Restored Plasma Anandamide and Endometrial Expression of Fatty Acid Amide Hydrolase in Women With Polycystic Ovary Syndrome by the Combination Use of Diane-35 and Metformin

Clin Ther. 2017 Apr;39(4):751-758. doi: 10.1016/j.clinthera.2017.02.007. Epub 2017 Mar 11.

Abstract

Purpose: Polycystic ovary syndrome (PCOS) is a metabolic and endocrinal disorder affecting a number of women of reproductive age. We aimed to reveal the correlation between the endocannabinoid system and PCOS, which may provide a new therapeutic target for PCOS treatment.

Methods: Serum levels of anandamide and 2-arachidonoylglycerol andexpression of cannabinoid receptors and fatty acid amide hydrolase (FAAH) in the endometrium were compared between women with PCOS and infertile women without PCOS, as well as women with PCOS before and after treatment with Diane-35 and metformin. Cannabinoid receptors and FAAH in the endometrium were stained using the immunohistochemical method. Results were analyzed by calculating integrated optical density.

Findings: Plasma anandamide was increased significantly in women with PCOS compared with infertile women without PCOS. Treatment with Diane-35 and metformin reversed this increase in women with PCOS. No significant difference in 2-arachidonoylglycerol was observed between the infertile women with or without PCOS. The women with PCOS had lower endometrial expression of FAAH compared with infertile women without PCOS, whereas no significant difference in endometrial expression of cannabinoid receptors was observed between the women with PCOS and infertile women without PCOS. We found that after treatment with Diane-35 and metformin, FAAH expression tended toward a significant increase compared with women before the treatment.

Implications: Endocannabinoid system may be involved in the progression of PCOS, and serum anandamide could serve as a potential biomarker of clinical diagnosis of PCOS.

Keywords: CB1; FAAH; PCOS; cannabinoid receptors; endocannabinoids; fatty acid amide hydrolase; metformin; polycystic ovary syndrome.

MeSH terms

  • Adult
  • Amidohydrolases / metabolism*
  • Androgen Antagonists / pharmacology*
  • Androgen Antagonists / therapeutic use
  • Arachidonic Acids / blood*
  • Cyproterone Acetate / pharmacology*
  • Cyproterone Acetate / therapeutic use
  • Drug Combinations
  • Endocannabinoids / blood*
  • Endometrium / drug effects
  • Endometrium / metabolism*
  • Ethinyl Estradiol / pharmacology*
  • Ethinyl Estradiol / therapeutic use
  • Female
  • Glycerides / blood
  • Humans
  • Infertility, Female / blood
  • Infertility, Female / metabolism
  • Metformin / pharmacology*
  • Metformin / therapeutic use
  • Polycystic Ovary Syndrome / blood
  • Polycystic Ovary Syndrome / drug therapy
  • Polycystic Ovary Syndrome / metabolism*
  • Polyunsaturated Alkamides / blood*
  • Receptors, Cannabinoid / metabolism
  • Young Adult

Substances

  • Androgen Antagonists
  • Arachidonic Acids
  • Drug Combinations
  • Endocannabinoids
  • Glycerides
  • Polyunsaturated Alkamides
  • Receptors, Cannabinoid
  • Ethinyl Estradiol
  • Cyproterone Acetate
  • Cyproterone acetate, ethinyl estradiol drug combination
  • glyceryl 2-arachidonate
  • Metformin
  • Amidohydrolases
  • fatty-acid amide hydrolase
  • anandamide