Kisspeptin-10

Kisspeptin-10 is a synthetic chain of ten amino acids. It sits one step further upstream than anything approved for the sex hormone axis: it switches on a receptor in the hypothalamus, which releases gonadotropin releasing hormone, which makes the pituitary put out luteinising hormone, which tells the testis to make testosterone. The naming is the trap. The gene makes a longer protein that the body cuts into several pieces, kisspeptin-54, -14, -13 and -10, all sharing the same tail, and much of the famous research uses kisspeptin-54 rather than this one. Nothing containing kisspeptin-10 is approved anywhere, on the strength of the search the American regulator describes, and in October 2024 its compounding advisory committee voted 0 in favour and 11 against adding it to the list pharmacies may compound with.

The signal is pulsed by design, and that is the fact the dosing turns on. Male rhesus monkeys on a continuous drip surge for about three hours and then fall back to baseline with the drip still running, while the same amount given as a one minute pulse every hour keeps them surging at full size for 48 hours. Kisspeptin-10 also clears extremely fast, at a plasma half life of 3.8 minutes in healthy men and 4.1 in women, against about 27.6 minutes for kisspeptin-54. The academic group still running trials of it under the skin doses it roughly every 90 minutes, around the clock.

Raising testosterone, libido and fertility in men. The human record is genuinely large, which is unusual here: the regulator tabulated 24 published human studies and roughly 300 subjects, footnoting that the total may be too high because subjects could overlap. It is thin in exactly one dimension, and that dimension is the product. The record for the sold route is one 2011 study in healthy women in which nothing moved.

Two things get read backwards. The first is that a large human record means a large record for what is being sold; here almost all of it is a drip in a clinic, on one day, and the product is an injection you give yourself. The second is the pulse. A compound cleared from the blood in under four minutes, whose receptor is designed to answer a rhythm and which goes quiet under a constant signal, is being sold on a once daily schedule. The nearest thing to a real test of that schedule is a pharmaceutical company's own programme: an analogue given under the skin on once daily, twice weekly and once weekly schedules in exactly this population, terminated for missing its primary endpoint, with placebo beating two of the three drug arms.

The published trial record is short and unremarkable, and both halves of that matter. The regulator states that no serious adverse events were reported in the studies it identified, then qualifies it in the same breath: the studies were short, the samples small, many carried no adverse event information at all, and it found no published trial assessing safety when the compound is given on a fixed schedule for longer than one day. Fourteen of the 24 rows in its appendix record safety findings as not reported. Its stated first concern is immunogenicity, because antibodies raised against the injected peptide could cross-neutralise the kisspeptin the body makes itself, and it notes that injection under the skin is generally more immunogenic than injection into a vein. Its surveillance database held one report, a 17 year old male on 100 micrograms daily under the skin for six weeks who gained weight and whose estrone, an oestrogen, rose.