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

Jayasena CN, Abbara A, Veldhuis JD, Comninos AN, Ratnasabapathy R, De Silva A, Nijher GM, Ganiyu-Dada Z, Mehta A, Todd C, Ghatei MA, Bloom SR, Dhillo WS

The Journal of clinical endocrinology and metabolism11 Feb 2014Cited by 95 (Europe PMC)

PMID24517142PMCIDPMC4207927DOI10.1210/jc.2013-1569PepBankPUB-24517142

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Summary

BackgroundHypothalamic 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.AimThe aim of the study was to determine whether constant iv infusion of kisspeptin-54 temporarily increases pulsatile LH secretion in women with HA.MethodsFive 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.ResultsKisspeptin 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 was 3-fold higher when compared with vehicle (number of LH pulses per 8 h: 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).ConclusionsKisspeptin-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.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

3 results from studies that gave the peptide. 3 results from people.

01HumanNon-randomized trialEfficacy outcome
In women with hypothalamic amenorrhea, kisspeptin‑54 infusion increased LH pulsatility in all patients, with peak responses at different doses.
In plain wordsIn women with hypothalamic amenorrhea, kisspeptin‑54 infusion raised luteinising hormone pulses in every patient.
Peptide
Kisspeptin-54 (metastin)
Outcome
IncreaseLH pulsatility in women with hypothalamic amenorrhea
Study
n = 5
Comparator
Vehicle
Outcome group
Sex hormones and fertility · Endocrine and hormones
Studied dose
0.01-1.00 nmol/kg/h · intravenous infusionAs given in this study (human).
Source sentences
Summary
Kisspeptin increased LH pulsatility in all patients with HA, with peak responses observed at different doses in each patient.
2 context sentences(design, population, supporting numbers)
Summary · context
Five patients with HA each underwent six assessments of LH pulsatility.
Summary · context
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.
Show in the study text Report a problemFND-2451714201
02HumanNon-randomized trialEfficacy outcome
In women with hypothalamic amenorrhea, the mean peak number of LH pulses during kisspeptin‑54 infusion was 3-fold higher than with vehicle (P < .01).
In plain wordsIn women with hypothalamic amenorrhea, kisspeptin‑54 infusion gave about three times as many luteinising hormone pulses as vehicle.
Peptide
Kisspeptin-54 (metastin)
Outcome
IncreasePeak number of LH pulses per 8 h
Study
n = 5
Comparator
Vehicle
Outcome group
Sex hormones and fertility · Endocrine and hormones
Studied dose
0.01-1.00 nmol/kg/h · intravenous infusionAs given in this study (human).
Measurements
LH pulses per 8 h
5 pulses
kisspeptin-54
LH pulses per 8 h
1.6 pulses
vehicle
Source sentences
Summary
The mean peak number of pulses during infusion of kisspeptin-54 was 3-fold higher when compared with vehicle (number of LH pulses per 8 h: 1.6 ± 0.4, vehicle; 5.0 ± 0.5, kisspeptin-54, P < .01 vs vehicle).
2 context sentences(design, population, supporting numbers)
Summary · context
Five patients with HA each underwent six assessments of LH pulsatility.
Summary · context
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.
Show in the study text Report a problemFND-2451714202
03HumanNon-randomized trialEfficacy outcome
In women with hypothalamic amenorrhea, the mean peak LH pulse secretory mass during kisspeptin‑54 infusion was 6-fold higher than with vehicle (P < .05).
In plain wordsIn women with hypothalamic amenorrhea, each luteinising hormone pulse released about six times more hormone with kisspeptin‑54 than with vehicle.
Peptide
Kisspeptin-54 (metastin)
Outcome
IncreasePeak LH pulse secretory mass
Study
n = 5
Comparator
Vehicle
Outcome group
Sex hormones and fertility · Endocrine and hormones
Studied dose
0.01-1.00 nmol/kg/h · intravenous infusionAs given in this study (human).
Measurements
LH pulse secretory mass
23.44 international units per liter
kisspeptin-54
LH pulse secretory mass
3.92 international units per liter
vehicle
Source sentences
Summary
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).
2 context sentences(design, population, supporting numbers)
Summary · context
Five patients with HA each underwent six assessments of LH pulsatility.
Summary · context
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.
Show in the study text Report a problemFND-2451714203

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Version 2Current
13 Oct 2026, 21:44 UTC
Study results updated
Version 1
13 Oct 2026, 16:31 UTC
First added · source update from Europe PMC

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