Is there a role for antiestrogens (estrogen antagonists) in the regulation of fertility.
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Date
1985-03
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Abstract
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.
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Keywords
Antiestrogens, clomiphene, tamoxifen, bonnet monkey, implantation, fertility regulation
Citation
M R N Prasad. Is there a role for antiestrogens (estrogen antagonists) in the regulation of fertility. Journal of Biosciences. 1985 Mar; 7(2): 161-173.