Effect of medroxyprogesterone on inspiratory flow shapes during sleep in postmenopausal women
Introduction
Despite many efforts there are no established pharmacologic treatments available for sleep-disordered breathing. Several respiratory stimulants have been suggested (Hudgel and Thanakitcharu, 1998) but in general they have proved inefficient or side effects have limited their usage. Electrical stimulation of the diaphragm causes secondary upper airway obstruction if the upper airway dilator muscles are not synchronously activated during inspiration. Certain pharmacologic respiratory stimulants have been suspected to do the same, resulting in worsening rather than improvement of upper airway obstruction.
Progestins are female hormones that stimulate ventilation (Skatrud et al., 1978; Zwillich et al., 1978; Saaresranta et al., 1999). Medroxyprogesterone acetate (MPA) has been a disappointment as a treatment of sleep apnea in men. Although MPA could be more efficient and better tolerated in females, only two studies (Block et al., 1981; Saaresranta et al., 2001) have evaluated MPA alone and few studies in combination with estrogen in controlling sleep-disordered breathing in postmenopausal women (Pickett et al., 1989; Cistulli et al., 1994; Keefe et al., 1999). During luteal phase of the menstrual cycle or on MPA therapy the upper airway muscle activity increases but the airway resistance does not change while awake (Popovic and White, 1998). The effect of MPA on the flow dynamics in the upper airway has not been studied during sleep.
Analysis of the nasal flow profile recorded with nasal prongs is a non-invasive method to monitor upper airway behavior during sleep. Flow profile analysis is particularly useful in studying partial upper airway obstruction where increase in the upper airway dilator muscle activity is still transformed into decreased collapsibility of the airway (Aittokallio et al., 1999, Aittokallio et al., 2001). Partial collapse of the upper airway during inspiration is identified as a plateau flow on the inspiratory flow signal (Condos et al., 1994; Montserrat et al., 1995; Hosselet et al., 1998). Nasal flow profile has been successfully applied to feed-back control the appropriate CPAP pressure during treatment of sleep apnea (Berthon-Jones, 1993). To evaluate whether MPA therapy improves or worsens the upper airway flow dynamics in women we analyzed the inspiratory flow shape changes on MPA.
Section snippets
Subjects
Initially, 71 healthy previously hysterectomized postmenopausal women were enrolled in the study evaluating the effect of short-term estrogen replacement therapy on sleep (Polo-Kantola et al., 1999). They were recruited from the city of Turku and the neighbourhood through announcements in local newspapers. Sixty-three out of 71 subjects completed the trial with two full polygraphic sleep recordings on and off estrogen replacement therapy (Polo-Kantola et al., 1999). Eleven out of the remaining
Results
All patients had normal flow-volume spirometry curves. Two of ten patients had marked sinus bradycardia (<50 BPM) without any other abnormal findings in their ECG. Eight of ten patients completed the study. The total number of respiratory cycles analyzed was 119 769, of which 94 417 in patients (51 054 or 54.1% during treatment nights) and 25 352 in controls. The mean proportion of wakefulness of the total recording time did not differ between controls (6.5%, range 1.0–14.6%) and patients at
Discussion
Our study shows that MPA 60 mg daily for 14 days significantly alters the inspiratory waveforms during sleep. Because MPA is a respiratory stimulant, increasing respiratory drive with MPA could lead to increased flow limitation and collapsibility in the upper airway if the upper airway dilators do not respond appropriately. MPA shortened inspiration, prolonged expiration, and tended to increase the maximum inspiratory slope during sleep. MPA decreased flow shape classes 5, 6 and 7, and
Acknowledgements
This work was supported by grants from The Finnish Anti-Tuberculosis Association Foundation, Finnish Sleep Research Society, The Research Foundation for Respiratory Diseases, The Väinö and Laina Kivi Foundation and The Turku University Foundation. Dr. Polo was supported by Paulo Foundation. MPA assessments were done and medication supplied by the drug company Orion Pharma, Espoo, Finland. The authors also thank Esa Wallius, BSc, for statistical assistance.
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