Premarin is the commercial name for compound drug consisting primarily of conjugated
estrogenEstrogens are a group of steroid compounds, named for their importance in the estrous cycle, and functioning as the primary female sex hormone, their name comes from estrus/oistros + gen/gonos = to generate.Estrogens are used as part of some oral contraceptives, in estrogen replacement...
s. Isolated from
mare'sThe horse is a hoofed mammal, a subspecies of one of seven extant species of the family Equidae. The horse has evolved over the past 45 to 55 million years from a small multi-toed creature into the large, single-toed animal of today...
urineUrine is a liquid waste product of the body secreted by the kidneys by a process of filtration from blood called urination and excreted through the urethra. Cellular metabolism generates numerous waste compounds, many rich in nitrogen, that require elimination from the bloodstream...
(
PREgnant
MARes' ur
INe), it is manufactured by
WyethWyeth, formerly known as American Home Products , was one of the largest pharmaceutical companies in the world. The company is based in Madison, New Jersey...
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.
The major forms of estrogen in Premarin are
estroneEstrone is an estrogenic hormone secreted by the ovary as well as adipose tissue.Estrone is one of the three estrogens, which also include estriol and estradiol...
(>50%),
equilinEquilin is an estrogen from horses with the chemical name 3-hydroxyestra-1,3,5,7-tetraen-17-one. Equilin is one of the estrogens present in the mixture of estrogens isolated from horse urine and marketed as Premarin. Premarin became the most commonly used form of estrogen for hormone replacement...
(15-25%) and
equileninEquilenin is a horse steroid. It is used as one of the components in Premarin....
.
Premarin is the commercial name for compound drug consisting primarily of conjugated
estrogenEstrogens are a group of steroid compounds, named for their importance in the estrous cycle, and functioning as the primary female sex hormone, their name comes from estrus/oistros + gen/gonos = to generate.Estrogens are used as part of some oral contraceptives, in estrogen replacement...
s. Isolated from
mare'sThe horse is a hoofed mammal, a subspecies of one of seven extant species of the family Equidae. The horse has evolved over the past 45 to 55 million years from a small multi-toed creature into the large, single-toed animal of today...
urineUrine is a liquid waste product of the body secreted by the kidneys by a process of filtration from blood called urination and excreted through the urethra. Cellular metabolism generates numerous waste compounds, many rich in nitrogen, that require elimination from the bloodstream...
(
PREgnant
MARes' ur
INe), it is manufactured by
WyethWyeth, formerly known as American Home Products , was one of the largest pharmaceutical companies in the world. The company is based in Madison, New Jersey...
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.
Pharmacology
The major forms of estrogen in Premarin are
estroneEstrone is an estrogenic hormone secreted by the ovary as well as adipose tissue.Estrone is one of the three estrogens, which also include estriol and estradiol...
(>50%),
equilinEquilin is an estrogen from horses with the chemical name 3-hydroxyestra-1,3,5,7-tetraen-17-one. Equilin is one of the estrogens present in the mixture of estrogens isolated from horse urine and marketed as Premarin. Premarin became the most commonly used form of estrogen for hormone replacement...
(15-25%) and
equileninEquilenin is a horse steroid. It is used as one of the components in Premarin....
. The estrogens in Premarin are often called "conjugated equine estrogens" (CEE) because the estrogen
moleculeA molecule is defined as an electrically neutral group of at least two atoms in a definite arrangement held together by very strong chemical bonds. Molecules are distinguished from polyatomic ions in this strict sense...
s are generally present with hydrophilic side-groups attached such as
sulfateIn inorganic chemistry, a sulfate is a salt of sulfuric acid.-Chemical properties:...
