Sleep, Menopause and Estrogen Therapy

Menopause can be grossly uncomfortable for women, with symptoms like insomnia, night sweats, hot flashes, and irritability, all of which can lead to further health concerns and decreased quality of life.  Early postmenopausal women often talk to their providers about the efficacy of low-dose estrogen therapy to help reduce or eliminate these symptoms.

The Kronos Early Estrogen Prevention Study (KEEPS) provided scientists with data that compared two forms of hormone therapy (HT) against menopausal symptoms.  These results were compared to those who were treated with a placebo for four years.  Results were published in the journal, Menopause. 

Most women in this stage of life are going to have symptoms, with vasomotor symptoms (VMS; night sweats and hot flashes) being the most common complaints.  VMS are reported in about 85% of cases.  While the link between declining estrogen levels and VMS is well known, it is less known as to why there is a link between these hormones and symptoms like insomnia, depression, and irritability.  Few studies have been dedicated to this research and even fewer have looked at whether HT given for an extended time could help with these symptoms.

The KEEPS study was a clinical trial that took place at multiple centers, using 727 female participants between the ages of 42 and 58, who were within three years of their last menstrual period.  This study was done to compare the effects of a placebo versus transdermal estradiol and low-dose oral conjugated estrogen (CEE).  The women in the study were randomized to receive one of the three treatments, along with progesterone for 12 days a month (except in the placebo group).

A menopause checklist was given to the participants before they were put into their group.  This checklist was redone at 6, 12, 24, 36, and 48 months.  Symptoms were self-reported and included current symptoms of insomnia, night sweats, irritability, and hot flashes.  There were several study drop-outs, with the end-of-study assessments including 211, 170 and 173 people in the placebo, transdermal estradiol, and CEE groups, respectively.

The screening showed the following results:

  • At baseline, hot flashes were reported as moderate to severe in 44% of participants.
  • At 6 months, hot flashes and severity had decreased to 29.3% in those on the placebo, 7.4% in those on transdermal, and 4.2% in those on CEE.
  • At baseline, night sweats were reported as moderate to severe in 35% of participants.
  • At 6 months, moderate to severe night sweats were reported in 19% of placebo patients, 5.3% in transdermal estradiol, and 4.7% in CEE patients.
  • Symptom reduction was maintained throughout the study in all groups.
  • From baseline to 6 months, insomnia and irritability decreased across the board in all groups.
  • Insomnia was reduced in active treatments and the placebo, but there was more significant improvement in those in CEE group at 36 and 48 months.
  • Transdermal estradiol was noted to be more effective for insomnia at 48 months.
  • Irritability was not significantly improved in either treatment group compared to the placebo.

Dr. JoAnn Pinkerton, Executive Director at the North American Menopause Society noted that this study shows improvement in the intensity of hot flashes with the use of low dose CEE or transdermal estradiol from baseline.  This improvement was sustained over a period of four years, which is a significant finding.  This indicates that low-dose HT should be considered when physicians are looking for how to treat menopausal symptoms based on the patient’s medical issues and needs.

For the first time, this study compared longitudinal menopause symptoms treated by different HT and micronized progesterone.  Either transdermal estradiol or CEE HT were noted to be highly effective in treating the traditional menopausal symptom of hot flashes and night sweats.  There was very little notable difference between the two groups, leaving options open for providers and patients.  HT offered a pronounced reduction in moderate to severe symptoms, which are often the cause of women seeking treatment to begin with.  Insomnia was also notably reduced with the use of HT.


Rachael Herman is a professional writer with an extensive background in medical writing, research, and language development. Her hobbies include hiking in the Rockies, cooking, and reading.


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