The Development and Usage of Clomiphene

In the early 1960's methods of promoting conception were based on therapy with compounds similar to follicle stimulating hormone (F.S.H.) and luteinizing hormone (L.H.) All were very expensive, had to be given by injection, and could lead to multiple pregnancies as individual sensitivity to them varied greatly. Interest in clomiphene was instigated when a similar compound MER-25, was given to four patients with Stein-Leventhal syndrome and effected a return to normal hormonal changes and ovulation (Kistner and Smith, 1959). Clomiphene itself was first investigated by Holtkamp et al (1960) who found that it stopped the oestrous cycle of mature female rats and hence acted as a contraceptive in these animals. It was hoped that this compound would act similarly in the human female. A year later, however, Greenblatt et al (1961) reported that clomiphene induced ovulation in women. This study was on four women with a normal ovula1 tory pattern, three girls with precocious puberty and forty-three women with primary or secondary amenorrhoea, and revealed that the drug had no marked effect on the women and young girls with established menstrual cycles nor on those with primary amenorrhoea. In those with secondary amenorrhoea or Stein-Leventhal