new FDA advisory on Estrogel

[Lani]

Estradiol Gel (EstroGel) Linked to Risks for Probable Dementia and Ovarian Cancer

On July 25, the FDA approved safety labeling revisions for estradiol 0.06% gel (EstroGel; Ascend Therapeutics, Inc) to warn of the risk for probable dementia and potential risk for ovarian cancer. Estrogen therapy should be limited to the lowest effective dose and for the shortest duration consistent with treatment goals.

Data from the Women's Health Initiative Memory Substudy (n = 2947) have linked daily use of 0.625 mg of conjugated estrogens (CE) monotherapy for an average of 5.2 years to an increased risk of developing probable dementia vs placebo in women aged 65 to 79 years who have undergone a hysterectomy (relative risk [RR], 1.49; 95% confidence interval [CI], 0.83 - 2.66; absolute risk per 10,000 women-years, 37 vs 25).

The FDA notes that a similar increase in risk was observed for women in this age group receiving CE with 2.5 mg of medroxyprogesterone [MPA] daily (n = 4532) for an average period of 4 years (RR, 2.05; 95% CI, 1.21 - 3.48; absolute risk per 10,000 women-years, 45 vs 22).

When data from the 2 groups were pooled, the overall risk for probable dementia was 1.76 (95% CI, 1.19 - 2.60). The relevance of this finding to younger postmenopausal women remains unclear.

The majority of cases occurred in women aged older than 70 years (CE alone, 79%; CE with MPA, 82%); the most common classification in the treatment and placebo groups was Alzheimer's disease.

Findings from the Women's Health Initiative study (n = 10,739) also revealed an increased risk for ovarian cancer in postmenopausal women taking CE with MPA for an average of 5.6 years. However, the risk was not statistically significant vs placebo (RR, 1.58; 95% CI, 0.77 - 3.24; absolute risk per 10,000 women-years, 4.2 vs 2.7).

According to the FDA, the risk for ovarian cancer in women receiving estrogen monotherapy remains unclear: some epidemiologic studies have revealed an increased risk, particularly with duration of therapy of 10 years or more; other studies have not supported these findings.

Estradiol gel is indicated for the treatment of moderate to severe vasomotor symptoms and for moderate to severe symptoms of vulvar and vaginal atrophy associated with menopause.

http://www.fda.gov/medwatch/safety/2...ekturna_PI.pdf

http://www.fda.gov/medwatch/safety/2.../Diovan_PI.pdf

http://www.fda.gov/medwatch/safety/2...stroGel_PI.pdf

[hutchibk]

So, I should assume that this would include Estrace vaginal cream, 0.1% estradiol?

[Hopeful]

hutchibk,

I wouldn't be so quick to throw the baby out with the bath water. Estrogel is used as systemic estrogen therapy, where Estrace cream is directed specifically to the vaginal cells, with the goal of keeping circulating estrogens to an absolute minimum. Estrogel is applied from the wrist to the shoulder; Estrace is applied directly to the vaginal area.

FYI, it is the third link Lani posted that has the black box warning.

Hopeful

[hutchibk]

Thanks Hopeful... that's what I was thinking, and Estrace has been a wonderful friend to me for the last 3 years. My non-scientific mind doesn't know how to apply some of the findings and reports... it's often just greek to me. But I do know that my onc believes that Estrace vaginally at the dose and frequency I use holds no danger of having a systemic effect.

[Hopeful]

hutchbik,

My gynecologist, oncologist and surgeon are all in favor of my use of Estrace cream. My gyn made me get blood tests weekly for the first month of use. There was some systemic absorption early on, but it never rose above the post-meno ER levels. One test had it down below the detection threshold, then it bounced up a little but not much over that. I do not think we are exposed to anywhere near the levels that the systemic users are.

Hopeful