Prasad, MRN (1985) Is there a role for antiestrogens (estrogen antagonists) in the regulation of fertility? In: Journal of Biosciences, 7 (2). pp. 161-173.
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Estrogens secreted by the ovary during the pre/periimplantation period and/or by the blastocyst and acting locally on the endometrium are involved in the initiation of implantation. Estrogens induce a cascade of metabolic changes in the uterus and blastocyst prior to and soon after the attachment and implantation of the blastocysts. Antiestrogens either administered intraluminally into the uterus prior to implantation or washing free blastocysts with antiestrogens prior to transfer to uteri of progesterone treated hamsters leads to failure of implantation. A number of antiestrogens which inhibit fertility in the rats do not interfere with implantation in the hamster and monkey when administered post-coitally. However, Zuclomiphene administered during days 5–11 of the menstrual cycle inhibits implantation in the rhesus monkey. Antiestrogens are being evaluated in other non-human primates to confirm the above results and to determine the time in the menstrual cycle susceptible to modification and inhibition of implantation. Tamoxifen administered from days 18–30 of the cycle to mated bonnet monkeys inhibited implantation despite maintenance of high levels of circulating progesterone. Neutralization of the vitamin carrier proteins (by active immunization against these proteins) interferes with established pregnancy in the rat and perhaps in the bonnet monkey. Whether antiestrogens can reduce the levels of vitamin carrier proteins to a level which is not adequate for maintenance of early pregnancy is not clear. Compounds which show antiestrogenic and antiprogestational properties may have advantages in inhibiting implantation or disruption of early pregnancy. Critical experiments need to be carried out in non-human primates to delineate the effectiveness of antiestrogens, with particular emphasis on time, dose, duration and route of administration in inhibition of implantation. Centchroman, an antiestrogen with antiprogestational properties, has been found to provide pregnancy protection with minimal side effects. However, several concerns relating to safety in toxicological studies in monkeys and a dose which would provide acceptable rate of contraceptive efficacy without major effects on the menstrual cycle need to be clarified before considering the potential of centchroman as a possible oral contraceptive administered either post-coitally or once a week. Inhibition of implantation by administration of tamoxifen opens up new possibilities of use of antiestrogens for fertility regulation.
| Item Type: | Journal Article |
|---|---|
| Publication: | Journal of Biosciences |
| Publisher: | Springer |
| Additional Information: | Copyright of this article belongs to Springer. |
| Keywords: | Antiestrogens;clomiphene;tamoxifen;bonnet monkey;implantation;fertility regulation. |
| Department/Centre: | Division of Biological Sciences > Biochemistry |
| Date Deposited: | 08 Jul 2008 |
| Last Modified: | 27 Aug 2008 13:33 |
| URI: | http://eprints.iisc.ac.in/id/eprint/14851 |
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