Disparate effects of pharmacotherapy on plasma plasminogen activator inhibitor-1 levels in women with the polycystic ovary syndrome.
OBJECTIVE
Polycystic ovary syndrome (PCOS) is characterized by obesity and insulin resistance (IR), which result in elevated plasminogen activator inhibitor-1 (PAI-1) levels. We aimed to assess the changes in PAI-1 levels in PCOS during treatment with metformin and during weight loss.


METHODS
Twenty-three normal weight women with PCOS were given metformin 850 mg bid for 6 months. Fifty overweight/obese women with PCOS were prescribed an energy-restricted diet, were instructed to exercise and were randomized to orlistat 120 mg tid or sibutramine 10 mg qd for 6 months.


RESULTS
In normal weight women, treatment with metformin reduced the body mass index (BMI) and circulating androgens, improved markers of IR and lowered PAI-1 levels. In overweight/obese women, sibutramine and orlistat yielded comparable reductions in BMI and markers of IR. In contrast, the effects on the free androgen index (FAI) differed (p=0.027): sibutramine reduced the FAI (p=0.005), whereas orlistat had no effect. The effects of sibutramine and orlistat on PAI-1 levels also differed (p=0.042): sibutramine reduced PAI-1 levels (p<0.001), whereas orlistat had no effect.


CONCLUSIONS
Metformin and sibutramine, but not orlistat, reduce PAI-1 levels in PCOS. The reduction in circulating androgens during metformin and sibutramine treatment might be implicated in this decline.
Division of Endocrinology and Human Reproduction, Second Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece.
Ekaterini
E
Koiou
First Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece.
Konstantinos
K
Tziomalos
Division of Endocrinology and Human Reproduction, Second Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece.
Ilias
I
Katsikis
Division of Endocrinology and Human Reproduction, Second Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece.
Dimitrios
D
Delkos
Division of Endocrinology and Human Reproduction, Second Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece.
Elena A
EA
Tsourdi
Division of Endocrinology and Human Reproduction, Second Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece.
Dimitrios
D
Panidis
D000293:Adolescent; D000328:Adult; D000728:Androgens / Q000097:blood; D019440:Anti-Obesity Agents / Q000494:pharmacology / Q000627:therapeutic use; D015897:Comorbidity; D003503:Cyclobutanes / Q000494:pharmacology* / Q000627:therapeutic use; D004038:Diet, Reducing; D004358:Drug Therapy; D015444:Exercise; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007783:Lactones / Q000494:pharmacology* / Q000627:therapeutic use; D008687:Metformin / Q000494:pharmacology* / Q000627:therapeutic use; D009765:Obesity / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology; D000077403:Orlistat; D050177:Overweight / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011085:Polycystic Ovary Syndrome / Q000097:blood* / Q000188:drug therapy* / Q000453:epidemiology; D016896:Treatment Outcome; D055815:Young Adult
D000728:Androgens; D019440:Anti-Obesity Agents; D003503:Cyclobutanes; D007004:Hypoglycemic Agents; D007783:Lactones; D017395:Plasminogen Activator Inhibitor 1; D008687:Metformin; D000077403:Orlistat; C058254:sibutramine