Gonadorelin

Gonadorelin is not a copy of a human hormone. It is the hormone, the same ten amino acids the hypothalamus releases to tell the pituitary to make the two signals that run the testicles and the ovaries. Britain licenses it as a diagnostic, a single 100 microgram injection to test how the pituitary responds. Canada licenses it for inducing ovulation, worn as a pod delivering 5 to 20 micrograms every 90 minutes. The United States approved two human products in the 1980s and lists every strength of both as discontinued; the only currently marketed American product carrying one of those names is a cattle drug whose label says it is not for human use. What it is sold for is none of those things: keeping the testicles working in men taking testosterone.

The signal is a rhythm rather than a level, and that is the whole pharmacology. Work published in Science in 1978, in monkeys whose own supply had been destroyed, showed that constant infusion failed to restore the pituitary hormones while a pulse once an hour restored them, and that putting a restored animal back on continuous delivery desensitised the process again. It works like a doorbell, which brings someone when pressed at intervals and gets the wire pulled out of the wall when held down. Gonadorelin also clears in about 4 minutes on the British label, so an injection on Monday is long gone before Thursday's.

Preserving testicular function and fertility in men on testosterone therapy, largely as a replacement for human chorionic gonadotropin after a rule change made that harder to compound. I found no published trial and no registered trial of gonadorelin in men on testosterone. The studies that do exist in men are pump studies in patients whose brains make no gonadotropin releasing hormone at all, which is close to the opposite population.

The premise is that testosterone silences the hypothalamus, so you put the hypothalamic signal back. That premise was put to a human test in 1989 and did not survive it. Six men whose brains make no such signal were fitted with a pump delivering it every two hours until their levels were normal, then given testosterone with the pump still running. Both pituitary hormones fell anyway, luteinising hormone to about half and follicle stimulating hormone to about 30 percent, and the pituitary's answer to each pulse fell with them. The authors concluded that testosterone suppresses them by a route that does not run through the hypothalamus at all, acting directly on the pituitary. The British licence says the same thing in its interactions section, telling prescribers to run the test in the absence of drugs that directly affect pituitary gonadotropin secretion, naming preparations containing androgens. Six men is six men, and that is a hypothesis rather than a verdict. It is also the closest published human test of the proposition that I could find, and it appears on no sales page I read.

The label record is unremarkable and should be reported that way. The British adverse reaction table lists nothing at common or very common frequency; pain, swelling and itching are uncommon, and hypersensitivity reactions, a fast heartbeat, hives, redness of the skin and of the eyelid and antibodies against the peptide sit in the rare column, between 1 in 10,000 and 1 in 1,000. Two limits matter. The label's reassurance about hypersensitivity is explicitly about a single diagnostic dose, and it tells prescribers to observe carefully if the injection is repeated, which should be read against roughly a hundred to a hundred and fifty injections a year. And it says gonadorelin and its analogues are not recommended in patients with a pituitary adenoma, a benign pituitary tumour common enough to be found by accident, because a sudden bleed into it may occur. The only real world adverse event figures in men I found describe a continuously worn pump rather than injections: 9 of 10 men on the pump had red hardened skin at the needle site and one developed a small abscess.