Implications of Premarin?

Question

I'm doing a report on Premarin.

I have to write about the biological, social, ethical, economic and environmental implications of the drug.

I have so far written about the ethics (the way the horses/foals are treated) but don't know about the other implications ... Could anyone please give me some ideas ?

Answer 1

Premarin® stands for Pregnant Mares' Urine (PREgnant MARes' urINe); PMU for short (we spell it both ways, with an "e", PREgnant MARes' urINE which is the older name used in Canada, and without -- which is the more popular recent spelling, and the one that is a U.S. registered trademark).

Premarin (including Prempro, Premphase, Prempac, and Premelle) is a drug made up of conjugated estrogens obtained from the urine of pregnant mares -- put out in many forms (pills, creams, injections, patches, vaginal rings) and is used to reduce the symptoms of menopause in women or women who have had a hysterectomy. It is also prescribed to nearly eliminate the risk of osteoporosis (the brittling of bones) and reduce the chance of heart disease in women over 50.

As of November 2003, approximately nine million American women are still taking some form of Premarin (1 million women in the United States were still taking Prempro pills as of June 2003, down from the 3.4 million taking the drug before the negative Women's Health Initiative study results became known). This is a reduction of 25% from the high figure of approximately 12 million women taking PMU based medications in 1999. See also HorseAid's "Prognosis for Premarin".

About a third of the approximately fifty-five million post menopausal women in the United States are on estrogen replacement therapy (ERT), or hormone replacement therapy (HRT), and of them, about 49% currently use PMU based products (down from a high of 79% in 1999) -- while there are a number of estrogens excreted by the pregnant mare, estrone sulfate, equilin, and equilenin are the most significant.

It is the only human estrogen replacement drug that is derived from an animal (hormones beginning with the letter "e" are specific to equines, hormones beginning with the letter "h" are specific to humans).

The company that distributes and markets it world-wide, Ayerst Organics Ltd. (the world's only producer of PMU) is a subsidiary of Wyeth Inc. (Wyeth Laboratories, Inc. traces its roots to Philadelphia, Pennsylvania, U.S.A., where, in 1860, John Wyeth and his brother Frank established a drugstore). Wyeth Inc. is the world's eight largest drug maker (2003), falling from the seventh position it had held for many years.

What's in it?

  

Premarin tablets contain:

  Ã¢Â€Â¢ estrone

  Ã¢Â€Â¢ equilin

  Ã¢Â€Â¢ 17 alpha-dihydroequilin

  Together with smaller amounts:

  Ã¢Â€Â¢ 17 alpha-estradiol

  Ã¢Â€Â¢ equilenin

  Ã¢Â€Â¢ 17 alpha-dihydroequilenin as salts of their sulfate esters

  Premarin tablets also contain the following inactive ingredients:

  Ã¢Â€Â¢ calcium phosphate tribasic

  Ã¢Â€Â¢ calcium sulfate anhydrous (white tablet only)

  Ã¢Â€Â¢ calcium sulfate

  Ã¢Â€Â¢ carnauba wax

  Ã¢Â€Â¢ cellulose

  Ã¢Â€Â¢ glyceryl monooleate

  Ã¢Â€Â¢ lactose

  Ã¢Â€Â¢ magnesium stearate

  Ã¢Â€Â¢ methylcellulose

  Ã¢Â€Â¢ pharmaceutical glaze

  Ã¢Â€Â¢ polyethylene glycol

  Ã¢Â€Â¢ stearic acid

  Ã¢Â€Â¢ sucrose

  Ã¢Â€Â¢ talc

  Ã¢Â€Â¢ titanium dioxide



ALL Premarin medications are non-synthetic organic, and ALL Premarin is derived from estrogens extracted from Pregnant Mares' Urine (PMU). If you ever doubt where Premarin comes from,  just break open a pill and smell it!



How Long Has This Drug Been in Use?

Introduced in 1942, long before synthetic or non PMU organic alternatives existed. Premarin was one of the first drugs available when hormonal therapy for menopause was introduced. The industry thrived (mostly in Ontario, Canada) for decades until allegations of catheterized mares living in squalor and foals being mistreated could no longer be ignored. The Ontario Government stepped in and issued regulations tied to licensing, citing, and revoking permits (PMU Farm Act, 1968-69, Regulation No. 217/70). In 1975, it became American Home Products (now Wyeth Inc.) biggest selling and most successful ever prescription drug.

How Long Has HorseAid Been Involved in The PMU/Premarin Controversy?

Since 1986. HorseAid was the first equine welfare organization to do an in depth "hands-on" (and on-site) investigation into the operation of the PMU farms and the suspected health risks to women taking PMU based medications. Up until that time, no animal rights/welfare organization had ever reported on the horse abuses that were occurring on the majority of the PMU farms or the linked risks in taking HRT medications.

