SFEBES2018 Poster Presentations Neuroendocrinology and pituitary (25 abstracts)
A single bolus of the novel kisspeptin analogue, MVT-602, induces a prolonged LH surge compared to kisspeptin-54 during the follicular phase in healthy women
Sophie A Clarke , Ali Abbara , Pei Chia Eng , Maria Phylactou , Deborah Papadopoulou , Koteshwara Muralidhara , Edouard Mills , Sophie Jones , C Pratibha Machenahalli , Germaine Chia , Lisa Yang , Chioma Izzi-Engbeaya , Mark Sykes , Julia K Prague , Alexander N Comninos & Waljit S Dhillo
Imperial College London, London, UK.
Background: Kisspeptin-54 (KP54) stimulates hypothalamic GnRH release. The kisspeptin analogue, MVT-602, has a longer half-life (t1/2108min) than KP54 (t1/228mins). MVT-602 potently stimulates gonadotrophin release in men. We sought to determine for the first time the effect of MVT-602 on gonadotrophin release in healthy women.
Methods: A two-phase dose-finding study was carried out in 9 healthy women, 18–35 yrs with regular menstrual cycles (mean±SEM 29.1±0.5days). Phase 1: three women received a subcutaneous injection of KP54 (9.6 nmol/kg), or MVT-602 (0.003, 0.03, 0.1, 0.3, or 1 nmol/kg) during the early follicular phase (days 1–4) of successive menstrual cycles. Serum gonadotrophin levels were measured regularly for 14 hrs, and at 24 hrs and 48 hrs post-injection. Phase 2: six further women received KP54 and MVT-602 (0.01 or 0.03 nmol/kg) with extended blood sampling for 24 hrs. Interventions were compared by one-way ANOVA with post hoc Dunn’s test.
Results: Phase 1: Peak mean (±SD) serum LH occurred at 285±41.3mins following KP54, but later following MVT-602 (MVT-602 0.01 nmol/kg: 1098±245.2 mins, MVT-602 0.03 nmol/kg: 1330±58.9mins). Phase 2: Peak serum LH following MVT-602 was similar to KP54 (KP54: 10.4±2.7iU/L; MVT-602 0.01 nmol/kg: 11.1±5.1iU/L; MVT-602 0.03 nmol/kg:12.3±5.8iU/L; P>0.05 vs KP54). MVT-602 0.01 nmol/kg additionally elicited a serum FSH rise 24 hrs post-injection (MVT-602 0.01 nmol/kg: 1.9±1.5 iU/L), sufficient to induce a rise in serum oestradiol 330±127 nmol/L (P=0.03 vs KP54).
Conclusion: MVT-602 resulted in a LH-surge that was of similar amplitude but more prolonged compared to KP54 9.6 nmol/kg. This dose of KP54 safely induces oocyte maturation in IVF treatment. Therefore further studies are indicated to determine if the more prolonged LH surge elicited by MVT-602 delivers therapeutic advantage in the treatment of women with reproductive disorders.
Volume 59
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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