Metformin and LH Reduction in PCOS
Metformin does reduce LH levels in women with PCOS, but this effect is most pronounced in those with hyperinsulinemia and hyperandrogenism, and occurs indirectly through improvement of insulin sensitivity rather than direct pituitary action.
Mechanism of LH Reduction
Metformin lowers LH levels indirectly by improving insulin sensitivity, which subsequently decreases ovarian androgen production 1, 2. The reduction in hyperandrogenism then modulates the hypothalamic-pituitary-ovarian axis, leading to decreased LH secretion 3. In vitro studies demonstrate that metformin does not directly affect LH gene expression in pituitary gonadotrophs, confirming the indirect mechanism 4.
Evidence for LH Reduction
Clinical Trial Data
In hyperinsulinemic PCOS patients: Plasma LH levels decreased significantly after 3 months of metformin (500-1,500 mg/day), with the LH/FSH ratio also significantly reduced 4.
In non-obese PCOS patients: After 6 months of metformin (500 mg twice daily), LH levels decreased significantly, with the greatest endocrine changes observed in hyperinsulinemic hyperandrogenic patients 3.
In insulin-resistant PCOS patients: Metformin treatment (dose not specified, 12 weeks) produced statistically significant decreases in LH concentrations and improvements in FSH/LH ratio 5.
Important Caveat: Variable Response Based on Phenotype
The LH-lowering effect is not universal and depends critically on baseline metabolic status:
In obese, nondiabetic PCOS women maintained at stable weight, metformin (850 mg three times daily for 12 weeks) did not reduce basal or stimulated LH levels when insulin sensitivity was not improved 6.
Another study showed no significant effect on ovarian steroidogenic response to GnRH agonist testing despite improvements in insulin levels, suggesting the LH reduction may not always translate to changes in ovarian hormone production 7.
Clinical Implications
Who Benefits Most
Metformin should be prioritized for PCOS patients with documented hyperinsulinemia and hyperandrogenism, as these patients demonstrate the highest rate of LH reduction and endocrine normalization 3, 5. The American College of Obstetricians and Gynecologists supports using metformin to improve insulin sensitivity, which is associated with decreased circulating androgens 8.
Dosing for LH Reduction
Effective doses range from 1,000-2,550 mg daily (typically 500 mg twice daily to 850 mg three times daily), administered for at least 3-6 months 3, 4, 6. Typical effective dosing ranges from 1.5 to 2 g daily 1.
Expected Timeline
Significant LH reduction occurs within 3-6 months of treatment 3, 4, 5.
Limitations and Contraindications
While metformin improves metabolic parameters and may reduce LH levels, it is not FDA-labeled for PCOS treatment 8. Metformin is contraindicated in patients with impaired renal function, hepatic disease, hypoxemic conditions, severe infections, or alcohol abuse 1. The most common side effects are gastrointestinal disturbances 1.
Clinical Bottom Line
Metformin reduces LH levels in PCOS primarily in hyperinsulinemic patients through indirect metabolic improvement rather than direct hormonal suppression 3, 4. However, LH reduction should not be the primary treatment goal—focus instead on clinically meaningful outcomes like ovulation restoration, metabolic improvement, and cardiovascular risk reduction 8, 2. For fertility specifically, clomiphene citrate remains superior to metformin for ovulation induction 2.