The Role of Insulin Resistance in PCOS
The Role of Insulin Resistance in PCOS
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.
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.
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.