Twice-daily subcutaneous injection of kisspeptin-54 does not abolish menstrual cyclicity in healthy female volunteers

C. N. Jayasena, A. N. Comninos, G. M K Nijher, A. Abbara, A. De Silva, Johannes D Veldhuis, R. Ratnasabapathy, C. Izzi-Engbeaya, A. Lim, D. A. Patel, M. A. Ghatei, S. R. Bloom, Waljit S. Dhillo

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background: Kisspeptin is a critical hypothalamic regulator of reproductive function. Chronic kisspeptin administration causes profound tachyphylaxis in male monkeys and in women with functional hypothalamic amenorrhea. The pharmacological effects of chronic kisspeptin exposure in healthy women with normal menstrual cycles have not been studied previously. Aim:Ouraimwasto determine the effects of follicular-phase kisspeptin-54 treatmentonmenstrual cyclicity in healthy women. Methods: We performed a prospective, single-blinded, 1-way crossover study. Healthy women received twice-daily sc injections of kisspeptin (6.4 nmol/kg) or 0.9% saline during menstrual days 7-14 (n=5 per treatment arm). Serial assessments of basal reproductive hormones, ultrasound parameters, LH pulsatility, and acute sensitivity to GnRH and kisspeptin-54 injection were performed. Results: Menstrual cyclicity persisted in all women after follicular-phase kisspeptin-54 treatment. Chronic exposure to kisspeptin-54 did not abolish acute stimulation of LH after injection of kisspeptin- 54 or GnRH. In addition, kisspeptin-54 treatment was associated with a shortermeanlength of the menstrual cycle (mean length of menstrual cycle was 28.6 ± 1.4 days with saline vs 26.8 ± 3.1 days with kisspeptin, P<.01), earlier onset of highest recorded serum LH (mean menstrual day of highest LH was 15.2 ± 1.3 with saline vs 13.0 ± 1.9 with kisspeptin, P < .05), and earlier onset of the luteal phase (mean menstrual day of progesterone increase was 18.0 ± 2.1 with saline vs 15.8 ± 0.9 with kisspeptin, P < .05). Conclusion: Our data suggest that 1 week of exogenous kisspeptin-54 does not abolish menstrual cyclicity in healthy women. Further work is needed to determine whether kisspeptin could be used to treat certain anovulatory disorders.

Original languageEnglish (US)
Pages (from-to)4464-4474
Number of pages11
JournalJournal of Clinical Endocrinology and Metabolism
Volume98
Issue number11
DOIs
StatePublished - Nov 1 2013

Fingerprint

Kisspeptins
Periodicity
Subcutaneous Injections
Healthy Volunteers
Menstrual Cycle
Follicular Phase
Gonadotropin-Releasing Hormone
Injections
Tachyphylaxis
Luteal Phase

ASJC Scopus subject areas

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

Cite this

Jayasena, C. N., Comninos, A. N., Nijher, G. M. K., Abbara, A., De Silva, A., Veldhuis, J. D., ... Dhillo, W. S. (2013). Twice-daily subcutaneous injection of kisspeptin-54 does not abolish menstrual cyclicity in healthy female volunteers. Journal of Clinical Endocrinology and Metabolism, 98(11), 4464-4474. https://doi.org/10.1210/jc.2013-1069

Twice-daily subcutaneous injection of kisspeptin-54 does not abolish menstrual cyclicity in healthy female volunteers. / Jayasena, C. N.; Comninos, A. N.; Nijher, G. M K; Abbara, A.; De Silva, A.; Veldhuis, Johannes D; Ratnasabapathy, R.; Izzi-Engbeaya, C.; Lim, A.; Patel, D. A.; Ghatei, M. A.; Bloom, S. R.; Dhillo, Waljit S.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 98, No. 11, 01.11.2013, p. 4464-4474.