This was before the advent of the public Internet or Web, so our information had to gathered the "old fashioned way", by on-site visits and following the paper and money trails of the various aspects of the PMU/Premarin industry. We published the results of that initial 1986/87 investigation (with photographs) in our 1988 Fall/Winter issue of Equine Times News (ET-News, forerunner of our current Running Free publication) under the heading, "The Pill that Kills".

In 1993, Animal People Magazine published an extensive article on the PMU farm abuses, also noting the suspected health risks to women taking PMU based medications. HorseAid collaborated with APM on some of the statistics for that article. APM was the first wide circulation magazine to do such a report. Both of these articles appeared long before PMU farms abuses and Premarin based medications became a favorite fundraising issue for some of the organizations that later became involved in the controversy.

HorseAid was also first to publish the PMU/Premarin controversy on the Internet — in 1994, under the page heading "PREgnant MARes' urINe, Curse or Cure?".  Second only to the HorseAid equine rescue and adoption programs, our PMU/Premarin research has been HorseAid's greatest expenditure in both funds and volunteer resources.

Why Are There Still PMU ("pee") Farms in Existence?

Good question. HRT drugs containing PMU, like the hormone replacement insulin before it, can now be 100% synthesized or organically compounded PMU free.In 1982, the U.S. Food and Drug Administration approved the use of insulin derived from recombinant-DNA techniques (using bacteria cultures) for diabetic patients who, heretofore, relied solely on insulin derived from the pancreases of pigs to control their disease ("pig"* sincerely thanks you, FDA!). So, like we no longer use pigs for human hormone replacement sources, we shouldn't (and don't have to) use horses either.

(*"the pig" content courtesy of Universal City Studios, Inc. © 1996, All Rights Reserved)

However, the FDA ruled in 1997, that because of the delta 8,9 DHES factor that the synthetics and non PMU organics lack, "generic" forms of the drug do not meet the "identical active ingredients/efficacy" test that is required under the federal Waxman-Hatch Act of 1984 of a "generic substitute".

Formerly, the FDA classified delta 8,9-dehydroestrone sulfate (named after the new molecule's shape) as an "impurity", now it's a "concomitant" (concomitants are defined by what they are not. They are not active ingredients and they are not impurities -- both the USPC and the FDA had declined in the past to re categorize delta 8,9 as an active ingredient).

Since the FDA readily admits it has no conclusive clinical proof what role, if any, delta 8,9 DHES plays in Premarin ERT/HRT (the FDA's Office of Clinical Pharmacology and Biopharmaceuticals found that "none of the pharmokinetic data presented by the firm [Wyeth] can be interpreted as demonstrating that delta 8,9 or its metabolite 17-B is essential to the estrogenic activity of Premarin." — also adding that "the data submitted by Wyeth was either incomplete or conflicting."), and since Wyeth has advanced no valid clinical claims for delta 8,9 DHES -- instead asking for the new "concomitant" category so it could use its patent on delta 8,9 to block its competitors from adding delta 8,9-dehydroestrone sulfate to any new synthetic or organic generic. HorseAid wonders what led to this "sudden" about-face by the FDA? We are sure we will get an honest answer to that question when "pig"* (who as you know, loves horses) also learns to sing a different tune.

While Wyeth-Ayerst and the FDA would like women to believe that the above decision was based on good health management practices, in reality -- it was the lobbyists that steered the FDA toward this decision (which seems to be entirely politically motivated), is full of unresolved conflict of interest issues, and characterized by some very questionable political maneuvering.

On March 24th, 1999, the FDA approved the New Drug Application (NDA) of Duramed Pharmaceuticals' "Cenestin" brand of plant based conjugated estrogens. It is important to note that Duramed Pharmaceuticals filed a NDA for Cenestin instead of the previous Abbreviated New Drug Application (ANDA) used when requesting a drug be classed as a generic to an already existing branded drug, thus not requesting the FDA classify Cenestin as a direct replacement generic form of Premarin (the previous ANDA, which the FDA denied, was to class Cenestin as a generic form of Wyeth-Ayerst's drug Premarin). Duramed Pharmaceuticals however, was unsuccessful in marketing the drug as an "alternative" to Premarin.

Despite synthetic and non PMU based organic FDA-approved alternatives (Ogen, Estrace, Estradiol Transdermal System, Estradiol tablets, Estropipate, Estrone, Meneste, and Cenestin, to name a few), production of the PMU based organic material is good for the Canadian agricultural industry. As in America, there aren't many ways for farmers to make a living anymore.

Most of the Canadian PMU farms have re-emerged in Manitoba, Alberta, and Saskatchewan, where there are relatively few laws governing the industry as there are i