Premarin

Combination of
Estrone sulfate	Estrogen
Equilin sulfate	Estrogen
Equilenin sulfate	Estrogen
Clinical data
AHFS/Drugs.com	Consumer Drug Information
Pregnancy cat.	X
Legal status	℞ Prescription only
Routes	Oral, topical
Identifiers
CAS number	12126-59-9 Y
ATC code	G03CA57
PubChem	CID 656613
ChemSpider	570974 Y
UNII	IU5QR144QX Y
Y (what is this?)  (verify)

Premarin is the commercial name for a compound cream of vaginally administered estrogens,^[1] 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 form.

Pharmacology[link]

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.

• 

  Estrone sulfate

• 

  Equilin sulfate

• 

  Equilenin sulfate

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.^[2] 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.

Bioequivalance[link]

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".^[3]

Controversy[link]

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Premarin is the subject of some contention. Animal welfare 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 mares involved.^[4] 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.^[5]

For six months of the year the mares are outside, where they are annually impregnated. The mares, stabled inside for the other six 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.^{[citation needed]} 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 spurred 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.

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.

Health effects[link]

Research starting in 1975 showed substantially increased risk of endometrial cancer.^[6][7] Since 1976 the drug has carried a label warning about the risk.^[8] 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.^[9] 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.^[10]

Litigation[link]

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.^[11] 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.^[12] In 2006, Mary Daniel, in a trial in Philadelphia, PA, was awarded $1.5 million in compensatory damages as well as undisclosed punitive damages,^[13] Daniel was represented by the firm of Littlepage Booth. In 2007 the same firm tried a case in Reno, Nevada, representing three plaintiffs who were awarded roughly $17–19 million apiece in damages.^[14] Wyeth appealed this outcome, and it is currently before the Nevada Supreme Court.^[15] 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^[16]. 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." ^[17] 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."^[12]

See also[link]

• Estrogen

References[link]

External links[link]

• 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

Bea Arthur
Bea Arthur in 2005
Born	Bernice Frankel (1922-05-13)May 13, 1922 New York City, New York
Died	April 25, 2009(2009-04-25) (aged 86) Los Angeles, California
Cause of death	Cancer
Nationality	American
Alma mater	Linden Hall School for Girls
Occupation	Actress, comedienne, singer, activist
Years active	1947–2008
Religion	Jewish
Spouse	Robert Alan Aurthur (first marriage; divorced) Gene Saks (m.1950-1978; divorced)

Beatrice "Bea" Arthur (May 13, 1922 – April 25, 2009) was an American actress, comedienne and singer whose career spanned seven decades. Arthur achieved fame as the character Maude Findlay on the 1970s sitcoms All in the Family and Maude, and as Dorothy Zbornak on the 1980s sitcom The Golden Girls, winning Emmy Awards for both roles. A stage actress both before and after her television success, she won the Tony Award for Best Featured Actress in a Musical for her performance as Vera Charles in the original cast of Mame (1966).

Early life[link]

Arthur was born Bernice Frankel on May 13, 1922 to Philip and Rebecca Frankel (1902–1986)^[1] in New York City.^[2][3] In 1933 her family moved to Cambridge, Maryland, where her parents operated a women's clothing shop. She attended Linden Hall School for Girls, an all girls boarding school in Lititz, Pennsylvania, before enrolling in the now-defunct Blackstone College for Girls in Blackstone, Virginia, where she was active in drama productions.

Arthur joined the United States Marine Corps in 1943. She worked at such jobs as typist and truck driver, and was honorably discharged with the rank of staff sergeant in 1945. She had a single misconduct report in 1944 for contracting venereal disease. During her time in the Marines, she married another Marine, Robert Aurthur, and changed her last name. She later denied having served in the military.^[4]

Career[link]

Theater[link]

From 1947, Bea Arthur studied at the Dramatic Workshop of The New School in New York with German director Erwin Piscator. Arthur began her acting career as a member of an off Broadway theater group at the Cherry Lane Theatre in New York City in the late 1940s. On stage, her roles included Lucy Brown in the 1954 Off-Broadway premiere of Marc Blitzstein's English-language adaptation of Kurt Weill's Threepenny Opera, Yente the Matchmaker in the 1964 premiere of Fiddler on the Roof on Broadway, and a 1966 Tony Award-winning portrayal of Vera Charles to Angela Lansbury's Mame. She reprised the role in the 1974 film version opposite Lucille Ball. In 1981, she appeared in Woody Allen's The Floating Light Bulb.^[5] She made her debut at the Metropolitan Opera in 1994 portraying the Duchess of Krakenthorp, a speaking role, in Gaetano Donizetti's La fille du régiment.^[6]

Television[link]

