Increasing LH pulsatility in women with hypothalamic amenorrhoea using intravenous infusion of Kisspeptin-54.
Jayasena. Channa N CN; Abbara. Ali A; Veldhuis. Johannes D JD; Comninos. Alexander N AN; Ratnasabapathy. Risheka R; De Silva. Akila A; Nijher. Gurjinder M K GM; Ganiyu-Dada. Zainab Z; Mehta. Amrish A; Todd. Catriona C; Ghatei. Mohammad A MA; Bloom. Stephen R SR; Dhillo. Waljit S WS
Key Findings
- Continuous IV kisspeptin-54 raised LH pulse frequency about three‑fold compared with placebo
- LH pulse secretory mass increased roughly six‑fold during kisspeptin infusion
- The optimal dose varied between individuals, showing a dose‑dependent therapeutic window
Practical Outcomes
- The study shows that kisspeptin can revive LH pulsatility in hypothalamic amenorrhea, suggesting a potential treatment path. For biohackers, it highlights the importance of finding a personal dose and that any benefit may be short‑lived, so any DIY protocol would need to consider dosing precision and delivery method (e.g., subcutaneous vs. IV).
Summary
Giving kisspeptin-54 through a steady IV drip temporarily boosts the rhythm and amount of the hormone LH in women who have lost periods because their brain isn’t signaling the reproductive system properly. The effect depends on the dose, with each woman responding best at a slightly different level, and the boost goes away after the infusion stops.
Abstract
Hypothalamic 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. The aim of the study was to determine whether constant iv infusion of kisspeptin-54 temporarily increases pulsatile LH secretion in women with HA. Five 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. Kisspeptin 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). Kisspeptin-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.
Study Information
pubmed
2014
2014-02-11T00:00:00.000Z
10.1210/jc.2013-1569
124
47