Doses studied · routes · the fading signal

Kisspeptin dosage in the literature: what was given, to whom, by which route.

Research-context only — every figure reported as a studied dose in a named population by a named route, never as a recommendation.

The short version

This page describes kisspeptin dosage the way the studies describe it — as research protocols, not advice. No number here is a recommendation, and there is no human-use instruction anywhere on this site. Two facts shape everything. First, the two main forms clear at very different speeds: kisspeptin-10 lasts only about four minutes in the blood, while kisspeptin-54 lasts around half an hour, so the longer form sustains its effect. Second — and this is the heart of it — giving kisspeptin continuously or at high doses makes the effect fade within days, because the receptor desensitizes (tachyphylaxis). That is why researchers care so much about how it is delivered: a brief, well-spaced pulse behaves very differently from a steady drip. The doses below are written only as 'studied at X in this group by this route.'

Kisspeptin dosage — the studied protocols

Across the human record, kisspeptin dosage has been explored by four routes — intravenous bolus, continuous IV infusion, subcutaneous injection and, most recently, intranasal spray. Reported as studied doses only:

  • Kisspeptin-54, IV infusion, healthy men: 4 pmol/kg/min over 90 min — the early HPG-axis study [8].
  • Kisspeptin-10, IV, healthy men: 0.3–1.0 µg/kg bolus; continuous infusion 1.5 µg/kg/h [3].
  • Kisspeptin-54, IV infusion, hypothalamic amenorrhea: 0.01–1.00 nmol/kg/h [4].
  • Kisspeptin-54, SC bolus, IVF oocyte-maturation trigger: 3.2–12.8 nmol/kg, with the highest live-birth rate at 9.6 nmol/kg [5].
  • Kisspeptin-54, intranasal, healthy men and women and amenorrhea: 12.8 nmol/kg primary dose [6].

Every one of these is a supervised research protocol in a defined population, not a self-administered dose.

Kisspeptin half life — the short flare and the long burn

The kisspeptin half life splits the two isoforms cleanly. Kisspeptin-10 has a functional plasma half-life of roughly 4 minutes in humans — plasma peptidases clear the short fragment quickly, so its signal is a brief, sharp flare [3]. Kisspeptin-54 lasts far longer: its measured human half-life is 27.6 ± 1.1 minutes [8]. The larger fifty-four-residue peptide resists endopeptidase cleavage better, which is why it reaches higher peak levels and sustains LH release longer at equimolar doses — a difference that mechanistic work has attributed directly to that greater enzymatic resistance [11]. The short half-life of kisspeptin-10 is not only a limitation: it may help preserve receptor sensitivity under well-spaced or pulsatile protocols, because the signal is not held on long enough to tire the receptor.

Why continuous dosing defeats itself: tachyphylaxis

The defining feature of kisspeptin dosing is that more is not better. Chronic twice-daily subcutaneous kisspeptin-54 in women with hypothalamic amenorrhea caused marked tachyphylaxis: the acute LH increment of about 24 IU/L on day 1 fell to roughly 2.5 IU/L by the fourteenth injection day [10]. High-dose continuous IV infusion (1.0 nmol/kg/h) likewise showed desensitization during the infusion [4]. The lesson is consistent across routes: sustained or frequent KISS1R activation downregulates the receptor, so the bolus-versus-continuous distinction is central, and pushing dose or duration tends to blunt the response rather than sustain it [10].

The investigational compound TAK-683, a metastin (kisspeptin) analogue, made the point in the opposite direction by design: in double-blind studies in healthy men, continuous dosing suppressed testosterone below castrate levels in most subjects — a demonstration that continuous kisspeptin-receptor agonism desensitizes the axis rather than driving it [12].

Kisspeptin nasal spray — the non-invasive route

The kisspeptin nasal spray is the newest delivery story. In the 2025 study, intranasal kisspeptin-54 at a 12.8 nmol/kg primary dose rapidly stimulated LH release across healthy men, healthy women and women with hypothalamic amenorrhea, with no adverse events reported, and the nasal-spray formulation was stable up to 60 days at 4 °C [6]. It is the first clinical demonstration that kisspeptin can work without a needle — a meaningful step for a peptide whose research has otherwise leaned on IV and subcutaneous routes. It remains an investigational protocol, not a product, and no human-use dose is recommended here.