Subcutaneous infusion of kisspeptin-54 stimulates gonadotrophin release in women and the response correlates with basal oestradiol levels

Shakunthala Narayanaswamy, Channa N. Jayasena, Noel Ng, Risheka Ratnasabapathy, Julia K. Prague, Deborah Papadopoulou, Ali Abbara, Alexander N. Comninos, Paul Bassett, Stephen R. Bloom, Johannes D Veldhuis, Waljit S. Dhillo

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background and objective: Kisspeptin stimulates hypothalamic GnRH secretion resulting in gonadotrophin release and has potential as a future therapeutic. Chronic subcutaneous infusion of kisspeptin via a pump (similar to an insulin pump) may provide an alternative route of administration in the future. We investigated for the first time in humans, the gonadotrophin response to subcutaneous (SC) infusions of kisspeptin-54 in healthy women. Women are markedly more responsive to exogenous kisspeptin in the late follicular phase preovulation when oestradiol levels are naturally high. Therefore, we further investigated whether there was a correlation between baseline oestradiol levels and LH response to kisspeptin. Design and patients: A prospective, single-blinded placebo-controlled study. Healthy women (n = 4) received an 8-h SC infusion of kisspeptin-54 0·1, 0·3 or 1·0 nmol/kg/h or saline in the early follicular phase of 4 separate menstrual cycles. Gonadotrophins and oestradiol were measured every 10 min during the infusions. Results: SC infusion of kisspeptin-54 increased LH and FSH. The LH response to SC infusion of kisspeptin-54 (0·3 and 1·0 nmol/kg/h) positively correlated with baseline oestradiol levels (P <0·001). Further statistical analyses showed that in the 1·0 nmol/kg/h group, a 100pmol/l rise in baseline oestradiol was associated with a 1·0 IU/l increase in LH. Conclusions: Kisspeptin administered via a SC infusion could be a viable future therapeutic route of administration for patients with infertility. Baseline oestradiol levels may be an important determinant of the gonadotrophin response to kisspeptin treatment in women and should be taken into consideration when evaluating gonadotrophin response.

Original languageEnglish (US)
JournalClinical Endocrinology
DOIs
StateAccepted/In press - 2015

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Kisspeptins
Subcutaneous Infusions
Gonadotropins
Estradiol
Follicular Phase
Menstrual Cycle
Gonadotropin-Releasing Hormone
Infertility
Therapeutics

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

Narayanaswamy, S., Jayasena, C. N., Ng, N., Ratnasabapathy, R., Prague, J. K., Papadopoulou, D., ... Dhillo, W. S. (Accepted/In press). Subcutaneous infusion of kisspeptin-54 stimulates gonadotrophin release in women and the response correlates with basal oestradiol levels. Clinical Endocrinology. https://doi.org/10.1111/cen.12977

Subcutaneous infusion of kisspeptin-54 stimulates gonadotrophin release in women and the response correlates with basal oestradiol levels. / Narayanaswamy, Shakunthala; Jayasena, Channa N.; Ng, Noel; Ratnasabapathy, Risheka; Prague, Julia K.; Papadopoulou, Deborah; Abbara, Ali; Comninos, Alexander N.; Bassett, Paul; Bloom, Stephen R.; Veldhuis, Johannes D; Dhillo, Waljit S.

In: Clinical Endocrinology, 2015.

Research output: Contribution to journalArticle

Narayanaswamy, S, Jayasena, CN, Ng, N, Ratnasabapathy, R, Prague, JK, Papadopoulou, D, Abbara, A, Comninos, AN, Bassett, P, Bloom, SR, Veldhuis, JD & Dhillo, WS 2015, 'Subcutaneous infusion of kisspeptin-54 stimulates gonadotrophin release in women and the response correlates with basal oestradiol levels', Clinical Endocrinology. https://doi.org/10.1111/cen.12977
Narayanaswamy, Shakunthala ; Jayasena, Channa N. ; Ng, Noel ; Ratnasabapathy, Risheka ; Prague, Julia K. ; Papadopoulou, Deborah ; Abbara, Ali ; Comninos, Alexander N. ; Bassett, Paul ; Bloom, Stephen R. ; Veldhuis, Johannes D ; Dhillo, Waljit S. / Subcutaneous infusion of kisspeptin-54 stimulates gonadotrophin release in women and the response correlates with basal oestradiol levels. In: Clinical Endocrinology. 2015.
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abstract = "Background and objective: Kisspeptin stimulates hypothalamic GnRH secretion resulting in gonadotrophin release and has potential as a future therapeutic. Chronic subcutaneous infusion of kisspeptin via a pump (similar to an insulin pump) may provide an alternative route of administration in the future. We investigated for the first time in humans, the gonadotrophin response to subcutaneous (SC) infusions of kisspeptin-54 in healthy women. Women are markedly more responsive to exogenous kisspeptin in the late follicular phase preovulation when oestradiol levels are naturally high. Therefore, we further investigated whether there was a correlation between baseline oestradiol levels and LH response to kisspeptin. Design and patients: A prospective, single-blinded placebo-controlled study. Healthy women (n = 4) received an 8-h SC infusion of kisspeptin-54 0·1, 0·3 or 1·0 nmol/kg/h or saline in the early follicular phase of 4 separate menstrual cycles. Gonadotrophins and oestradiol were measured every 10 min during the infusions. Results: SC infusion of kisspeptin-54 increased LH and FSH. The LH response to SC infusion of kisspeptin-54 (0·3 and 1·0 nmol/kg/h) positively correlated with baseline oestradiol levels (P <0·001). Further statistical analyses showed that in the 1·0 nmol/kg/h group, a 100pmol/l rise in baseline oestradiol was associated with a 1·0 IU/l increase in LH. Conclusions: Kisspeptin administered via a SC infusion could be a viable future therapeutic route of administration for patients with infertility. Baseline oestradiol levels may be an important determinant of the gonadotrophin response to kisspeptin treatment in women and should be taken into consideration when evaluating gonadotrophin response.",
author = "Shakunthala Narayanaswamy and Jayasena, {Channa N.} and Noel Ng and Risheka Ratnasabapathy and Prague, {Julia K.} and Deborah Papadopoulou and Ali Abbara and Comninos, {Alexander N.} and Paul Bassett and Bloom, {Stephen R.} and Veldhuis, {Johannes D} and Dhillo, {Waljit S.}",
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T1 - Subcutaneous infusion of kisspeptin-54 stimulates gonadotrophin release in women and the response correlates with basal oestradiol levels

