Menopause "Discovered"
1686: Fourteen “witches” are executed at Salem – thirteen of them are menopausal women.
1821: A French physician named de Gardanne coins the
term “menopause” a century prior to the isolation of the hormone
estrogen and publishes a book “De la ménopause, ou de l’âge critique des
femmes”. Thus begins the search for the “cure”.
1872: Menopausal women are considered mentally
deranged and are classified by Lawson Tait, an influential physician and
surgeon of London, as having incurable dementia. In his opinion relief
can be achieved by the use of “an occasional purgative” and “removal
from home at frequent intervals” – the asylum!
1890: Merck suggests that menopausal symptoms can
be treated with wine, cannabis, opium, and a product made out of powered
ovaries, among others.
1899: An idea was emerging that sex hormones might
be involved in menopause. A Parisian woman medicates herself with
liquids derived from pigs’ ovaries with positive effects.
1929: Estrogen is isolated and identified by Edward Doisy at Washington University in St. Louis.
Premarin® –The “Cure”?
1930: Water soluble estrogens are discovered in
pregnant mares’ urine by a German doctor, Bernhard Zondek. Other
researchers reveal that decomposed and hydrolyzed pregnant mare’s urine
contain estradiol.
1933: The first estrogen replacement product
marketed in the US is developed – Emmenin, a product made from the urine
of pregnant women. However, it is costly and the search continues for a
cheap alternative.
1942: Wyeth’s predecessor Ayerst receives approval
for the patent of Premarin, formulated from the urine of pregnant mares,
and is approved by the FDA to market. Initial approval was based on a
“replacement” therapy to “replace” a woman’s depleted estrogen levels.
1943: Wyeth merges with Ayerst, McKenna and
Harrison, Ltd. Of Canada. With this came Premarin®, the world’s first
conjugated estrogen medicine.
The Journal of Clinical Endocrinology publishes four independent
studies of Premarin® use in five US cities praising its ease of use and
effective relief of symptoms.
1965: The growth in use of estrogen replacement
therapy (ERT) and the HRT concept is supported by a book written by Dr.
Robert Wilson titled “Feminine Forever”. Unbeknownst to the general
public, he is a consultant for Wyeth.
1972: The FDA publishes a Federal Register notice
indicating that estrogen products including Premarin® are effective in
treating menopausal symptoms. At the same time, the FDA provides for
submission and approval of abbreviated new drug applications (ANDAs) for
generic conjugated estrogens.
1973: The belief that estrogen was beneficial for
the heart in women led to a trial in which men took Premarin® for the
prevention of heart attacks and strokes. The trial was abruptly halted
since the men receiving the treatments had increased incidences of heart
attacks and blood clots. Instead of a wakeup call to the deleterious
side effects, they simply attributed this to dosage issues and continued
to praise the drug for its use in relieving menopausal symptoms in
women.
1975: The New England Journal of Medicine publishes
two articles that indicate a four to fourteen times increased risk of
endometrial cancer with post-menopausal use of ERT.
1976: Ayerst sends a “Dear Doctor” letter to every
physician in the country regarding the use of Premarin®. The FDA
reprimands the letter maintaining it is misleading and minimizes the
risk of the association of CEEs and uterine cancer. In turn, the FDA
issues a drug bulletin underscoring the increased risk of uterine cancer
with prolonged use of estrogen products.
The New England Journal of Medicine publishes the first report of a link between estrogen use and breast cancer.
1977: Ayerst Laboratories Premarin® is definitively
linked to uterine cancer. Ayerst responds by adding a warning to the
label but Hill and Knowlton, a public relations firm, simply attribute
the cancer risk a “public relations” issue.
Premarin® becomes the fifth most frequently prescribed drug in the US with more than 30 million prescriptions written.
1980s: Several smaller companies offer a generic form of Premarin®.
1982: Cancer research journals report that CEE menopausal hormones are a major factor in the development of cancer indications.
1989: A Swedish study indicates that women on a
regimen of estrogen or estrogen-progestin had a slightly increased risk
of breast cancer when on estrogen yet when on the combined drug therapy
their risk more than doubled (New England Journal of medicine).
1990s: Premarin® becomes the most frequently dispensed drug in the US.
1991: The Women’s Health Initiative (WHI) is
launched. The clinical trials were designed to test the effects of
postmenopausal hormone therapy, diet modification, and calcium and
vitamin D supplements on heart disease, fractures, and breast and
colorectal cancer.
