2010 » More surveys implicate HRT as a risk factor for asthma, lung cancer, malignant melanoma and reduced insulin resistance. Wyeth (bought out by Pfizer) battles lawsuits about use of Premarin and its siblings that span from 1976 onward. Some 5000 cases alone are breast cancer focused. Still, Pfizer Q4 Biopharmaceutical earnings boast a 30% spike at $24.6 billion, compared to $11.2 billion in Q4 2008. Pfizer-Wyeth anticipate sales over $1 billion by 2015, for Premarin and Aprela. Even as profits rise, Pfizer-Wyeth closes eight plants, with 6000 job lay-offs at six others. Wyeth begins to trim PMU ranches, with projected closure of 39 sites. In fact, the drug giant seeks new locales where societies consume horse meat. The Western Producer reports: “Wyeth plans to ramp up production of PMU facilities in China, Kazakhstan and Poland, out of the scrutiny of North American values. The byproduct of meat foals has a lucrative market, while Wyeth can continue to make statements relating to supply and demand to justify price of HRT.”¹⁴

2011 » Wyeth-biased research urges doctors to prescribe more HRT at younger ages, rather than restrict disputed Premarin family drugs. Such marketing contradicts past studies that show elevated breast cancer risk in early-use patients. Oh well… Meanwhile, Pfizer hosts a teleconference on “solutions to the unwanted horse problem.” Tom Lenz, Senior Director of Equine Veterinary Services at Pfizer Animal Health — a known defender of horse slaughter — leads the call. Pfizer, in alliance with North American equine groups (AQHA, AAEP, AVMA, UHC, UOH, NAERIC, AHC), casts horse slaughter as the “humane” answer to spent mares and unneeded foals. Oct 2011: New Jersey state court is home to 150 HRT lawsuits, though an appeals court dismisses claims that Prempro, Provera and Premarin fail to warn users about breast cancer risk and delude federal regulators.

Expanded WHI research at Buffalo University indicates that conjugated equine estrogen obscures breast cancer detection, allowing the disease to progress to lymph nodes and lower survival rates. The study also links estrogen to kidney stones regardless of other risk factors such as age, ethnicity, weight. Alongside bad-news data, Pfizer muddles through lawsuits with 52% of HRT actions still open as of 12/31/11. The pharma behemoth incurs $336 million in 2011 and $300 million before that. Another $359 million, to cover nominal costs for unsettled HRT suits, is paid out in 2011. Jan 2011: A woman in Puerto Rico gets $1.5 million for claims that Prempro caused her breast cancer. Feb 2011: A Prempro breast cancer case garners more than $10 million for litigants in Pennsylvania. Jun 2011: Pfizer owes $58 million to three women who sue the company's Wyeth division over breast cancer diagnoses. The U.S. Supreme Court denies Pfizer's appeal. Dec 2011: Pfizer is slapped with a $72.6 million verdict for three Philadelphia women who develop breast cancer after HRT use.¹⁵

2012 » Pfizer seeks U.S. clearance to market Aprela, a newer mix of Premarin and bazedoxifene — a Selective Estrogen Receptor Modulator (SERM), with brand name Viviant, to deter postmenopausal osteoporosis. But Viviant is stuck behind FDA gateways due to heightened risks for stroke and thromboembolic incidents. If greenlit, Aprela intends to overshadow Prempro and Premarin, both tainted by raised cancer and cardiovascular risks. Pfizer predicts sales in the $1 billion range by 2013.

2/17/12: With Premarin's patent set to expire, Pfizer joins forces with Zhejiang Hisun Pharmaceutical, a top pharma firm in China, to manufacture off-patent drugs in global markets. PMU farms have operated in Northern China for 8 years by now, coinciding with WHI's breakout findings about health risks from CEE-based HRT. Wyeth, with knowledge their lucrative Premarin line boosts chances for breast cancer, cardiac disease and more, appears to transfer PMU farms offshore to avoid public backlash.

