AP-IUD may provide an effective contraception that also controls endometrial bleeding.  In fact,  it (ZK 230 211)  induced in macaques extended, frank menstruation, when inserted during the late luteal phase,  an indication of local APs action. Over time, endometrial glandular and arterial proliferation were inhibited,  steroid receptors were elevated,  spiral arteries showed degenerative changes,  progesterone   withdrawal   bleeding   was   prevented,  and   estradiol-dependent proliferation was suppressed by the AP-IUDs. In conclusion, AP-IUDs suppressed the effects of progesterone on endometrial development and blocked the effects of estrogen on endometrial proliferation,  as previously showed for systemic   treatment   with   APs.  Therefore,  AP   IUDs   may   provide   novel contraceptive devices with minimal breakthrough bleeding ⁽¹⁰⁾. 

Modulation of endometrial receptivity is a promising approach for fertility regulation since it allows   a   contraceptive   to   act   specifically   at   the   endometrium.  This   was corroborated by previous observations that treatment with low doses of a pure progesterone antagonist (PA,  antiprogestin),  onapristone (ZK 98.299),  in bonnet monkeys inhibited fertility by selectively retarding endometrial development, without affecting the hypophyseal-hypothalamic function.⁽¹¹⁾. Hence, the properties of PAs and PRMs open up new applications in contraceptive strategies introducing the new concept of “Endometrial Contraception”.

—
Rosa Sabatini and Raffele Cagiano
Department of Obstetrics and Gynecology
Department of Pharmacology General Hospital Policlinico-University of Bari, Italy
—

REFERENCES

1.   Chabbert-Buffet N., Meduri G., Bouchard P., Spitz I.M. (2005). Selective progesterone receptor modulators and progesterone antagonists: mechanisms of action and clinical applications. Hum. Reprod. Update, 11(3), 293-307.
2.   Chwalisz K., Brenner R.M., Fuhrmann U.U., Hess-Stumpp H., Elger W. (2000). Antiproliferative effects of progesterone antagonists and progesteron e receptor modulators on the endometrium. Steroids, 65(10-11), 741-51. 
3.   Wardell S.E.,  Edwards D.P.  (2005). Mechanisms controlling agonist and antagonist   potential   of   selective   progesterone   receptor modulators(SPRMs). Semin. Reprod. Med, 23(1), 9-21.
4.   Spitz I.M.,  Chwalisz K.  (2000).  Progesterone receptor modulators and progesterone antagonists in women’s health. Steroids,65, 807-15.
5.   Katkam R.R., Gopalkrishnan K., Chwalisz K.,  Schillinger E.,  Puri C.P. (1995).  Onapristone(ZK 98.299): a potential antiprogestin for endometrial contraception. Am. J. Obstet. Gynecol, 173(3), 779-87. 
6.   Spitz I.M.,  Van Look P.F., Coelingh Bennink H.J.  (2000). The use of progesterone   antagonists   and   progesterone   receptor   modulators   in contraception. Steroids, 65 (10-11), 817-23.
7.   Bygdeman M., Danielsson K.G., Swahn M.L. (1907). The possible use of antiprogestins for contraception. Acta Obstet. Gynecol. Scand. Suppl,  164,75-7.
8.   Slayden O.D., Chwalisz K.,  Brenner R.M.  (2001). Reversible suppression of menstruation with progesterone antagonists in rhesus macaques. Human Reprod, 16(8), 1562-74.
9.   Spitz I.M., Robbins A. (1990). Mechanism of action and clinical effects of progestins on the non-pregnant uterus. Hum. Reprod. Update, 4(5), 584-93. 
10.   Nayak   N.R.,  Slayden O.D.,  Mah K., Chwalisz K.,  Brenner R.M. (2007). Antiprogestin-releasing intrauterine devices:  a novel approach to endometrial contraception. Contraception, 75(6), S104-11. 
11.   Puri C.P.,  Katkam R.R.,  Sachdeva G.,  Patil V.,  Manjramkar D.D., Kholkute S.D. (2000). Endometrial contraception: modulation of molecular determinants of uterine receptivity. Steroids, 65(10-11), 783-94.