Metabolic and hormonal changes induced by pioglitazone in polycystic ovary syndrome: a randomized, placebo-controlled clinical trial.
BACKGROUND
Polycystic ovary syndrome (PCOS) is characterized by insulin resistance, compensatory hyperinsulinemia, increased prevalence of impaired glucose tolerance, and increased ovarian androgen biosynthesis.


OBJECTIVE
The aim of the study was to evaluate effects of pioglitazone on whole body insulin action and ovarian androgen biosynthesis in PCOS.


METHODS
We performed a randomized placebo-controlled trial.


METHODS
The study was conducted at the Special Diagnostic and Treatment Unit of the Veterans Affairs Medical Center, San Diego, and the University of California, San Diego, General Clinical Research Center.


METHODS
A total of 23 subjects with PCOS were evaluated at baseline and end of treatment. Six age- and body mass index-matched women without PCOS were normal controls for baseline evaluation.


METHODS
Subjects with PCOS were randomized to oral placebo or pioglitazone 45 mg daily for 6 months.


METHODS
The primary outcome measures were whole body insulin action as measured by hyperinsulinemic euglycemic clamp and ovarian androgen biosynthesis as measured by leuprolide-stimulated production of 17-hydroxyprogesterone (17-OHP).


RESULTS
Compared with placebo, pioglitazone treatment significantly improved multiple measures of insulin action, including glucose disposal rate (P < 0.01), 2-h glucose during 75-g oral glucose tolerance test (P < 0.01), area under the curve glucose during oral glucose tolerance test (P < 0.01), serum adiponectin (P < 0.01), and fasting hyperinsulinemia (P < 0.01). Compared to placebo, pioglitazone treatment reduced the increment of leuprolide-stimulated 17-OHP (P < 0.02). Improvements in glucose disposal rate correlated with reductions in 17-OHP stimulation (P < 0.02).


CONCLUSIONS
Compared to placebo, pioglitazone treatment in PCOS was associated with improvements in insulin action and glucose homeostasis and ameliorated the hyperandrogenic ovarian response.
Aroda
Vanita R
VR
Veterans Affairs San Diego Healthcare System, San Diego, California, USA. vanita.aroda@medstar.net
Ciaraldi
Theodore P
TP
Burke
Paivi
P
Mudaliar
Sunder
S
Clopton
Paul
P
Phillips
Susan
S
Chang
R Jeffrey
RJ
Henry
Robert R
RR
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D018149:Glucose Intolerance / Q000378:metabolism; D005951:Glucose Tolerance Test; D012739:Gonadal Steroid Hormones / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000077205:Pioglitazone; D010919:Placebos; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use*
D001786:Blood Glucose; D012739:Gonadal Steroid Hormones; D007004:Hypoglycemic Agents; D007328:Insulin; D010919:Placebos; D045162:Thiazolidinediones; D000077205:Pioglitazone