4/1/12: The Nurse's Health Study (NHS), with data recorded from 1980 to 2008, shows women on estrogen and progesterone (Prempro) are at 88% greater risk for breast cancer after 10 years on the drugs. A decade of estrogen use alone intensifies breast cancer risk by 22%; the risk jumps to 43% at 15+ years. May 2012: Massachusetts General Hospital (Boston) research affirms NHS findings that tie postmenopausal HRT to ulcerative colitis, with a 1.7 higher rate of this colon/rectum disease. Around the same time, Pfizer downsizes it mass estrogen extraction plant in Brandon, Manitoba with plans to cut staff by 40% in 2013. Other pharma firms jump in to nab the generic Premarin market, with contract bids for PMU ranches at sites that Pfizer abandons. Lawsuits carry on, amid mounting evidence of pee-based HRT's adverse affects. Pfizer pays $896 million to cover 60% of patient suits (some 6000 cases) with $330 million reserved for Prempro liability (about 4000 suits). Pricetag: $1.226 billion for 10,000 cases. Yet even as damages are paid out to Premarin/Prempo sufferers, 15 top medical entities — North American Menopause Society, American Society for Reproductive Medine, Endocrine Society, American Academy of Family Physicians, etc. — issue a message to restore faith in HRT. No worries, PMU drugs are “acceptable” and comparably “safe.” By now, health hazards related to PMU HRT are well documented. 7/31/12: Newark, CA based pharma company Depomed Inc. submits a New Drug Application (NDA) for Serada™, a non-hormonal remedy for hot flashes with less adverse reactions. 8/29/12: Noven Pharmaceuticals seeks FDA approval for low-dose mesylate salt of paroxetine, LDMP, to alleviate vasomotor symptoms (hot flashes, night sweats). Both treatments, free of pee from abused horses, mark a turning point. At the time, pregnant mare's urine HRT is the only FDA-endorsed therapeutic for menopausal hot flashes.¹⁶

December 2013: Horse Urine A Profitable Industry In China airs on BONTV, verifying Int'l Fund for Horses disclosure about transfer of most North American PMU ranches to China.

2013 » Jan 2013: Pfizer minimizes Prempro's threat of breast cancer, a theme behind ongoing lawsuits. The company has settled 60% of 10,000 claims thus far. 3/4/13: U.S. FDA Reproductive Health Drugs Advisory Committee rejects promising non-hormonal drugs Serada and LDMP. HRT from pregnant mare's urine remains the sole single-agent drug for menopausal symptoms. May 2013: A French National Institute For Health analysis links estrogen pills to heightened risk for gallstones that require gallbladder removal surgery. Data is logged from 70,000 females in France, 1992 to 2008. Jun 2013: FDA greenlights Bisdell, the first non-hormonal therapy for hot flashes. Originally rejected under brand name Sereda, the drug's primary ingredient is paroxetine mesylate, a selective serotonin reuptake inhibitor. Sep 2013: A Group Health Research Institute study shows estradiol (bioequivalent estrogen) triggers far less harmful vascular effects than conjugated equine estrogens (Premarin). Specifically, estradiol users are not at high risk for leg vein blot clots (deep vein thrombosis) and lung clots (pulmonary emboli). Premarin users are.

10/3/13: Pfizer-Wyeth's Duavee (formerly Aprela) gets FDA approval, despite safety concerns for its dual-acting components. Bazedoxifene alone lacks U.S. authorization; it boosts risk for stroke, deep vein thrombosis and retinal thrombosis. Premarin is classified as a carcinogen, with longstanding research to show it amplifies chance for stroke, heart attack and breast cancer. By year's end, 95% of Prempro/Premarin legal actions are settled, with Pfizer out $1.6 billion. Though lawsuits demonstrate how Pfizer-Wyeth dupes consumers about risks tied to their CEE/Premarin drugs, the company robustly markets its noxious products.¹⁷

