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This Article Full Text Full Text (PDF) All Versions of this Article: 291/3/E631    most recent 00467.2005v2 00467.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Spratt, D. I. Articles by Vary, C. P. H. Search for Related Content PubMed PubMed Citation Articles by Spratt, D. I. Articles by Vary, C. P. H.

Increases in serum estrogen levels during major illness are caused by increased peripheral aromatization

¹Division of Reproductive Endocrinology, Department of Ob/Gyn; ²Department of Cardiac Services, Maine Medical Center, Portland, Maine; ³Detartment of Obstetrics and Gynecology, University of Massachusetts Medical School, Worcester, Massachusetts; and ⁴Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine

Submitted 25 September 2005 ; accepted in final form 13 April 2006

Although serum testosterone levels decrease acutely in critically ill patients, estrogen levels rise. We hypothesized that increased rates of aromatization of androgens to estrogens underlie the increase in serum estrogen levels. Eleven men and three women (age 42–69 yr) were prospectively studied before and again after elective coronary artery bypass graft surgery (CABG). Each patient received priming doses of [¹⁴C]androgen and [³H]estrogen that were immediately followed by peripheral infusions for 210 min. Eight men and three women received androstenedione (A₄)/estrone (E₁) and three men received testosterone (T)/estradiol (E₂). Adipose tissue biopsies were obtained in another six men before and after CABG to evaluate levels of P450 aromatase mRNA. Serum T levels decreased postoperatively in all 17 men (P < 0.001), whereas E₁ levels rose (P = 0.004), with a trend toward a rise in E₂ (P = 0.23). Peripheral aromatization rates of androgens to estrogens rose markedly in all 14 patients (P < 0.0001). Estrogen clearance rates rose (P < 0.002). Mean serum A₄ levels increased slightly postoperatively (P = 0.04), although no increase in A₄ production rates (PRs) was observed. T PRs decreased in two of three men, whereas clearance rates increased in all three. Adipose tissue P450 aromatase mRNA content increased postoperatively (P < 0.001). We conclude that the primary cause of increased estrogen levels in acute illness is increased aromatase P450 gene expression, resulting in enhanced aromatization of androgens to estrogens, a previously undescribed endocrine response to acute illness. Both increased T clearance and decreased T production contribute to decreased serum T levels. Animal studies suggest that these opposing changes in circulating estrogen and androgen levels may be important to reduce morbidity and mortality in critical illness.

aromatase; cardiac surgery; estradiol; testosterone

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