Ignite Creation Date:
2024-05-05 @ 11:55 AM
Last Modification Date:
2024-10-26 @ 9:16 AM
Study NCT ID:
NCT00173043
Status:
UNKNOWN
Last Update Posted:
2005-11-24
First Post:
2005-09-12
Brief Title:
The Role of Insulin Resistance in PCOS
Sponsor:
National Taiwan University Hospital
Organization:
National Taiwan University Hospital
Study Overview
Official Title:
The Role of Insulin Resistance and Adiponectin in the Pathogenesis of Polycystic Ovary Syndrome
Status:
UNKNOWN
Status Verified Date:
2004-10
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Polycystic ovary syndrome PCOS phenotype can be structured into three components anovulation hyperandrogenism and the metabolic syndrome of which hyperinsulinemia secondary to insulin resistance is the central abnormality1 It is the most common endocrinologic disease seen in Gynecologic clinic The follicular excess in polycystic ovaries and the failure of selection of one dominant follicle contribute to the anovulation of PCOS The infertile PCOS female usually suffered from difficult ovulation induction and high risk of ovarian hyperstimulation syndrome because of extensive stimulation
PCOS is the main androgen disorder in women and has been suggested to be associated with a high risk of developing cardiovascular disease and type-2 diabetes In many PCOS patients overweight or central obesity is generally associated with increases in fasting insulin levels insulin resistance and glucose intolerance and has been identified as a target for new therapeutic strategy including early change in lifestyle
Insulin resistance defined as decreased insulin-mediated glucose utilization is commonly 10-25 found in the normal population In women with PCOS insulin resistance appears even more common up to 50 in both obese and non-obese womenHyperinsulinemia appears to play a key pathogenic role in the ovarian androgen overproduction because of the stimulatory effect of insulin on ovarian steroid production
PCOS is the main androgen disorder in women and has been suggested to be associated with a high risk of developing cardiovascular disease and type-2 diabetes In many PCOS patients overweight or central obesity is generally associated with increases in fasting insulin levels insulin resistance and glucose intolerance and has been identified as a target for new therapeutic strategy including early change in lifestyle
Insulin resistance defined as decreased insulin-mediated glucose utilization is commonly 10-25 found in the normal population In women with PCOS insulin resistance appears even more common up to 50 in both obese and non-obese womenHyperinsulinemia appears to play a key pathogenic role in the ovarian androgen overproduction because of the stimulatory effect of insulin on ovarian steroid production
Detailed Description:
Because of the menstrual irregularity and the hirsutismacne caused by hyperandrogenism the treatment of choice for PCOS in young teenagers is to given the oral contraceptive however such oral contraceptives fail to correct the endocrinometabolic anomalies and the excess of fat Therefore there are some alternative treatments as adding the novel progesterone which is claimed to have antimineralocorticoid and antiandrogenic activities or giving an insulin-sensitizing compound such as metformin These treatments were reported to be effective in changing the endocrinometabolic state and the adiposity of PCOS Besides they were also reported to have efficacy in aiding ovulation induction
PCOS is the main androgen disorder in women and has been suggested to be associated with a high risk of developing cardiovascular disease and type-2 diabetes In many PCOS patients overweight or central obesity is generally associated with increases in fasting insulin levels insulin resistance and glucose intolerance and has been identified as a target for new therapeutic strategy including early change in lifestyle
The plasma concentrations of adiponectin were lower in men than in women but were not different between pre- and postmenopausal women It suggests that androgen act to reduce plasma adiponectin concentration In animal experiment testosterone supplement reduced plasma adiponectin concentration in male mice In cultured 3T3-L1 adipocytes testosterone and 5α-DHT suppressed the secretion of adiponectin suggesting that androgen decreased plasma adiponectin concentration through its effect on adipocytes
Clinical andor biochemical signs of hyperandrogenism are one of the three diagnostic criteria defining the PCOS Hyperandrogenemia may cause hirsutism alopecia acne and also strongly affect the ovulatory function Some hormone therapy such as ethinylestradiol cyproterone and ethinlyestradiol drosipirenone were usually used to reduce the serum androgen level and correct the amenorrheaoligomenorrhea while its effect in improving the endocrine-metabolic state and the adiposity of PCOS was still undetermined Obese women with PCOS are known to have high serum concentrations of C-reactive protein CRP a marker of inflammation and cardiovascular risk factor metformin monotherapy reduces the CRP levels whereas combined treatment with ethinylestradiol and cyproterone-acetate raises CRP further Therefore I am interesting about how do the metformin and ethinylestradiolcyproterone acetate influence the serum adiponectin level
