Government panel just says no to hormone replacement therapy

Robin Wulffson MD's picture
hormone replacement therapy, HRT, osteoporosi, cardiovascular disease
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In recent months, the US Preventive Services Task Force (USPSTF) has taken stands on medical issues that have sparked significant controversy. Last week, the task force published a report that claimed that the prostate specific antigen (PSA) cancer screening test did more harm than good. Many urologists and the American Urological Association (AUA) disputed the decision; the AUA responded that they were “outraged” by the recommendation. Earlier this year, the USPSTF recommended against routine breast cancer screenings for most women under the age of 50. This sparked rebuttals from breast cancer surgeons, radiologists, and other healthcare professionals involved in diagnosing and treating breast cancer. It has also urged that the prostate-specific antigen (or PSA) test that has become a standard part of older men’s yearly physicals be abandoned. The USPSTF’s current hot button topic was published on May 29 in the Annals of Internal Medicine. The panel reported that evidence was lacking that hormone replacement therapy (HRT) reduced the incidence of bone fractures, dementia, and cardiovascular disease (i.e., strokes and heart attacks).

In their report, the USPSTF noted that “menopausal hormone therapy to prevent chronic conditions is currently not recommended because of its adverse effects.” The authors noted that the goal of their study was to update evidence regarding the effectiveness of HRT in reducing risk for chronic conditions and adverse effects, and to examine whether outcomes vary among women in different subgroups. The investigators searched out randomized, placebo-controlled trials of menopausal hormone therapy published in English since 2002 that assessed primary prevention of chronic conditions. They reviewed the following data sources: Cochrane Central Register of Controlled Trials; Cochrane Database of Systematic Reviews (through the 3rd quarter of 2011); MEDLINE (January 2002 to November 2011); Scopus; and reference lists.

The researchers noted that nine “fair-quality trials” met the inclusion criteria. They noted that the large Women's Health Initiative (WHI) study reported most of the results; this study had 11 years of follow-up and contained had data most applicable to postmenopausal women in the US. They noted that the WHI reported that estrogen plus progestin reduced fractures (46 fewer per 10 000 woman-years); however, it increased invasive breast cancer (8 more per 10 000 woman-years), stroke (9 more per 10 000 woman-years), deep venous thrombosis (12 more per 10 000 woman-years), pulmonary embolism (9 more per 10 000 woman-years), lung cancer death (5 more per 10 000 woman-years), gallbladder disease (20 more per 10 000 woman-years), dementia (22 more per 10 000 woman-years), and urinary incontinence (872 more per 10 000 woman-years). Estrogen-only therapy reduced fractures (56 fewer per 10 000 woman-years) and invasive breast cancer incidence (8 fewer per 10 000 woman-years) and death (2 fewer per 10 000 woman-years); however, it increased stroke (11 more per 10 000 woman-years), deep venous thrombosis (7 more per 10,000 woman-years), gallbladder disease (33 more per 10,000 woman-years), and urinary incontinence (1,271 more per 10,000 woman-years). Outcomes did not consistently differ by age or comorbid conditions.

The authors noted several limitations of the studies: adherence (continued of medication as recommended), high attrition (discontinuance), inadequate power to detect risks for some outcomes, and evaluation of few regimens.

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The authors concluded that estrogen plus progestin and estrogen alone decreased risk for fractures; however, they increased the risk for strokes, thromboembolic events (blood clots), gallbladder disease, and urinary incontinence. Estrogen plus progestin increased the risk for breast cancer and probable dementia; estrogen alone decreased risk for breast cancer.

Take home message:
Estrogen has been proven to reduce the troublesome symptoms of menopause such as hot flashes, vaginal dryness, and night sweats. Interestingly, the panel noted that its report does not refute those findings. A number of studied have reported that HRT reduces bone loss in postmenopausal women. Others have reported a decreased risk of Alzheimer’s disease and dementia. It is well known that women in their premenopausal years have a lower incidence of cardiovascular disease. The theory is that estrogen exerts a protective incidence. Some studies have noted that initiating HRT at the time of menopause reduces the risk of cardiovascular disease. Some studies have noted that the risk of cardiovascular disease is increased in women who begin HRT several years after the menopause. One hypothesis regarding that finding is that atherosclerotic plaques form during the years without HRT. Then, after HRT is initiated, the estrogen causes these plaques to dislodge; thus, resulting in heart attacks and stroke.

Another issue is smoking history. Smoking increases the risk of cardiovascular disease and other health conditions. Studies have reported that smokers go through menopause earlier than non-smokers. The type of hormone, route of administration, and dosage are other factors. For decades Premarin (conjugated estrogens, equine) was the most commonly prescribed form of estrogen. It is still prescribed today. (Premarin is an acronym for PREgnant MARes uRINe.) A higher dosage of estrogen is required for Premarin and other oral preparations because, after digestion, the hormone passes through the portal system in the liver. The liver senses the high estrogen level and removes it from the circulation. The same effect can be obtained at a lower dosage if given by injection or a skin patch (estrogen in the skin patch is released into the circulation in a similar manner as it is naturally released from the ovaries before menopause. Many obstetrician gynecologists now recommend a low-dosage estrogen patch because of its risk vs. benefits. Last September, Canadian researchers affiliated with the Analysis Group, Inc. reported that their findings added to evidence that transdermal hormone delivery (skin patches) is a safer alternative to pills for these women. A study, of 27,000 women who used transdermal HRT and 27,000 matched controls taking estrogen-only pills, reported that the women who used estrogen patches were one-third less likely to develop deep vein thrombosis or pulmonary embolism.

References:
Annals of Internal Medicine
The Analysis Group, Inc.

See also:
Urology group asserts support for PSA prostate cancer test
PSA prostate screening test does more harm than good says government panel

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