Freeman E, Guthrie K, Caan B, et al. Efficacy of escitalopram for hot flashes in healthy menopausal women: a randomized controlled trial. JAMA. 2011;305(3):267–74.
What was Known?
Hormone replacement therapy is the most effective treatment for relieving menopausal vasomotor symptoms, but its use is limited by increased rates of stroke and venous thromboembolic disease.11
Non-hormonal therapies, including antidepressants and neuroleptics, reduce hot flashes by 40–84%.12
Few studies have examined whether the effectiveness of non-hormonal therapies is influenced by race, menopausal status, or a personal history of anxiety or depression.
What this Study Adds
250) with moderately severe hot flashes were randomized to escitalopram 10 mg daily or placebo for 8 weeks. Almost half of the study participants were African-American, and 14–23% reported mild depression or anxiety at baseline. After 8 weeks of treatment, patients in the escitalopram group experienced 1.40 fewer hot flashes per day and a reduction in severity than those in the placebo group. Although there was a substantial placebo effect, more women in the escitalopram group experienced at least a 50% reduction in hot flash frequency (55% vs 36%, p
0.009). Race, menopausal status, and a history of depression or anxiety did not modify the treatment effect, and adverse events were few. Patient satisfaction and desire to continue with treatment was higher with escitalopram than placebo (70% vs 43%, p <0.001, and 64% vs 42%, p
How Should I Change my Practice? Escitalopram may be a good treatment option for symptomatic women who want to avoid systemic hormone therapy, and will be effective even in those without anxiety or depression.Renoux C, Dell'aniello S, Garbe E, Suissa S. Transdermal and oral hormone replacement therapy and the risk of stroke: a nested case-control study. BMJ. 2010;340:c2519.
What Was Known?
Oral hormone therapy for relief of menopausal symptoms increases the risk for ischemic stroke.13
Transdermal hormone therapy, while equally efficacious, avoids the hepatic first-pass effect and is less likely than oral therapy to increase cardiovascular risk markers.14
To date, no studies have compared the effects of transdermal and oral hormone therapy on stroke risk.
What this Study Adds Using a large British medical record database and a nested case-control study design, the investigators examined the rates of stroke among older women who were exposed to hormone therapy. The route (oral vs transdermal) and dose (high vs low dose estrogen) of hormone therapy were compared among 15,710 cases and 59,958 controls. After adjustment for multiple cardiovascular risk factors, women who used transdermal estrogen or estrogen/progesterone hormone therapy had no increased risk of stroke compared with non-users (rate ratio 0.95, 95% CI 0.75–1.20), although this was only true with doses of estrogen less than 50 μg. Conversely, treatment with oral estrogen significantly increased the risk of stroke by 35%, an effect that was mitigated only slightly if oral estrogen was combined with progesterone (rate ratio 1.24, 95% CI 1.08–1.41). Stroke risk with oral hormone therapy did not vary significantly when stratified according to low or high estrogen doses (rate ratio 1.25, 95% CI 1.12–1.40 vs 1.48, 95% CI 1.16–1.90, respectively). In a direct comparison, treatment with transdermal hormone therapy was associated with a lower risk of stroke than oral therapy (rate ratio 0.74, 95% CI 0.58–0.95).
How Should I Change my Practice? This study suggests that transdermal hormone therapy is safer than oral therapy. Although case control study designs have inherent biases, there is biological plausibility for these results based on prior studies. Providers should consider selecting transdermal routes of hormone administration to minimize the risks associated with systemic therapy.Chlebowski R, Anderson G, Gass M, et al. Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women. JAMA. 2010;304(15):1684–92.
What was Known?
In the Women’s Health Initiative (WHI) placebo-controlled trial, women who were treated with combined estrogen and progestin (E/P) therapy had an increased risk of invasive breast cancer. Moreover, these breast cancers tended to be larger and at a more advanced stage at the time of detection.15
Although the risk of breast cancer declined significantly after discontinuation of E/P 16
, the long-term effects of E/P on breast cancer incidence, characteristics at diagnosis, and breast cancer mortality are unclear.
What this Study Adds Although the WHI was stopped early in 2002, all subjects were followed for an additional 3 years, until the original trial completion date (“post-intervention phase”). Eighty-three percent of women consented to participate in the “extension phase,” and data regarding breast cancer incidence and mortality were collected prospectively until 2009. In total, after a mean follow-up of 11.0 years, 678 cases of breast cancer were identified. Treatment with E/P, as compared to placebo, was associated with a significantly increased incidence of invasive breast cancer (HR 1.25, 95% CI 1.07–1.46). Women in the treatment group, as compared to those receiving placebo, were more likely to have positive lymph nodes at the time of diagnosis and were more likely to die from breast cancer (25 deaths vs 12 deaths, HR 1.96, 95% CI 1.00–4.04). Overall mortality after a diagnosis of breast cancer was higher in the E/P group than in the placebo group (51 deaths vs 31 deaths, HR 1.57, 95% CI 1.01–2.48).
How Should I Change my Practice? Treatment with E/P increases the incidence of invasive breast cancer, and the risk persists after discontinuation of therapy. Moreover, E/P increased breast cancer mortality and overall mortality, although the number of deaths in both groups was relatively small. In light of these new data, practitioners should continue to carefully weigh the risks and benefits of E/P therapy and counsel patients appropriately.