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In a well controlled study esterified estrogen has a .92 risk of venous thrombosis (less than the control group)!!! 

Esterified Estrogens and Conjugated Equine Estrogens and the Risk of Venous Thrombosis

Nicholas L. Smith, PhD; Susan R. Heckbert, MD, PhD; Rozenn N. Lemaitre, PhD; Alex P. Reiner, MD, MPH; Thomas Lumley, PhD; Noel S. Weiss, MD, DrPH; Eric B. Larson, MD, MPH; Frits R. Rosendaal, MD; Bruce M. Psaty, MD, PhD

JAMA. 2004;292:1581-1587.

Context  Clinical trial evidence indicates that estrogen therapy with or without progestins increases venous thrombotic risk. The findings from these trials, which used oral conjugated equine estrogens, may not be generalizable to other estrogen compounds.

Objective  To compare risk of venous thrombosis among esterified estrogen users, conjugated equine estrogen users, and nonusers.

Design, Setting, and Participants  This population-based, case-control study was conducted at a large health maintenance organization in Washington State. Cases were perimenopausal and postmenopausal women aged 30 to 89 years who sustained a first venous thrombosis between January 1995 and December 2001 and controls were matched on age, hypertension status, and calendar year.

Main Outcome Measure  Risk of first venous thrombosis in relation to current use of esterified or conjugated equine estrogens, with or without concomitant progestin. Current use was defined as use at thrombotic event for cases and a comparable reference date for controls.

Results  Five hundred eighty-six incident venous thrombosis cases and 2268 controls were identified. Compared with women not currently using hormones, current users of esterified estrogen had no increase in venous thrombotic risk (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.69-1.22). In contrast, women currently taking conjugated equine estrogen had an elevated risk (OR, 1.65; 95% CI, 1.24-2.19). When analyses were restricted to estrogen users, current users of conjugated equine estrogen had a higher risk than current users of esterified estrogen (OR, 1.78; 95% CI, 1.11-2.84). Among conjugated equine estrogen users, increasing daily dose was associated with increased risk (trend P value   = .02). Among all estrogen users, concomitant progestin use was associated with increased risk compared with use of estrogen alone (OR, 1.60; 95% CI, 1.13-2.26).

Conclusion  Our finding that conjugated equine estrogen but not esterified estrogen was associated with venous thrombotic risk needs to be replicated and may have implications for the choice of hormones in perimenopausal and postmenopausal women.

Author Affiliations: Departments of Epidemiology (Drs Smith, Heckbert, Reiner, Weiss, and Psaty), Medicine (Drs Lemaitre and Psaty), Biostatistics (Dr Lumley), and Health Services (Dr Psaty), University of Washington, Seattle; Center for Health Studies, Group Health Cooperative, Seattle, Wash (Drs Heckbert, Larson, and Psaty); and Leiden University Medical Center, Leiden, the Netherlands (Dr Rosendaal).




This is Prempro (CD is conjugated estrogen &MPA is the synthetic  progesterone in Prempro). For detailed account see http://healthfully.org/highinterestmedical/id3.html 


Vivelle-Dot (estradiol transdermal system, delivery for twice weekly application.  The patches come in 5 doses, the highest having the largest dose.  The delivery rates are from .025 to .1 mg of estradiol per day via the skin.  At .1 the plasma concentration averages 89 pg/mL, while for the .0375 it averages 30 pg/mL.  Estradiol half life is from 5.9 to 7.7 hours


CE/MPA is Prempro the worst of opposed HRT.  As bad as these results are the opposite is true if the HRT is estradiol plus either progesterone or testosterone. 

Table 2

Relative and Absolute Risk Seen in the CE/MPA Sub-study of WHIa

Event                                      Relative Risk                                    Placebo          CE/MPA

CE/MPA vs. Placebo                        n=8102            n=8506

at 5.2 Years                                        Absolute Risk per

(95% CI*)                                            10,000 Women-Years

CHD events                            1.29 (1.02-1.63)                                  30                    37

Non-fatal MI                            1.32 (1.02-1.72)                                 23                    30

CHD death                              1.18 (0.70-1.97)                                  6                     7

Invasive breast cancer           1.26 (1.00-1.59)                                  30                    38

Stroke                                                 1.41 (1.07-1.85)                                  21                   29

Pulmonary embolism              2.13 (1.39-3.25)                                  8                      16

Colorectal cancer                   0.63 (0.43-0.92)                                  16                    10

Endometrial cancer                0.83 (0.47-1.47)                                  6                      5

Hip fracture                             0.66 (0.45-0.98)                                  15                    10

Death due to causes other      0.92 (0.74-1.14)                                  40                    37

than the events above

Global index                            1.15 (1.03-1.28)                                  151                  170

Deep vein thrombosis             2.07 (1.49-2.87)                                  13                    26

Vertebral fractures                  0.66 (0.44-0.98)                                  15                    9

Other osteoporotic fractures   0.77 (0.69-0.86)                                  170                  131

Dementia                                2.05(1.21-3.48)                                   21                    40


Interesting health consequence/side effects, placebo to .1mg

Placebo was higher for dyspepsia (10-0), influenza like illness (10 vs 3), hot flashes 6 vs 0


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