Insulin resistance defined as decreased insulin-mediated glucose utilization is commonly 10-25 found in the normal population In women with PCOS insulin resistance appears even more common up to 50 in both obese and non-obese women Criteria developed for defining a metabolic syndrome in PCOS includes components associated with insulin resistance syndrome including centripetal obesity hypertension fasting hyperglycemia and dyslipidemia Since serum adiponectin concentrations correlate inversely with the severity of insulin resistance was well established however the adiponectin levels in women with PCOS is still controversial and need further elucidation Such as Orio et al suggested that insulin sensitivity does not play any pivotal role in the control of adiponectin in PCOS women and Ducluzeau et al mentioned that glucose-to-insulin level is better than adiponectin in predicting insulin resistance in PCOS Besides adiponectin level reduced in obese women with PCOS was reported Currently only a clinical trial suggested that the oral contraceptives plus metformin may reduce the adipocytokine imbalance
Hyperinsulinemia appears to play a key pathogenic role in the ovarian androgen overproduction because of the stimulatory effect of insulin on ovarian steroid production The mechanism that allows the ovary to remain sensitive to insulin when classical target organs for insulin action liver fat and muscle exhibit insulin resistance was supported by the presence of phosphatidyl inositol 3 PI-3 kinase independent insulin signaling pathway in human ovarian cells theca and granulosa cell Insulin is proposed to directly stimulate activity of cytochrome P450c17α an enzyme involved in ovarian androgen synthesis that is found in thecal cells
PCOS is the main androgen disorder in women and has been suggested to be associated with a high risk of developing cardiovascular disease and type-2 diabetes In many PCOS patients overweight or central obesity is generally associated with increases in fasting insulin levels insulin resistance and glucose intolerance and has been identified as a target for new therapeutic strategy including early change in lifestyle
The plasma concentrations of adiponectin were lower in men than in women but were not different between pre- and postmenopausal women It suggests that androgen act to reduce plasma adiponectin concentration In animal experiment testosterone supplement reduced plasma adiponectin concentration in male mice In cultured 3T3-L1 adipocytes testosterone and 5α-DHT suppressed the secretion of adiponectin suggesting that androgen decreased plasma adiponectin concentration through its effect on adipocytes
Clinical andor biochemical signs of hyperandrogenism are one of the three diagnostic criteria defining the PCOS Hyperandrogenemia may cause hirsutism alopecia acne and also strongly affect the ovulatory function Some hormone therapy such as ethinylestradiol cyproterone and ethinlyestradiol drosipirenone were usually used to reduce the serum androgen level and correct the amenorrheaoligomenorrhea while its effect in improving the endocrine-metabolic state and the adiposity of PCOS was still undetermined Obese women with PCOS are known to have high serum concentrations of C-reactive protein CRP a marker of inflammation and cardiovascular risk factor metformin monotherapy reduces the CRP levels whereas combined treatment with ethinylestradiol and cyproterone-acetate raises CRP further Therefore I am interesting about how do the metformin and ethinylestradiolcyproterone acetate influence the serum adiponectin level
Insulin resistance defined as decreased insulin-mediated glucose utilization is commonly 10-25 found in the normal population In women with PCOS insulin resistance appears even more common up to 50 in both obese and non-obese women Criteria developed for defining a metabolic syndrome in PCOS includes components associated with insulin resistance syndrome including centripetal obesity hypertension fasting hyperglycemia and dyslipidemia Since serum adiponectin concentrations correlate inversely with the severity of insulin resistance was well established however the adiponectin levels in women with PCOS is still controversial and need further elucidation Such as Orio et al suggested that insulin sensitivity does not play any pivotal role in the control of adiponectin in PCOS women and Ducluzeau et al mentioned that glucose-to-insulin level is better than adiponectin in predicting insulin resistance in PCOS Besides adiponectin level reduced in obese women with PCOS was reported Currently only a clinical trial suggested that the oral contraceptives plus metformin may reduce the adipocytokine imbalance
Hyperinsulinemia appears to play a key pathogenic role in the ovarian androgen overproduction because of the stimulatory effect of insulin on ovarian steroid production The mechanism that allows the ovary to remain sensitive to insulin when classical target organs for insulin action liver fat and muscle exhibit insulin resistance was supported by the presence of phosphatidyl inositol 3 PI-3 kinase independent insulin signaling pathway in human ovarian cells theca and granulosa cell Insulin is proposed to directly stimulate activity of cytochrome P450c17α an enzyme involved in ovarian androgen synthesis that is found in thecal cells
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NSC 94-2314-B-002-195- | None | None | None |