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Study · Randomized controlled trial · n = 8 · 2020

6 results

Kisspeptin and neurokinin B interactions in modulating gonadotropin secretion in women with polycystic ovary syndrome.

Skorupskaite K, George JT, Veldhuis JD, Millar RP, Anderson RA

Human reproduction (Oxford, England)1 Jun 2020Cited by 47 (Europe PMC)

PMID32510130 (opens in a new tab)PMCIDPMC7316500 (opens in a new tab)DOI10.1093/humrep/deaa104 (opens in a new tab)PepBankPUB-32510130
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Summary

Study questionWhat is the role of the hypothalamic neuropeptide neurokinin B (NKB) and its interaction with kisspeptin on GnRH/LH secretion in women with polycystic ovary syndrome (PCOS)?Summary answerAdministration of neurokinin 3 receptor antagonist (NK3Ra) for 7 days reduced LH and FSH secretion and LH pulse frequency in women with PCOS, whilst the stimulatory LH response to kisspeptin-10 was maintained.What is known alreadyPCOS is characterized by abnormal GnRH/LH secretion. NKB and kisspeptin are master regulators of GnRH/LH secretion, but their role in PCOS is unclear.Study design, size, durationThe NK3Ra MLE4901, 40 mg orally twice a day, was administered to women with PCOS for 7 days (n = 8) (vs no treatment, n = 7). On the last day of NK3Ra administration or the equivalent day in those not treated, women were randomized to 7-h kisspeptin-10 (4 µg/kg/h i.v.) or vehicle infusion. This was repeated with the alternate infusion in a subsequent cycle.Participants/materials, setting, methodsSubjects were women with PCOS, studied in a Clinical Research Facility. Reproductive hormones were measured before and after NK3Ra administration. On the last day of NK3Ra administration (or the equivalent cycle day in untreated women), all women attended for an 8-h frequent blood sampling to allow analysis of the pulsatile LH secretion.Main results and the role of chanceNK3Ra reduced LH secretion (4.0 ± 0.4 vs 6.5 ± 0.8 IU/l, P < 0.05) and pulse frequency (0.5 ± 0.1 vs 0.8 ± 0.1 pulses/h, P < 0.05); FSH secretion was also reduced (2.0 ± 0.3 vs 2.5 ± 0.4 IU/l, P < 0.05). Without NK3Ra pre-treatment, kisspeptin-10 increased LH secretion (5.2 ± 0.5 to 7.8 ± 1.0 IU/L, P < 0.05), with a positive relationship to oestradiol concentrations (r2 = 0.59, P < 0.05). After NK3Ra administration, the LH response to kisspeptin-10 was preserved (vehicle 3.5 ± 0.3 vs 9.0 ± 2.2 IU/l with kisspeptin-10, P < 0.05), but the positive correlation with oestradiol concentrations was abolished (r2 = 0.07, ns. after NK3Ra). FSH secretion was increased by kisspeptin-10 after NK3Ra treatment, but not without NK3Ra treatment.Limitations, reasons for cautionThe study did not explore the dose relationship of the effect of NK3R antagonism. The impact of obesity or other aspects of the variability of the PCOS phenotype was not studied due to the small number of subjects.Wider implications of the findingsThese data demonstrate the interactive regulation of GnRH/LH secretion by NKB and kisspeptin in PCOS, and that the NKB system mediates aspects of oestrogenic feedback.Study funding/competing interest(s)Wellcome Trust through Scottish Translational Medicine and Therapeutics Initiative (102419/Z/13/A) and MRC grants (G0701682 to R.P.M. and R.A.A.) and MR/N022556/1 to the MRC Centre for Reproductive Health. This work was performed within the Edinburgh Clinical Research Facility. J.T.G. has undertaken consultancy work for AstraZeneca and Takeda Pharmaceuticals and is an employee of Boehringer Ingelheim. R.P.M. has consulted for Ogeda and was CEO of Peptocrine. R.A.A. has undertaken consultancy work for Merck, Ferring, NeRRe Therapeutics and Sojournix Inc. J.D.V. and K.S. have nothing to disclose.Trial registration numberN/A.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

6 results from studies that gave the peptide. 6 results from people.

