Premarin
From Wikipedia, the free encyclopedia
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Estrone, sulfated form
(main constituent of Premarin) |
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| Systematic (IUPAC) name | |
| sodium 13-methyl-17-oxo-3-sulfonatooxy-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[ a] phenanthrene | |
| Identifiers | |
| CAS number | |
| ATC code | G03 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C18H21NaO5S |
| Mol. mass | 372.412 g/mol |
| SMILES | & |
| Synonyms | conjugated estrogens equilin sulfate |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Protein binding | >90% |
| Metabolism | ? |
| Half life | 7.2 hours |
| Excretion | renal |
| Therapeutic considerations | |
| Pregnancy cat. |
X |
| Legal status |
℞ Prescription only |
| Routes | Oral, topical |
Premarin is the commercial name for compound drug consisting primarily of conjugated estrogens. Isolated from mare's urine (PREgnant MARes' urINe), it is manufactured by Wyeth Pharmaceuticals and has been marketed since 1942. It is available in oral (0.3/ 0.45/ 0.625/ 0.9/ 1.25mg), IV, and topical form.
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[edit] Pharmacology
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 molecule 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. It is 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 and breast cancers, heart attack, stroke, blood clots, and 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.
As Premarin is not a single compound, but a mixture of many naturally derived compounds, the structural diagram above does not show Premarin but its primary ingredient, Estrone in its sulfated form. Thus, Premarin cannot be characterized by the structure of just one of its many compounds.
[edit] Bioequivalance
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".[1]
[edit] Production
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This section's representation of one or more viewpoints about a controversial issue may be unbalanced or inaccurate. Please improve the article or discuss the issue on the talk page. |
Premarin is the subject of some contention. Animal rights activists claim that animal husbandry and urine collection methods used in Premarin's production cause undue stress and suffering to the mares involved.[2] Allegations of abuse range from concern over stall size, access to water, exercise, cruel treatment, collection system and continuous breeding cycles, resulting in premature death for thousands of mares and foals.
Much of this contention may stem from the looser standards formerly held in the industry. The pregnant mare urine (PMU) farms have been in existence since 1942. At that time, many farms were breeding large amounts of foals because more pregnant mares meant more urine and more income. A large number of these foals were unwanted. Many of them were out of draft mares because the larger horses could produce more urine. These foals, in many cases, were reported as being sent to slaughter.
Around the time of the turn of the century, however, the industry was cut. In part, this was from research showing that the amount of the drug prescribed was often too high, and that lower amounts of the drug were safer for the women using Premarin. As a result, standards within the industry increased dramatically, and farms that did not comply with the changes, which included limiting the numbers of mares they use and updating facilities, were cut.
This cut was both positive and negative for the PMU industry. The cut spurned much controversy of its own. Many animal rights activists were (and still are) very against the industry, and so this downsizing represented a victory for them— fewer farms meant fewer animals likely to be mistreated or cared for improperly. However, it also brought about a glut in the horse market, as the mares no longer being used for Premarin production needed to find new homes or uses. Many ended up in slaughterhouses, though there was an effort by rescue organizations and the general public to re-home many of these horses.
The controversy surrounding the issue of unwanted horses—both the retired mares and the foals produced—is akin to any of the controversies surrounding breeding practices of horses. Both the Thoroughbred racehorse industry and the Quarter Horse industry have also come under scrutiny for the number of animals produced each year that must find homes. So, while the concern aimed at the Premarin-producing industry is valid, it is not one strictly limited to that industry. Today, many of the foals become good sport horses and find great homes.
The downsizing of the industry led to another change. With a lesser quantity of urine needed for the production of Premarin, the ranchers involved in the industry were no longer limited to using only draft horses. More of a focus on breeding saleable foals has been seen, with an emphasis on selecting good quality stallions to sire the foals. Crosses now popular within the industry may include such breeds as Quarter Horses, Thoroughbreds, Hanoverians, Paints, and other such breeds, in addition to the more traditionally-used draft breeds. The ranchers rely on selling quality crops of foals as much as they rely upon the urine collected from the pregnant mares. Many of these farms utilize websites and forms of promotion identical to non-Premarin related horse breeders, and, in nearly all ways, are indistinguishable from the average breeder of equines.
Currently, standards on farms are strict and meticulous records must be kept. All ranchers must follow the “Recommended Code of Practice for the Care and Handling of Horses in PMU Operations” in order to keep their contract. The ranchers are regularly inspected to ensure they are following these codes in order to ascertain well-maintained animals and facilities.
For the warmer 6 months of the year, April through September, the mares are outside on expansive amounts of pasture 24/7. There is one stallion present for many mares in each herd, so breeding is allowed to occur naturally. All of the horses display normal herd behavior. During this time they still have access to human-provided feed and veterinary care.
The colder 6 months of the year, from October until March, they are kept inside the barn where their urine is collected and then shipped off. During this time, temperatures in the region where the industry is most highly concentrated (North Dakota and Canada) can often be extremely low, with high snowfall. The mares, stabled inside, are not exposed to the harsh elements. They would prefer to stay inside where it’s warm rather than go outside in that weather. [3] There are codes in place that require the mares get some exercise while they are enclosed for the winter.
The collection equipment used nowadays allows the mares a full range of motion, letting them easily lie down if they wish. They are primarily stabled in straight-stalls, conforming to regulations on size. While some animal rights activists claim the straight-stalls to be too confining and cruel, other studies have suggested that the arrangement might be beneficial for the mares. The mares are fed and watered on a tightly monitored routine to meet the requirements of the industry.[4]
[edit] References
- ^ "F.D.A. Makes No Recommendation on Generic Estrogen Drug". New York Times. 1995. http://www.nytimes.com/1995/07/30/us/fda-makes-no-recommendation-on-generic-estrogen-drug.html. Retrieved on 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
- ^ Horse Gazette Article
- ^ Naeric.org
[edit] See also
[edit] External links
- 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
- Facts about Premarin - from the Humane Society
- Equine Advocates - clarification of care and fate of PMU mares and foals
- [1] - NIH article on the risks of hormone therapy
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