Postmenopausal Women,Treatment of Sleep Apnea and Co-morbidities

Study Overview
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Brief Summary
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The purposes of this study are to evaluate the degree and duration of medroxyprogesterone acetate effect as well as tolerability in postmenopausal women with nasal continuous positive airway pressure (CPAP) treated sleep apnea and to compare the effects with nasal CPAP.

Detailed Description
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Sleep apnea is a common condition affecting both genders. It is affecting more often males than females but after menopause the prevalence of sleep apnea increases in females compared to premenopausal ones and is nearly as high as in males. Continuous positive airway pressure (CPAP) device is the best and standard treatment for the disease. All patients are not adherent to the CPAP treatment and new methods are needed. At the moment no medication is available for sleep apnea. Progesterone hormone is a known respiratory stimulant. Menopause alters significantly women's hormonal balance, for example progesterone levels decrease. Progesterone has been investigated in the treatment of sleep apnea but mostly with male and small populations and the results have been conflicting. Progestins (like medroxyprogesterone acetate, MPA) are female hormones and act through progesterone receptors, so it would be likely women to have less side effects from MPA therapy than men. The purposes of the present study are to evaluate the degree and duration of MPA effect as well as tolerability in postmenopausal women with nasal CPAP treated sleep apnea and to compare the effects with nasal CPAP. The study is a placebo-controlled double-blind parallel group trial. We included 34 postmenopausal women (17 in placebo and 17 in MPA group) who had been treated for their sleep apnea with CPAP for 1 to 8 years. The trial included measurements at baseline with CPAP, after 14 days of placebo or MPA (60 mg daily) and after three-week washout. The patients discontinued their CPAP one week after the baseline measurements, when they went on with medication. The patients were allowed to continue additional two cycles of MPA treatment before continuing their normal CPAP treatment if they wanted to. Those who continued the additional MPA cycles had the same measurements as in visit 3. The measurements included questionnaires about their symptoms and possible adverse events of MPA, Visual analog scale (VAS) questionnaire with 14 items of sleep quality, Epworth Sleepiness Scale (ESS) and the quality of life questionnaire. Laboratory assays included blood hemoglobin concentration, hematocrit and WBC count, serum creatinine, alanine aminotransferase, total cholesterol, and triglycerides, high-density lipoprotein, estradiol, FSH and thyroid-stimulating hormone and serum MPA concentrations. Overnight polygraphic sleep studies included simultaneous recordings of electroencephalogram (EEG), electro-oculogram (EOG), chin electromyogram (EMG), and electrocardiogram (ECG). Respiration was monitored with a finger probe pulse oximeter (Ohmeda Biox 3700 Pulse Oximeter, BOC Health Care, USA), side-stream capnograph (Datex Normocap® CO2 & O2 Monitor, Instrumentarium, Finland) and the static-charge-sensitive bed (SCSB). During the first visit's CPAP study, Autoset was used in a treatment mode. In the morning after sleep study, subjects completed a questionnaire inquiring their subjective sleep quality during the study night.

Official Title
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Postmenopausal Women,Treatment of Sleep Apnea and Co-morbidities

Conditions
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Sleep Apnea

Intervention / Treatment
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* Drug: medroxyprogesterone acetate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: postmenopausal female regular controls of CPAP treatment in pulmonary clinic and regular use of CPAP device Exclusion Criteria: severe or unstable chronic illnesses heavy current smoking (over 10 cigarettes per day) medication which effects on the central nervous system contraindications to progesterone therapy and current participation in any other clinical study

Ages Eligible for Study
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Minimum Age: 42 Years
Maximum Age: 77 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: medroxyprogesterone acetate<br> | Drug: medroxyprogesterone acetate<br>* MPA hormone therapy 30mg two hours before bedtime and 30mg right before going to bed every night for two weeks period<br>|
| Placebo Comparator: Placebo<br>Placebo pills taken in the same way as the active comparator | Drug: Placebo<br>* Placebo pills were taken in same way as active comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| polysomnography measures of sleep apnea and sleep | Sleep stages, apnea-hypopnea index, overnight oxygen saturation values and capnograph values. | first visit, after 14 days of MPA/placebo use and after 3 weeks washout period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| subjective questionnaires | Questionnaires about subjects' symptoms and possible adverse events of MPA, Visual analog scale (VAS) questionnaire with 14 items of sleep quality, Epworth Sleepiness Scale (ESS) and the quality of life questionnaire | first visit, after 14 days of MPA/placebo use and after 3 weeks washout period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sleep apnea, women, postmenopause, hormone treatment