Influence of norethisterone acetate and estradiol on the serotonin metabolism of postmenopausal women.

Previous studies have shown that estradiol increases urinary excretion of the main stable metabolite of serotonin, 5-hydroxyindole acetic acid (5-HIAA), reflecting an increase in serotonin production. In the present study, the effect of the progestin norethisterone acetate (NETA) on serotonin metabolism was investigated, both alone and in addition to estradiol replacement in 20 postmenopausal women. Urinary excretion of 5-HIAA was measured after treatment with NETA orally for 8 days, estradiol valerate orally for 9 days and a combination of both hormones for 12 days. 5-HIAA values, expressed as percentages of the pretreatment values, were significantly increased only after the estrogen treatment phase. NETA alone did not significantly alter the serotonin metabolite excretion; in combination with estradiol, the estradiol effect on serotonin metabolism was abolished. This indicates that adding norethisterone acetate to estradiol replacement therapy may have a negative impact on the effect of estradiol on serotonin metabolism.