occurred in women that were older than 70 years for the CE alone group, and 82 percent of the cases of probable dementia occurred in women who were older than 70 years in the CE/MPA group. The most common classification of probable dementia in both the treatment groups and placebo groups was Alzheimer’s disease.
When data from the two populations were pooled as planned in the WHIMS protocol, the reported overall relative risk for probable dementia was 1.76 (95 percent CI, 1.19-2.60). Since both substudies were conducted in women aged 65 to 79 years, it is unknown whether these findings apply to younger postmenopausal women. (See BOXED WARNINGS and WARNINGS, Dementia.)
ADVERSE EVENTS
See BOXED WARNINGS, WARNINGS and PRECAUTIONS.
Because clinical trials are conducted under widely varying conditions, adverse event rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in pratice.
EstroGel 1.25 g was studied in 2 well-controlled 12-week clinical trials. Incidence of adverse events ≥5 percent for 1.25 g EstroGel and placebo is given below in Table 4.
TABLE 4 Incidence of Treatment-emergent Signs and Symptoms ≥5 Percent By COSTART Body System and by Descending Frequency of Occurrence in the EstroGel Treatment Group for the Intent-to-Treat Safety Population in 2 Well-controlled Clinical Studies (Expressed as Percent of Treatment Group) *
Infection: upper respiratory infection, common cold, eye infection.
Pain: generalized and extremity aches/pains, cramps.
Rash and pruritus: more than half of the EstroGel-treated patients who had pruritus reported itching at a body site other than the arms or reported generalized itching or itching skin. Similarly, most of the EstroGel-treated patients with rash had rash on 1 or more areas of the body in addition to the arms.
Endometrial disorder: proliferative endometrium, benign endometrial disorders.
Pap smear suspicious: atypical squamous cells of undetermined significance, inflammatory changes, epithelial cell abnormality.
Body System/Treatment-emergent
Signs and Symptoms EstroGel 1.25 g day
(n=168) Placebo
(n=73)
BODY AS A WHOLE
Headache 20.2 17.8
Infection* 17.3 6.8
Pain† 7.1 11.0
Abdominal pain 7.7 1.4
Back pain 4.8 4.1
Flu syndrome 5.4 1.4
Asthenia 4.8 4.1
CARDIOVASCULAR SYSTEM
Palpitations 0.6 1.4
DIGESTIVE SYSTEM
Nausea 6.0 4.1
Flatulence 6.5 5.5
Diarrhea 4.2 0.0
METABOLIC and NUTRITIONAL SYSTEMS
Weight gain 2.4 0.0
NERVOUS SYSTEM
Nervousness 2.4 1.4
Depression 3.0 2.7
Anxiety 1.8 0.0
RESPIRATORY SYSTEM
Sinusitis 3.6 1.4
Rhinitis 2.4 6.8
SKIN AND APPENDAGES
Rash‡ 7.1 5.5
Pruritus‡ 4.8 2.7
Application-site reaction 0.6 0.0
UROGENITAL
Breast pain 12.5 9.6
Met |