Research output: Contribution to journalArticle

Jayasena, CN, Comninos, AN, Nijher, GMK, Abbara, A, De Silva, A, Veldhuis, JD, Ratnasabapathy, R, Izzi-Engbeaya, C, Lim, A, Patel, DA, Ghatei, MA, Bloom, SR & Dhillo, WS 2013, 'Twice-daily subcutaneous injection of kisspeptin-54 does not abolish menstrual cyclicity in healthy female volunteers', Journal of Clinical Endocrinology and Metabolism, vol. 98, no. 11, pp. 4464-4474. https://doi.org/10.1210/jc.2013-1069
Jayasena, C. N. ; Comninos, A. N. ; Nijher, G. M K ; Abbara, A. ; De Silva, A. ; Veldhuis, Johannes D ; Ratnasabapathy, R. ; Izzi-Engbeaya, C. ; Lim, A. ; Patel, D. A. ; Ghatei, M. A. ; Bloom, S. R. ; Dhillo, Waljit S. / Twice-daily subcutaneous injection of kisspeptin-54 does not abolish menstrual cyclicity in healthy female volunteers. In: Journal of Clinical Endocrinology and Metabolism. 2013 ; Vol. 98, No. 11. pp. 4464-4474.
@article{0fbd455a2dce4486ab8c4135c3761766,
title = "Twice-daily subcutaneous injection of kisspeptin-54 does not abolish menstrual cyclicity in healthy female volunteers",
abstract = "Background: Kisspeptin is a critical hypothalamic regulator of reproductive function. Chronic kisspeptin administration causes profound tachyphylaxis in male monkeys and in women with functional hypothalamic amenorrhea. The pharmacological effects of chronic kisspeptin exposure in healthy women with normal menstrual cycles have not been studied previously. Aim:Ouraimwasto determine the effects of follicular-phase kisspeptin-54 treatmentonmenstrual cyclicity in healthy women. Methods: We performed a prospective, single-blinded, 1-way crossover study. Healthy women received twice-daily sc injections of kisspeptin (6.4 nmol/kg) or 0.9{\%} saline during menstrual days 7-14 (n=5 per treatment arm). Serial assessments of basal reproductive hormones, ultrasound parameters, LH pulsatility, and acute sensitivity to GnRH and kisspeptin-54 injection were performed. Results: Menstrual cyclicity persisted in all women after follicular-phase kisspeptin-54 treatment. Chronic exposure to kisspeptin-54 did not abolish acute stimulation of LH after injection of kisspeptin- 54 or GnRH. In addition, kisspeptin-54 treatment was associated with a shortermeanlength of the menstrual cycle (mean length of menstrual cycle was 28.6 ± 1.4 days with saline vs 26.8 ± 3.1 days with kisspeptin, P<.01), earlier onset of highest recorded serum LH (mean menstrual day of highest LH was 15.2 ± 1.3 with saline vs 13.0 ± 1.9 with kisspeptin, P < .05), and earlier onset of the luteal phase (mean menstrual day of progesterone increase was 18.0 ± 2.1 with saline vs 15.8 ± 0.9 with kisspeptin, P < .05). Conclusion: Our data suggest that 1 week of exogenous kisspeptin-54 does not abolish menstrual cyclicity in healthy women. Further work is needed to determine whether kisspeptin could be used to treat certain anovulatory disorders.",
author = "Jayasena, {C. N.} and Comninos, {A. N.} and Nijher, {G. M K} and A. Abbara and {De Silva}, A. and Veldhuis, {Johannes D} and R. Ratnasabapathy and C. Izzi-Engbeaya and A. Lim and Patel, {D. A.} and Ghatei, {M. A.} and Bloom, {S. R.} and Dhillo, {Waljit S.}",
year = "2013",
month = "11",
day = "1",
doi = "10.1210/jc.2013-1069",
language = "English (US)",
volume = "98",
pages = "4464--4474",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "11",

}

TY - JOUR

T1 - Twice-daily subcutaneous injection of kisspeptin-54 does not abolish menstrual cyclicity in healthy female volunteers

AU - Jayasena, C. N.

AU - Comninos, A. N.

AU - Nijher, G. M K

AU - Abbara, A.

AU - De Silva, A.

AU - Veldhuis, Johannes D

AU - Ratnasabapathy, R.

AU - Izzi-Engbeaya, C.

AU - Lim, A.

AU - Patel, D. A.

AU - Ghatei, M. A.

AU - Bloom, S. R.

