Growth Hormone & GHRH Analogs

•RCT evidence— Approved for GH deficiency; longevity case runs the opposite way

The longevity paradox

Across species, lower GH/IGF-1 signalling is associated with longer lifespan:

• Laron-syndrome humans (GH-receptor-deficient) have very low cancer and diabetes despite obesity.
• Ames and Snell dwarf mice (GH-deficient) live 40–70% longer.
• Centenarian cohorts over-represent IGF-1R loss-of-function variants.

Supplementing GH in healthy older adults runs against this gradient.

What GH does (and what trials show)

• Modest increases in lean mass and decreases in fat mass in older adults.
• Functional strength gains are small to absent.
• Insulin resistance, joint pain, oedema, carpal tunnel syndrome common.
• 2007 systematic review (Liu et al.): clinically meaningless benefit with substantial side-effect burden in healthy elderly.

GHRH analogs

• Sermorelin (GHRH 1-29): short-acting.
• CJC-1295 with DAC: long-acting; produces sustained pulsatile GH release.
• Tesamorelin: approved for HIV-associated lipodystrophy.
• Ipamorelin: ghrelin agonist; preserves pulsatility, less ACTH/ cortisol effects than older secretagogues.

GHRH analogs preserve more of the physiological pulsatility than direct GH replacement, with potentially better safety. They still raise IGF-1.

Cancer signal

GH and IGF-1 are mitogens. Long-term GH-replacement studies suggest a small increase in second cancer risk in childhood cancer survivors and possibly in adults. The mechanistic concern is real even when epidemiological signal is small.

Related entries

Insulin/IGF-1 signalling, IGF-1, Peptides (overview), TRT.