by JANE ALLIN
Contrary to popular belief, the FDA has yet to approve any generic as a substitute for Premarin and its daughter products (i.e. Prempro, Premphase, Duavee).
Accordingly no prescription drugs used to treat menopausal symptoms, other than the Premarin family, contain pregnant mare’s urine.
However much confusion arises when the subject of HRT is broached, particularly in terms of the safety aspect of FDA-approved versions that are not derived from pregnant mare’s urine.
The vast majority of FDA-approved HRT prescription drugs are synthetic bioidenticals — hormones identical on a molecular level to endogenous hormones that are synthesized in the lab from natural plant sources.
These are not to be confused with the compounded bioidenticals, none of which are approved by the FDA.
Premarin and its derivatives are also synthetics but, of course, sourced from an animal by-product.
Apart from Brisdelle, the only non-hormonal FDA-approved HRT, the rest fall into three categories of hormone combinations as follows:
• Estrogen combinations (e.g. Estrace, Cenestin, Enjuvia, Menest)
• Estrogen/Progestin combinations (e.g. Activella)
• Estrogen/Androgen combinations (e.g. Menogen, Covaryx)
The estrogen combinations are intended as substitutes for Premarin and Duavee while the estrogen/progestin versions are proposed alternatives to Prempro and Premphase.
Estrogen/androgen replacement therapy primarily represents mainstay therapy for young women who have undergone a hysterectomy. See http://www.medscape.com/viewarticle/438357.
A good proportion of these drugs contain estradiol or esterified estrogens (non-equine) as the estrogen component (e.g. Estrace, Femtrace, Activella, Femhrt, Angeliq). However several have identical equine estrogens that are derived from plant-based sources versus pregnant mare’s urine.
That said, these drugs are not entirely identical nor are they exactly equivalent in constituents. Cenestin, Enjuvia, and Menest are three such HRTs included in this group.
Cenestin was originally developed as a generic for Premarin by Duramed/Barr but in 1997, the FDA refused to approve the abbreviated new drug applications from Duramed and Barr Laboratories for a generic version of Premarin.
The FDA’s rationale was quite straightforward. A synthetic generic version of Premarin could not be approved because the exact chemical composition of Premarin could not be fully identified. This has been a controversial topic for years, a topic The Horse Fund has visited in the past. See https://tuesdayshorse.wordpress.com/2014/11/14/the-quest-for-a-generic-premarin-a-bitter-pill-to-swallow/.
In any case, all three of these drugs – Cenestin, Enjuvia, and Menest – contain similar estrogen components that are found in Premarin and its derivatives.
Premarin however is a complex mixture of numerous hormonal components, of which only some of the estrogenic components are found in the plant-based synthetics.
The table below compares the ingredients of Premarin, Cenestin and Enjuvia. I was unable to locate the same information for Menest.
However the pharmacology is similar to the others and contains a mixture of esterified estrogenic substances, principally estrone, that are of the type excreted by pregnant mares (e.g. sodium estrone sulfate, sodium equilin sulfate).
|sodium estrone sulfate||Yes||Yes||Yes|
|sodium equilin sulfate||Yes||Yes||Yes|
|sodium 17 alpha-dihydroequilin sulfate||Yes||Yes||Yes|
|sodium 17 beta-dihydroequilin sulfate||Yes||Yes||Yes|
|sodium 17 alpha-betahydroequilenin sulfate||Yes||Yes||Yes|
|sodium 17 beta-betahydroequilenin sulfate||Yes||Yes||Yes|
|sodium 17 alpha-estradiol sulfate||Yes||Yes||Yes|
|sodium equilenin sulfate||Yes||Yes||Yes|
|sodium 17 beta-estradiol sulfate||Yes||Yes||Yes|
|sodium D8,9-dehydroestrone sulfate||Yes||No||Yes|
|5,7,9 (10) estratrien-3beta, 17 beta-diol||Yes||No||No|
|17 alpha-dihydro-delta, 8,9-dehydroestrone||Yes||No||No|
|17 beta-dihydro-delta, 8,9-dehydroestrone||Yes||No||No|
|5,7,9 (10) estratrien-3betal-ol-17-one||Yes||No||No|
|Prempro / Premphase||CEEs / Progestin||No||Expired||$5.77||$173|
|Brisdelle||SSRI (paroxetine)||No||Apr 2029||$5.74||$172|
|Duavee||CEEs / SERM (bazedoxifene)||No||Oct 2016||$4.77||$143|
|Angeliq||Estrogen / Progestin||No||Oct 2017||$4.31||$129|
|Cenestin||CEEs — plant based||No||Expired||$3.97||$119|
|Prefest||Estradiol / Progestin||No||March 2020||$3.37||$112|
|Enjuvia||CEEs — plant based||No||Feb 2021||$2.75||$83|
|Femtrace||Estradiol acetate||No||Dec 2021||$2.68||$80|
|Activella||Estradiol / Progestin||Yes||Expired||$2.06||$78|
|Menest||CEEs — plant based||No||Expired||$1.77||$53|
|Femhrt||Estrogen / Progestin||Yes||Expired||$1.32||$40|
Clearly, Pfizer is laughing all the way to the bank at the expense of women and horses alike.
© The Horse Fund
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2 thoughts on “FDA-Approved Alternatives to Premarin Derivatives – are they safer ?”
Thank you Jane for another brilliant article. You really brought this issue home for me in a different way. More eye-opening data.
I find this amazing considering the body of work you have already done on this subject. No one rivals you on this issue though they have tried (smile) or just outright taken it (unsmile).
My concern is this — women don’t seem to care about the mares and foals abused and killed. It was the WHI study that hurt sales for awhile.
Has society become numb to animal testing and use? Have people become numb to the alarming side effects because they take so many drugs all with a laundry list of warnings and side effects?
Menopause, like so other natural occurrences has been marketed as a disease for which material medica conveniently have drugs.
But we will soldier on. We will not leave these horses voiceless.
LikeLiked by 1 person
You probably already know about this but I saw this mentioned in a article in Sunday paper a few weeks ago. It said that Pine Bark extract seems to work for hot flashes. Its generally hot flashes that most women don’t want to be bothered with.