WARNING: CARDIOVASCULAR DISORDERS, ENDOMETRIAL CANCER, BREAST CANCER and PROBABLE
DEMENTIA
Estrogen-Alone Therapy
Endometrial Cancer
There is an increased risk of endometrial cancer in a woman with a uterus who
uses unopposed estrogens. Adding a progestin to estrogen therapy has been shown
to reduce the risk of endometrial hyperplasia, which may be a precursor to
endometrial cancer. Adequate diagnostic measures, including directed or random
endometrial sampling when indicated, should be undertaken to rule out
malignancy in postmenopausal women with undiagnosed persistent or recurring
abnormal genital bleeding.
Cardiovascular Disorders and Probable Dementia
Estrogen-alone therapy should not be used for the prevention of cardiovascular
disease or dementia.
The Women’s Health Initiative (WHI) estrogen-alone substudy reported increased
risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to
79 years of age) during 7.1 years of treatment with daily oral conjugated
estrogens (CE) [0.625 mg], relative to placebo.
The WHI Memory Study (WHIMS) estrogen-alone ancillary study of WHI reported an
increased risk of developing probable dementia in postmenopausal women 65 years
of age or older during 5.2 years of treatment with daily CE (0.625 mg) alone,
relative to placebo. It is unknown whether this finding applies to younger
postmenopausal women.
In the absence of comparable data, these risks should be assumed to be similar
for other doses of CE and other dosage forms of estrogens. 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.
Estrogen Plus Progestin Therapy
Cardiovascular Disorders and Probable Dementia
Estrogen plus progestin therapy should not be used for the prevention of
cardiovascular disease or dementia.
The WHI estrogen plus progestin substudy reported increased risks of DVT,
pulmonary embolism, stroke and myocardial infarction in postmenopausal women
(50 to 79 years of age) during 5.6 years of treatment with daily oral CE (0.625
mg) combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to
placebo.
The WHIMS estrogen plus progestin ancillary study of the WHI, reported an
increased risk of developing probable dementia in postmenopausal women 65 years
of age or older during 4 years of treatment with daily CE (0.625 mg) combined
with MPA (2.5 mg), relative to placebo. It is unknown whether this finding
applies to younger postmenopausal women.
Breast Cancer
The WHI estrogen plus progestin substudy also demonstrated an increased risk of
invasive breast cancer.
In the absence of comparable data, these risks should be assumed to be similar
for other doses of CE and MPA, and other combinations and dosage forms of
estrogens and progestins.
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.