Sex differences in the hypothalamus in the different stages of human life

Dick F. Swaab, Wilson C.J. Chung, Frank P.M. Kruijver, Michel A. Hofman, Andon Hestiantoro, Pfaff, Finch, Kessler, Buitelaar, Heuser, Brosens, Slob, Kloet De Kloet, Goodwin

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69 Citations (Scopus)


Quite a number of structural and functional sex differences have been reported in the human hypothalamus and adjacent structures that may be related to not only reproduction, sexual orientation and gender identity, but also to the often pronounced sex differences in prevalence of psychiatric and neurological diseases. One of the recent focuses of interest in this respect is the possible beneficial effect of sex hormones on cognition in Alzheimer patients. The immunocytochemical localization of estrogen receptors (ER) α, β and androgen receptors has shown that there are indeed numerous targets for sex hormones in the adult human brain. Observations in the infundibular nucleus have, however, indicated that in this brain area the hyperactivity resulting from a lack of estrogens in the menopause seems to protect females against Alzheimer changes, in contrast to males. It is thus quite possible that estrogen replacement therapy may, in these brain areas, lead to inhibition of neuronal metabolism and thus to the same proportion of Alzheimer changes as are observed in men. Knowledge about the functional sex differences in the brain and the effect of sex hormones on neuronal metabolism may thus provide clues not only for the possible beneficial effects of these hormones (e.g., on cognition or hypertension), but also on possible central side effects of estrogen replacement therapy.

Original languageEnglish
Pages (from-to)S1-S19
JournalNeurobiology of Aging
Issue numberSUPPL. 1
Publication statusPublished - 2003


  • Alzheimer patients
  • Estrogen receptors
  • Estrogen replacement therapy
  • Hypothalamus
  • Sex differences


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