Progesterone Reduces Wakefulness in Sleep EEG and Has no Effect on Cognition in Healthy Postmenopausal Women
Condition: Healthy; Postmenopausal
Study type: Interventional
Phase: Phase 4

Summary: 
      Sleep is impaired in postmenopausal women (difficulty falling asleep, frequent awakenings).
      Progesterone prompted benzodiazepine-like effects on sleep EEG in young normal male subjects.

      Aim of this study was to test if replacement therapy with progesterone improves sleep after
      menopause.

      Design, Setting, and Participants: A double blind cross-over design study with 2 treatment
      intervals of 21 days duration separated by a 2 weeks washout was performed. A oral dose of
      300mg micronized progesterone was given each for 21 days. At the beginning and the end of the
      two intervals a sleep EEG was recorded and cognitive performance was assessed in 10 healthy
      postmenopausal women (age: 54-70 yrs).
    

Detailed description: 
      Objectives/ Mode of administration: To characterise the effects of progesterone in a dose of
      300mg each for 21 days on changes of sleep EEG and cognition in postmenopausal healthy women,
      in comparison with placebo.

      Methodology:The study was performed as double blind randomized placebo controlled crossover
      design with two treatment intervals of 21 days duration separated by 2 weeks washout.
      Progesterone was administered as tablets in a dose of 300mg each for 21 days. At the
      beginning and the end of the two intervals a sleep EEG was recorded after one night of
      adaptation to laboratory conditions, during which EEG electrodes were attached without
      recording an EEG.For the registration nights the subjects arrived at the sleep laboratory at
      21.00 h. Sleep EEG was recorded from 23.00 h until 07.00 h hours next morning.Cognitive
      performance was tested after the registration nights at 09.00h.All pharmacodynamic
      investigations were carried out in the sleep laboratory of the Max Planck Institute of
      Psychiatry in Munich.

      Main criteria for inclusion: Subjects consisted of 10 healthy women (age: range 54-70 years)
      who entered the study after passing rigid psychiatric, physical and laboratory examinations.
      They had been drug free at least 4 weeks. Reasons for exclusion from the study were:
      psychiatric disorder in the subjects own or family history, including dementia or other
      cognitive impairment; recent stressful life events; substance abuse; a transmeridian flight
      during the last three months; shift work; medical illness; and aberrations in blood chemistry
      or in the waking EEG or electrocardiogram.All subjects underwent a polysomnographic
      examination in the sleep laboratory before entering the study to exclude sleep disorder
      including sleep related respiratory disorders and sleep related movement disorders.

      Statistical methode: Expolatory and inferential statistical analysis of certain aggregated
      sleep variables after classifying the sleep EEG in dinstinct stages according to
      Rechtschafen/Kales and of the results of EEG spectral analysis. Inferential statistics were
      based on multivariate analyses of variance (MANOVAs) with treatment as influential factor and
      on one sample t-tests for placebo related power changes of progesterone in non-REM sleep as
      well.
    

Intervention name(s): progesterone
Intervention type(s): Drug
Intervention description(s): 300mg progesterone /placebo each for 21 days
Other intervention name(s): Utrogest/ Utrogest Placebo Ch.-B.: 0503
Intervention MeSH terms: Progesterone
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: progesterone, postmenopause, sleep-EEG