. Thus,
estrone sulfateEstrone sulfate is a sulfated estrone....
is actually the major molecule in Premarin. Estrone sulfate is easily
absorbedIn pharmacology , absorption is the movement of a drug into the bloodstream.Absorption involves several phases...
into the
bloodBlood is a specialized bodily fluid that delivers necessary substances to the body's cells — such as nutrients and oxygen — and transports waste products away from those same cells....
after Premarin
pillA tablet is a mixture of active substances and excipients, usually in powder form, pressed or compacted into a solid. The excipients include binders, glidants and lubricants to ensure efficient tabletting; disintegrants to ensure that the tablet breaks up in the digestive tract; sweeteners or...
s are taken by women. Estrone sulfate is
convertedIn chemistry, the phrase conversion has several meanings* specifically the property 'X' related to the yield 'Y' by multiplication with the selectivity 'S', i.e. the mathematical definition X * S = Y, all calculated on a molar basis; e.g...
to
estradiolEstradiol is a sex hormone. Estradiol is the predominant sex hormone present in females; however, it is present in males, albeit at lower levels, as well. It represents the major estrogen in humans...
, 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 syndromeAndrogen insensitivity syndrome , also referred to as androgen resistance syndrome, is a set of disorders of sex development caused by mutations of the gene encoding the androgen receptor. The nature of the resulting problem varies according to the structure and sensitivity of the abnormal receptor...
.
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,
EstroneEstrone is an estrogenic hormone secreted by the ovary as well as adipose tissue.Estrone is one of the three estrogens, which also include estriol and estradiol...
in its sulfated form. Thus, Premarin cannot be characterized by the structure of just one of its many compounds.
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".
Production
Premarin is the subject of some
contentionContention may refer to:* The main contention, in rhetoric, the main point being argued* Resource contention, a general concept in communications and computing, is competition by users of a system for the facility at the same time:...
.
Animal rightsAnimal rights, also referred to as animal liberation, is the idea that the most basic interests of animals should be afforded the same consideration as the similar interests of humans...
groups and those opposing the industry claim that animal husbandry and urine collection methods used in Premarin's production cause undue stress and suffering to the
mareA mare is an adult female horse or other equine.Most of the time, a mare is a female horse over the age of three, and a filly is a female horse age three and younger. However, in Thoroughbred horse racing, a mare is defined as a female horse more than four years old; in harness racing a mare is a...
s involved. 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. Some claim the numbers are more accurately in the millions.
For 6 months of the year the mares are outside, where they are annually impregnated. The mares, stabled inside for the other 6 months of the year, are restrained in a variety of ways, with plastic urine-collection bags in place. These bags can limit movement on their own, but many of these horses are restrained part or all of the time, further restricting natural movement. Morbidity can result, with infection and other skin injury resulting from the urine bags, and the restriction of movement can also lead to disability. Fluid (water) intake is severely restricted, as well (allowing concentration of the urine, something desired by the drug manufacturer). Most horses have a far shorter life-span in this environment than would be expected.
Some of this contention may stem from the looser standards formerly held in the industry, although accurate records are lacking. 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 indicating that lower doses of the drug might instead be safer. As a result, some facilities reduced the number of mares that were contained on-site, and some contend that other aspects of the industry were updated as well.
The cut spurned much controversy of its own. Many animal rights groups 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 killed. However, it also led many of these farms to sell off large numbers of horses for slaughter, although there was an effort by rescue organizations and the general public to re-home some of these horses.
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 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, those in favor of the industry claim that standards on farms are strict and meticulous records must be kept, and that 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. They further state that ranchers are regularly inspected to ensure they are following these codes in order to ascertain well-maintained animals and facilities. However, with these operations out-of-view and inaccessible to the public, current practices cannot be verified.
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
The Food and Drug Administration is a Government agency of the United States Department of Health and Human Services and is responsible for regulating and supervising the safety of foods, tobacco products, dietary supplements, Medication drugs, vaccines, Biopharmaceutical, blood transfusion,...
(FDA) website
- Menopause resource - from Wyeth
Wyeth, formerly known as American Home Products , was one of the largest pharmaceutical companies in the world. The company is based in Madison, New Jersey...
- Facts about Premarin - from the Humane Society
- Equine Advocates - clarification of care and fate of PMU mares and foals
- http://public.nhlbi.nih.gov/newsroom/home/GetPressRelease.aspx?id=2554 - NIH article on the risks of hormone therapy