er plasma proteins may be increased (angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin).
Increased plasma HDL and HDL2 cholesterol subfraction concentrations, reduced LDL cholesterol concentration, increased triglyceride levels.
Impaired glucose tolerance.
E. Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term, continuous administration of natural and synthetic estrogens in certain animal species increases the frequency of carcinomas of the breast, uterus, cervix, vagina, testis, and liver.
F. Pregnancy
EstroGel should not be used during pregnancy. (See CONTRAINDICATIONS.)
There appears to be little or no increased risk of birth defects in children born to women who have used estrogens and progestins as an oral contraceptive inadvertently during early pregnancy.
G. Nursing Mothers
EstroGel should not be used during lactation. Estrogen administration to nursing mothers has been shown to decrease the quantity and quality of the milk. Detectable amounts of estrogen have been identified in the milk of mothers receiving this drug.
H. Pediatric Use
EstroGel is not indicated for pediatric use and no clinical data have been collected in children.
I. Geriatric Use
There have not been sufficient numbers of geriatric patients involved in studies utilizing EstroGel to determine whether those over 65 years differ from younger subjects in their response to EstroGel.
In the estrogen alone substudy of the Women’s Health Initiative (WHI) study, 46 percent (n=4,943) of subjects were 65 years and older, while 7.1 percent (n=767) of subjects were 75 years and older. There was a higher relative risk (daily CE 0.625 mg versus placebo) of stroke in women less than 75 years of age compared to women 75 years and older.
In the estrogen alone substudy of the Women’s Health Initiative Memory Study (WHIMS), a substudy of WHI, a population of 2,947 hysterectomized women aged 65 to 79 years was randomized to receive daily conjugated estrogens (CE 0.625 mg) or placebo. After an average follow-up of 5.2 years, the relative risk (CE versus placebo) of probable dementia was 1.49 (95 percent CI, 0.83-2.66). The absolute risk of developing probable dementia with estrogen alone was 37 versus 25 cases per 10,000 women-years compared with placebo.
Of the total number of subjects in the estrogen plus progestin substudy of WHI, 44 percent (n=7,320) were aged 65 years and older, while 6.6 percent (n=1,095) were 75 years and older. In women 75 years of age and older compared to women less than 75 years of age, there was a higher relative risk of non-fatal stroke and invasive breast cancer in the estrogen plus progestin group versus placebo. In women greater than 75, the increased risk of non-fatal stroke and invasive breast cancer observed on the estrogen plus progestin group compared to placebo was 75 versus 24 per 10,000 women-years and 52 versus 12 per 10,000 women-years, respectively.
In the estrogen plus progestin substudy of WHIMS, a population of 4,532 postmenopausal women, aged 65 to 79 years, was randomized to receive daily CE 0.625 mg /MPA 2.5 mg or placebo. In the estrogen plus progestin group, after an average follow-up of 4 years, the relative risk (CE/MPA versus placebo) of probable dementia was 2.05 (95 percent CI, 1.21-3.48). The absolute risk of developing probable dementia with CE/MPA was 45 versus 22 cases per 10,000 women-years compared with placebo.
Seventy-nine percent of the cases of probable dementia |
