Clomiphene Citrate and Its effects Upon Ovulation and Estrogen

Abstract

This paper reports a clinical evaluation of the mechanism of action of clomiphene citrate and describes selection of the most responsive patients. Patients were 121 women, aged 21-37 years, who desired pregnancy. Their infertility was diagnosed as being due to anovulation. Primary amenorrhea or special endocrine disorders were not present. All the women who had no vaginal bleeding for more than 2 months were diagnosed amenorrhea and treated with 65 mg of progesterone capronate intramuscularly. They were then divided into two subgroups on the basis of the presence or absence of vaginal bleeding within 2 weeks. Clinical studies included: basal body temperature charts; daily vaginal smears evaluated by the ink acidophilic stain index (ISI); cervical mucus evaluated by amount, spresence of spinnbarkeit, and ferning; 24-hour urines examined for estrogen and total gonadotropic activity; and a pregnanediol determination. Each group received daily 50 mg doses of clomiphene citrate for 5 days. Estrogen inhibiting effect of the drug was suggested by vaginal cytology and the disappearance of ferning and decrease in quantity of cervical mucus. However, the excretion of the total urinary estrogen was increased in ovulatory cases (81 of the 121 patients). In 17 patients having no bleeding within 2 weeks after progesterone injection no ovulation could be induced. In patients with withdrawal flow 54 of 70 achieved ovulation. Of 37 patients with previous anovulatory bleeding 27 achieved ovulation. There were 11 of the 121 who became pregnant. In those with early ovulation the antiestrogen effect is believed to be in the hypothalamus and pituitary bringing about the estrogen surge and stimulating LH secretion. In those with later ovulation the antiestrogenic effect increased FSH secretion followed by ovulation. The type of patient most likely to respond to clomiphene citrate is one with nearly normal pituitary-gonadal axis. Inducing withdrawal bleeding with progesterone in those amenarrheic patients who are to be treated with clomiphene citrate is believed to be a good method of anticipating the result of the treatment.