WHAT THIS STUDY IS
A landmark randomized controlled trial published in the New England Journal of Medicine, examining whether biosynthetic human growth hormone could reverse the age-related decline in body composition in older men. Conducted by Daniel Rudman, M.D. and colleagues at the Medical College of Wisconsin and affiliated Veterans Affairs Medical Centers, this study is among the most cited papers in the history of endocrinology and growth hormone research — and remains the foundational clinical evidence linking the decline of the growth hormone–IGF-1 axis to the physical changes associated with aging.
THE CORE FINDING
Diminished secretion of growth hormone is directly responsible for the loss of lean body mass, the expansion of adipose tissue, and the thinning of skin that characterize normal aging. When biosynthetic human growth hormone was administered to men over 60 with documented growth hormone deficiency, those changes were substantially reversed — with effects equivalent in magnitude to what would normally occur over 10 to 20 years of aging.
THE TRIAL
21 healthy men between the ages of 61 and 81 with confirmed low plasma IGF-1 concentrations (below 350 U/L) completed a 12-month protocol. After a 6-month baseline observation period, 12 men received subcutaneous injections of biosynthetic human growth hormone three times per week for 6 months; 9 men received no treatment. Lean body mass, adipose tissue mass, skin thickness, and bone density were measured at the end of each period.
KEY DATA POINTS
Lean body mass increased by 8.8% in the treatment group (p < 0.0005), with no significant change in the control group
Adipose tissue mass decreased by 14.4% in the treatment group (p < 0.005), with no significant change in the control group
Lumbar vertebral bone density increased by 1.6% in the treatment group (p < 0.04)
Skin thickness increased by 7.1% in the treatment group (p = 0.07)
Mean plasma IGF-1 levels rose from approximately 200–250 U/L to 830 U/L within the first month of treatment — reaching the normal range for healthy men aged 20–40
Body weight did not change significantly in either group, meaning the compositional changes reflected true remodeling: more muscle, less fat — not simply weight gain
WHY IGF-1 MATTERS
Because growth hormone is secreted in short pulses — primarily during early sleep — it is difficult to measure directly. IGF-1, produced by the liver in response to growth hormone, serves as the practical clinical proxy. In healthy men aged 20–40, plasma IGF-1 typically ranges from 500 to 1,500 U/L. In men over 60, nearly one third fall below 350 U/L — the threshold below which no detectable spontaneous growth hormone pulses can be measured. This study confirmed that men with IGF-1 below this threshold respond normally to exogenous growth hormone, restoring IGF-1 to the youthful range and reversing the downstream body composition effects of deficiency.
WHY THIS MATTERS
Prior to this study, the progressive loss of lean mass and accumulation of fat with aging were considered inevitable consequences of time. Rudman et al. demonstrated they are not — they are consequences of measurable hormonal decline, and they respond to hormonal restoration. The effects observed over six months of treatment were comparable in magnitude to what would otherwise occur over a decade or two of aging. This finding established the mechanistic case for targeting the growth hormone–IGF-1 axis as a strategy for maintaining physical function and body composition in aging men — the same axis that secretagogues like sermorelin stimulate through an endogenous, pulsatile pathway.
Rudman et al. | New England Journal of Medicine | Vol. 323, No. 1 | July 1990
Read the full journal here: https://www.nejm.org/doi/10.1056/NEJM199007053230101