Elevated sex steroid hormones in great saphenous veins in men.
BACKGROUND
High serum levels of estradiol are associated with clinical evidence of varicose veins in women; however, the relationship between serum sex steroid hormones and varicose veins in men is unclear. To address this issue, serum levels of testosterone, estradiol, and androstenedione were determined in the great saphenous (GSV) and cubital veins of men with varicose veins. Messenger RNA (mRNA) expression of sex steroid hormones, metabolizing enzymes, and their receptors was investigated in tissue samples of leg veins.


METHODS
This prospective study included 40 men, comprising 20 with varicose veins and reflux of the GSV (VM) and 20 with healthy veins (HM). All limbs were assessed by duplex ultrasound scanning of selected superficial and deep leg veins. Blood samples were taken from the cubital vein and from the GSV. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis for sex steroid hormones, their metabolizing enzymes, and receptors in saphenous veins was performed in tissue samples of varicose (n = 6) and healthy veins (n = 6).


RESULTS
The VM group had significantly higher (P < .001) mean levels for serum testosterone (44.9 nmol/L; range, 8.8-225.1) and estradiol (242.2 pmol/L; range, 79-941) in varicose saphenous veins compared with cubital veins (testosterone, 15.5 nmol/L; range, 8.4-23.3; estradiol, 93.2 pmol/L; range, 31-147). Moreover, significantly (P < .001) higher mean serum estradiol levels (133.2 pmol/L; range, 63-239) were detected in the saphenous veins of the HM group compared with cubital veins (88.15 pmol/L; range, 37-153). Both groups had similar blood counts and serum androstenedione levels in the upper and lower extremity. Interestingly, qRT-PCR revealed that the mRNA expression of 5alpha-reductase type 1, 5alpha-reductase type 2, 17, 20 lyase, 17beta-hydroxysteroid dehydrogenase (17beta-HSD), aromatase and 3beta-HSD type 2, androgen and estrogen receptor 1 was down-regulated (P < .05) in all samples of varicose veins vs veins obtained from healthy men.


CONCLUSIONS
Elevated serum estradiol and testosterone levels were detected in men with varicose veins and reflux in the GSV compared with the patient's own arm veins. Enzymes and hormonal receptors involved in steroid metabolism were down-regulated in patients with GSV reflux and varicose veins, suggestive of a negative feedback regulation. These data support the notion of a possible causal relationship between sex steroids and varicose veins in men.
Kendler
Michael
M
Department of Dermatology, Venerology and Allergology, Leipzig University Medical Center, Leipzig, Germany. michael.kendler@medizin.uni-leipzig.de
Makrantonaki
Evgenia
E
Tzellos
Thrasivoulos
T
Kratzsch
Jürgen
J
Anderegg
Ulf
U
Wetzig
Tino
T
Zouboulis
Christos
C
Simon
Jan C
JC
D000328:Adult; D000368:Aged; D000735:Androstenedione / Q000032:analysis; D016022:Case-Control Studies; D004958:Estradiol / Q000032:analysis; D015971:Gene Expression Regulation, Enzymologic; D012739:Gonadal Steroid Hormones / Q000032:analysis* / Q000097:blood / Q000235:genetics; D006801:Humans; D008297:Male; D054526:Men's Health; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis; D011987:Receptors, Steroid / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012501:Saphenous Vein / Q000737:chemistry* / Q000000981:diagnostic imaging; D013739:Testosterone / Q000032:analysis; D018616:Ultrasonography, Doppler, Duplex; D015854:Up-Regulation; D034941:Upper Extremity / Q000098:blood supply*; D014648:Varicose Veins / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism*; D014689:Venous Insufficiency / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism*
D012739:Gonadal Steroid Hormones; D012333:RNA, Messenger; D011987:Receptors, Steroid; D013739:Testosterone; D000735:Androstenedione; D004958:Estradiol