TY - JOUR
T1 - Neurokinin B receptor antagonism in women with polycystic ovary syndrome
T2 - A randomized, placebo-controlled trial
AU - George, Jyothis T.
AU - Kakkar, Rahul
AU - Marshall, Jayne
AU - Scott, Martin L.
AU - Finkelman, Richard D.
AU - Ho, Tony W.
AU - Veldhuis, Johannes
AU - Skorupskaite, Karolina
AU - Anderson, Richard A.
AU - McIntosh, Stuart
AU - Webber, Lorraine
N1 - Publisher Copyright:
Copyright © 2016 by the Endocrine Society.
PY - 2016/11
Y1 - 2016/11
N2 - 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).
AB - 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).
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U2 - 10.1210/jc.2016-1202
DO - 10.1210/jc.2016-1202
M3 - Article
C2 - 27459523
AN - SCOPUS:84994899414
SN - 0021-972X
VL - 101
SP - 4313
EP - 4321
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 11
ER -