In response to the 1962 Kefauver Harris Amendment the FDA had its efficacy reviewed, and in 1972 found it effective for menopausal symptoms and probably effective for osteoporosis. The review also determined  that two estrogens – estrone sulfate and equilin sulfate – were primarily responsible for the activity of Premarin, and it laid the groundwork for Abbreviated New Drug Application (ANDA) submissions of generic versions. In 1984 an NIH consensus panel found that estrogens were effective for preventing osteoporosis and 1986 the FDA announced in the Federal Register that Premarin was effective for preventing osteoporosis. This announcement led to a rapid growth in sales, and interest from generic manufacturers to introduce generic versions.Conjugated estrogens was introduced for medical use under the brand name Premarin in Canada in 1941, in the United States in 1942, and in the United Kingdom in 1956. Society and culture
Names
Estrogens, conjugated is the generic name of the drug and its USP and JAN. It is also known as conjugated estrogens or as conjugated equine estrogens. The brand name Premarin is a contraction of "pregnant mares urine".CEEs are marketed under a large number of brand names throughout the world. The major brand name of the natural form of CEEs manufactured from the urine of pregnant mares is Premarin. Major brand names of fully synthetic versions of CEEs include Cenestin and Enjuvia in the United States and C.E.S. and Congest in Canada. CEEs are also formulated in combination with progestins.
There are many different steroids in natural CEE products like Premarin, as many as 230 compounds and including even androgens and progestogens, but only the estrogens are present in sufficient amounts to produce clinically-relevant effects.A dosage of 0.625 mg/day oral CEEs has been found to increase SHBG levels by 100%. For comparison, 1 mg/day oral estradiol increased SHBG levels by 45%, while 50 µg/day transdermal estradiol increased SHBG levels by 12%. Ethinylestradiol is more potent in its effects on liver protein synthesis than either CEEs or estradiol, with 10 µg/day oral ethinylestradiol having been found to be approximately equivalent to 1.25 mg/day CEEs. Antigonadotropic effects
A preliminary study of ovulation inhibition in women found that oral CEEs was 33% effective at 1.25 mg/day and 94% at 3.75 mg/day. A dosage of oral CEEs of 2.5 mg three times daily (7.5 mg/day total) has been found to suppress total testosterone levels in men to an equivalent extent as 3 mg/day oral diethylstilbestrol, which is the minimum dosage of diethylstilbestrol required to consistently suppress total testosterone levels into the castrate range (<50 ng/dL). Pharmacokinetics
CEEs are hydrolyzed in the intestines during first-pass metabolism upon oral administration. Following their absorption, they are resulfated mainly in the liver also during the first pass.