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Food And Drug Administration Black Box Warning Estrogens and progestins should not be used for the prevention of cardiovascular disease or dementia. The Women’s Health Initiative (WHI) study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50 to 79 years of age) during 5 years of treatment with conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg)... |
Food And Drug Administration Black Box Warning Estrogens and progestins should not be used for the prevention of cardiovascular disease or dementia. The Women’s Health Initiative (WHI) study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50 to 79 years of age) during 5 years of treatment with conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) relative to placebo. The WHI study reported increased risks of stroke and deep vein thrombosis [blood clots] in postmenopausal women (50 to 79 years of age) during 6.8 years of treatment with conjugated estrogens (0.625 mg) relative to placebo. The Women’s Health Initiative Memory Study (WHIMS), a substudy of WHI, reported increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with conjugated estrogens combined with medroxyprogesterone acetate and during 5.2 years of treatment with conjugated estrogens alone, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women. Other doses of conjugated estrogens and medroxyprogesterone acetate, and other combinations and dosage forms of estrogens and progestins were not studied in the WHI clinical trials and, in the absence of comparable data, these risks should be assumed to be similar. Because of these risks, estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman. |
Research published in the November 2005 issue of the medical journal Obstetrics & Gynecology found that estrogen plus progestin therapy in postmenopausal women, known as hormone replacement therapy (HRT), increases the risk of urge and stress incontinence within four months of beginning treatment. The researchers were from the University of California, San Francisco and the University of California, Davis.
Commonly used hormone replacement drugs are conjugated estrogens (PREMARIN) taken in conjunction with the progestin medroxyprogesterone (PROVERA). Combination products are also available, such as conjugated estrogens with medroxyprogesterone (PREMPRO, PREMPHASE).
Because the risks of HRT outweigh its benefits for most uses, these products now have the black box warning that appears above in their professional product labels. The Food and Drug Administration (FDA) has also limited the approved uses of HRT to the short-term treatment of moderate to severe hot flashes associated with menopause. HRT is no longer approved for the long-term treatment of the symptoms of menopause. The FDA cautions prescribers that women with postmenopausal osteoporosis should use other products, such as alendronate (FOSAMAX), before resorting to HRT. In other words, HRT is the last choice for postmenopausal osteoporosis.
The research involved a subset of 1,208 women from the Heart Estrogen/progestin Replacement Study, known by the acronym HERS, who reported no urinary incontinence in the seven days prior to the start of the study. The HERS study was a scientific “gold standard” randomized clinical trial looking at HRT in preventing heart disease in postmenopausal women who already had heart disease. We first wrote about this study in 1998 when no statistical difference in the rate of heart problems was found between those postmenopausal women using HRT and women given an inactive placebo (see November 1998 Worst Pills, Best Pills News). The July 2000 newsletter reported on a further analysis of the HERS study that concluded there was increased risk of blood clots in women using HRT (see Worst Pills, Best Pills News July 2000).
At the beginning of the study, women were asked to complete an incontinence questionnaire that asked participants how many times during the previous week, on average, they had “unintentionally leaked some urine with coughing, sneezing, straining, laughing or lifting.” This was defined as stress incontinence. Women were also asked “have you unintentionally leaked some urine before you could get to the bathroom?” This was defined as urge incontinence.
The study lasted 4.2 years. During this time, 64 percent of women using HRT reported weekly incontinence compared to 49 percent of those given a placebo. This result was statistically significant. The increased risk of incontinence in women using HRT was evident four months after starting HRT and persisted throughout the study. Four years of treatment with HRT caused an excess risk of 12 percent for weekly urge incontinence and 16 percent for weekly stress incontinence.
The researchers also calculated how many women would need to take HRT for 4.2 years, the duration of the HERS study, for one of them to develop weekly urge incontinence and weekly stress incontinence. This is called the number needed to harm. The number needed to harm for weekly urge incontinence was 8.6 women. It is possible that as few as about six women taking HRT for 4.2 years would result in one case of HRT-induced weekly urge incontinence.
The number needed to harm for weekly stress incontinence was calculated to be 6.2 women taking HRT for 4.2 years. It is possible that for as few as five women taking HRT, one will develop stress incontinence.
The researchers concluded:
... oral estrogen plus progestin therapy increased the risk for stress and urge urinary incontinence in postmenopausal women. Women who are using or consider hormone therapy should be informed about this increased risk.
A number of other drugs can cause drug-induced urinary incontinence. Check this list. The extent to which urinary incontinence is drug-induced is unknown, but if you start taking one of the drugs listed below and begin experiencing urinary incontinence, you should suspect th e drug as the cause of your new symptom. This is Rule Seven of our Ten Rules for Safer Drug Use: Assume that any new symptom you develop after starting a new drug may be caused by the drug.
What You Can Do
If you are taking HRT and have experienced either urge or stress urinary incontinence, talk to the prescribing health care professional about the possibility that the urinary incontinence is drug-induced. This advice also applies to the other drugs listed with this article, all of which have been implicated in causing drug-induced urinary incontinence.
If you are considering starting HRT, the possibility of experiencing urinary incontinence should be taken into account along with its other potential harms, which are outlined in the black box warning accompanying this article.
