Neurokinin B Receptor Antagonism in Women With Polycystic Ovary Syndrome: A Randomized, Placebo-Controlled Trial

J Clin Endocrinol Metab. 2016 Nov;101(11):4313-4321. doi: 10.1210/jc.2016-1202. Epub 2016 Jul 26.


Context: Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women, is characterized by high secretion levels of LH and T. Currently, there is no treatment licensed specifically for PCOS.

Objective: The objective of this study was to investigate whether a targeted therapy would decrease LH pulse frequency in women with PCOS, subsequently reducing serum LH and T concentrations and thereby presenting a novel therapeutic approach to the management of PCOS.

Design: This study is a double-blind, double-dummy, placebo-controlled, phase 2 trial.

Settings: University hospitals and private clinical research centers were included.

Participants: Women with PCOS aged 18-45 years participated.

Intervention: Intervention included AZD4901 (a specific neurokinin-3 [NK3] receptor antagonist) at a dose of 20, 40, or 80 mg/day or matching placebo for 28 days.

Main outcome measure: Change from baseline in the area under the LH serum concentration-time curve over 8 hours (area under the curve) on day 7 relative to placebo was measured.

Results: Of a total 67 randomized patients, 65 were evaluable. On day 7, the following baseline-adjusted changes relative to placebo were observed in patients receiving AZD4901 80 mg/day: 1) a reduction of 52.0% (95% confidence interval [CI], 29.6-67.3%) in LH area under the curve; 2) a reduction of 28.7% (95% CI, 13.9-40.9%) in total T concentration; and 3) a reduction of 3.55 LH pulses/8 hours (95% CI, 2.0-5.1) (all nominal P < .05).

Conclusions: The NK3 receptor antagonist AZD4901 specifically reduced LH pulse frequency and subsequently serum LH and T concentrations, thus presenting NK3 receptor antagonism as a potential approach to treating the central neuroendocrine pathophysiology of PCOS.

Trial registration: NCT01872078.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aminoquinolines / administration & dosage
  • Aminoquinolines / pharmacology*
  • Double-Blind Method
  • Female
  • Humans
  • Luteinizing Hormone / blood*
  • Luteinizing Hormone / drug effects
  • Middle Aged
  • Outcome Assessment, Health Care*
  • Polycystic Ovary Syndrome / drug therapy*
  • Receptors, Neurokinin-3 / antagonists & inhibitors*
  • Sulfonamides / administration & dosage
  • Sulfonamides / pharmacology*
  • Testosterone / blood*
  • Young Adult


  • 3-((methylsulfonyl)amino)-2-phenyl-N-(1-phenylpropyl)quinolin-4-carboxamide
  • Aminoquinolines
  • Receptors, Neurokinin-3
  • Sulfonamides
  • Testosterone
  • Luteinizing Hormone

Associated data