In 1971, Arthur was invited by Norman Lear to guest-star on his sitcom All in the Family, as Maude Findlay, the cousin of Edith Bunker. An outspoken liberal feminist, Maude was the antithesis to the bigoted, conservative Archie Bunker, who decried her as a "New Deal fanatic". Then nearly 50, Arthur's tart turn appealed to viewers and to executives at CBS, who, she would later recall, asked "'Who is that girl? Let's give her her own series.'"^[7]

That show, previewed in her second All in the Family appearance, would be simply titled Maude. The show, debuting in 1972, would find her living in the affluent community of Tuckahoe, Westchester County, New York, with her fourth husband Walter (Bill Macy) and divorced daughter Carol (Adrienne Barbeau). Her performance in the role garnered Arthur several Emmy and Golden Globe nominations, including her Emmy win in 1977 for Outstanding Lead Actress in a Comedy Series.

It would also earn a place for her in the history of the women's liberation movement.^[8] The groundbreaking series didn't shirk from addressing serious sociopolitical topics of the era that were fairly taboo for a sitcom, from the Vietnam War, the Nixon Administration and Maude's bid for a Congressional seat to divorce, menopause, drug use, alcoholism, nervous breakdown and spousal abuse. A prime example is "Maude's Dilemma", a two-part episode airing near Thanksgiving of 1972 in which Maude's character grapples with a late-life pregnancy, ultimately deciding to have an abortion.

Even though abortion was legal in New York State, it was illegal in many other regions of the country, and as such sparked controversy. As a result, dozens of affiliates refused to broadcast the episode when it was originally scheduled, substituting either a repeat from earlier in the season or a Thanksgiving TV special in its place. However, by the time of the summer rerun season six months later all the flak had died down, and the stations that refused to air the episode upon its first run reinstated it for the reruns the following summer. As a result, a reported 65 million viewers watched the two episode arc either in their first run that November or during the following summer as a re-run.^[9]

As the episode aired two months before the U.S. Supreme Court legalized the procedure nationwide in the Roe v. Wade outcome in early 1973, it was said to have had influence on the Supreme Court Justices' decision.^[10] By 1978, however, Arthur decided to move on from the series.

That year, she costarred in The Star Wars Holiday Special, in which she had a song and dance routine in the Mos Eisley Cantina. She hosted The Beatrice Arthur Special on CBS on January 19, 1980, which paired the star in a musical comedy revue with Rock Hudson, Melba Moore and Wayland Flowers and Madame.^[11]

After appearing in the short-lived 1983 sitcom Amanda's (an adaptation of the British series Fawlty Towers), Arthur was cast in the sitcom The Golden Girls in 1985, in which she played Dorothy Zbornak, a divorced substitute teacher living in a Miami house owned by Blanche Devereaux (Rue McClanahan). Her other roommates included widow Rose Nylund (Betty White) and Dorothy's Sicilian mother, Sophia Petrillo (Estelle Getty). Getty was actually a year younger than Arthur in real life, and was heavily made up to look significantly older. The series became a hit, and remained a top-ten ratings fixture for seven seasons. Her performance led to several Emmy nominations over the course of the series and an Emmy win in 1988. During the series run, Arthur became an LGBT icon.^{[original research?]} Arthur decided to leave the show after seven years, and in 1992 the show was moved from NBC to CBS and retooled as The Golden Palace in which the other three actresses reprised their roles. Arthur made a guest appearance in a two-part episode.

Film[link]

Arthur also sporadically appeared in films, reprising her stage role as Vera Charles in the 1974 film adaption of Mame, opposite Lucille Ball. Additionally, Arthur portrayed overbearing mother Bea Vecchio in Lovers and Other Strangers (1970), and had a cameo as a Roman unemployment clerk in Mel Brooks' History of the World, Part 1 (1981).

Later career[link]

After Arthur left The Golden Girls, she made several guest appearances on television shows and organized and toured in her one-woman show, alternately titled An Evening with Bea Arthur and And Then There's Bea. She made a guest appearance on the American cartoon Futurama, in the Emmy-nominated 2001 episode "Amazon Women in the Mood", as the voice of the Femputer who ruled the giant Amazonian women. She also appeared in a first-season episode of Malcolm in the Middle as Mrs. White, Dewey's babysitter. She was nominated for an Emmy for Outstanding Guest Actress in a Comedy Series for her performance. She also appeared as Larry David's mother on Curb Your Enthusiasm.

In 2002, she returned to Broadway starring in Bea Arthur on Broadway: Just Between Friends, a collection of stories and songs (with musician Billy Goldenberg) based on her life and career. The show was nominated for a Tony Award for Best Special Theatrical Event. The previous year had been the category's first, and there had been only one nominee. That year, Arthur was up against solo performances by soprano Barbara Cook, comedian John Leguizamo, and Arthur's fellow student in Piscator's program at The New School, actress Elaine Stritch, who won for Elaine Stritch: At Liberty.

