Growth Hormone Replacement in Older Men

Updated: Dec 14, 2015
  • Author: Angela Gentili, MD; Chief Editor: George T Griffing, MD  more...
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Discussion in this article is limited to hyposomatotropism of aging. For more information on adult growth hormone deficiency (GHD), see Hypopituitarism (Panhypopituitarism).

The decrease in lean body mass and increase in adipose tissue that occurs with aging have been suggested to be partly due to the age-associated decrease in growth hormone (GH) secretion and insulin-like growth factor-1 (IGF-1), also known as somatomedin C, which is produced by the liver and other tissues in response to GH. This decline in the secretory activity of the GH–IGF-1 axis has been termed somatopause or hyposomatotropism of aging. Whether this decrease in GH secretion should be treated is debatable. [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11]



GH secretion

GH is released from the anterior pituitary gland in a pulsatile manner. Two hypothalamic hormones control GH secretion: Growth hormone-releasing hormone (GHRH) stimulates GH secretion, and somatostatin inhibits it. The majority of GH secretion occurs at night during slow-wave sleep, when somatostatin release is diminished.

GH stimulates production of IGF-1 in the liver and other tissues. IGF-1 circulates through the bloodstream bound to 6 specific binding proteins in several combinations. The major serum IGF-binding protein is insulinlike growth factor binding protein-3 (IGFBP-3). Both GH and IGF-1 have important metabolic actions in several tissues.

A single measurement of plasma GH levels is difficult to interpret because of the pulsatile secretion of GH. Levels of IGF-1 vary little during the day; therefore, assays of IGF-1 have been used as a better screening indicator of the status of the GH-IGF-1 axis.

Effect of age on GH secretion

Several studies have shown that the amplitude of GH pulses is reduced with aging both in men and women. [12] In aging men, GH secretion declines by 50% every 7 years after age 18-25 years. The negative effect of age on 24-hour mean serum GH is twice as much in men as in premenopausal women. Estrogens may have a protective effect that limits the rate of decline of GH secretion with aging.

IGF-1 and IGFBP-3 levels also decrease with aging. This decline of the GH–IGF-1 axis is probably caused by altered hypothalamic regulation (ie, decrease in GHRH and increase in somatostatin), rather than a decreased capacity to secrete GH.

The pathophysiology of the somatopause is confounded by several variables that can contribute to the decline in GH secretion associated with aging. These variables include the following:

  • Adiposity: Individuals who are moderately to markedly obese have profound suppression of GH secretion at any age.

  • Decreased production of sex steroid hormones: Falling levels of testosterone in men and estrogens in women affect GH secretion.

  • Decreased physical fitness: A strong correlation exists between aerobic capacity and 24-hour serum GH concentration.

  • Fragmented sleep: GH secretion can be affected by altered sleep patterns because it occurs predominantly during slow-wave sleep.

  • Malnutrition: Poor nutritional status negatively affects IGF-1 synthesis and action.




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Incidence is unknown because somatopause may be part of normal aging rather than a disease.


In aging men, GH secretion declines by 50% every 7 years after age 18-25 years.