AU - Narayanaswamy, Shakunthala

AU - Jayasena, Channa N.

AU - Ng, Noel

AU - Ratnasabapathy, Risheka

AU - Prague, Julia K.

AU - Papadopoulou, Deborah

AU - Abbara, Ali

AU - Comninos, Alexander N.

AU - Bassett, Paul

AU - Bloom, Stephen R.

AU - Veldhuis, Johannes D

AU - Dhillo, Waljit S.

PY - 2015

Y1 - 2015

N2 - Background and objective: Kisspeptin stimulates hypothalamic GnRH secretion resulting in gonadotrophin release and has potential as a future therapeutic. Chronic subcutaneous infusion of kisspeptin via a pump (similar to an insulin pump) may provide an alternative route of administration in the future. We investigated for the first time in humans, the gonadotrophin response to subcutaneous (SC) infusions of kisspeptin-54 in healthy women. Women are markedly more responsive to exogenous kisspeptin in the late follicular phase preovulation when oestradiol levels are naturally high. Therefore, we further investigated whether there was a correlation between baseline oestradiol levels and LH response to kisspeptin. Design and patients: A prospective, single-blinded placebo-controlled study. Healthy women (n = 4) received an 8-h SC infusion of kisspeptin-54 0·1, 0·3 or 1·0 nmol/kg/h or saline in the early follicular phase of 4 separate menstrual cycles. Gonadotrophins and oestradiol were measured every 10 min during the infusions. Results: SC infusion of kisspeptin-54 increased LH and FSH. The LH response to SC infusion of kisspeptin-54 (0·3 and 1·0 nmol/kg/h) positively correlated with baseline oestradiol levels (P <0·001). Further statistical analyses showed that in the 1·0 nmol/kg/h group, a 100pmol/l rise in baseline oestradiol was associated with a 1·0 IU/l increase in LH. Conclusions: Kisspeptin administered via a SC infusion could be a viable future therapeutic route of administration for patients with infertility. Baseline oestradiol levels may be an important determinant of the gonadotrophin response to kisspeptin treatment in women and should be taken into consideration when evaluating gonadotrophin response.

AB - Background and objective: Kisspeptin stimulates hypothalamic GnRH secretion resulting in gonadotrophin release and has potential as a future therapeutic. Chronic subcutaneous infusion of kisspeptin via a pump (similar to an insulin pump) may provide an alternative route of administration in the future. We investigated for the first time in humans, the gonadotrophin response to subcutaneous (SC) infusions of kisspeptin-54 in healthy women. Women are markedly more responsive to exogenous kisspeptin in the late follicular phase preovulation when oestradiol levels are naturally high. Therefore, we further investigated whether there was a correlation between baseline oestradiol levels and LH response to kisspeptin. Design and patients: A prospective, single-blinded placebo-controlled study. Healthy women (n = 4) received an 8-h SC infusion of kisspeptin-54 0·1, 0·3 or 1·0 nmol/kg/h or saline in the early follicular phase of 4 separate menstrual cycles. Gonadotrophins and oestradiol were measured every 10 min during the infusions. Results: SC infusion of kisspeptin-54 increased LH and FSH. The LH response to SC infusion of kisspeptin-54 (0·3 and 1·0 nmol/kg/h) positively correlated with baseline oestradiol levels (P <0·001). Further statistical analyses showed that in the 1·0 nmol/kg/h group, a 100pmol/l rise in baseline oestradiol was associated with a 1·0 IU/l increase in LH. Conclusions: Kisspeptin administered via a SC infusion could be a viable future therapeutic route of administration for patients with infertility. Baseline oestradiol levels may be an important determinant of the gonadotrophin response to kisspeptin treatment in women and should be taken into consideration when evaluating gonadotrophin response.

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