Early effects of metformin in women with polycystic ovary syndrome: a prospective randomized, double-blind, placebo-controlled trial.
BACKGROUND
Metformin is successfully used in the treatment of cycle disorders and anovulation in women with polycystic ovary syndrome (PCOS). No data of the exact point and the impact of insulin resistance (IR) on metformin's efficacy exist.


OBJECTIVE
The objective of the study was to evaluate the early potential effects of metformin treatment, their time of onset, and the role of IR on metformin's efficacy.


METHODS
This was a prospective randomized, double-blind, placebo-controlled trial.


METHODS
The study was conducted at the University of Heidelberg, Heidelberg, Germany.


METHODS
The patient population was 45 oligo-/anovulatory PCOS women with typical ovaries.


METHODS
Women were stratified for IR (32 of 13) and then randomly allocated to receive either metformin (n = 22) or placebo (n = 23) and were assessed before and every 4 wk within a treatment period of 12 wk.


METHODS
Menstrual disturbance and markers of insulin metabolism were measured.


RESULTS
The main outcome criterion menstrual disturbance was successfully improved in the metformin-treated group, depending on IR (12 of 15 vs. three of 17), whereas women without IR (four of seven vs. four of six) had no significant amelioration of their menstrual irregularities (P < 0.05). Estradiol levels increased continuously only in the treatment group (P < 0.005), indicating an improvement of ovulatory function. Sixty-seven percent of metformin-treated women had at least one ovulation, compared with only 45% in the placebo group, shown by biphasic body temperature curves. Insulin sensitivity improved within 4 wk after beginning of metformin as shown by an increased area under the curve glucose to insulin ratio, compared with baseline (P < 0.005).


CONCLUSIONS
IR is a baseline predictor of clinical efficacy in metformin treatment in PCOS women measured by improved menstrual cyclicity and ovulatory function.
Eisenhardt
S
S
Women's University Hospital, Department of Gynecological Endocrinology and Reproductive Medicine and Department of Obstetrics and Gynecology, Vossstr. 9, 69115 Heidelberg, Germany. stefan.eisenhardt@med.uni-heidelberg.de
Schwarzmann
N
N
Henschel
V
V
Germeyer
A
A
von Wolff
M
M
Hamann
A
A
Strowitzki
T
T
D000328:Adult; D000858:Anovulation / Q000209:etiology; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D015992:Body Mass Index; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D008687:Metformin / Q000627:therapeutic use*; D010919:Placebos; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010919:Placebos; D008687:Metformin