A very incisive analysis of two long-term studies of hormone replacement therapy (HRT) by the Women’s Health Initiative (WHI) has just been reported. The principal instigator, Dr. Joann Manson, is one of the leading researchers on women’s health issues.Just take a minute to read the study and you will see why.
The report is relevant to women as they make decisions, regarding hormone therapy. Besides studying the difference in effects of HRT vs. no HRT, this research looked at the difference between HRT in patients who had intact uteri and those who had had hysterectomies. They further analyzed the effects as follows:
1. Women with an intact uterus received
a. Conjugated equine estrogens (CEE; 0.625 mg/d) plus medroxyprogesterone acetate (MPA; 2.5 mg/d) (n = 8506)
b. Or placebo (n = 8102).
2. Women with prior hysterectomy received
a. CEE alone (0.625 mg/d) (n = 5310)
b. Or Placebo (n = 5429).
Further, the statistical power of the study was strong, more than 27,000 participated.
The Conclusion:
Breast cancer risk was raised in the long-term HRT group – women who had been taking it most of their postmenopausal lives. Findings from the intervention and extended post-intervention follow-up of the 2 WHI hormone therapy trials do not support use of this therapy for chronic disease prevention, although it is appropriate for symptom management in some women:
The authors note that findings from the two hormone therapy trials have been published in many journals over the past decade, but no previous WHI (Women’s Health Initiative) publication has synthesized results for primary, secondary, and quality-of-life outcomes of the two trials during their intervention and post-intervention phases. In addition, for some end points, analyses have not been previously stratified by age or time since menopause. The goal of this report is to provide a comprehensive, integrated overview of findings from the two WHI hormone therapy trials with extended post-intervention follow-up (median, 13 years of cumulative follow-up) and stratification by age and other important variables.
These data provide further guidance to making HRT decisions. They can be found in this report and the online supplement which is provided by a PDF document, linked to the report, as provided online by JAMA.
Click on the title to read the full PDF and view the excellent charts.
Manson JE, Chlebowski RT, Stefanick ML, Aragaki AK, Rossouw JE, et al.
JAMA. 2013;310(13):1353-1368. doi:10.1001/jama.2013.278040.
IMPORTANCE Menopausal hormone therapy continues in clinical use but questions remain regarding its risks and benefits for chronic disease prevention.
OBJECTIVE To report a comprehensive, integrated overview of findings from the 2 Women’s Health Initiative (WHI) hormone therapy trials with extended postintervention follow-up.
DESIGN, SETTING, AND PARTICIPANTS A total of 27, 347 postmenopausal women aged 50 to 79 years were enrolled at 40 US centers.
INTERVENTIONS
Women with an intact uterus received
1. conjugated equine estrogens (CEE; 0.625 mg/d) plus medroxyprogesterone acetate (MPA; 2.5 mg/d) (n = 8506)
2. or placebo (n = 8102).
Women with prior hysterectomy received
3. CEE alone (0.625 mg/d) (n = 5310)
4. or placebo (n = 5429).
The intervention lasted a median of 5.6 years in CEE plus MPA trial and 7.2 years in CEE alone trial with 13 years of cumulative follow-up until September 30, 2010.
MAIN OUTCOMES AND MEASURES Primary efficacy and safety outcomes were coronary heart disease (CHD) and invasive breast cancer, respectively. A global index also included stroke, pulmonary embolism, colorectal cancer, endometrial cancer, hip fracture, and death.
RESULTS During the CEE plus MPA intervention phase, the numbers of CHD cases were 196 for CEE plus MPA vs 159 for placebo (hazard ratio [HR], 1.18; 95% CI, 0.95-1.45) and 206 vs 155, respectively, for invasive breast cancer (HR, 1.24; 95% CI, 1.01-1.53).
Other risks included increased stroke, pulmonary embolism, dementia (in women aged ≥65 years), gallbladder disease, and urinary incontinence; benefits included decreased hip fractures, diabetes, and vasomotor symptoms.
Most risks and benefits dissipated post-intervention, although some elevation in breast cancer risk persisted during cumulative follow-up (434 cases for CEE plus MPA vs 323 for placebo; HR, 1.28 [95% CI, 1.11-1.48]).
The risks and benefits were more balanced during the CEE alone intervention with 204 CHD cases for CEE alone vs 222 cases for placebo (HR, 0.94; 95% CI, 0.78-1.14) and 104 vs 135, respectively, for invasive breast cancer (HR, 0.79; 95% CI, 0.61-1.02); cumulatively, there were 168 vs 216, respectively, cases of breast cancer diagnosed (HR, 0.79; 95% CI, 0.65-0.97).
Results for other outcomes were similar to CEE plus MPA. Neither regimen affected all-cause mortality. For CEE alone, younger women (aged 50-59 years) had more favorable results for all-cause mortality, myocardial infarction, and the global index (nominal P < .05 for trend by age).
Absolute risks of adverse events (measured by the global index) per 10 000 women annually taking CEE plus MPA [absolute risks] ranged from:
12 excess cases for ages of 50-59 years to 38 for ages of 70-79 years;
for women taking CEE alone, [the range was] from:
19 fewer cases for ages of 50-59 years to 51 excess cases for ages of 70-79 years.
Quality-of-life outcomes had mixed results in both trials.
CONCLUSIONS AND RELEVANCE Menopausal hormone therapy has a complex pattern of risks and benefits. Findings from the intervention and extended post-intervention follow-up of the 2 WHI hormone therapy trials do not support use of this therapy for chronic disease prevention, although it is appropriate for symptom management in some women.
The Women’s Health Initiative (WHI) trials were designed to determine the benefits and risks of hormone therapy when taken for chronic disease prevention by predominantly healthy postmenopausal women.1– 3 Although originally prescribed primarily to treat vasomotor symptoms, menopausal hormone therapy had been increasingly viewed as a way to prevent many chronic diseases of aging, including coronary heart disease (CHD) and cognitive impairment.4– 5 At least 40% of postmenopausal women in the United States were using hormone therapy shortly before the publication of the initial WHI findings.6 Even though observational studies had suggested net benefit for hormone therapy use,4– 5 no previous large-scale randomized prevention trial had addressed the balance of risks and benefits. In this context, the WHI hormone therapy trials were conceived and the most commonly used hormone therapy formulations in the United States at that time, conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA) and CEE alone, were chosen as the interventions.1
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Expert CR scientist, Dr. Roz Anderson, also expressed her opinion about HRT in this blog:
Should Calorie Restricted Women Take Estrogen?
Thanks to many LivingTheCRWay members for letting us know that the HRT replacement issue is important to them.
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