2014 » Menopause-osteoporosis drug Duavee hits drug markets, but with stipulations. Pfizer must carry out post-marketing pharmacokinetic trials to assess how conjugated equine estrogens (Premarin) + bazedoxifene (Selective Estrogen-Receptor Modulator) may cause hyperplasia, a predecessor to endometrial cancer. For unknown reasons, FDA okays Duavee a full year before trials for cancer risk are completed (4/2015).¹⁸ With declining Q1 profits and no breakout new drugs, Pfizer aggressively markets Duavee¹⁹, along with Premarin tablets and vaginal cream. Lawsuits are consumers only recourse. One class action suit in Canada amasses formerly unexposed evidence linking Premplus to invasive breast cancer. Pfizer dismisses Canadian Cancer Society research that shows drugs with equine estrogens induced breast cancer in thousands of Canadian women. 10/27/14: European Medicines Agency (EMA) approves conjugated equine estrogen + bazedoxidfene, sold as Duavine. U.S. version Duavee climbs $100 million in sales with 5000 monthly scripts… NAERIC (North American Equine Information Council) lists 2000 mares still warehoused on PMU farms. By now, peeing for Premarin occurs offshore in China and likely India. No precise horse count exists, but Asian PMU sources far exceed those in North America. Pfizer launches vigorous new campaigns. They target 50-something women about painful intercourse and vaginal atrophy with celebrity sex-and-aging ads. Kim Cattrall of Sex And The City fame and Desperate Housewives’ Brenda Strong are among stars who hawk horse-pee drugs, including Estring — an estrogen-release vaginal ring.^{20, 21}

2015 » Unbiased, scientific studies, rather than Big Pharma, finally begin to influence menopause therapy. The Guardian newspaper's pioneering report Women Have Been Oversold HRT For Decades chronicles how HRT is sold as the miracle meno-cure for cardiovascular disease, dementia, stress incontinence, hair loss, need for dentures, osteoporosis, depression and a sluggish sex life — since Robert A Wilson's 1966 book Feminine Forever. “For 10,000 people-years of taking HRT, there were 15 more heart attacks or strokes, eight more pulmonary emboli (blood clots to the lungs) and eight more breast cancers. An analysis published in the Lancet found that for every 1,000 women using HRT for five years, there is one extra case of ovarian cancer, a higher risk than seen in previous studies.”²² 5/9/15: Collaborative Group On Epidemiological Studies Of Ovarian Cancer publishes Menopausal Hormone Use and Ovarian Cancer Risk: individual participant meta-analysis of 52 epidemiological studies.^{23, 24}

2016 » Estrogen taken from continually impregnated mares (Premarin, Prempro) is sourced in cruelty. PMU mares are restrained on pee lines to collect horse estrogens in their urine, ultimately ingested by humans. Spent mares and their foals are discarded as trash, routinely auctioned off to kill-buyers for slaughterhouses and foreign horse meat markets. Countries that consume the most horse flesh (2018-2023) include: China, Kazakhstan, France, Switzerland. Top horse meat producers are China, Kazakhstan, Mexico, Mongolia, Russia, United States, Canada, Brazil, Australia, Kyrgyzstan.^{25, 26} The Big Premarin Lie? Pfizer labeling does not say equine, as in: “conjugated equine estrogens (CEEs)”. Pfizer knowingly removes equine from Premarin, Prempro, Duavee… labels and instead calls its active ingredient: “conjugated estrogens.” U.S. Food and Drug Admin allows this mislabeling to occur, even though World Health Organization cites CEEs as known carcinogens. Conjugated estrogen may also come from plants. The root component in Premarin comes exclusively from horses. Premarin = PREgnant MARe's urINe.

China now appears to do the biggest business in Premarin-style drugs, with an Asian copycat drug in mass production there. Xinjiang Xinzi Biopharmaceutical Limited Liability Company sources horse pee into estrogen drugs, declaring itself as one of two companies worldwide to do so. The other company? Pfizer-Wyeth, of course. Jane Allin, Chief Research Analyst for Int'l Fund For Horses and regular contributor to Tuesday's Horse writes in Pfizer Consigns PMU Horses To Killing Fields Of Asia, “If anyone believes that the downsizing of the PMU industry here in North America is advantageous for the mares and foals who suffer at the hands of Big Pharma, they are sadly mistaken.”²⁷

