The "multiple hormone deficiency" theory of aging: is human senescence caused mainly by multiple hormone deficiencies?

Ann N Y Acad Sci. 2005 Dec;1057:448-65. doi: 10.1196/annals.1322.035.


In the human body, the productions, levels and cell receptors of most hormones progressively decline with age, gradually putting the body into various states of endocrine deficiency. The circadian cycles of these hormones also change, sometimes profoundly, with time. In aging individuals, the well-balanced endocrine system can fall into a chaotic condition with losses, phase-advancements, phase delays, unpredictable irregularities of nycthemeral hormone cycles, in particular in very old or sick individuals. The desynchronization makes hormone activities peak at the wrong times and become inefficient, and in certain cases health threatening. The occurrence of multiple hormone deficits and spilling through desynchronization may constitute the major causes of human senescence, and they are treatable causes. Several arguments can be put forward to support the view that senescence is mainly a multiple hormone deficiency syndrome: First, many if not most of the signs, symptoms and diseases (including cardiovascular diseases, cancer, obesity, diabetes, osteoporosis, dementia) of senescence are similar to physical consequences of hormone deficiencies and may be caused by hormone deficiencies. Second, most of the presumed causes of senescence such as excessive free radical formation, glycation, cross-linking of proteins, imbalanced apoptosis system, accumulation of waste products, failure of repair systems, deficient immune system, may be caused or favored by hormone deficiencies. Even genetic causes such as limits to cell proliferation (such as the Hayflick limit of cell division), poor gene polymorphisms, premature telomere shortening and activation of possible genetic "dead programs" may have links with hormone deficiencies, being either the consequence, the cause, or the major favoring factor of hormone deficiencies. Third, well-dosed and -balanced hormone supplements may slow down or stop the progression of signs, symptoms, or diseases of senescence and may often reverse or even cure them. If hormone deficiencies and imbalances are the major causes of senescence, what then is the treatment? Crucial for the treatment of senescent persons is to make a correct diagnosis by making up an anamnesis of all symptoms related to hormone disturbances, conducting a thorough physical examination, and getting laboratory tests done such as serum and 24-hour urine analyses. The physician should look not only for hormone deficiencies, including the mildest ones, but also for any alterations in hormone circadian cycles, and for the presence of any factors--nutritional, dietary, behavioral, lifestyle, environmental (including illumination and indoor, outdoor, or dietary pollutants)--that cause or aggravate hormone deficiencies. After completion of the detailed diagnostic phase and obtaining and analyzing the results of the tests, treatment can start. In general, before supplying hormones, all other factors that contribute to senescence should be eliminated. After that, supplements of the missing hormones can then be administered, carefully respecting an appropriate timing of their intake, and eventually recommending measures such as lifestyle changes to restore circadian rhythmicity.

Publication types

  • Review

MeSH terms

  • Aging / physiology*
  • Circadian Rhythm / physiology
  • Hormone Replacement Therapy
  • Hormones / deficiency*
  • Humans
  • Models, Theoretical*


  • Hormones