  1. 01HumanRandomized controlled trialEfficacy outcome

    In women with PCOS after NK3Ra administration, the LH response to kisspeptin‑10 was preserved compared with vehicle.

    In plain wordsIn women with PCOS who took an NK3 blocker, kisspeptin‑10 still raised luteinizing hormone compared with vehicle.

    Peptide
    Kisspeptin-10
    Outcome
    IncreaseLH response to kisspeptin-10 after NK3Ra
    Study

    n = 8

    Comparator
    Vehicle infusion
    Outcome group
    Sex hormones and fertility · Reproductive and sexual health
    Studied dose
    4 µg/kg/h · intravenous · 7 hAs given in this study (human).

    Measurements

    LH
    3.5 IU/l
    vehicle
    LH
    9 IU/l
    kisspeptin-10

    Source sentences

    Summary
    After NK3Ra administration, the LH response to kisspeptin-10 was preserved (vehicle 3.5 ± 0.3 vs 9.0 ± 2.2 IU/l with kisspeptin-10, P < 0.05)
    2 context sentences
    Summary · context
    The NK3Ra MLE4901, 40 mg orally twice a day, was administered to women with PCOS for 7 days (n = 8) (vs no treatment, n = 7).
    Summary · context
    On the last day of NK3Ra administration or the equivalent day in those not treated, women were randomized to 7-h kisspeptin-10 (4 µg/kg/h i.v.) or vehicle infusion.
  2. 02HumanRandomized controlled trialOther

    In women with PCOS after NK3Ra administration, the positive correlation between the LH response to kisspeptin‑10 and oestradiol concentrations was abolished.

    In plain wordsIn women with PCOS who took an NK3 blocker, the link between the kisspeptin‑10 response and oestradiol disappeared.

    Peptide
    Kisspeptin-10
    Outcome
    No significant changeRelationship of LH response to oestradiol, after NK3Ra
    Study

    n = 8

    Outcome group
    Sex hormones and fertility · Reproductive and sexual health
    Studied dose
    4 µg/kg/h · intravenous · 7 hAs given in this study (human).

    Measurements

    r2
    0.07
    LH vs oestradiol after NK3Ra

    Source sentences

    Summary
    but the positive correlation with oestradiol concentrations was abolished (r2 = 0.07, ns. after NK3Ra).
    2 context sentences
    Summary · context
    The NK3Ra MLE4901, 40 mg orally twice a day, was administered to women with PCOS for 7 days (n = 8) (vs no treatment, n = 7).
    Summary · context
    On the last day of NK3Ra administration or the equivalent day in those not treated, women were randomized to 7-h kisspeptin-10 (4 µg/kg/h i.v.) or vehicle infusion.
  3. 03HumanRandomized controlled trialEfficacy outcome

    In women with PCOS after NK3Ra treatment, kisspeptin‑10 increased FSH secretion.

    In plain wordsIn women with PCOS who took an NK3 blocker, kisspeptin‑10 raised follicle-stimulating hormone.

    Peptide
    Kisspeptin-10
    Outcome
    IncreaseFSH secretion with kisspeptin-10 after NK3Ra
    Study

    n = 8

    Outcome group
    Sex hormones and fertility · Reproductive and sexual health
    Studied dose
    4 µg/kg/h · intravenous · 7 hAs given in this study (human).

    Source sentences

    Summary
    FSH secretion was increased by kisspeptin-10 after NK3Ra treatment, but not without NK3Ra treatment.
    2 context sentences
    Summary · context
    The NK3Ra MLE4901, 40 mg orally twice a day, was administered to women with PCOS for 7 days (n = 8) (vs no treatment, n = 7).
    Summary · context
    On the last day of NK3Ra administration or the equivalent day in those not treated, women were randomized to 7-h kisspeptin-10 (4 µg/kg/h i.v.) or vehicle infusion.
  4. 04HumanRandomized controlled trialEfficacy outcome

    In women with PCOS without NK3Ra pre-treatment, kisspeptin‑10 increased LH secretion.

