. Preexisting menstrual abnormalities predicted higher levels of 17 alpha-OH progesterone, free testosterone, and estrone as well as development of new menstrual abnormalities. Body mass index (BMI) was significantly positively correlated with free testosterone levels and insulin resistance (HOMA) across all subjects, regardless of medication used. CONCLUSIONS: Rates of menstrual disturbances are high in women with bipolar disorder and, in many cases, precede the diagnosis and treatment for the disorder. Treatment with valproate additionally contributes significantly to the development of menstrual abnormalities and an increase in testosterone levels over time. A number of bipolar women, regardless of type of medication treatment received, have reproductive and metabolic hormonal abnormalities, yet the etiology of such abnormalities requires further study. Women with preexisting menstrual abnormalities may represent a group at risk for development of reproductive dysfunction while being treated for bipolar disorder.

Adolescent↗

PubMed2006

Insulin-lowering agents inhibit synthesis of testosterone in ovaries of DHEA-induced PCOS rats.

BACKGROUND: Insulin-lowering agents are reported to be useful in treating polycystic ovary syndrome (PCOS) anovulation. It has been suggested that lower insulin levels secondarily affect ovarian tissue, although the direct mechanism of action has not yet been verified. Here we investigated if these agents directly affect the ovary. METHODS: Thirty female Wister rats were studied. Six control rats were injected subcutaneously with 0.2 ml sesame oil, while 24 rats used as PCOS models were injected subcutaneously with dehydroepiandrosterone (DHEA) and divided into four groups. Six rats were injected with only DHEA, while the remaining 18 rats received metformin, pioglitazone or troglitazone. The ovaries were immunohistochemically stained with anti- testosterone and anti-17beta-HSD antibodies, and then evaluated for morphological changes. RESULTS: In the DHEA administration group, the number of atretic follicles significantly increased compared to that of control rats. The insulin-lowering agents did not improve the multicystic appearance. Serum testosterone concentrations significantly increased with DHEA administration, but the increase was inhibited by oral administration of insulin-lowering agents. Testosterone deposits in ovarian tissue were also reduced by feeding rats insulin-lowering agents. CONCLUSION: Insulin-lowering agents affected ovarian tissue by inhibiting testosterone biosynthesis in vivo.

17-Hydroxysteroid Dehydrogenases↗

PubMed1990

A study on follicle stimulation and ovulation induction in polycystic ovary syndrome (PCOS).

The present study was undertaken to verify the efficacy of preparations for inducing follicular maturation and ovulation in patients with polycystic ovary syndrome (PCOS). Successful induction of ovulation in patients with PCOS was observed in treatment cycles with daily injections or pulsatile subcutaneous administration of human menopausal gonadotropin (hMG), the combination of clomiphene citrate and bromocriptine, or the combination of clomiphene citrate and hMG. The incidence of ovarian hyperstimulation syndrome varied with the different clinical conditions in which ovulation was induced, the types of preparations administered, and the doses and schedules administered.

Bromocriptine↗

PubMed2006

Insulin resistance, the metabolic syndrome, diabetes, and cardiovascular disease risk in women with PCOS.

Polycystic ovary syndrome is the most common endocrinopathy of reproductive aged women affecting 6-10% of the population. Traditionally considered a reproductive disorder manifesting as chronic anovulation, infertility, and hyperandrogenism, management has primarily focused on short-term reproductive outcomes. Recently, however, significant metabolic aspects in conjunction with longer-term health sequealae of PCOS have been recognized. The metabolic features are primarily related to underlying insulin resistance (IR), which is now understood to play an important role in both the pathogenesis and long-term sequelae of PCOS.

Cardiovascular Diseases↗

PubMed2001

Benefit of FSH priming of women with PCOS to the in vitro maturation procedure and the outcome: a randomized prospective study.

The aim of this study was to determine whether the rates of in vitro oocyte maturation, fertilization and cleavage, as well as implantation rate and pregnancy rate, could be improved by low-dose priming with FSH in vivo before retrieval of immature oocytes in patients with polycystic ovary syndrome (PCOS). From March 1998 to June 2000, a total of 28 women underwent 36 completed treatment cycles, randomized sequentially in one of two groups. Women in group 1 (n = 12 cycles) received no stimulation and women in group 2 (n = 24 cycles) received 150 iu recombinant FSH day(-1) for 3 days, initiated on day 3 after menstruation. Aspiration was performed transvaginally between day 9 and day 17 in the unstimulated group and on day 8 or day 9 in the FSH-primed group after FSH deprivation for 2 or 3 days. All cumulus-enclosed oocytes of healthy appearance were matured in culture medium (TCM-199) in vitro for 28-36 h before intracytoplasmic sperm injection (ICSI). After oocyte retrieval the women were given oestradiol (6 mg day(-1)) and progesterone administration (300 mg day(-1)) was initiated 2 days later. Suitable embryos (maximum two embryos) were transferred on day 3 after ICSI. The percentage of oocytes reaching metaphase II was significantly higher (P < 0.05) in the FSH-primed group (59%, 92/156) compared with the non-primed group (44%, 36/81). There were no significant differences in the rates of oocyte fertilization and cleavage between these groups. No pregnancies were obtained in group 1 (0%, 0/12), whereas seven clinical pregnancies were obtained in group 2 (29%, 7/24) (P < 0.05). In group 2, 37 embryo transfers resulted in eight implantations (21.6%). Three healthy singleton children have been born at term; the remaining pregnancies ended with spontaneous abortions in the first trimester. These results indicate that priming with recombinant FSH before harvesting of immature oocytes from patients with PCOS may improve the maturational potential of the oocytes and the implantation rate of the cleaved embryos.

Adult↗

PubMed2001

Simplification of continuous infusion of glucose with model assessment in the evaluation of insulin resistance in women with PCOS.

