FEMALE HORMONE REPLACEMENT

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Prempro settlement $330M
alcohol and higher estradiol and testosterone levels in postmenopausal women

 

 

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).

 

Wikipedia:

e.g. women who didn't take it seem to have had—on average—a 70% higher relative risk of dementia).  This is consistent with research that hormone therapy improves executive and attention processes in postmenopausal women. . . . . A recent large well-designed randomized controlled trial recently showed that increased breast cancer risk applies only to those women who take progesterone analogues (as was done in the WHI) but not to those taking progesterone itself. 

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Increased Libido

Comparative effects of oral esterified estrogens with and without methyltestosterone on endocrine profiles and dimensions of sexual function in postmenopausal women with hypoactive sexual desire
Fertility and Sterility, Volume 79, Issue 6, Pages 1341-1352

Abstract

Objective

In some women, a decline in sexual interest accompanies a relative androgen insufficiency after menopause. We sought to characterize the hormonal effects of the combination of oral esterified estrogens and methyltestosterone and to investigate whether this regimen improves hypoactive sexual desire.

Design

Double-blind randomized trial.

Setting

Healthy volunteers in a multicenter research environment.

Patient(s)

Postmenopausal women taking estrogen therapy who were experiencing hypoactive sexual desire.

Intervention(s)

4 months of treatment with 0.625 mg of esterified estrogens (n = 111) or the combination of 0.625 mg of esterified estrogens and 1.25 mg of methyltestosterone (n = 107).

Main outcome measure(s)

Baseline and end-of-study measurements of total and bioavailable testosterone and sex hormone–binding globulin (SHBG), and mean change in level of sexual interest or desire as rated on the Sexual Interest Questionnaire.

Result(s)

Treatment with the combination of esterified estrogens and methyltestosterone significantly increased the concentration of bioavailable testosterone and suppressed SHBG. Scores measuring sexual interest or desire and frequency of desire increased from baseline with combination treatment and were significantly greater than those achieved with esterified estrogens alone. Treatment with the combination was well tolerated.

Conclusion(s)

Increased circulating levels of unbound testosterone and suppression of SHBG provide a plausible hormonal explanation for the significantly improved sexual functioning in women receiving the combination of esterified estrogen and methyltestosterone.

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J Reprod Med. 1998 Oct;43(10):847-56.

 

RESULTS: Estrogen-androgen therapy significantly improved sexual sensation and desire after four and eight weeks of double-blind treatment in comparison to previous estrogen therapy and postplacebo baseline assessments. . . . CONCLUSION: Sexual desire, satisfaction and frequency in postmenopausal women taking hormonal therapy were improved significantly by combined estrogen-androgen therapy but not by estrogen or estrogen-progestin therapy. Sexual function improved with estrogen-androgen therapy even though circulating estrogen levels were lower than those measured during previous estrogen therapy. This leads to the conclusion that androgens play a pivotal role in sexual function but that estrogens are not a significant factor determining levels of sexual drive and enjoyment.

 

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.

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Past estrogen use decreases Alzheimer’s disease in older women (83% for those using estrogen over 10 years)

December 2002 report of NAMS (North American Menopause Society)

Zandi PP, Carlson MC, Plassman BL, et al, for the Cache County Memory Study Investigators. Hormone replacement therapy and incidence of Alzheimer disease in older women: the Cache County study. JAMA 2002;288:2123-2129.

Use of hormone therapy is associated with a reduced risk of Alzheimers disease (AD), especially use for longer than 10 years, according to results from this prospective observation al study conducted in Cache County (Logan, Utah). A total of 1,889 women (mean age, 74.5 years) were enrolled. A similarly aged group of men (n = 1,357) served as controls. History of hormone therapy use (either estrogen alone or estrogen plus a progestogen), as well as intakes of calcium and multivitamin supplements, were assessed at baseline. After 3 years of follow-up, 88 women (4.7%) and 35 men (2.6%) had developed AD. Women aged 80 and older had more than twice the rate of AD as men of that age (hazard ratio [HR], 2.11; 95% CI, 1.22-3.86). Overall, hormone therapy significantly reduced the risk of AD by 41% compared with nonusers (95% CI, 0.36-0.96). Hormone use for at least 10 years resulted in a 69% reduction in risk (95% CI, 0.17-0.86), which was statistically the same as the risk for matched males. When the results were assessed by current and former hormone use, current use (72% unopposed estrogen) was not associated with decreased AD risk unless the duration of treatment exceeded 10 years. For former users, 3 or more years of use significantly reduced the AD risk, with more than 10 years use reducing the risk by 83% (95% CI, 0.01-0.80). No similar effects were seen with either calcium or multivitamin use.

NOTE:  the results are based taking the best combination, other studies using different combinations obtain lower results and those with Prempro no benefit. A earlier (1999) NAMS meta-study, not separating types of HRT or duration of usage found a 29% reduction--jk. 

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Hormone therapies effect on atherosclerosis associated with presence of apolipeprotein A gene.

November 2002 report of NAMS (North American Menopausal Society).  Lehtimaki T, Dastidar P, Jokela H, et al. Effects of long-term hormone replacement therapy on atherosclerosis progression in postmenopausal women relates to functional apolipoprotein E genotype. J Clin Endocrinol Metab 2002;87:4147-4153.

Postmenopausal hormone therapy appears to have a beneficial effect on atherosclerosis progression in women who do not have the apolipoprotein E (apoE) genotype, based on results from this prospective, cohort study conducted in Finland. The study enrolled 141 postmenopausal women aged 45 to 71 with no clinically evident cardiovascular disease or hypertension. Women were classified into three groups: estrogen plus progestogen, estrogen alone, and no hormone use (control). Estradiol valerate (2 mg/day) was used, with either levonorgestrel (0.25 mg/day) or medroxyprogesterone acetate (10 mg/day) administered cyclically to women with a uterus. In all, 93 women completed the 5-year follow-up study. Sonography was used to determine atherosclerosis severity. In apoE-negative women, hormone therapy significantly slowed the progression of atherosclerosis when compared with the control group. In apoE-positive women, no significant between-group differences were seen.

In the commentary it was pointed out that compared with apoE-positive women. Since apoE genetic polymorphism may affect plasma lipids and the severity of atherogenesis, it is possible that the hormone-related adverse effects in the WHI and HERS studies manifested themselves specifically in apoE-positive women, therefore reflecting a biased study population.

 

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