General Information

EstroGel is a topical gel containing 0.06% estradiol in an absorptive hydroalcoholic gel base, formulated to provide a controlled release of the hormone. It is designed to treat symptoms associated with menopause.

It is specifically indicated for the treatment of moderate to severe vasomotor symptoms associated with menopause, including hot flashes. It is also indicated for the treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated with the menopause, especially when the atrophy is concurrent to vasomotor symptoms.

The recommended topical dose of EstroGel is 1.25 g once daily, delivered via metered pump. Recommended application is to the posterior surface of the arm, from the back of the wrist to the shoulder.

Mechanism of Action

EstroGel supplies systemic estradiol, the primary estrogenic hormone secreted by the human ovaries, which is lost during and following menopause. Estradiol binds to widely distributed nuclear receptors in estrogen sensitive tissues. It also acts to inhibit the pituitary release of leutenizing hormone and follicle stimulating hormone via negative feedback loop (elevated levels of these hormones are customarily observed in postmenopausal women).

Side Effects

Adverse events associated with the use of EstroGel may include (but are not limited to) the following:

headache

flatulence

breast pain

The drug label comes with the following Black Box Warning:

Estrogen-Alone Therapy

There is an increased risk of endometrial cancer in women with a uterus who use unopposed estrogens. The Women’s Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT). The WHI Memory Study (WHIMS) estrogen-alone ancillary study of WHI reported an increased risk of probable dementia in postmenopausal women 65 years of age and older. Do not use estrogen-alone therapy for the prevention of cardiovascular disease or dementia.

Estrogen Plus Progestin Therapy
The WHI estrogen plus progestin substudy reported increased risks of stroke, DVT, pulmonary embolism (PE), and myocardial infarction (MI). The WHI estrogen plus progestin substudy reported increased risks of invasive breast cancer. The WHIMS estrogen plus progestin ancillary study of WHI reported an increased risk of probable dementia in postmenopausal women 65 years of age and older. Do not use estrogen plus progestogen therapy for the prevention of cardiovascular disease or dementia

Clinical Trial Results

FDA approval of EstroGel for the treatment of menopausal vasomotor symptoms was based on a double-blind, placebo-controlled study enrolling 145 women between 29 and 67 years of age. Subjects received either 1.25g EstroGel (n=72) or placebo (n=73) once daily for 12 weeks. Primary endpoint efficacies, measured by reduction in the occurrence of moderate-to-severe hot flashes and reduction in severity of hot flashes, were assessed at 4, 8, and 12 weeks. Results showed that EstroGel produced a statistically significant decrease in both the number and severity of hot flashes at 4 and 12 weeks (reduction at 8 weeks was not significant). Specifically, at 4 weeks, subjects receiving EstroGel experienced 0.85 fewer hot flashes per day, and a reduction in severity score of 0.32; at 12 weeks, EstroGel subjects experienced 1.71 fewer hot flashes and a severity score reduction of 0.49.

FDA approval of EstroGel for the treatment of vulvar and vaginal atrophy was based on results of vagina wall cytology examinations performed on all subjects at 12 weeks. A significant increase in superficial epithelial cells was observed for the EstroGel group; no significant increase was seen among the placebo group.