Slow Clockreference notes on healthy ageing

Growth hormone after fifty: what two randomised trials actually measured

Two six-month randomised trials in men aged 65 to 80 give a surprisingly clean answer. Lean mass rose on growth hormone alone, but mid-thigh muscle cross-section and aerobic capacity rose only when testosterone came with it, and only one of six strength measures moved at all.

mixedStudies disagree, or the mechanism is contested.Revised

A small labelled vial beside a folded paper document on a pale wooden table, lit from one side

The interesting column in both papers is the one where growth hormone stood alone, and the one where testosterone stood beside it.

The anti-ageing section of every clinic website eventually arrives at the same sentence: growth hormone falls, and what falls can be replaced. Two randomised trials published in the Journal of Clinical Endocrinology & Metabolism — one on eighty men, one on twenty-one — are the cleanest reading of what that sentence is actually backed by, and they are worth reading side by side because the interesting result is in the comparison between the arms, not in the headline.

If you want the history of the secretagogue side of the same story, younglab.eu has written it up as a case study in how a compound gets approved and then disappears: sermorelin, approved and then gone.

The larger trial: eighty men, six months, four arms

The 2006 trial randomised 80 healthy, community-dwelling older men aged 65 to 80 over six months into four arms: placebo growth hormone plus placebo testosterone; growth hormone alone; testosterone alone; and both. Growth hormone was titrated over eight weeks to push IGF-I into the upper half of the age-specific reference range — a deliberately physiological target, not a supra-physiological one.

The outcomes are the part that matters, because they are reported arm by arm:

  • Lean body mass increased with growth hormone alone (p = 0.004) and with the combination (p = 0.008), against placebo.
  • Total body fat decreased with the combination only (p = 0.02).
  • Mid-thigh muscle cross-section area increased only after both together (p = 0.006).
  • Aerobic capacity increased only after both together (p < 0.001).
  • Muscle strength was variable: of six measures, one increased significantly, and only in the combination arm.
  • Bodily pain increased with growth hormone alone (p = 0.003).
  • There were no major adverse effects.

Read that list again and the structure is unmistakable. Growth hormone alone moved a quantity. The combination moved a function.

The smaller trial: the same arms, a different question

The 2008 paper used the same four-arm design in 21 healthy older men aged 65 to 75, again over six months, and asked a mechanistic question rather than a functional one. Proteolysis and protein synthesis were measured with a stable isotope infusion of leucine; muscle biopsies were taken for gene expression.

  • Serum IGF-I rose significantly with growth hormone and with the combination (p < 0.001), confirming the titration worked.
  • Whole-body protein breakdown and synthesis both increased with growth hormone alone and with the combination — the hormones were doing something to turnover, and the increase was comparable between them.
  • Mid-thigh muscle mass and maximal oxygen capacity increased with the combination only (p < 0.04).
  • Muscle function gene expression did not change significantly in any arm. The within-group comparison did show increased androgen receptor expression in the combination group (p = 0.001).

The last two lines are the ones people skip. Protein turnover rose, and functional capacity still only rose when testosterone was alongside it.

What these trials do not show

  • Nothing about women. Both studies enrolled men. The hormonal context after menopause is not the same, and these data do not transfer.
  • Nothing about long-term outcomes. Six months, and the endpoints are body composition and oxygen capacity. Neither paper reports fractures, cognition, cardiovascular events or lifespan — the outcomes that would matter if the claim is about ageing rather than about a number.
  • Nothing about the shape of the curve. Titration targeted the upper half of the age-specific IGF-I range. The trials do not tell you what happens above that band, or what happens with chronic elevation.
  • No separation of growth hormone from the titration effect. IGF-I was pushed up in both growth hormone arms; the trials do not isolate growth hormone from the resulting IGF-I state.
  • The strength finding is one measure out of six. A single significant strength measure in one arm of eighty men is a hypothesis, not a result to generalise from.

The line worth keeping

Growth hormone alone in these trials did what growth hormone is biochemically expected to do: it shifted protein towards lean tissue. What it did not do, on its own, was improve how well those men walked, breathed or lifted. The second paper is blunter still — turnover up, gene expression in muscle unchanged.

That is the whole argument, and it is a narrow one. It is not that the hormone does nothing. It is that the claim about ageing is doing considerably more work than these two trials support.

Sources

  1. J Clin Endocrinol Metab 2006 — The effects of growth hormone and/or testosterone in healthy elderly men: a randomized controlled trial (PMID 16332938)
  2. J Clin Endocrinol Metab 2008 — The effects of growth hormone and/or testosterone on whole body protein kinetics and skeletal muscle gene expression in healthy elderly men (PMID 18477661)