Increasing LH pulsatility in women with hypothalamic amenorrhoea using intravenous infusion of kisspeptin-54

Channa N. Jayasena, Ali Abbara, Johannes D Veldhuis, Alexander N. Comninos, Risheka Ratnasabapathy, Akila De Silva, Gurjinder M K Nijher, Zainab Ganiyu-Dada, Amrish Mehta, Catriona Todd, Mohammad A. Ghatei, Stephen R. Bloom, Waljit S. Dhillo

Research output: Contribution to journalArticle

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Abstract

Background: Hypothalamic amenorrhea (HA) is the one of the most common causes of period loss in women of reproductive age and is associated with deficient LH pulsatility. High-dose kisspeptin- 54 acutely stimulates LH secretion in women with HA, but chronic administration causes desensitization. GnRH has paradoxical effects on reproductive activity; we therefore hypothesized that a dose-dependent therapeutic window exists within which kisspeptin treatment restores the GnRH/LH pulsatility in women with HA. Aim: The aim of the study was to determine whether constant iv infusion of kisspeptin-54 temporarily increases pulsatile LH secretion in women with HA. Methods: Five patients with HA each underwent six assessments of LH pulsatility. Single-blinded continuous iv infusion of vehicle or kisspeptin-54 (0.01, 0.03, 0.10, 0.30, or 1.00 nmol/kg/h) was administered. The LH pulses were detected using blinded deconvolution. Results: Kisspeptin increased LH pulsatility in all patients with HA, with peak responses observed at different doses in each patient. The mean peak number of pulses during infusion of kisspeptin-54 was3-fold higher when compared with vehicle (number ofLHpulses per 8h: 1.6±0.4, vehicle; 5.0± 0.5, kisspeptin-54, P = .01 vs vehicle). The mean peak LH pulse secretory mass during kisspeptin-54 was 6-fold higher when compared with vehicle (LH pulse secretory mass in international units per liter: 3.92 ± 2.31, vehicle; 23.44 ± 12.59, kisspeptin-54; P = .05 vs vehicle). Conclusions: Kisspeptin-54 infusion temporarily increases LH pulsatility in women with HA. Furthermore, we have determined the dose range within which kisspeptin-54 treatment increases basal and pulsatile LH secretion in women with HA. This work provides a basis for studying the potential of kisspeptin-based therapies to treat women with HA.

Original languageEnglish (US)
JournalJournal of Clinical Endocrinology and Metabolism
Volume99
Issue number6
DOIs
StatePublished - 2014

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Kisspeptins
Amenorrhea
Intravenous Infusions
Gonadotropin-Releasing Hormone
Deconvolution
Therapeutics

ASJC Scopus subject areas

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

Cite this

Jayasena, C. N., Abbara, A., Veldhuis, J. D., Comninos, A. N., Ratnasabapathy, R., De Silva, A., ... Dhillo, W. S. (2014). Increasing LH pulsatility in women with hypothalamic amenorrhoea using intravenous infusion of kisspeptin-54. Journal of Clinical Endocrinology and Metabolism, 99(6). https://doi.org/10.1210/jc.2013-1569

Increasing LH pulsatility in women with hypothalamic amenorrhoea using intravenous infusion of kisspeptin-54. / Jayasena, Channa N.; Abbara, Ali; Veldhuis, Johannes D; Comninos, Alexander N.; Ratnasabapathy, Risheka; De Silva, Akila; Nijher, Gurjinder M K; Ganiyu-Dada, Zainab; Mehta, Amrish; Todd, Catriona; Ghatei, Mohammad A.; Bloom, Stephen R.; Dhillo, Waljit S.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 99, No. 6, 2014.

Research output: Contribution to journalArticle

Jayasena, CN, Abbara, A, Veldhuis, JD, Comninos, AN, Ratnasabapathy, R, De Silva, A, Nijher, GMK, Ganiyu-Dada, Z, Mehta, A, Todd, C, Ghatei, MA, Bloom, SR & Dhillo, WS 2014, 'Increasing LH pulsatility in women with hypothalamic amenorrhoea using intravenous infusion of kisspeptin-54', Journal of Clinical Endocrinology and Metabolism, vol. 99, no. 6. https://doi.org/10.1210/jc.2013-1569
Jayasena, Channa N. ; Abbara, Ali ; Veldhuis, Johannes D ; Comninos, Alexander N. ; Ratnasabapathy, Risheka ; De Silva, Akila ; Nijher, Gurjinder M K ; Ganiyu-Dada, Zainab ; Mehta, Amrish ; Todd, Catriona ; Ghatei, Mohammad A. ; Bloom, Stephen R. ; Dhillo, Waljit S. / Increasing LH pulsatility in women with hypothalamic amenorrhoea using intravenous infusion of kisspeptin-54. In: Journal of Clinical Endocrinology and Metabolism. 2014 ; Vol. 99, No. 6.
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abstract = "Background: Hypothalamic amenorrhea (HA) is the one of the most common causes of period loss in women of reproductive age and is associated with deficient LH pulsatility. High-dose kisspeptin- 54 acutely stimulates LH secretion in women with HA, but chronic administration causes desensitization. GnRH has paradoxical effects on reproductive activity; we therefore hypothesized that a dose-dependent therapeutic window exists within which kisspeptin treatment restores the GnRH/LH pulsatility in women with HA. Aim: The aim of the study was to determine whether constant iv infusion of kisspeptin-54 temporarily increases pulsatile LH secretion in women with HA. Methods: Five patients with HA each underwent six assessments of LH pulsatility. Single-blinded continuous iv infusion of vehicle or kisspeptin-54 (0.01, 0.03, 0.10, 0.30, or 1.00 nmol/kg/h) was administered. The LH pulses were detected using blinded deconvolution. Results: Kisspeptin increased LH pulsatility in all patients with HA, with peak responses observed at different doses in each patient. The mean peak number of pulses during infusion of kisspeptin-54 was3-fold higher when compared with vehicle (number ofLHpulses per 8h: 1.6±0.4, vehicle; 5.0± 0.5, kisspeptin-54, P = .01 vs vehicle). The mean peak LH pulse secretory mass during kisspeptin-54 was 6-fold higher when compared with vehicle (LH pulse secretory mass in international units per liter: 3.92 ± 2.31, vehicle; 23.44 ± 12.59, kisspeptin-54; P = .05 vs vehicle). Conclusions: Kisspeptin-54 infusion temporarily increases LH pulsatility in women with HA. Furthermore, we have determined the dose range within which kisspeptin-54 treatment increases basal and pulsatile LH secretion in women with HA. This work provides a basis for studying the potential of kisspeptin-based therapies to treat women with HA.",
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AU - Jayasena, Channa N.

AU - Abbara, Ali

AU - Veldhuis, Johannes D

AU - Comninos, Alexander N.

AU - Ratnasabapathy, Risheka

AU - De Silva, Akila

AU - Nijher, Gurjinder M K

AU - Ganiyu-Dada, Zainab

AU - Mehta, Amrish

AU - Todd, Catriona

AU - Ghatei, Mohammad A.

AU - Bloom, Stephen R.

AU - Dhillo, Waljit S.

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N2 - Background: Hypothalamic amenorrhea (HA) is the one of the most common causes of period loss in women of reproductive age and is associated with deficient LH pulsatility. High-dose kisspeptin- 54 acutely stimulates LH secretion in women with HA, but chronic administration causes desensitization. GnRH has paradoxical effects on reproductive activity; we therefore hypothesized that a dose-dependent therapeutic window exists within which kisspeptin treatment restores the GnRH/LH pulsatility in women with HA. Aim: The aim of the study was to determine whether constant iv infusion of kisspeptin-54 temporarily increases pulsatile LH secretion in women with HA. Methods: Five patients with HA each underwent six assessments of LH pulsatility. Single-blinded continuous iv infusion of vehicle or kisspeptin-54 (0.01, 0.03, 0.10, 0.30, or 1.00 nmol/kg/h) was administered. The LH pulses were detected using blinded deconvolution. Results: Kisspeptin increased LH pulsatility in all patients with HA, with peak responses observed at different doses in each patient. The mean peak number of pulses during infusion of kisspeptin-54 was3-fold higher when compared with vehicle (number ofLHpulses per 8h: 1.6±0.4, vehicle; 5.0± 0.5, kisspeptin-54, P = .01 vs vehicle). The mean peak LH pulse secretory mass during kisspeptin-54 was 6-fold higher when compared with vehicle (LH pulse secretory mass in international units per liter: 3.92 ± 2.31, vehicle; 23.44 ± 12.59, kisspeptin-54; P = .05 vs vehicle). Conclusions: Kisspeptin-54 infusion temporarily increases LH pulsatility in women with HA. Furthermore, we have determined the dose range within which kisspeptin-54 treatment increases basal and pulsatile LH secretion in women with HA. This work provides a basis for studying the potential of kisspeptin-based therapies to treat women with HA.

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