Progesterone Reduces Wakefulness in Sleep EEG and Has no Effect on Cognition in Healthy Postmenopausal Women
Information source: Max-Planck-Institute of Psychiatry
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy; Postmenopausal
Intervention: progesterone (Drug)
Phase: Phase 4
Sponsored by: Max-Planck-Institute of Psychiatry
Official(s) and/or principal investigator(s):
Axel Steiger, Prof., MD, Principal Investigator, Affiliation: Max-Planck-Institute of Psychiatry
Sleep is impaired in postmenopausal women (difficulty falling asleep, frequent awakenings).
Progesterone prompted benzodiazepine-like effects on sleep EEG in young normal male
Aim of this study was to test if replacement therapy with progesterone improves sleep after
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).
Official title: Progesterone Reduces Wakefulness in Sleep EEG and Has no Effect on Cognition in Healthy Postmenopausal Women
Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Crossover Assignment, Efficacy Study
Primary outcome: sleep-EEG parameters
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
Minimum age: 54 Years.
Maximum age: 70 Years.
- Healthy female elderly subjects
- Age between 55-70 years
- Normal physical examination including a neurological and gynecological examination
- Medical history without major or chronic diseases (e. g. diabetes, heart failure,
- No previous psychiatric or chronic neurological disorder (e. g. schizophrenia,
- Normal standard electrocardiograpy (ECG)
- Normal laboratory results
- Body Mass Index <30
- Normal sleep EEG concerning restless leg and sleep apnoe syndrom
- Normal EEG, according to the guidelines of the Deutsche EEG Gesellschaft (German EEG
- Written informed consent
- Written consent from the gynecologist, who examined the subjects, that there is no
contradiction for the oral application of Utrogest
- Gastrointestinal disorder
- Gynecological disorder
- Heart and lung disorder
- Liver and kidney disorders
- Creatinin serum >2,5 mg%
- Thyroid diseases
- Psychiatric disorders
- Psychiatric disorder in the family history
- Peripheral and central nervous system disorder
- Metabolic diseases
- Endocrine diseases
- Muscular or dermatological diseases
- Haematological diseases
Further exclusion criteria were:
- Sleeping disorder
- Shift work
- Transmerdian flight in the last three months
- Malignant diseases
- Acute infective diseases
- Clinically relevant allergies
- Lack of compliance to study procedures
- Participation in another clinical study within the last 4 month
Locations and Contacts
Max Planck Institute of Psychiatry, Munich, Bavaria 80804, Germany
Dzaja A, Arber S, Hislop J, Kerkhofs M, Kopp C, Pollmacher T, Polo-Kantola P, Skene DJ, Stenuit P, Tobler I, Porkka-Heiskanen T. Women's sleep in health and disease. J Psychiatr Res. 2005 Jan;39(1):55-76.
Ehlers CL, Kupfer DJ. Slow-wave sleep: do young adult men and women age differently? J Sleep Res. 1997 Sep;6(3):211-5.
Friess E, Tagaya H, Trachsel L, Holsboer F, Rupprecht R. Progesterone-induced changes in sleep in male subjects. American Journal of Physiology: Endocrinology & Metabolism 1997; 272:E885-E891.
Grön G, Friess E, Herpers M, Rupprecht R. Assessment of cognitive performance after progesterone administration in healthy male volunteers. Biol Psychiatry 1997; 35:147-151.
Heuser G, Ling GM, Kluver M. Sleep induction by progesterone in the pre-optic area in cats. Electroencephalography & Clinical Neurophysiology 1966; 22:122-127.
Lancel M, Faulhaber J, Schiffelholz T, Romeo E, Di Michele F, Holsboer F, Rupprecht R. Allopregnanolone affects sleep in a benzodiazepine-like fashion. Journal of Pharmacology & Experimental Therapeutics 1997; 282(3):1213-1218.
Montplaisir J, Lorrain J, Denesle R, Petit D. Sleep in menopause: differential effects of two forms of hormone replacement therapy. Menopause 2001;10-16.
Steiger A, Trachsel L, Guldner J, Hemmeter U, Rothe B, Rupprecht R, Vedder H, Holsboer F. Neurosteroid pregnenolone induces sleep-EEG changes in man compatible with inverse agonistic GABAA-receptor modulation. Brain Research 1993; 615:267-274.
Starting date: November 2003
Ending date: July 2004
Last updated: September 14, 2007