Salicylate administration suppresses the inflammatory response to nutrients and improves ovarian function in polycystic ovary syndrome

Am J Physiol Endocrinol Metab. 2020 Oct 1;319(4):E744-E752. doi: 10.1152/ajpendo.00228.2020. Epub 2020 Aug 24.

Abstract

Oxidative stress (OS) and inflammation are often present in polycystic ovary syndrome (PCOS). We examined the effects of salsalate treatment on nutrient-induced OS and inflammation, ovarian androgen secretion, ovulation, and insulin sensitivity in PCOS. Eight lean insulin-sensitive women with PCOS and eight age- and body composition-matched ovulatory controls for baseline comparison participated in the study. The women with PCOS underwent a 12-wk treatment of salsalate, a nonsteroidal anti-inflammatory drug, at a dose of 3 g daily. Markers of OS and inflammation were quantified in mononuclear cells (MNC) and plasma from blood drawn fasting and 2 h after saturated fat ingestion before and after treatment. Ovarian androgen secretion was assessed from blood drawn fasting and 24, 48, and 72 h after human chorionic gonadotropin (HCG) administration before and after treatment. Ovulation was documented based on biphasic basal body temperatures and luteal range progesterone elevations. A two-step pancreatic clamp was performed pre- and posttreatment to measure basal endogenous glucose production (EGP) and the steady-state glucose disposal rate (GDR) during the euglycemic phase and markers of OS and inflammation in MNC and plasma during the hyperglycemic phase. Salsalate administration suppressed lipid- and glucose-stimulated reactive oxygen species generation, activated nuclear factor-κB and circulating tumor necrosis factor-α, normalized basal androgen levels, and lowered HCG-stimulated androgen secretion without altering EGP or GDR. Four salsalate-treated subjects responded with two consecutive ovulations. We conclude that in PCOS, salsalate-induced suppression of OS and inflammation ameliorates ovarian androgen hypersecretion and may induce ovulation while maintaining insulin action.

Keywords: inflammation; nutrients; ovarian hyperandrogenism; oxidative stress; polycystic ovary syndrome; salicylates.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Androgens / metabolism
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Body Composition
  • Chorionic Gonadotropin / pharmacology
  • Female
  • Glucose Clamp Technique
  • Glucose Tolerance Test
  • Humans
  • Monocytes / metabolism
  • Nutrients*
  • Ovary / drug effects*
  • Ovulation / drug effects
  • Oxidative Stress
  • Polycystic Ovary Syndrome / drug therapy*
  • Polycystic Ovary Syndrome / physiopathology*
  • Salicylates / adverse effects
  • Salicylates / therapeutic use*

Substances

  • Androgens
  • Anti-Inflammatory Agents, Non-Steroidal
  • Chorionic Gonadotropin
  • Salicylates