The Role of Insulin Resistance in PCOS

November 23, 2005 updated by: National Taiwan University Hospital

The Role of Insulin Resistance and Adiponectin in the Pathogenesis of Polycystic Ovary Syndrome

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 abnormality)(1). 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 women.Hyperinsulinemia appears to play a key pathogenic role in the ovarian androgen overproduction, because of the stimulatory effect of insulin on ovarian steroid production.

Study Overview

Status

Unknown

Conditions

Detailed Description

Because of the menstrual irregularity and the hirsutism/acne 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 and/or 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 amenorrhea/oligomenorrhea, 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 ethinylestradiol/cyproterone 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 Type

Observational

Enrollment

500

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Taiwan
      • Taipei, Taiwan, 100
        • Recruiting
        • National Taiwan University Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

10 years to 48 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Criteria for the definition of PCOS: (2 out of 3 in the following) Oligomenorrhea / chronic anovulation, defined as less than eight cycles of spontaneous menstrual period in one year.

Clinical and /or biochemical signs of hyperandrogenism Polycystic ovaries Exclusion of other aetiologies, such as congenital adrenal hyperplasia, androgen-secreting tumors, Cushing's syndrome

Exclusion Criteria:

  • ever received hormone therapy in the past 6 months, having pregnancy in the past 6 months, having acute illness found in the past 3 months, or having systemic diseases including autoimmune disease, malignancy, hepatic, renal or CVS disease, and ever received chemotherapy or immunosuppressive agents.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Taiwan University Hospital

Investigators

  • Principal Investigator: Yang Yu-Shih, M.D., PhD, Department of Obstetrics and Gynecology, NTUH

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2004

Study Completion

August 1, 2005

Study Registration Dates

First Submitted

September 12, 2005

First Submitted That Met QC Criteria

September 12, 2005

First Posted (Estimate)

September 15, 2005

Study Record Updates

Last Update Posted (Estimate)

November 24, 2005

Last Update Submitted That Met QC Criteria

November 23, 2005

Last Verified

October 1, 2004

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 9361701208
  • NSC 94-2314-B-002-195-

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Obesity

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Japan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe