New pack insert for Premarin

[miriam]

Hi girls (sorry guys!) who are on HRT,

Mid August a new pack insert was published at the FDA website:

http://www.fda.gov/cder/foi/label/2004/04782s137lbl.pdf

The information in the PDF-file is a bit technical, but the warnings are quite clear. I guess you should ask your doctor if the new information is relevant to you.

Groeten, Miriam

[Dana Gold]

It is my opinion that this "compound" should be taken off the market, which will, of course, never happen because it is the most widely prescribed form of estrogen in the US, if not the world (Wyeth-Ayerst's $$$$)
It should be noted that none of the "estrogens" that comprise this formulation include significant amounts of 17-Beta Estradiol (the estrogen that is secreted by the ovaries and goes directly into the bloodstream), only sulfate conjugates of estrone, (some little alpha/beta forms of horse estradiol) and equilin (a xeno-estrogen). In fact, I don't have the analysis results right with me....but Premarin also has small amounts of testosterone metabolites. The majority of Premarin (taken orally) results in plasma levels of estrone and not estradiol. Some clinical studies have implicated this form of estrogen (there are 3: estradiol, estrone, and estriol that make up the totality of the major estrogens) and its delta-form metabolites as the probable cause for the negative consequences of HRT....tissue and cell hyperplasia....endometriosis and breast cancer. Refer to the thread below...posts # 2 and 3 (mine) which elucidates some more information about estrogens:

http://www.bodieslikeours.org/forums/showthread.php?t=714

In addition to the link, please be aware that inflammation is the precursor to arterial plaque formation (atherosclerosis) and increased coagulation factors (decreased pro-thrombin time)....bloodclot formation .. resulting in heart attack from arterial blockages due to both plaques and clots, stroke, and deep-vein thrombosis (predominent in the legs).

I have read that in Europe, either estriol itself, or tri-est formulation of estradiol, estrone, and estriol (appx 10,10, and 80 percent composition respectively) is administered as HRT and has been reported to have much less consequences and better efficacy as the Premarin, the drug which most of all clinical and research studies have been based upon indicating negative benefit.

Alternatives are available, except for estriol , which is not available or marketed in the US.....and only compounding pharmacies offer the tri-est formulation. Whatever the case, the method of administration should assure that the estrogen goes into the bloodstream (patches, sub-lingual, or injections) as 17-B estradiol....oral administration results in first bypass by the liver and consequent metabolism of the original estradiol being converted to 95 percent plus estrone. This may also present in somewhat erroneous laboratory test values, when the doctor specifies lab test for estradiol (when the bloodstream has the 95% estrone content) and comes to the conclusion that one's estradiol is low (i.e. estrogen is low) and maybe prescribes a higher dosage to compensate. It is for that reason that whenever a person gets a blood test (actually plasma or serum is tested) both estradiol and estrone should be evaluated.

The metabolites of estrone stay in the blood longer (stasis) with oral administration (especially with the potent estrones/equilins from Premarin)....with dermal, sub-lingual, and intramuscular the estrogens are cleared faster after connecting up with the respective receptor sites ...meaning reuptake is quicker....hence less side affects (hyperplasia of endometrial and breast cells) from estrone "stasis".

Finally this excerpt from weblink below (analysis of generic form of Premarin)

1. Composition

At least ten estrogenic compounds have been identified and quantified in Premarin. The composition data for the ten estrogenic compounds cited in the Conjugated Estrogens, USP monograph, and listed in Table 1, were generated by the Center's Division of Drug Analysis from an analysis of two batches of Premarin 0.625 mg tablets. These results agree generally with other data available to the Center.

Table 1


Sodium Estrogen Sulfate Mg/Tablet

Estrone 0.370
Equilin 0.168

17a-Dihydroequilin 0.102
17a-Estradiol 0.027
17b-Dihydroequilin 0.011

l7a-Dihydroequilenin 0.011
17b-Dihydroequilenin 0.021
Equilenin 0.015

l7b-Estradiol 0.005
D8,9-dehydroestrone 0.026

Additional information on the component DHES and its metabolite are discussed later in this section (IV.C.4). Additionally, the fact that Premarin contains progestational agents (composition unspecified) has been disclosed by Wyeth-Ayerst. It is known that Premarin also contains additional steroidal compounds.52 However, precise data on Premarin's composition are currently very limited.,,,

Progestins (as opposed to natural progesterone) have androgenic effects. ( my line)

http://www.fda.gov/cder/news/celetterjw.htm


Premarin, Preempro and related "horse-p*ss drugs? :sick:

[Dana Gold]

1.

http://story.news.yahoo.com/news?tmpl=story&cid=571&ncid=751&e=3&u=/nm/20041008/hl_nm/hormones_heart_dc
========================================================

2.

Laurie Barclay, MD


Oct. 5, 2004 — Esterified estrogen is not linked to increased risk of venous thrombosis, according to the results of a population-based, case-control study published in the Oct. 6 issue of JAMA. However, in this study and in the Women's Health Initiative, there was about a twofold risk of venous thrombosis from conjugated estrogen.

"Clinical trial evidence indicates that estrogen therapy with or without progestins increases venous thrombotic risk," write Nicholas L. Smith, PhD, from the University of Washington in Seattle, and colleagues. "The findings from these trials, which used oral conjugated equine estrogens, may not be generalizable to other estrogen compounds."

Between January 1995 and December 2001, there were 586 incident cases at a large health maintenance organization in Washington State of perimenopausal and postmenopausal women aged 30 to 89 years who sustained a first venous thrombosis. Based on age, hypertension status, and calendar year, 2,268 control subjects were matched to these cases. The primary outcome was risk of first venous thrombosis in relation to current use of esterified or conjugated equine estrogens, with or without concomitant progestin. For cases, current use was defined as use at thrombotic event, and a comparable reference date was used for control subjects.

Risk of venous thrombosis was not increased in current users of esterified estrogen compared with women not currently using hormones (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.69 - 1.22). However, risk was increased in women currently taking conjugated equine estrogen (OR, 1.65; 95% CI, 1.24 - 2.19). In analyses of estrogen users only, risk was higher in current users of conjugated equine estrogen than in current users of esterified estrogen (OR, 1.78; 95% CI, 1.11 - 2.84).

In users of conjugated equine estrogen, increasing daily dose was associated with increased risk (P = .02 for trend). Compared with use of estrogen alone, concomitant progestin use in all estrogen users was associated with increased risk (OR, 1.60; 95% CI, 1.13 - 2.26).

Study limitations include lack of randomization in use of hormone therapy and lack of generalizability to populations other than white perimenopausal and postmenopausal women without previous venous thrombosis.

"Compared with nonuse of hormone therapy, oral conjugated equine estrogen therapy increases the risk of venous thrombosis dose-dependently, esterified estrogen does not influence venous thrombosis risk, and the use of any estrogen in combination with medroxyprogesterone acetate increases risk as well," the authors write. "If replicated, these findings for venous thrombosis may have implications for the choice of hormone in treating menopause-related vasomotor symptoms in perimenopausal and postmenopausal women."

The National Heart, Lung, and Blood Institute and the National Institute on Aging supported this study.



http://www.medscape.com/viewarticle/490679


The conclusion to be drawn from the above links is that conjugated estrogens (Premarin) and the leading progestin (medroxyprogesterone acetate) both increase inflammatory responses of tissues and cells found in smooth muscle (arteries) and striated muscle (heart) leading to further damage.

PS: esterfied estrogen example: Trade name Menest