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May 10, 2015
If you prescribe hormones for menopausal hot flashes please take a minute to read this information.
I am a recently retired physician with extensive experience in this practise area for 37 years. I am not getting paid to write this nor have I any connection with the pharmaceutical industry.
As the director of a Medical Center and a staff physician at Kelowna General Hospital in British Columbia, Canada, I prescribed the Premarin family of drugs from 1974. I stopped in 1994 in favor of newer, purer, non-equine based estrogens. From 1994 to my retirement in 2011, not one patient in thousands of prescriptions written needed to be put back on a Premarin based drug. One or another of the newer fully approved estrogens always worked well.
Premarin, at 73 years, is by far the oldest estrogen marketed for menopause. Only 17% of it is bioidentical with human estrogen. An overwhelming 83% is still a variable mixture including horse hormones of various types, metabolites, degradation byproducts, and impurities. The Premarin in cream form is the same Premarin as in pill form. A number of studies have shown that some of the metabolites of those horse hormones are significantly more carcinogenic than those of other FDA approved estrogens, none of which contain horse hormones [1, 2]. A further concern is the fact that not all the ingredients in Premarin have yet even been identified.
The GHRI study of 2013 confirmed that there is less risk of both DVT and pulmonary emboli with a human type estrogen, estradiol, than with Premarin . A study from Stanford in 2014 has shown that human type estradiol protects the brain against dementia relative to Premarin in high risk patient groups . Studies like these further highlight the difference between the beneficial effects that pure products can have compared to a mixture like Premarin that contains multiple ingredients with detrimental or conflicting effects.
And now, the FDA has approved use of Duavee for HRT. Duavee contains Premarin plus the SERM bazedoxifine. Bazedoxifine as a stand-alone product has not been passed by the FDA due to it increasing clot risk.
But yet it is the Premarin component of Duavee that concerns me the most. Why are we still prescribing an old drug whose composition is uncertain and which contains hormones that increase multiple risks significantly more than the newer, well-defined, FDA approved estrogens?
This question has been raised by others , starting even before the damning revelations of the WHI and its substudies. I add my voice to that chorus. Since the revelations of the WHI came to light, Pfizer/ Wyeth has had to pay out 1.7 billion dollars due to successful lawsuits claiming health damages associated with the Premarin family of drugs.
I realize fully the constraints on a busy doctor’s time and the effectiveness of the constant, continuing marketing barrage to keep doctors prescribing what they have become used to prescribing.
I ask only that in the name of good science you take a moment to look critically at the rationale for still prescribing Premarin products rather than estrogens that could better minimize health risks for your menopausal patients.
If you have already done that, then I thank you for your commitment to exemplary patient care.
Very best regards,
Raimo Markus Kellosalmi, BSc., MD
1] Zhang F, Chen Y, Pisha E, et al. The major metabolite of equilin, 4-hydroxyequilin, autooxidizes to an o-quinone which isomerizes to the potent cytotoxin 4-hydroxyequilenin-o-quinone. Chem Res Toxicol. 1999; 12:204-213
2] Shen L, Qiu S, Chen Y, et al. Alkylation of 2′-deoxynucleosides and DNA by the Premarin metabolite 4-hydroxyequilenin semiquinone radical. Chem Res Toxicol. 1998; 11:94-101
3] Smith NL. Lower Risk of Cardiovascular Events in Postmenopausal Women Taking Oral Estradiol Compared with Oral Conjugated Equine Estrogens. JAMA Internal Medicine, 2013; DOI: 10.1001/jamainternmed. 2013.11074
4] Rasgon N. Estradiol Preserves Key Brain Regions in Postmenopausal Women at Risk for Dementia. Plos One, March 12, 2013
5] Lippert TH, Mueck AO, Seeger H. Is the use of conjugated equine estrogens in hormone replacement therapy still appropriate? BJCP, May 2000; 49(5) 489-490