Cyclic clomiphene citrate treatment lowers cytosol estrogen and progestin receptor concentrations in the endometrium of postmenopausal women on estrogen replacement therapy.
Clinical and experimental studies have indicated that a nonsteroidal antiestrogen, clomiphene citrate, might prevent the stimulatory action of estrogens on the human endometrium. To investigate the mechanisms of this effect, the treatment of 19 postmenopausal patients with conjugated estrogens for 6 months was supplemented cyclically for 10 days with clomiphene citrate after every 7 weeks. Ten patients ingested clomiphene citrate alone, whereas 9 patients continued estrogen treatment during clomiphene supplementation. Estrogen and progestin receptors were measured from the cytosol of the endometrium after the first estrogen period and after the first and third clomiphene treatment. The estrogen receptor concentration was significantly lower after both clomiphene supplementation periods than after the initial estrogen administration. The progestin receptor concentration was significantly lower only after the first clomiphene citrate period. The effect of clomiphene citrate was independent of the initial histological appearance of the endometrium and led to atrophy of the endometrium in most of the patients. Because the effect of clomiphene citrate was independent of simultaneous estrogen administration, it acted as a pure antiestrogen in this treatment modality. The relative decreases in estrogen and progestin receptor concentrations on the present treatment regimen were different from those previously found on progestin treatment and most likely occur via different mechanisms. It is not known whether these two treatment types will have additive effects.
D002996:Clomiphene / Q000008:administration & dosage / Q000031:analogs & derivatives*; D003600:Cytosol / Q000378:metabolism; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism; D004965:Estrogen Antagonists / Q000008:administration & dosage; D004967:Estrogens / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008593:Menopause / Q000187:drug effects*; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*
D004965:Estrogen Antagonists; D004967:Estrogens; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D002996:Clomiphene