Journal
CLINICAL ENDOCRINOLOGY
Volume 84, Issue 6, Pages 939-945Publisher
WILEY
DOI: 10.1111/cen.12977
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Funding
- NIHR Clinical research facility
- Biomedical Research Centre at Imperial College Healthcare NHS Trust
- MRC
- BBSRC
- NIHR, an Integrative Mammalian Biology (IMB) Capacity Building Award [FP7- HEALTH- 2009- 241592]
- NIHR Biomedical Research Centre Funding Scheme
- NIHR Imperial Biomedical Research Centre Funding Scheme
- NIHR
- Wellcome Trust/GlaxoSmithKline Translational Medicine Training Fellowship
- MRC [G1000455] Funding Source: UKRI
- Medical Research Council [G1000455] Funding Source: researchfish
- National Institute for Health Research [ACF-2010-21-015, CL-2014-21-003, RP-2014-05-001, NF-SI-0513-10080, ACF-2011-21-004, CL-2015-21-003, ACF-2012-21-003, CL-2009-21-004, ACF-2008-21-018, CDF-2009-02-05, NF-SI-0507-10337] Funding Source: researchfish
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Background and objectiveKisspeptin 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 patientsA prospective, single-blinded placebo-controlled study. Healthy women (n = 4) received an 8-h SC infusion of kisspeptin-54 01, 03 or 10 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. ResultsSC infusion of kisspeptin-54 increased LH and FSH. The LH response to SC infusion of kisspeptin-54 (03 and 10 nmol/kg/h) positively correlated with baseline oestradiol levels (P < 0001). Further statistical analyses showed that in the 10 nmol/kg/h group, a 100pmol/l rise in baseline oestradiol was associated with a 10 IU/l increase in LH. ConclusionsKisspeptin 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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