Metformin administration modulates and restores luteinizing hormone spontaneous episodic secretion and ovarian function in nonobese patients with polycystic ovary syndrome
Genazzani AD,Battaglia C,Malavasi B,Strucchi C,Tortolani F,Gamba O
Published January 9, 2004Fertility and Sterility, 81(1), 114-119
Genazzani, A. D., Battaglia, C., Malavasi, B., Strucchi, C., Tortolani, F., & Gamba, O. (2004). Metformin administration modulates and restores luteinizing hormone spontaneous episodic secretion and ovarian function in nonobese patients with polycystic ovary syndrome. Fertility and Sterility, 81(1), 114-119. https://doi.org/10.1016/j.fertnstert.2003.05.020
Genazzani AD, Battaglia C, Malavasi B, Strucchi C, Tortolani F, Gamba O. Metformin administration modulates and restores luteinizing hormone spontaneous episodic secretion and ovarian function in nonobese patients with polycystic ovary syndrome. Fertil Steril. 2004;81(1):114-119. doi:10.1016/j.fertnstert.2003.05.020
Genazzani, Alessandro D., et al. "Metformin administration modulates and restores luteinizing hormone spontaneous episodic secretion and ovarian function in nonobese patients with polycystic ovary syndrome." Fertility and Sterility, vol. 81, no. 1, 2004, pp. 114-119.
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Metformin lowered LH and androgens in nonobese women with PCOS
Metformin lowered luteinizing hormone and androgen levels in 20 nonobese women with PCOS after 6 months of treatment. PCOS is now also called PMOS (polyendocrine metabolic ovarian syndrome). Normal cycles came back in most women, both those who had no periods and those who had rare ones.
Key Findings
After 6 months of metformin, plasma LH, 17-hydroxyprogesterone, androstenedione and testosterone levels and the LH/FSH ratio were significantly lower than before treatment in the 20 women.
LH pulse amplitude was significantly reduced after 6 months, while LH pulse frequency did not change.
Normal menstrual cycles returned in 10 of 12 women who had no periods and 6 of 8 who had infrequent periods. Two women in each group still had infrequent periods.
The Ferriman-Gallwey score, a hair-growth score, fell from 22.3 to 14.0, and ovarian volume also fell significantly.
Insulin response to a glucose load shrank and the glucose-to-insulin ratio rose along the test curve, while fasting insulin and the fasting ratio stayed the same.
Interpretation
This before-and-after study followed 20 women aged 20 to 28 with PCOS at one center in Modena, Italy, each measured against her own results before treatment. The women had a body mass index below 25 and high androgens. The authors propose that improved ovarian function and lower androgens produced the smaller LH pulses, and note this mechanism is a hypothesis. The findings support larger studies of metformin's effect on ovulation in nonobese women with PCOS.
RRM Context
The 20 women had a high insulin response to a glucose load despite normal fasting values. Insulin handling can sit behind PCOS even in nonobese women. Restorative reproductive medicine looks for drivers of missed ovulation like this one. Its aim is ovulatory cycles, and cycle charting can follow cycle length.
Our editorial summary of this paper, not the article's abstract.
Abstract
Objective
To evaluate the effects of metformin administration on spontaneous LH episodic release in a group of nonobese polycystic ovary (PCOS) patients.
Design
Controlled clinical study.
Setting
PCOS patients in a clinical research environment.
Patients
Twenty nonobese PCOS patients were enrolled after informed consent.
Interventions
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.
Main Outcome Measures
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).
