Objective: To identify clinical, laboratory and molecular genetic predictors of menstrual circle regulation in patients with polycystic ovary syndrome (PCOS) undergoing metformin treatment.

Materials and methods: The study included 143 women with PCOS (mean age is 26.4±4.6 years, mean body mass index is 23.8 (4.8) kg/m2). The assessment of androgen profile and levels of AMH, LH, FSH was performed before and 6 months after the treatment. Also, 2-hour oral glucose tolerance test with insulin level examination and dual-energy X-ray absorptiometry were done. Single-nucleotide polymorphisms (SNPs) were genotyped using polymerase chain reaction and next generation sequencing for 45 loci. All patients were administered metformin (Glucophage Long) 1500 mg/day with dose titration for 6 months. Depending on the response to the therapy, the patients were divided into two groups:

  • group 1 included 70 (53.1%) patients whose menstrual cycle was regulated,
  • group 2 consisted of 48 (36.3%) patients without any effect of therapy;
  • 14 (10.6%) patients with partial response to therapy were not included in the analysis of predicting the effectiveness of the treatment.

Results: The following independent predictors of the effectiveness of metformin therapy in PCOS were revealed:

  • AMH level less than 13.3 ng/ml,
  • total testosterone level less than 1.81 ng/ml,
  • index of adipose tissue distribution A/G less than 0.90, as well as
  • polymorphism of loci in the genes SLCO1B1 (rs4149056), ACE (rs4340), FSHR (rs2349415), OST1 (rs113569197).

The model which was developed for predicting menstrual cycle regulation in patients with PCOS undergoing metformin therapy included the baseline level of AMH and rs2349415 SNPs of FSHR gene.

Conclusion: The most significant factors determining metformin effectiveness in PCOS patients were AMH level and genotype С/С of FSHR (rs2349415).

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