How a drug first thought to be a contraceptive took on a completely different role in fertility medicine.
Did you know that Clomid, the fertility pill, was discovered in Augusta, Georgia?
Clomiphene, an atypical steroid, more commonly known by its first brand name “Clomid,” is the most prescribed oral drug to infertile women and men. It is often known as the “Fertility Pill.” It can be given for specific reasons such as a lack of ovulation due to polycystic ovaries or enhancement of a deficient ovulation.
Also, perhaps unfortunately, it’s often prescribed empirically, meaning because the physician does not know what else to do and because it has minimal risks. Its effects on the ovarian function were discovered by pure hazard or as scientists say, by serendipity.
Clomiphene was first synthesized in 1956 by a team from the William S. Merrell Chemical Laboratory. Dr. Robert B. Greenblatt and his collaborators conducted the first clinical trials in Augusta, Georgia, in 1960. First believed to be an anti-estrogenic substance, it was initially promoted and studied as a contraceptive pill.
Administered cyclically (21 days on – 7 days off) for periods of 2 or 3 cycles, it was quickly discovered that instead of suppressing the ovarian function, it was causing a strong stimulation of both ovaries. The patients were returning to the clinic with very large ovaries filled with functional or benign cysts.
Clomid’s Augusta discoverer proposed for Nobel Prize
Dr. Greenblatt’s team had the merit of discovering that the effects of the drug were totally opposite to the initial researchers’ expectation. We are reminded that, at the time, ultrasound and minimally invasive laparoscopy were not available to clinicians. Therefore, the doctors had to use their manual pelvic and abdominal examination skills.
One or two patients had to undergo surgery and have their tissue submitted to pathology to be sure that they were not dealing with a cancerous process. This was never published, and the story was related to me in 1970 during my fellowship in the department of endocrinology at the Medical College of Georgia.
The first paper published in 1961 was titled “Induction of Ovulation with MRL 41, a Preliminary Report” (Greenblatt et al.). The trials concluded that MRL 41, later to be named Clomiphene, induced ovulatory-type menses in certain “amenorrheic anovulatory” women.
In 1963 the Food and Drug Administration introduced new rules and regulations for medications and Clomiphene was the third Investigational New Drug submitted for approval. It was approved in 1967 for the treatment of polycystic ovary syndrome (PCOS) and it has since been available in the United States by prescription. The original publications were a few of the reasons for Dr. Greenblatt’s international recognition.
In the spring of 1969 Dr. Jean Rivière, my professor of endocrinology in Bordeaux, France, proposed to send me to Augusta, Georgia, for a reproductive endocrinology fellowship. Consequently, I knew I was going to have the privilege to work in the department chaired by the originator of Clomid. Because of this discovery, Dr. Greenblatt was proposed for a Nobel Prize in the early ’70s but the request failed to succeed. The medical school library in Augusta is named the Robert B. Greenblatt Library, in his memory.
Greenblatt, R.B., Barfield, W.E., Jungck, E.C. and Ray, A.W. (1961) Induction of ovulation with MRL/41, Preliminary Report. J. Am. Med. Assoc., 178, 255.
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