Hormone Replacement Therapy Review Confirms Recommendations for Caution

It has been 10 years since the U.S. Preventive Services Task Force (USPSTF) raised a red flag of concern for women who take hormone replacement therapy (HRT). A systematic review of scientific research published on the subject since 2002, the task force concluded last week, confirms the initial call for caution.

HRT is most often prescribed to alleviate the symptoms of menopause, including hot flashes, vaginal dryness, sleep disturbances and mood swings. Although HRT might be appropriate for people in this situation, the task force said that the risks for most women taking HRT for the long term still outweigh any benefits it confers in preventing chronic conditions.

As reported widely, including on MedPage Today, the hormones at issue-estrogen and progestin-do help prevent bone fractures, used alone and together. But they increase the risk of stroke, thromboembolisms (blood clots that dislodge and move through the circulation system), gallbladder disease and urinary incontinence.

The review of HRT was published on the Annals of Internal Medicine.

Most women prescribed HRT are given estrogen plus progestin because unalloyed estrogen increases the risk of uterine cancer, so plain estrogen is generally prescribed only for women who have had a hysterectomy. The new study indicates that the estrogen/progestin compound also increases risk for breast cancer and dementia. Estrogen alone decreases the risk for breast cancer.

In 2002, the USPSTF recommended against routine, long-term HRT use, and in 2005 recommended against long-term us of estrogen alone. The recommendations did not address short-term use of HRT to relieve menopause symptoms.

The new review of nearly a decade’s worth of clinical studies evaluated HRT’s effect on cardiovascular disease, cognitive decline, osteoporosis (thinning of the bones) and cancer.

Use of estrogen alone showed significant decreases in invasive breast cancer and mortality. Use of estrogen/progestin showed significant decreases in diabetes. Bone fractures were reduced significantly with both hormone regimens in some studies but not others.

But the harms significantly increased by one or both hormone replacement regimens were:

  • invasive breast cancer (estrogen plus progestin);
  • stroke (both);
  • deep vein thrombosis (DVT/blood clot-both);
  • pulmonary embolism (blood clot in the lung-estrogen plus progestin);
  • breast cancer mortality (estrogen plus progestin);
  • lung cancer mortality (estrogen plus progestin);
  • gallbladder disease (both);
  • probable dementia (estrogen plus progestin);
  • urinary incontinence (both).

The number of women who would be expected to suffer harm, the study concluded, was far greater than those who would benefit from either regimen. With estrogen alone, there would be eight fewer invasive breast cancers, 56 fewer fractures and two fewer breast cancer deaths, but 11 more strokes, seven more DVT episodes, 33 more gallbladder disease cases and 1,271 cases of urinary incontinence per 10,000 person-years (the product of the number of years times the number of people in a population who have been affected by a certain condition; that is, years of treatment with a given drug).

The corresponding numbers for estrogen plus progestin, according to the study, were just as unfavorable.

There might be benefits worthy of HRT (and different harms) for certain people with certain conditions, for which the study was inconclusive. Such different results could occur because of differences in age, type of hormone therapy, natural versus premature menopause or other medical conditions.

But the bottom line for most women is that hormone replacement therapy generally should be used only for short-term relief of menopausal symptoms. Individuals should discuss its suitability for other concerns only in the context of a complete medical history and an understanding of the risks.

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