Effects of Micronized Progesterone in Menopausal Hormone Replacement Therapy on Sleep

In Japan, only synthetic progestins were available for menopausal hormone therapy until 2021. Since then, micronized progesterone has become available. Micronized progesterone binds to gamma-aminobutyric acid type A receptors and exerts sedative and hypnotic effects. This study evaluated the effects of micronized progesterone on sleep in women receiving estrogen-progestogen therapy.

This retrospective study was approved by the institutional review board. Eligible participants were women who switched from synthetic progestins to micronized progesterone between December 2022 and September 2024. Women using sleep medications were excluded. Sleep quality was assessed using the Athens Insomnia Scale before switching, 3 months, and 1 year after initiating micronized progesterone. Progesterone was administered cyclically or continuously. In cyclic users, the Insomnia Severity Index was used to compare sleep during treatment and treatment-free phases.

A total of 36 participants were included, of whom 22 completed a 1-year follow-up. At 3 months, sleep induction (p = 0.002) and awakenings during the night (p = 0.028) on the Athens Insomnia Scale improved, although the total score remained unchanged. At 1 year, no significant changes were observed. Among 11 participants with baseline scores ≤ 3, the total Athens Insomnia Scale scores significantly worsened at 3 months and 1 year. No significant differences in Insomnia Severity Index scores were observed between treatment and non-treatment periods.

Micronized progesterone improved sleep induction and reduced awakenings during the night at 3 months; however, benefits diminished by 1 year. Sleep conditions worsened in women without preexisting sleep disorders. Regular monitoring is recommended during long-term micronized progesterone therapy.