Growth Hormone Replacement in Older Men

Updated: Apr 14, 2020
  • Author: Angela Gentili, MD; Chief Editor: George T Griffing, MD  more...
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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. Hyposomatotropism of aging is associated with age-related loss of vitality and vigor, muscle mass, and physical function. In addition, frailty, central adiposity, accelerated risks for cardiovascular complications, and deterioration of mental function can occur. [1]

The pathophysiology of somatopause is confounded by several variables that can contribute to the decline in GH secretion associated with aging: adiposity, decreased production of sex steroid hormones, decreased physical fitness, fragmented sleep, and malnutrition (see Pathophysiology).

Whether the decrease in GH secretion should be treated is debatable. [2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12] In the United States, adult GH replacement is approved for acquired pituitary deficiency, proven prior childhood-onset GHD, and for the treatment of muscle wasting in HIV-infected adults. [13] Guidelines recommend GH replacement therapy only be offered to those patients diagnosed with GH-deficiency and an established etiology for the disorder. [14, 15]

The American Geriatrics Society 2015 updated Beers criteria for potentially inappropriate medication use in older adults make a strong recommendation against the use of GH in older adults because "the impact on body composition is small and associated with edema, arthralgia, carpal tunnel syndrome, gynecomastia and impaired fasting glucose." The only exception is its use as hormone replacement after pituitary gland removal. [16]

Discussion in this article is limited to hyposomatotropism of aging. For more information, see Growth Hormone Deficiency in Adults and Hypopituitarism (Panhypopituitarism).

For patient education information, see the Thyroid & Metabolism Center as well as Growth Hormone Deficiency Medications and Growth Hormone Deficiency FAQs.



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 six 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. [17] In aging men, GH secretion declines by 50% every 7 years after age 18-25 years. [1] 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.



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. In men 60 years or older, 35% are GH-deficient. Serum IGF-1 levels also decline with 85% of healthy men older than 59 years demonstrating low serum IGF-1 levels below the 2.5th percentile for younger men. [1]