Observations on the Mechanism of Action of Clomiphene (MRL-41)

Current concepts in the treatment of anovulation.

“…The criteria of positive response were identical with those employed in gonadotropic treatment. As to the dosage schedules, numerous authors (Naville et al, 1964;Dickey et al, 1965;Pildes, 1965;Serr et at., 1966;Shearman, 1966) pointed out that lower dosage and shorter treatment resulted in a decrease of more serious side-effects related to ovarian overstimulation, while the overall pregnancy rate remained unaffected. We generally start with a dose of 50 mg. of clomiphenefl daily for seven consecutive days.…”

“…The exact mechanism of action of clomiphene in inducing ovulation is as yet unclear. Since urinary excretion of gonadotropins was reported to be increased during or immediately after administration of clomiphene (Dickey et al, 1965), it has been suggested that the drug acts either directly or indirectly on * Department of Obstetrics and Gynaecology, Tel-Hashomer Government Hospital and Tel Aviv University Medical School, Tel Aviv, Israel. the release of gonadotropins.…”

Clomiphene citrate inhibits gonadotropin-induced ovulation by reducing cyclic adenosine 3′,5′-cyclic monophosphate and prostaglandin E2 levels in rat ovary

“…Clomiphene citrate (CC; a nonsteroidal estrogen agonist and antagonist) is a first choice for the induction of ovulation in majority of women with anovulatory dysfunction (12). Despite good ovulation induction with the use of CC, the pregnancy rate is much lower (13)(14)(15). Moreover, a higher than expected incidence of miscarriage in conception cycles after CC treatment has been reported (16).…”

Effects of Cyclophenyl and Clomiphene on Excretion of Urinary LH

“…However, in the patients of ovulatory failure in whom the increase of LH excretion can be detected, further investigation of FSH and estrogen excretion will be necessary. Dickey (1965) and Sexena et al(1968) reported that FSH was gradually increased with treatment of clomiphene in the cases of sucessful induction of ovulation. When Roy, Greenblatt (1963) and Riley, Evans (1964) administered clomiphene to anovulatory patients, they reported that an increase in pituitary secretion was discernible.…”