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 D Veldhuis, Karolina Skorupskaite, Richard A. Anderson, Stuart McIntosh, Lorraine Webber

Research output: Contribution to journalArticle

27 Citations (Scopus)

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 1 2016

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Neurokinin-3 Receptors
Polycystic Ovary Syndrome
Randomized Controlled Trials
Placebos
Confidence Intervals
Area Under Curve
Serum
Therapeutics
Research

ASJC Scopus subject areas

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

Cite this

George, J. T., Kakkar, R., Marshall, J., Scott, M. L., Finkelman, R. D., Ho, T. W., ... Webber, L. (2016). Neurokinin B receptor antagonism in women with polycystic ovary syndrome: A randomized, placebo-controlled trial. Journal of Clinical Endocrinology and Metabolism, 101(11), 4313-4321. https://doi.org/10.1210/jc.2016-1202

Neurokinin B receptor antagonism in women with polycystic ovary syndrome : A randomized, placebo-controlled trial. / George, Jyothis T.; Kakkar, Rahul; Marshall, Jayne; Scott, Martin L.; Finkelman, Richard D.; Ho, Tony W.; Veldhuis, Johannes D; Skorupskaite, Karolina; Anderson, Richard A.; McIntosh, Stuart; Webber, Lorraine.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 101, No. 11, 01.11.2016, p. 4313-4321.

Research output: Contribution to journalArticle

George, JT, Kakkar, R, Marshall, J, Scott, ML, Finkelman, RD, Ho, TW, Veldhuis, JD, Skorupskaite, K, Anderson, RA, McIntosh, S & Webber, L 2016, 'Neurokinin B receptor antagonism in women with polycystic ovary syndrome: A randomized, placebo-controlled trial', Journal of Clinical Endocrinology and Metabolism, vol. 101, no. 11, pp. 4313-4321. https://doi.org/10.1210/jc.2016-1202
George, Jyothis T. ; Kakkar, Rahul ; Marshall, Jayne ; Scott, Martin L. ; Finkelman, Richard D. ; Ho, Tony W. ; Veldhuis, Johannes D ; Skorupskaite, Karolina ; Anderson, Richard A. ; McIntosh, Stuart ; Webber, Lorraine. / Neurokinin B receptor antagonism in women with polycystic ovary syndrome : A randomized, placebo-controlled trial. In: Journal of Clinical Endocrinology and Metabolism. 2016 ; Vol. 101, No. 11. pp. 4313-4321.
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