Neurokinin B receptor antagonism in women with polycystic ovary syndrome: A randomized, placebo-controlled trial

Jyothis T. George, Rahul Kakkar, Jayne Marshall, Martin L. Scott, Richard D. Finkelman, Tony W. Ho, Johannes Veldhuis, Karolina Skorupskaite, Richard A. Anderson, Stuart McIntosh, Lorraine Webber

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

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. MainOutcomeMeasure: Change from baseline in the area under theLHserum 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 baselineadjusted 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. (J Clin Endocrinol Metab 101: 4313-4321, 2016).

Original languageEnglish (US)
Pages (from-to)4313-4321
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume101
Issue number11
DOIs
StatePublished - Nov 2016

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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