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Labrie [1] recently published a review describing that, while DHEA (dehydroepiandrosterone, prasterone) is present in the blood during the whole life of women, the sex steroid precursor DHEA becomes the only source of sex steroids after menopause [2,3], a time when the ovaries have stopped secreting estrogens [3,4], most likely to protect the endometrium [5].


It took 500 million years of evolution to insert the sequences of the proper peripheral steroidogenic enzymes in the human genome [6], a condition joined 20 million years ago in the primates by a high secretion rate of DHEA by the adrenals [4]. The conditions were then finally favorable for the introduction of menopause characterized mainly by the arrest of ovarian estrogen secretion in the blood, thus leading to biologically inactive serum levels of estradiol [3,4]. However, while the uterus is protected by the arrest of ovarian estradiol secretion, sex steroids remain very important in women after menopause for proper functioning of most other tissues. This requirement for a permanent supply of sex steroids after menopause is met by the continuing availability of DHEA (Table), mostly (~80%) secreted by the adrenals and about 20% by the ovary [2]. 


[b]Table[/b] Origin of sex steroids in pre- and postmenopausal women. After menopause, all estrogens are made in peripheral target tissues from DHEA [2,4]. The androgens made in the ovary during premenopause are mostly used to make estrogens and are not secreted as such in the blood in significant amounts. Some DHEA, however, is secreted in the blood, where it adds to the DHEA of adrenal origin. DHEA then reaches the peripheral tissues where it can make androgens and/or estrogens depending upon the level of expression of the steroidogenic enzymes present. In fact, androgens are all made in peripheral tissues from DHEA during the whole life of women [2]


[table][tr][td][i]Sex steroids[/i][/td][td][i]Premenopause[/i][/td][td][i]Postmenopause[/i][/td][/tr][tr][td]Estrogens[/td][td]Ovary[/td][td]No[/td][/tr][tr][td][/td][td]+ DHEA[/td][td]DHEA only[/td][/tr][tr][td]Androgens[/td][td]DHEA only [/td][td]DHEA only [/td][/tr][/table]


DHEA is then transformed specifically in each cell of each peripheral tissue into the proper amounts of estrogens and/or androgens, depending upon the level of expression of the appropriate steroid-metabolizing enzymes in each cell type [7]. Most importantly, the sex steroids synthesized and acting intracellularly in each cell according to the mechanisms of intracrinology [3,8] are also inactivated locally [9], thus maintaining the serum levels of estradiol and testosterone at biologically inactive concentrations [3,4]. Accordingly, systemic exposure to sex steroids is avoided during menopause [4].


  • Fernand Labrie
    EndoCeutics Inc., Quebec City, Canada


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