KEEPS was a multicenter clinical trial designed to compare effects of low-dose oral conjugated estrogens (CEE) with those of transdermal estradiol versus placebo on cardiovascular endpoints in recently postmenopausal women. 727 women aged 42 to 58 years and within three years of their final menstrual period were randomized to receive oral conjugated estrogens (CEE) 0.45 mg (n = 230) or transdermal estradiol 50 μg (n = 225), both with micronized progesterone 200 mg for 12 days each month, or placebo (n = 275).

All participants completed a menopause symptom checklist before randomization and again at six, 12, 24, 36, and 48 months. Menopause symptoms were self-assessed and included only current symptoms of hot flashes, night sweats, insomnia, and irritability. Because of study dropout from screening to 48 myonths, 173, 170, and 211 women randomized to CEE, transdermal estradiol, and placebo, respectively, completed the end-of-study assessments.

At baseline screening, moderate to severe hot flashes were reported by 44% of participants. By six months, moderate to severe hot flashes had decreased to 28.3% for those women randomized to placebo, 7.4% for those randomized to transdermal estradiol, and 4.2% for those randomized to CEE. Moderate to severe night sweats reported by 35% of participants at baseline decreased to 19% for placebo, 5.3% for transdermal estradiol, and 4.7% for CEE at six months. This initial magnitude of symptom reduction was maintained throughout the entire study in all treatment groups.

Insomnia and irritability decreased from baseline to six months after randomization in all groups. There was an intermittent reduction in insomnia in both active treatment arms versus placebo, with CEE being more effective than placebo at 36 and 48 months and transdermal estradiol being more effective than placebo at 48 months. Neither hormone treatment significantly affected irritability compared with placebo.

"Women who were highly symptomatic at baseline with hot flashes and night sweats had a significant improvement in frequency and intensity of hot flashes when using lower doses of either oral conjugated estrogen or transdermal estradiol, with sustained improvement over four years," says Dr. JoAnn Pinkerton, Executive Director of The North American Menopause Society. "Lower doses are effective and should be considered when providers are looking to find the appropriate dose, type of therapy, and duration for an individual woman based on her needs and medical issues."

This study is the first to compare menopause symptoms longitudinally by treatment regimen and route of administration in women taking different types of low-dose estrogen therapy in combination with oral micronized progesterone. Overall, HT with either CEE or transdermal estradiol was highly effective in relieving the more traditional menopause symptoms of hot flashes and night sweats, with little difference in effectiveness between the two treatment groups. There was pronounced reduction of moderate to severe symptoms, which typically drive women to seek treatment. Other symptoms such as irritability and insomnia were less influenced by HT.

Source: Eurekalert