Effect on biochemical vasoactive markers during postmenopausal hormone replacement therapy: estradiol versus estradiol/dienogest.
OBJECTIVE
Aim was to compare the effects of estradiol-only therapy with combined estradiol/progestin treatment on the excretion of vasoactive mediators surrogating on possible effects in the vascular system. The progestin used was dienogest, a new C19-progestin with antiandrogenic properties.


METHODS
Prospective, randomized trial, 25 healthy postmenopausal women treated for 3 months with estradiol valerate (2 mg/day) and 27 women with estradiol valerate (2 mg/day) continuously combined with dienogest (2 mg/day). Assessment of the following markers or their stable metabolites in nocturnal urine: cGMP, serotonin, prostacyclin and thromboxane, and urodilatin.


RESULTS
Estradiol alone increased the excretion of cGMP and serotonin significantly suggesting vasodilating effects. The prostacyclin/thromboxane ratio known to be crucial for the relation of vasorelaxation to vasoconstriction significantly increased. No significant changes were found for urodilatin, which is known to elicit different effects in the cardiovascular and renal system, respectively. Combined estradiol/dienogest therapy also led to significant increases in cGMP and serotonin excretion suggesting that progestin addition for three months does not affect these markers. However, in contrast to estrogen-only treatment, there was no significant increase for the prostacyclin/thromboxane ratio, which can be explained by antagonistic action of the progestin. The excretion of urodilatin was increased significantly, which might be due to counterbalancing progestin effects in the renal vascular system.


CONCLUSIONS
The changes in vasoactive markers suggest an estrogen effect that is vasorelaxant. Since there were no significant differences between the two groups, possible vascular effects of the progestin dienogest, for the first time evaluated, might not be of clinical relevance, at least not in women without cardiovascular diseases.
Mueck
A O
AO
Section of Endocrinology and Menopause, Department of Obstetrics and Gynecology, University Hospital, University of Tuebingen, Schleichstrasse 4, 72 076, Tuebingen, Germany. endo.meno@med.uni-tuebingen.de
Seeger
H
H
Lüdtke
R
R
Gräser
T
T
Wallwiener
D
D
D000284:Administration, Oral; D009320:Atrial Natriuretic Factor / Q000652:urine; D015415:Biomarkers / Q000652:urine*; D002318:Cardiovascular Diseases / Q000517:prevention & control* / Q000652:urine; D006152:Cyclic GMP / Q000652:urine; D004958:Estradiol / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D008875:Middle Aged; D009277:Nandrolone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000652:urine; D017698:Postmenopause; D011446:Prospective Studies; D012701:Serotonin / Q000652:urine; D014664:Vasodilation
D015415:Biomarkers; D010446:Peptide Fragments; D012701:Serotonin; C023635:dienogest; D004958:Estradiol; D009277:Nandrolone; C056452:Ularitide; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP