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Premarin is the commercial name for a medication consisting primarily of conjugated estrogens. Isolated from mares' urine (pregnant mares' urine), it is manufactured by Wyeth Pharmaceuticals (part of Pfizer since January 2009) and has been marketed since 1942. It is available in oral (0.3/0.45/0.625/0.9/1.25 mg), IV, and topical (vaginal) form.
Premarin is a form of hormone replacement therapy. Premarin pills are used most commonly in post menopausal women who have had a hysterectomy to treat hot flashes, and burning, itching, and dryness of the vagina and surrounding areas. It can also be used in conjunction with a progestin pill in women who have not had a hysterectomy. For women already taking the drug it can be used to treat osteoporosis, although it is not recommended solely for this use. Some lesser known uses are the treatment of breast cancer in both men and women and the treatment of prostate cancer in men.
The most common side effects associated with Premarin use are vaginal yeast infections, vaginal spotting or bleeding, painful menses, and cramping of the legs.While there are some contradictory data, estrogen alone does not appear to increase the risk of coronary heart disease or breast cancer, like estrogen with progestin does. 
The major forms of estrogen in Premarin are estrone (>50%), equilin (15-25%) and equilenin. The estrogens in Premarin are often called "conjugated equine estrogens" (CEE) because the estrogen molecules are generally present with hydrophilic side-groups attached such as sulfate. Thus, estrone sulfate is actually the major active constituent in Premarin. Estrone sulfate is easily absorbed into the blood after the tablets are taken by women.
Society and culture
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Premarin was first introduced in 1942 by Wyeth Ayerst as a treatment for hot flashes and other symptoms of menopause; at that time, Wyeth Ayerst only had to prove its safety, and not its efficacy. 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 Premarin’s activity, and it laid the groundwork for Abbreviated New Drug Application (ANDA) submissions of generic versions. In 1984 an NIH consensus panel found that estogens 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.
Research starting in 1975 showed substantially increased risk of endometrial cancer. Since 1976 the drug has carried a label warning about the risk. As part of the Women's Health Initiative sponsored by the National Institutes of Health, a large-scale clinical trial for Hormone Replacement Therapy showed that long-term use of progestin and estrogen may increase the risk of strokes, heart attacks, blood clots, and breast cancer. Following these results, Wyeth experienced a significant decline in its sales of Premarin, Prempro (conjugated equine estrogens) and related hormones, from over $2 billion in 2002 to just over $1 billion in 2006.
This drug has been the subject of litigation; more than 13,000 people have sued Wyeth between 2002 and 2009. Wyeth and Pharmacia & Upjohn prevailed in the vast majority of hormone therapy cases previously set for trial through a combination of rulings by judges, verdicts by juries, and dismissals by plaintiffs themselves. Of the company’s losses, two of the jury verdicts were reversed post-trial and others are being challenged on appeal. Wyeth also won five summary judgments on Prempro cases and had 15 cases voluntarily dismissed by plaintiffs. The company won dismissals in another 3,000 cases. In 2006, Mary Daniel, in a trial in Philadelphia, was awarded $1.5 million in compensatory damages as well as undisclosed punitive damages. As of 2010, Wyeth had won the last four of five cases, most recently in Virginia, finding that they were not responsible for the breast cancer of plaintiff Georgia Torkie-Tork. Wyeth has been quoted as saying "many risk factors associated with breast cancer have been identified, but science cannot establish what role any particular risk factor or combination play in any individual woman's breast cancer."  Wyeth's counsel in the case also noted that in the WHI trial, 99.62 percent of women took the drug and "did not get breast cancer."
Animal welfare groups claim that animal husbandry and urine collection methods used in Premarin's production cause undue stress and suffering to the mares involved. Allegations of abuse range from concern over stall size, access to water, exercise, cruel treatment, collection system, continuous breeding cycles, and premature death.
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- Federal Register 37, July 25, 1972 pp 14826-28
- National Institutes of Health Consensus Development Conference Statement. April 2-4, 1984 Osteoporosis
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- "Earnings Results for the 2006 Fourth Quarter and Full Year" (PDF) (Press release). Wyeth.
- "Pfizer Statement on Prempro". Indy News Channel.[dead link]
- Jef Feeley (February 24, 2010). "Pfizer wins trial over claim Prempro caused cancer". Bloomberg.
- "Pfizer properly warned about Prempro risks, jury finds". 3 December 2010.
- "Legal Intelligencer: Philadelphia jury returns defense verdict in HRT case, Amaris Elliott Engel".
- The HRT horses (NBC)
- Information page of the manufacturer
- Premarin information at the Food and Drug Administration (FDA) website
- WHI Follow-up Study Confirms Health Risks of Long-Term Combination Hormone Therapy Outweigh Benefits for Postmenopausal Women NIH press release, March 4, 2008
- National Health Lung and Blood Institute's WHI website