Elevated sex steroid hormones in great saphenous veins in men

Kendler, Michael; Makrantonaki, Evgenia; Kratzsch, Jürgen; Anderegg, Ulf; Wetzig, Tino; Zouboulis, Christos; Simon, Jan C.

doi:10.1016/j.jvs.2009.07.128

« Previous Next »Journal of Vascular Surgery
Volume 51, Issue 3 , Pages 639-646, March 2010

Elevated sex steroid hormones in great saphenous veins in men

A part of the investigation data was accepted for presentation at the XVI World Meeting of the Union Internationale de Phlébologie, Fiftieth Anniversary, Monaco, Aug 31-Sept 4, 2009.

Michael Kendler, MD
- Department of Dermatology, Venerology and Allergology, Leipzig University Medical Center, Leipzig, Germany
- Reprint requests: Michael Kendler, MD, Department of Dermatology, Venerology and Allergology, University Medical Center, Ph.-Rosenthal-Str. 23, D-04103 Leipzig, Germany
Evgenia Makrantonaki, MD
- Departments of Dermatology, Venerology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany
- Laboratory for Biogerontology, Dermato-Pharmacology and Dermato-Endocrinology, Institute of Clinical Pharmacology and Toxicology, Charité Universitaetsmedizin Berlin, Berlin, Germany
Jürgen Kratzsch, PhD
- Institute for Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig University Medical Center, Leipzig, Germany
Ulf Anderegg, PhD
- Department of Dermatology, Venerology and Allergology, Leipzig University Medical Center, Leipzig, Germany
Tino Wetzig, MD
- Department of Dermatology, Venerology and Allergology, Leipzig University Medical Center, Leipzig, Germany
Christos Zouboulis, MD, PhD
- Departments of Dermatology, Venerology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany
- Laboratory for Biogerontology, Dermato-Pharmacology and Dermato-Endocrinology, Institute of Clinical Pharmacology and Toxicology, Charité Universitaetsmedizin Berlin, Berlin, Germany
Jan C. Simon, MD, PhD
- Department of Dermatology, Venerology and Allergology, Leipzig University Medical Center, Leipzig, Germany

Received 20 May 2009; accepted 18 July 2009. published online 04 January 2010.

Introduction

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 5α-reductase type 1, 5α-reductase type 2, 17, 20 lyase, 17β-hydroxysteroid dehydrogenase (17β-HSD), aromatase and 3β-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.

Conclusion

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.

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Competition of interest: none.

The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a competition of interest.

PII: S0741-5214(09)02047-3

doi:10.1016/j.jvs.2009.07.128