Effect of sequential estrogen/progestin treatment on biochemical vasoactive markers in postmenopausal women comparing...

Estrogen replacement in postmenopause can elicit vasodilatory effects which may be important for cardiovascular protection. Progestin addition can antagonise this beneficial effect, but until now, only a few studies have been performed on this issue. In the present study the effect of estradiol as well as of added norethisterone acetate (NETA), a C19-progestin, on the renal excretion of various biochemical markers which can reflect vasoactive actions was investigated.

37 postmenopausal women were treated for one sequential estrogen/progestin treatment cycle, i.e. two weeks with estradiol alone followed by two weeks with an estradiol/progestin combination. Both oral (n = 20) as well as 'complete' transdermal (n = 17) hormone substitution was applied, and the excretion of the following vasoactive substances or the stable metabolites, respectively, were measured in nocturnal urine prior to treatment, after 14 and 28 days: cGMP, which can reflect the production of nitric oxide, prostacyclin, thromboxane and serotonin.

The excretion of cGMP was increased with both forms of administration during the estrogen phase as well as during the consecutive estrogen/progestin treatment. The prostacyclin-thromboxane quotient increased during estrogen phases, but decreased significantly by the addition of oral, but not with transdermal NETA, reflecting possible vasoconstrictory effects. Serotonin excretion increased, but this only was significant after the oral estrogen-only phase (2 weeks treatment), and after one cycle of complete transdermal treatment (4 weeks treatment), respectively.

The observed effects can be explained by vasodilatory actions during the estrogen phases which can be maintained or even increased during the consecutive estrogen/progestin treatment suggesting a time-dependent beneficial estrogen effect. However, oral progestin addition may antagonise this effect already within two weeks of treatment whereby the prostacyclin-thromboxane quotient seems to be the most sensitive marker surrogating on vasoconstrictory progestin action.