AU - Dhillo, Waljit S.

PY - 2013/11/1

Y1 - 2013/11/1

N2 - Background: Kisspeptin is a critical hypothalamic regulator of reproductive function. Chronic kisspeptin administration causes profound tachyphylaxis in male monkeys and in women with functional hypothalamic amenorrhea. The pharmacological effects of chronic kisspeptin exposure in healthy women with normal menstrual cycles have not been studied previously. Aim:Ouraimwasto determine the effects of follicular-phase kisspeptin-54 treatmentonmenstrual cyclicity in healthy women. Methods: We performed a prospective, single-blinded, 1-way crossover study. Healthy women received twice-daily sc injections of kisspeptin (6.4 nmol/kg) or 0.9% saline during menstrual days 7-14 (n=5 per treatment arm). Serial assessments of basal reproductive hormones, ultrasound parameters, LH pulsatility, and acute sensitivity to GnRH and kisspeptin-54 injection were performed. Results: Menstrual cyclicity persisted in all women after follicular-phase kisspeptin-54 treatment. Chronic exposure to kisspeptin-54 did not abolish acute stimulation of LH after injection of kisspeptin- 54 or GnRH. In addition, kisspeptin-54 treatment was associated with a shortermeanlength of the menstrual cycle (mean length of menstrual cycle was 28.6 ± 1.4 days with saline vs 26.8 ± 3.1 days with kisspeptin, P<.01), earlier onset of highest recorded serum LH (mean menstrual day of highest LH was 15.2 ± 1.3 with saline vs 13.0 ± 1.9 with kisspeptin, P < .05), and earlier onset of the luteal phase (mean menstrual day of progesterone increase was 18.0 ± 2.1 with saline vs 15.8 ± 0.9 with kisspeptin, P < .05). Conclusion: Our data suggest that 1 week of exogenous kisspeptin-54 does not abolish menstrual cyclicity in healthy women. Further work is needed to determine whether kisspeptin could be used to treat certain anovulatory disorders.

AB - Background: Kisspeptin is a critical hypothalamic regulator of reproductive function. Chronic kisspeptin administration causes profound tachyphylaxis in male monkeys and in women with functional hypothalamic amenorrhea. The pharmacological effects of chronic kisspeptin exposure in healthy women with normal menstrual cycles have not been studied previously. Aim:Ouraimwasto determine the effects of follicular-phase kisspeptin-54 treatmentonmenstrual cyclicity in healthy women. Methods: We performed a prospective, single-blinded, 1-way crossover study. Healthy women received twice-daily sc injections of kisspeptin (6.4 nmol/kg) or 0.9% saline during menstrual days 7-14 (n=5 per treatment arm). Serial assessments of basal reproductive hormones, ultrasound parameters, LH pulsatility, and acute sensitivity to GnRH and kisspeptin-54 injection were performed. Results: Menstrual cyclicity persisted in all women after follicular-phase kisspeptin-54 treatment. Chronic exposure to kisspeptin-54 did not abolish acute stimulation of LH after injection of kisspeptin- 54 or GnRH. In addition, kisspeptin-54 treatment was associated with a shortermeanlength of the menstrual cycle (mean length of menstrual cycle was 28.6 ± 1.4 days with saline vs 26.8 ± 3.1 days with kisspeptin, P<.01), earlier onset of highest recorded serum LH (mean menstrual day of highest LH was 15.2 ± 1.3 with saline vs 13.0 ± 1.9 with kisspeptin, P < .05), and earlier onset of the luteal phase (mean menstrual day of progesterone increase was 18.0 ± 2.1 with saline vs 15.8 ± 0.9 with kisspeptin, P < .05). Conclusion: Our data suggest that 1 week of exogenous kisspeptin-54 does not abolish menstrual cyclicity in healthy women. Further work is needed to determine whether kisspeptin could be used to treat certain anovulatory disorders.

UR - http://www.scopus.com/inward/record.url?scp=84887417775&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84887417775&partnerID=8YFLogxK

U2 - 10.1210/jc.2013-1069

DO - 10.1210/jc.2013-1069

M3 - Article

VL - 98

SP - 4464

EP - 4474

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 11

ER -