2017 » More non-estrogen remedies compete with Pfizer-Wyeth in the menopause field. Feb 2017: AMAG Pharmaceuticals nabs rights to Intrarosa, an estrogen-free treatment that touts safer profiles than Premarin cream and Estring vaginal ring. Intrarosa's key component is the hormone precursor prasterone. “This drug is a steroid, of which estrogen is a metabolite… So basically it's just another form of estrogen that isn't derived from horse pee. Safer but still has risks associated with estrogen. It would be nice if the pharmaceutical companies could come up with something that isn't a steroid/estrogen. But that's all they seem to know — and because it's easy” (Jane Allin, horse advocate and expert on drugs formulated with pregnant mare's urine)²⁸

2018 » July 2018: Though Pfizer sales rise by 2% to $53,647 billion in revenues, Premarin sales are down by 15% at $832 million.²⁹ Nov 2018: Pfizer considers selling its women's health portfolio, including menopause therapies Premarin, Prempro and Premphase. Pfizer has no feedback on speculation, but has “narrowed its full-year forecast amid manufacturing challenges within the business that makes it older medicines.”³⁰ Translation: Backlash over cruel PMU farms — that send throwaway colts, fillies and mares to slaughter by the tens of thousands — continues to push pee production offshore to China, with steady closure of North American CEE ranches. The last 800 PMU horses in America are mostly situated in North Dakota, down from 35,000 horses in prior years. PMU farms are on the rise in China, where 90,000 mares pee for the estrogen replacement industry.⁸

2019 » Jan 2019: FDA refutes Pfizer's citizen petition for new ways to appraise Premarin generics. Pfizer wants their criterion used to measure uniformity in generic versions of Premarin. FDA refuses to make generics sponsors use the “Pfizer method” in place of FDA guidelines. Apr 2019: TherapeuticsMD kicks off Bijuva sales. The first bioidentical estradiol + progesterone duo treats vasomotor issues (hot flashes( for menopausal women with intact uterus. Unlike synthetic hormone drugs, bioidenticals structurally match female hormones. Bijuva bears an FDA Boxed Warning about related cardiovascular disease, breast/endometrial cancers, and dementia.

Jun 2019: In an article for The Western Producer, the PMU industry laments job cuts as five producers face closure under new Pfizer reductions: 3 SW Manitoba ranches, 1 Interlake Manitoba ranch and 1 Saskatchewan ranch.³¹ Jul 2019: San Diego U.S. District Judge John Houston rules Pfizer-Wyeth can't dodge a class action lawsuit that claims the pharma firm deceived California women about known breast cancer risk tied to Prempro, Premarin and Premphase. Aug 2019: The Lancet publishes yet another study to confirm that conventional HRT during menopause accelerates breast cancer risk for over a decade beyond cessation. Researchers find that women on these drugs have a higher chance for invasive breast cancer, notably if usage is long-term.³²

Oct 2019: Premarin sales slip by 14.8% to $832 million as its horse-urine products rank #11 on a 2018 best seller list. In initial 6 months of 2019, sales generate $361 million, a 10% decline for the same span in 2018. Third quarter sales for Premarin-line drugs recede 11% at $182 million.³³ 11/25/19: Where have all the pee farms gone? Down from 55-60,000 North American PMU barns in the late 1990s, just 24 family-owned equine ranches are registered with NAERIC to collect pregnant mares’ urine for Pfizer-Wyeth. Zero PMU farms remain in the United States. Canadian ranches are in the provinces of Manitoba (19) and Saskatchewan (5). It's presumed most PMU sourcing has shifted to China.

2020-2023 » The most recent NAERIC count shows just 12 family-owned equine ranches under Pfizer contract to amass pregnant mares’ urine in North America. These pee-line farms are in the Canadian provinces of Manitoba (9) and Saskatchewan (3).⁶ PMU farms, once in abundance across the U.S. and Canada, have rightfully been targeted by animal rights/rescue groups. Public outcry, along with stricter animal welfare rules, have driven production overseas. Why end a brutal trade when you can relocate elsewhere to keep revenues steady? Pfizer pee farms are situated in China these days, where some 80,000 to 100,000+ mares (2021) are repeatedly impregnated, immobilized upright and forced to pee into strap-on buckets — over and over till too worn down to produce. Most go to slaughter with their unneeded foals.