|Routes||Oral, topical, IV|
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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.
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 Premarin pills are taken by women. Estrone sulfate is converted to estradiol, an active estrogen normally found in women. It is not clear if estrogens such as equilin that are foreign to the human body have effects in women that are significantly different from the estrogens like estradiol that are normally made in the human body.
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. 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. While estrogen alone appears to decrease the risk of hip fracture for women who have had a hysterectomy, it is still suggested that Premarin be used for the shortest period of time and at the smallest possible dose that is effective in alleviating symptoms because it can increase the risk of endometrial cancer, stroke, blood clots, and possibly dementia. Premarin cream is only used for vaginal burning, dryness and itching.
Some of Premarin’s lesser known uses are the treatment of symptoms associated with metastatic breast cancer in men and women and prostate cancer in men. It can also be used for individuals that do not produce enough estrogen due to hypogonadism, castration, and ovarian failure, or who have certain intersex conditions such as Androgen insensitivity syndrome.
Wyeth-Ayerst has filed petitions opposing the creation of a bioequivalent version by Duramed Pharmaceuticals. They have argued that the generic version, using synthetic steroids, "lacked an important substance that is in Premarin".
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. And last but not least, the immediate killing of the foal and her immediate insemination. 
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. However, Wyeth and Pharmacia & Upjohn have 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 has won five summary judgments on Prempro cases and had 15 cases that were set for trial voluntarily dismissed by plaintiffs. The company has won dismissals in another 3,000 cases. In 2006, Mary Daniel, in a trial in Philadelphia, PA, was awarded $1.5 million in compensatory damages as well as undisclosed punitive damages. Wyeth has won the last four of five cases, most recently in Virginia, finding that Wyeth was not responsible for Plaintiff Georgia Torkie-Tork's breast cancer. 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."
- Premarin (conjugated estrogens) Vaginal Cream - Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) -- November 2008
- http://www.nhlbi.nih.gov/whi/estro_alone.htm NHLBI Women's Health Initiative Estrogen Alone Study
- "F.D.A. Makes No Recommendation on Generic Estrogen Drug". New York Times. 1995-07-30. Retrieved 2009-04-29. "Wyeth-Ayerst filed a petition opposing that request, arguing that the generic compound, which uses synthetic ingredients, lacked an important substance that is in Premarin, a drug refined from the urine of pregnant mares. ... A generic form of the drug proposed by Duramed Pharmaceuticals followed the five-estrogen formula. In its petition, Wyeth-Ayerst claimed that DHES was an important component and that there was uncertainty about whether an estrogen replacement pill without DHES would have the same beneficial effects as its Premarin."
- premarin.org site, a part of equinerescue.net
- website of Equine Advocates
- Ziel HK, Finkle WD. "Increased risk of endometrial carcinoma among users of conjugated estrogens.". New England Journal of Medicine 293: 1167–1170. doi:10.1056/NEJM197512042932303. PMID 171569.
- McDonald, TW et al. "Exogenous estrogen and endometrial carcinoma: case-control and incidence study.". American J Obstet Gynecol 127: 572–580. PMID 190887.
- Natasha Singer and Duff Wilson (2009-12-12). "Menopause, as Brought to You by Big Pharma". New York Times.
- Brunner, RL et al; Womens Health Initiative Investigators (2005). "Effects of conjugated equine estrogen on health-related quality of life in postmenopausal women with hysterectomy: results from the Women's Health Initiative Randomized Clinical Trial.". Archives of Internal Medicine 165 (17): 1976–1986. doi:10.1001/archinte.165.17.1976. PMID 16186467.
- Wyeth press release: Earnings Results for the 2006 Fourth Quarter and Full Year
- Pfizer Statement on Prempro, Indy News Channel: http://www.theindychannel.com/health/21716786/detail.html
- Bloomberg: Pfizer Wins Trial Over Claim Prempro Caused Cancer, February 24, 2010, Jef Feeley
- Pfizer Properly Warned About Prempro Risks, Jury Finds http://www.bloomberg.com/news/2010-12-03/pfizer-properly-warned-about-prempro-health-risks-jury-finds.html
- Legal Intelligencer: Philadelphia Jury Returns Defense Verdict in HRT Case, Amaris Elliott Engel http://www.law.com/jsp/article.jsp?id=1202444500915.
- Information page of the manufacturer
- Premarin Vaginal Cream approved by FDA for Postmenopausal Dyspareunia (Painful Sexual Intercourse)
- Premarin information at the Food and Drug Administration (FDA) website
- Menopause resource - from Wyeth
- Equine Advocates - clarification of care and fate of PMU mares and foals
- 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