[Effects of metformin on the plasminogen activator system, endocrine, metabolic profiles in patients with polycystic ovary syndrome and clomiphene resistant cases].
OBJECTIVE
To assess the therapeutic effects of metformin in patients with polycystic ovary syndrome (PCOS) and clomiphene (CC) resistant cases.


METHODS
Thirty one patients with PCOS, including 8 CC resistant cases were studied. Serum tissue-type plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1), menstrual and reproductive hormone patterns, lipid and glucose metabolic parameters, bilateral ovarian volume, side effects were determined before and after oral administration of metformin 375 mg three times daily for 12 - 16 weeks. Metformin and CC were co-administered in CC resistant cases who had not restored their menstrual cycle after the treatment with metformin alone for investigating ovulation rate. In the remaining non-CC resistant metformin failure cases the dosage of metformin was incrersed to 500 mg three times daily for investigating menstrual cycle.


RESULTS
After administration of metformin for 12 - 16 weeks, serum PAI-1, luteinizing hormone (LH)/follicle stimulating hormone (FSH) ratio, androstenedione, testosterone, low density liproprotein-cholesterol, total cholesterol, fasting insulin concentration and response to oral glucose tolerant test (OGTT), diastolic blood pressure decreased significantly, while FSH and estradiol levels increased, bilateral ovarian volume shrunk significantly (P < 0.05 - 0.01). Body mass index, waist hip ratio, LH, tPA, systolic blood pressure, prolactin, fasting glucose concentration and response to OGTT, high density liproprotein-cholesterol, apoliprotein A, apoliprotein B, triglycerides levels did not change significantly (P > 0.05). Nineteen out of thirty one cases (61%) had restoration of menstrual cycle, 2 became pregnant. In 6 CC resistant cases who had not restoration of menstrual cycle after the treatment with metformin, CC induced ovulation in 12/18 cycles or 5/6 cases and 2 pregnancies achieved. In others 6 metformin failure cases the dosage of metformin was increased to 500 mg three times daily, one restored menstrual cycle and became pregnant.


CONCLUSIONS
Metformin may ameliorate the PAI-1, endocrine, metabolic profiles and menstrual abnormalities and improve the ovarian response to CC in CC resistant cases. Metformin provides a safe and effective approach to the treatment of PCOS.
Song
Juxiang
J
Department of Obstetrics and Gynecology, People's Hospital of Shanxi Province, Taiyuan 030001, China.
Shen
Hongmin
H
Li
Jianye
J
Huang
Zhenguo
Z
Zhang
Yuhua
Y
D000328:Adult; D000735:Androstenedione / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D002996:Clomiphene / Q000627:therapeutic use*; D004351:Drug Resistance; D004958:Estradiol / Q000097:blood; D005260:Female; D005300:Fertility Agents, Female / Q000378:metabolism / Q000627:therapeutic use; D005640:Follicle Stimulating Hormone / Q000097:blood; D006728:Hormones / Q000097:blood*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008687:Metformin / Q000627:therapeutic use*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D010960:Plasminogen Activators / Q000097:blood*; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D011247:Pregnancy; D013739:Testosterone / Q000097:blood; D016896:Treatment Outcome
D001786:Blood Glucose; D008078:Cholesterol, LDL; D005300:Fertility Agents, Female; D006728:Hormones; D007004:Hypoglycemic Agents; D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; D002996:Clomiphene; D013739:Testosterone; D000735:Androstenedione; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D008687:Metformin; D002784:Cholesterol; D010960:Plasminogen Activators