Ninety-seven women with polycystic ovary syndrome (PCOS) were tested for insulin resistance and glucose tolerance by means of the continuous infusion of glucose with model assessment (CIGMA) test. The mean concentrations of glucose and insulin at 50, 55 and 60 min of glucose infusion were interpreted using a mathematical model of glucose and insulin homeostasis, and an insulin resistance index (IR1) was obtained. Using insulin and glucose values at 60 min only, a new insulin resistance index (IR2) was obtained using the same mathematical method. In addition, fasting insulin, fasting C-peptide, fasting glucose, fasting insulin:glucose ratio and fasting C-peptide:glucose ratio were also used to assess insulin resistance. There were significant correlations between IR1 and IR2, fasting glucose, fasting insulin, fasting insulin:glucose ratio, fasting C-peptide:glucose ratio. IR2 had the highest correlation with IR1 (r = 0.97, p < 0.001) and provided the best combination of sensitivity (82.9%), specificity (93.9%), positive predictive value (91.9%) and negative predictive value (86.8%). In conclusion, the simplified CIGMA test, using insulin and glucose concentration at 60 min of glucose infusion only, is a highly sensitive and specific measure of insulin sensitivity in women with PCOS.

Adult↗

PubMedDate not supplied

The changes of hormonal serum levels and ovulation/pregnancy rates after ovarian electrocautery in microlaparoscopy and laparoscopy in patients with PCOS.

OBJECTIVES: To compare the efficacy of ovarian electrocautery performed during microlaparoscopy and laparoscopy, basing on ovulation and pregnancy rates obtained within one year of follow-up. MATERIALS AND METHODS: Ovarian drillings, performed with the use of endoscopic methods, were carried out in 135 women with hormonal and ultrasound features of PCOS, aged 30-39 (average age 36 +/- 3.3). Laparoscopic ovarian electrocautery was carried out in 65 cases, whereas microlaparoscopic drilling was conducted in 70 cases. The obtained results were compared in regard to duration of the procedure and ovulation/pregnancy rates within one year of follow-up. Changes in hormonal profiles were also compared in both groups, measured in patients who did not get pregnant before, and 3 months after, the procedures. RESULTS: The difference in durations between the two studied procedures was statistically significant (19 +/- 3 min vs. 24 +/- 4.4 min; p<0.001). However, the ovulation and pregnancy rates did not differ significantly between the two groups (72% vs. 77.7%; p<0.5 and 19.4% vs. 20%; p<0.95, respectively). There were also similar trends in hormonal changes after microlaparoscopic and laparoscopic drilling. CONCLUSIONS: The efficacy of ovarian drilling in PCOS, estimated by ovulation and pregnancy rates within 12 months of follow-up is similar for microlaparoscopy and laparoscopy, as well as the trends in hormonal changes. Ovarian electrocautery is significantly longer in microlaparoscopy, but the difference in time is of no practical impact.

Adult↗

PubMedDate not supplied

The role of metformin in the treatment of polycystic ovary syndrome (PCOS).

Hyperinsulinemia is believed to be a key link in the enigmatic generation of the symptoms of polycystic ovarian syndrome (PCOS), which include anovulatory infertility and the skin stigmata induced by hyperandrogenism. Regression of these symptoms may be achieved by reducing the hyperinsulinemia. Metformin, an insulin-sensitizing agent, has been proven to be of clinical usefulness both in the short-term aiding of infertility treatments and, potentially, in the prevention of the long-term sequelae for patients with PCOS.

Androgen Antagonists↗

PubMed1998

Characterization of pulsatile secretion of gonadotropin and prolactin in women with normal menstrual cycle, secondary amenorrhea and polycystic ovary syndrome (PCOS).

To characterize the episodic fluctuations of serum LH, FSH and PRL in women with normally cycling, secondary amenorrhea and polycystic ovary syndrome (PCOS), four groups of women were studied: group I (N = 8) consisted of normal women in the follicular phase of the cycle; group II (N = 10) of women with secondary amenorrhea and positive progesterone withdrawal bleeding; group III (N = 8) of women with secondary amenorrhea and negative progesterone withdrawal bleeding; group IV (N = 9), women with polycystic ovary syndrome (PCOS). Blood samples were obtained at 15 minute intervals for 4 hours during one admission day. Ovarian steroids were measured to evaluate the baseline endocrine environment in each group. Distinct pulsatile fluctuations of serum LH, FSH and PRL were observed in all subjects. These pulses showed a high degree of coincidence in LH with FSH and LH with PRL in each group. However, the mean (+/- SD) frequencies of LH in group III and group IV were significantly lower (P < 0.01) and higher (P < 0.01) than in group I, respectively. The mean frequencies of FSH in groups III and IV were lower (P < 0.05), as compared with those of group I. The mean amplitude of LH in group IV was significantly higher (P < 0.001) than in group I. These results suggest that loss of the regulatory pulsatility of gonadotropin releases may be a contributory cause to anovulation and secondary amenorrhea. The concomitant pulsatile releases of gonadotropin and PRL are essential to reproductive function and their regulatory controls in the follicular phase may be mediated through a common neuroendocrine mechanism in normal and hypogonadal women.

Adult↗

PubMed2005

PCOS: an ovarian disorder that leads to dysregulation in the hypothalamic-pituitary-adrenal axis?

This review focuses on the role of the ovaries in the pathogenesis of the polycystic ovarian syndrome. In particular, the failure of follicular development, hypothalamo-pituitary dysregulation, alterations in adrenal steroid output and derangement of intermediary metabolism are discussed in the context of the ovaries. It is concluded that the central and adrenal alterations associated with PCOS are unlikely to be primary but rather are secondary to the events within the ovary.

Adrenal Glands↗