    In plain wordsIn women with PCOS, kisspeptin‑10 increased luteinizing hormone secretion.

    Peptide
    Kisspeptin-10
    Outcome
    IncreaseLH secretion with kisspeptin-10, without NK3Ra pre-treatment
    Study

    n = 7

    Outcome group
    Sex hormones and fertility · Reproductive and sexual health
    Studied dose
    4 µg/kg/h · intravenous · 7 hAs given in this study (human).

    Measurements

    LH secretion
    5.2 IU/L
    first value reported
    LH secretion
    7.8 IU/L
    with kisspeptin-10

    Source sentences

    Summary
    Without NK3Ra pre-treatment, kisspeptin-10 increased LH secretion (5.2 ± 0.5 to 7.8 ± 1.0 IU/L, P < 0.05)
    2 context sentences
    Summary · context
    The NK3Ra MLE4901, 40 mg orally twice a day, was administered to women with PCOS for 7 days (n = 8) (vs no treatment, n = 7).
    Summary · context
    On the last day of NK3Ra administration or the equivalent day in those not treated, women were randomized to 7-h kisspeptin-10 (4 µg/kg/h i.v.) or vehicle infusion.
  5. 05HumanRandomized controlled trialOther

    In women with PCOS without NK3Ra pre-treatment, the LH response to kisspeptin‑10 had a positive relationship with oestradiol concentrations.

    In plain wordsIn women with PCOS, the luteinizing hormone response to kisspeptin‑10 was linked to higher oestradiol levels.

    Peptide
    Kisspeptin-10
    Outcome
    Not applicableRelationship of LH response to oestradiol, without NK3Ra
    Study

    n = 7

    Outcome group
    Sex hormones and fertility · Reproductive and sexual health
    Studied dose
    4 µg/kg/h · intravenous · 7 hAs given in this study (human).

    Measurements

    r2
    0.59
    LH vs oestradiol

    Source sentences

    Summary
    with a positive relationship to oestradiol concentrations (r2 = 0.59, P < 0.05).
    2 context sentences
    Summary · context
    The NK3Ra MLE4901, 40 mg orally twice a day, was administered to women with PCOS for 7 days (n = 8) (vs no treatment, n = 7).
    Summary · context
    On the last day of NK3Ra administration or the equivalent day in those not treated, women were randomized to 7-h kisspeptin-10 (4 µg/kg/h i.v.) or vehicle infusion.
  6. 06HumanRandomized controlled trialEfficacy outcome

    In women with PCOS without NK3Ra treatment, kisspeptin‑10 did not increase FSH secretion.

    In plain wordsIn women with PCOS who did not take an NK3 blocker, kisspeptin‑10 did not raise follicle-stimulating hormone.

    Peptide
    Kisspeptin-10
    Outcome
    No significant changeFSH secretion with kisspeptin-10 without NK3Ra
    Study

    n = 7

    Outcome group
    Sex hormones and fertility · Reproductive and sexual health
    Studied dose
    4 µg/kg/h · intravenous · 7 hAs given in this study (human).

    Source sentences

    Summary
    FSH secretion was increased by kisspeptin-10 after NK3Ra treatment, but not without NK3Ra treatment.
    2 context sentences
    Summary · context
    The NK3Ra MLE4901, 40 mg orally twice a day, was administered to women with PCOS for 7 days (n = 8) (vs no treatment, n = 7).
    Summary · context
    On the last day of NK3Ra administration or the equivalent day in those not treated, women were randomized to 7-h kisspeptin-10 (4 µg/kg/h i.v.) or vehicle infusion.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    9 Oct 2026, 18:17 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:04 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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