Abstract

Short-term and long-term progestin exposures elicit secretory and atrophic changes, respectively, in the human endometrium. To understand the mechanisms for these diverse effects of progestins, we administered medroxyprogesterone acetate (100 mg daily orally) alone or together with the antiestrogen tamoxifen (20 mg daily) for 3 weeks (from the third through twenty-third day of the cycle) to healthy, normally cycling women. Medroxyprogesterone acetate administration led to atrophic changes in the endometrium and reduced the activity of endometrial 17β-hydroxysteroid dehydrogenase on the twenty-third day of the cycle below the values measured on the same day of the preceding control cycle. These changes were accompanied by decreased cytosol estrogen and progestin receptor concentrations, while the respective nuclear receptor levels remained unchanged. Since the diminished cytosol progestin receptor content could be the primary reason for the aforementioned results, the 3-week progestin treatment was supplemented with the antiestrogen tamoxifen, also known to be a partial estrogen agonist. This combination elicited, however, endometrial atrophy and an even more pronounced reduction in the 17β-hydroxysteroid dehydrogenase activity, although it increased cytosol progestin and nuclear estrogen receptor concentrations. Tamoxifen alone did not alter endometrial receptor concentrations or 17β-hydroxysteroid dehydrogenase activity. However, tamoxifen markedly increased circulating sex steroid concentrations, which changes were abolished by a concomitant medroxyprogesterone acetate administration. It thus appears that the initial and stimulatory effect of progestins on the endometrial function is relatively short-lived and that the later depressive actions of these steroids are achieved as soon as 3 weeks. Therapeutic implications of these findings are discussed.

Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call