title: Higher endogenous estrogen levels in 70-year-old women and men:  an endogenous response to counteract developing atherosclerosis?
abstract: OBJECTIVE
  Reported associations between endogenous steroid hormone levels and cardiovascular disease in the older population have been contradictory. We evaluated plasma steroid concentrations in terms of the dimensions of the common carotid artery wall layers as a measure of the extent of atherosclerosis.
  
  
  METHODS
  A subgroup of 70-year-old participants (32 women and 50 men) from the Prospective Investigation of the Vasculature in Uppsala Seniors study was investigated. All participants had assessments of common carotid artery wall layer parameters (intima thickness, media thickness, and intima-media thickness [IMT] ratio; measured by high-frequency ultrasound at 22 MHz) and endogenous steroid hormone concentrations (measured by liquid chromatography-tandem mass spectrometry).
  
  
  RESULTS
  Low androgen levels, high aromatase enzyme activity (estrone [E1]/androstenedione and estradiol [E2]/testosterone), high E2/E1 ratio, and high estrogen levels (E1, E2, estriol, and E2/sex hormone-binding globulin) were consistently associated (often significantly) with a more unhealthy artery wall (thick intima, thin media, and high IMT ratio) in both sexes. Consistently strong associations were found between the aromatase index E2/testosterone and intima, media, and the IMT ratio. For IMT ratio, in both men (rs = 0.52) and women (rs = 0.58), P was <0.001 for both and remained significant after adjustment for cardiovascular disease risk factors and the Framingham risk score (both P < 0.01).
  
  
  CONCLUSIONS
  Low androgens, high aromatase enzyme activity, and high estrogen levels are often significantly associated with an unhealthy artery wall on ultrasound. We suggest that the steroid hormone profile of older individuals with higher estrogens most probably reflects an endogenous response to developing atherosclerosis, rather than a cause-and-effect relationship. However, the reverse causality cannot be excluded.
authors.affiliation: Department of Women’s and Children’s Health, Section for Obstetrics and Gynecology, Uppsala University, Uppsala, SE-751 85 Sweden. Tord.Naesssen@kbh.uu.se
authors.forename: Tord
authors.initials: T
authors.lastname: Naessen
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergquist
authors.forename: Lars
authors.initials: L
authors.lastname: Lind
authors.forename: Mark M
authors.initials: MM
authors.lastname: Kushnir
mesh_terms: D000368:Aged; D000728:Androgens / Q000097:blood; D001141:Aromatase / Q000378:metabolism; D050197:Atherosclerosis / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D015992:Body Mass Index; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D059168:Carotid Intima-Media Thickness; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000097:blood*; D004970:Estrone / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D011446:Prospective Studies; D013739:Testosterone / Q000097:blood; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000473:pathology; D017540:Tunica Media / Q000000981:diagnostic imaging / Q000473:pathology
chemical_list: D000728:Androgens; D004967:Estrogens; D004970:Estrone; D013739:Testosterone; D004958:Estradiol; D001141:Aromatase