Kisspeptin, bremelanotide and the meal test
I trust an appetite argument more when somebody has measured the meal.
Hunger ratings and food intake
In women with overweight or obesity, intravenous kisspeptin increased LH but left both self-rated hunger and objectively measured food intake unchanged compared with vehicle. LH, a reproductive hormone, supplied a check that the peptide had biological activity during the experiment.
That combination is unusually informative. The body registered an effect in the measured hormonal system; the meal result stayed quiet. The unchanged intake carries considerable weight in my judgment because it addresses the appetite question directly.
An elegant account of energy sensing could make an appetite effect sound inevitable. Here the investigators actually asked about hunger and measured consumption. I prefer to let that result complicate the story.
Bremelanotide in metabolic research
Bremelanotide's Phase 1 metabolic experiments in obese premenopausal women reported reductions in body weight and caloric intake. Those experiments used high-frequency research dosing. The compound's appetite finding belongs to that exposure and that population.
I resist adding it as a casual extra benefit to a conversation about sexual desire. A metabolic experiment deserves its own scrutiny. Its outcome also cannot supply the missing postmenopausal result simply because the participants were women.
The kisspeptin and bremelanotide results come from separate experiments. I would reserve any ranking for a direct comparison; here, the useful comparison concerns the questions each experiment actually put to the body.
The mouse genetics
In adult female mice lacking the kisspeptin receptor, researchers found greater body weight and adiposity, impaired glucose tolerance and reduced energy expenditure. This experiment gives the kisspeptin system a role in metabolic biology in mice.
The genetic experiment removes receptor function. The food-intake experiment administers kisspeptin to women and measures hunger and food intake. They probe different interventions. Both findings can stand: a metabolic role in the mouse experiment and unchanged intake in the human study.
I like the friction between these papers. It prevents a smooth story in which a pathway's involvement automatically predicts the result of administering its signal.
Menopause and the appetite claim
For the question suggested by Meno Peptides, a postmenopausal experiment would finally address the intended population. The kisspeptin paper describes women with overweight or obesity; the bremelanotide paper specifies obese premenopausal women. Their results deserve those descriptions whenever they travel.
The null result has earned its space in this notebook. I much prefer the unremarkable meal to an appetite claim made more exciting than the experiment. The desire chapter follows bremelanotide back to the outcome for which the larger trials were conducted.