1995: Prempro® is the first estrogen-progestin HRT drug approved by the FDA
NAERIC (North American Equine Ranching Council) is established. An
organization engaged in the collection of pregnant mares urine (PMU)
that reportedly is dedicated to the progressive science-based horse
management techniques to ensure the highest possible care standards are
utilized in the equine ranching industry.
NAERIC is heavily funded by Wyeth and supports horse slaughter.
1997: Premarin® becomes Wyeth-Ayerst’s first brand to reach $1 billion in sales.
The FDA rejects an application for a generic version of the drug
Premarin®. Both the FDA and Wyeth-Ayerst want the public to believe it
was in their best interest to protect and safeguard the public. In
reality it was motivated by scores of lobbyists, fraught with conflicts
of interest, and epitomized by questionable surreptitious political
manipulation.
Data from 51 epidemiological studies is published in The Lancet (a UK
medical journal) further implicating an increased risk of breast cancer
with post-menopausal estrogen use.
1998: The first major placebo controlled trial of
HRT indicates no benefit to women who have had heart attacks, in fact,
increasing their risk and advises them to withdraw.
2001: First results of the WHI study are released
spreading bad news to not only doctor’s offices but also Wall Street.
Although physicians remained ambiguous about the results of increased
cancer risk and heart attacks, shares of Wyeth fell 19%. The company
responded by emphasizing it was the combination therapy of
estrogen-progestin Prempro® and not Premarin® that was at fault.
2002: Barr Laboratories suffers at the hands of
Wyeth. A Minnesota Federal judge finds that Barr misappropriated trade
secrets thereby protecting Wyeth’s lucrative monopoly of Premarin®.
Government scientists abruptly end the WHI HRT study – the nation’s
largest – which states that long-term use of estrogen and progestin
significantly increases women’s risk of breast cancer, strokes and heart
attacks.
After the government’s announcement, millions of women discontinue
the use of HRT – down from about 6 million users for Prempro® to 3.3
million.
FDA announces it will more thoroughly evaluate HRT use – the first official response from the government.
Prempro®’s sales plummet 32% for 2002.
2003: Further studies indicate there were increased
incidences of cardiovascular events, and breast cancer in women taking
the combination therapy drug Prempro®.
FDA orders that both medications – Premarin® and Prempro® – carry
warning labels advising users of the increased risk of heart disease,
stroke, breast cancer, pulmonary embolisms and blood clots.
Additional results from the NIH study indicate that HRT contributes to dementia.
Media reports escalate the public awareness of the sequestered
pregnant mares and slaughtered foals – the “by-products” of the PMU
industry.
2004: As a result of falling sales of Premarin®
and Prempro®, Wyeth introduces a lower dosage estrogen-progestin drug
claiming it is safe.
The estrogen-only (Premarin®) division of the WHI study continues to
2004 but it also is terminated prematurely due to indications of
increased risk of stroke, deep vein thrombosis and without benefit in
terms of coronary heart disease.
Sales of Premarin® and Prempro® freefall from $1.3 billion in 2002 to $880 million in 2004.
2005: Wyeth closes a manufacturing plant and eliminates 15% of its sales force as sales of Prempro® falls 76% and Premarin® 47%.
Wyeth asks the FDA to investigate independent pharmacies producing
bio-identical hormone replacement therapy (BHRT) claiming there are
potential risks to women’s health and possible violations of
manufacturing practices. In October of 2005, Wyeth files a “Citizen’s
Petition” demanding the ban of bio-identical hormones which
coincidentally compete with their synthetic hormones.
2007: Numerous cancellations of contracts for the Premarin® family of drugs results in herd reductions on PMU farms.
A report in The Lancet found that HRT increases the risk of ovarian cancer by 20%.
FDA declines to approve Pristiq – a non-hormonal drug for menopausal
symptoms produced by Wyeth – without further testing due to some
indications that the drug causes serous heart and liver complications.
After years of research, analysis, and debate, the International
Agency for Research on Cancer, the U.N.’s cancer research agency, has
reclassified HRT from “possibly carcinogenic” to “carcinogenic.”
2008: Wyeth announces that it plans to meet with
the FDA in February to discuss product formulation, bioequivalence and
clinical study efforts to support the planned NDA filing of Aprela – a
new drug containing CEEs for menopausal symptoms and a selective
estrogen receptor modulator, for the prevention of postmenopausal
osteoporosis.
