Metformin administration modulates and restores luteinizing hormone spontaneous episodic secretion and ovarian function in nonobese patients with polycystic ovary syndrome.
OBJECTIVE
To evaluate the effects of metformin administration on spontaneous LH episodic release in a group of nonobese polycystic ovary (PCOS) patients.


METHODS
Controlled clinical study.


METHODS
PCOS patients in a clinical research environment.


METHODS
Twenty nonobese PCOS patients were enrolled after informed consent.


METHODS
All patients underwent hormonal evaluations and a pulsatility study (sampling every 10 minutes for 4 hours) before and at the sixth month of therapy (metformin, 500 mg, p.o. b.i.d.). Ultrasound examinations and Ferriman-Gallwey scoring were also performed.


METHODS
Measurements of plasma LH, FSH, estradiol (E(2)), androstenedione (A), 17-hydroxy-progesterone (17-OHP), and testosterone (T), glucose, insulin, and C-peptide concentrations.


RESULTS
After 6 months of metformin administration, the plasma LH, 17-OHP, A, and T levels and LH/FSH ratio were significantly reduced. Insulin sensitivity, expressed as the glucose-to-insulin ratio, was significantly improved under glucose load after 6 months of treatment. Spontaneous LH episodic release showed a significant reduction in pulse amplitude with no changes in pulse frequency. Menstrual cyclicity was restored in all amenorrheic and oligomenorrheic women. The ovarian volume and Ferriman-Gallwey scores also were significantly reduced.


CONCLUSIONS
Metformin administration improves reproductive axis functioning in hyperandrogenic nonobese PCOS patients. By acting on the ovary and restoring normal ovarian activity, metformin positively modulates the reproductive axis (namely GnRH-LH episodic release).
Genazzani
Alessandro D
AD
Department of Obstetrics and Gynecology, University of Modena, Modena, Italy. algen@unimore.it
Battaglia
Cesare
C
Malavasi
Barbara
B
Strucchi
Claudia
C
Tortolani
Francesca
F
Gamba
Ombretta
O
D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000328:Adult; D000735:Androstenedione / Q000097:blood; D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D007986:Luteinizing Hormone / Q000378:metabolism*; D008597:Menstrual Cycle / Q000187:drug effects; D008687:Metformin / Q000627:therapeutic use*; D009765:Obesity / Q000209:etiology; D010053:Ovary / Q000187:drug effects / Q000502:physiology*; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy* / Q000378:metabolism*; D013739:Testosterone / Q000097:blood
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D013739:Testosterone; D000735:Androstenedione; D004958:Estradiol; D019326:17-alpha-Hydroxyprogesterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D008687:Metformin