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Influence of Sex Hormones on Plasma Endothelin Levels

Kees H. Polderman, MD; Coen D. A. Stehouwer, MD; Gerard J. van Kamp, PhD; Gustaaf A. Dekker, MD, PhD; Freek W. A. Verheugt, MD, PhD; and Louis J. G. Gooren, MD, PhD
[+] Article, Author, and Disclosure Information

From Free University Hospital, Amsterdam, The Netherlands. Requests for Reprints: Kees H. Polderman, MD, Department of Internal Medicine, Free University Hospital, P.O. Box 7057, 1007 MB Amsterdam, the Netherlands. Acknowledgments: The authors thank J.A.J. Megens for assistance in the logistics of this study and for recruitment of patients; and J. van Bezu for technical assistance.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1993;118(6):429-432. doi:10.7326/0003-4819-118-6-199303150-00006
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Objective: To determine whether a sex-associated difference in endothelin levels exists and to assess whether this difference is mediated by sex hormones.

Design: Initial survey in healthy persons, followed by a nonrandomized intervention.

Setting: A university teaching hospital.

Patients: Twenty-three healthy men, 29 healthy women, 20 pregnant women, and 12 male-to-female and 13 female-to-male transsexual patients.

Measurements: Plasma levels of endothelin were first assessed in healthy men, healthy women, and pregnant women; subsequently, endothelin levels were determined in male-to-female and female-to-male transsexual patients both before and during cross-gender hormone treatment. This treatment involves administration of testosterone esters to women and of ethynylestradiol and cyproterone acetate to men.

Results: Endothelin levels were higher in men than in women (5.9 ± 1.2 compared with 4.17 ± 0.67 pg/mL; P < 0.01). Endothelin levels were lower in pregnant women than in age- and sex-matched nonpregnant controls (2.19 ± 0.73 compared with 4.17 ± 0.67 pg/mL; P < 0.01). In 12 male-to-female transsexuals treated with estradiol and the progestational agent cyproterone acetate, endothelin levels decreased from 8.1 ± 3.0 to 5.1 ± 2.0 pg/mL (P < 0.01). In 13 female-to-male transsexuals treated with testosterone, endothelin levels increased from 6.2 ± 1.1 to 7.8 ± 1.2 pg/mL (P < 0.01).

Conclusion: Sex hormones may modulate plasma endothelin levels, with male hormones raising levels and female hormones lowering them. This finding may be important in explaining sex-associated differences in susceptibility to atherosclerotic cardiovascular disease.


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Figure 1.
Plasma endothelin levels in 23 men, 29 women, and 20 pregnant women.PP

Each square denotes one participant. Levels of endothelin were higher in men than in women (  <0.01) and lower in pregnant women than in nonpregnant controls ( < 0.01).

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Figure 2.
Effects of cross-gender sex hormone treatment on plasma endothelin levels in transsexual patients.Left panel.PRight panel.

The thin lines show changes in individual patients; the horizontal bars indicate averages. Endothelin levels decreased in men treated with ethynylestradiol and cyproterone acetate ( < 0.01). Endothelin levels increased in biological women treated with testosterone.

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