In addition to appearing in a number of programs looking back at her own work, Arthur performed in stage and television tributes for Jerry Herman, Bob Hope, Peggy Lee, and Ellen DeGeneres. In 2005, she participated in the Comedy Central roast of Pamela Anderson, where she recited sexually explicit passages from Anderson's book Star Struck in a deadpan fashion.

Influences[link]

In 1999, Arthur told an interviewer of the three influences in her career: "Sid Caesar taught me the outrageous; [method acting guru] Lee Strasberg taught me what I call reality; and [original Threepenny Opera star] Lotte Lenya, whom I adored, taught me economy."^[12]

Personal life[link]

Arthur was married twice. Her first marriage took place during her time in the military, when she married fellow Marine Robert Alan Aurthur (see Early life, above),^[13] a screenwriter, television, and film producer and director, whose surname she took and kept (though with a modified spelling). Shortly after they divorced, she married director Gene Saks from 1950 to 1978 with whom she adopted two sons, Matthew (born in 1961), an actor, and Daniel (born in 1964), a set designer.^[14]

In 1972, she moved to the Greater Los Angeles Area and sublet her apartment on Central Park West in New York City and her country home in Bedford, New York.^[15]

Arthur was a committed animal rights activist and frequently supported People for the Ethical Treatment of Animals campaigns. Arthur joined PETA in 1987 after a Golden Girls anti-fur episode.^[16] Arthur wrote letters, made personal appearances and placed ads against the use of furs, foie gras, and farm animal cruelty by KFC suppliers. In Norfolk, Virginia near the site of the PETA headquarters, there is a dog park named Bea Arthur Dog Park in her honor.

Arthur's longtime championing of civil rights for women, the elderly, and the Jewish & LGBT communities—in her two television roles and through her charity work and personal outspokenness—has led her to be cited as an LGBT icon.^[17][18][19]

Death[link]

Arthur died at her home in the Greater Los Angeles Area in the early morning hours of Saturday, April 25, 2009. She had been ill with cancer,^[12][20][21] and her body was cremated after her death.^[22]

On April 28, 2009, the Broadway community paid tribute to Arthur by dimming the marquees of New York City's Broadway theater district in her memory for one minute at 8:00 P.M.^[23][24]

Arthur's co-stars from The Golden Girls, Rue McClanahan and Betty White, commented on her death via telephone on an April 27 episode of Larry King Live^[25][26] as well as other news outlets such as ABC.^[27] Longtime friends Adrienne Barbeau (with whom she had worked on Maude) and Angela Lansbury (with whom she had worked in Mame) released amicable statements: Barbeau said, "We've lost a unique, incredible talent. No one could deliver a line or hold a take like Bea and no one was more generous or giving to her fellow performers";^[28] and Lansbury said, "She became and has remained my Bosom Buddy [...] I am deeply saddened by her passing, but also relieved that she is released from the pain".^[29]

Arthur bequeathed $300,000 to The Ali Forney Center, a New York City organization that provides housing for homeless LGBT youths.^[30][31]

Awards[link]

Arthur won the American Theatre Wing's Tony Award in 1966 as Best Featured Actress in a Musical for her performance that year as Vera Charles in the original Broadway production of Jerry Herman's musical Mame.

Arthur has received the second most nominations for the Primetime Emmy Award for Outstanding Lead Actress in a Comedy Series with 9. Only Mary Tyler Moore, with 10 nominations, has more. She received the Academy of Television Arts & Sciences' Emmy Award for Outstanding Lead Actress in a Comedy Series twice, once in 1977 for Maude and again in 1988 for The Golden Girls.^[32] She was inducted into the Academy's Hall of Fame in 2008.^[33]

On June 8, 2008, The Golden Girls was awarded the Pop Culture award at the Sixth Annual TV Land Awards. Arthur (in one of her final public appearances) accepted the award with co-stars Rue McClanahan and Betty White.^[34]

Television credits[link]

Theater performances[link]

References[link]

External links[link]

Biography portal

Wikinews has related news: American actress Bea Arthur dies at age 86

Wikimedia Commons has media related to: Bea Arthur

• Bea Arthur at the Internet Movie Database
• Bea Arthur at the Internet Broadway Database
• Bea Arthur Interview at Archive of American Television
• Bea Arthur at the Internet Off-Broadway Database
• Bea Arthur at The Comedy Hall of Fame
• Kirsten Fermaglich, Beatrice Arthur, Jewish Women Encyclopedia
• CBC obituary
• N.Y. Times obituary
• "Huffington Post" article about her death
• L.A. Times memorial
• Entertainment Weekly article about her death
• Beatrice Arthur – Daily Telegraph obituary