Treatment with a capsule containing bioidentical 17-beta-estradiol and progesterone (TX-001HR) improves sleep in postmenopausal women with vasomotor symptoms (VMS), according to a new analysis of industry research.

"In general, postmenopausal women continue to suffer from moderate-severe VMS and sleep disturbance which affects the overall quality of life, despite excellent therapeutic options with proven efficacy and safety," Dr. Risa Kagan of Sutter East Bay Medical Foundation, in Berkeley, California, told Reuters Health by email. In the REPLENISH trial, TX-001HR significantly improved the frequency and severity of moderate to severe VMS with no evidence of endometrial hyperplasia.

In the new report, online December 21 in Menopause, Dr. Kagan and colleagues describe the effects of TX-001HR versus placebo on sleep parameters using the validated Medical Outcomes Study (MOS) -Sleep questionnaire, a secondary outcome of REPLENISH.

Total scores for the 12-item MOS-Sleep questionnaire range from 12 to 71. Ratings for the Sleep Problems Index I and Sleep Problems Index II subscales were linearly transformed to range from 0 to 100. In the modified intent-to-treat population , which included all 1,833 women who were randomized and took at least one dose (two capsules) of the investigational product, MOS-Sleep total scores improved from 43.2-48.1 at baseline to 27.5-29.4 with TX-001HR (depending on dose) and to 37.4 with placebo at month 12.

At months 6 and 12, MOS-Sleep total scores were significantly improved in all active treatment groups compared with placebo. Compared with placebo, all doses of TX-001HR significantly improved the Sleep Problems Index I subscale, and all but the lowest dose (0.25 mg estradiol / 50 mg progesterone at week 12) also significantly improved the Sleep Problems Index II subscale.


Most doses of TX-001HR significantly improved the sleep disturbance, sleep somnolence and sleep adequacy subscales, compared with placebo, but TX-001HR had no beneficial effects on the snoring or sleep shortness of breath or headache subscales. "Improvements in the MOS-Sleep scale scores suggest that TX-001HR improves sleep quality based on its ability to reduce the frequency and severity of VMS, which was the primary endpoint of the REPLENISH trial," the note.

"For symptomatic women, the benefits outweigh the risks of HT (hormone treatment) if women are within the first ten years since last menses and under age 60 and have no contraindications," Dr. Kagan said. "But women continue to fear HT due to the negative press from the Women's Health Initiative (WHI) Hormone Therapy Trials, yet women perceive that compounded bioidentical hormone therapy (BHT) is safer, etc."

"Since the WHI, there has been an increase in unregulated prescriptions of 'Bioidentical HT' products, mostly compounded with no proven safety or efficacy and not adequately studied," she said. "These BHT products are the most often prescribed type of HT, despite reports of adverse outcomes, which I have personally witnessed, especially an increase in endometrial (cancer)."