Pharmacogenetics of Metformin Action in PCOS
The polycystic ovary syndrome (PCOS) affects approximately 6-10% of women of childbearing
age, i.e., 3.5-5.5 million women in the United States. PCOS is the most common endocrine
disturbance of young women and the major cause (75%) of anovulatory infertility in the
United States. We hypothesize that women with the polycystic ovary syndrome (PCOS) who have
the G/G genotype of single nucleotide polymorphism (SNP)_ rs8111699 in STK11 will exhibit a
significantly greater response to metformin, in terms of ovulation, compared with women with
either the C/G or C/C genotype. Specifically, we anticipate the frequency of ovulation
(defined by number of ovulations/9 months/subject) to be at least 2-fold higher in women
with the G/G STK11 genotype compared with women with either the C/G or C/C genotype.
To test this hypothesis, we will obtain DNA for STK11 genotyping in 36 women with PCOS who
are treated with metformin and carefully monitored for ovulation for 9 months. STK11
genotype status will be determined, and the ovulation rates in the G/G, G/C and C/C genotype
groups will be compared with one another. Our goal is to identify the genes that predict or
modify response to commonly prescribed medications that will allow physicians to better
choose among existing therapies and individualize treatment. While metformin has been shown
to increase ovulatory frequency in PCOS and is widely used in clinical practice to treat
infertility, a substantial number of women either do not respond or are slow to respond to
Knowing that a specific STK11 genotype predicts the effect of metformin on ovulation would
facilitate more efficient and effective treatment of infertility in PCOS.
Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determine if ovulations/9months/woman is greater in women with the G/G genotype of STK11 rs8111699 compared with women with the C/G and C/C genotypes.
John E. Nestler, M.D.
Virginia Commonwealth University
United States: Federal Government
VCU IRB HM11153
|Virginia Commonwealth University||Richmond, Virginia|
|University Of Virginia General Clinical Research Center||Charlottesville, Virginia 22908|