Medroxyprogesterone improves nocturnal breathing in postmenopausal women with chronic obstructive pulmonary disease

Abstract

Background: Progestins as respiratory stimulants in chronic obstructive pulmonary disease (COPD) have been investigated in males and during wakefulness. However, sleep and gender may influence therapeutic responses. We investigated the effects of a 2-week medroxyprogesterone acetate (MPA) therapy on sleep and nocturnal breathing in postmenopausal women.

Methods: A single-blind placebo-controlled trial was performed in 15 postmenopausal women with moderate to severe COPD. A 12-week trial included 2-week treatment periods with placebo and MPA (60 mg/d/14 days). All patients underwent a polysomnography with monitoring of SaO2 and transcutaneous PCO2 (tcCO2) at baseline, with placebo, with medroxyprogesterone acetate (MPA 60 mg/d/14 days), and three and six weeks after cessation of MPA.

Results: Thirteen patients completed the trial. At baseline, the average +/- SD of SaO2 mean was 90.6 +/- 3.2 % and the median of SaO2 nadir 84.8 % (interquartile range, IQR 6.1). MPA improved them by 1.7 +/- 1.6 %-units (95 % confidence interval (CI) 0.56, 2.8) and by 3.9 %-units (IQR 4.9; 95% CI 0.24, 10.2), respectively. The average of tcCO2 median was 6.0 +/- 0.9 kPa and decreased with MPA by 0.9 +/- 0.5 kPa (95% CI -1.3, -0.54). MPA improved SaO2 nadir and tcCO2 median also during REM sleep. Three weeks after cessation of MPA, the SaO2 mean remained 1.4 +/- 1.8 %-units higher than at baseline, the difference being not significant (95% CI -0.03, 2.8). SaO2 nadir was 2.7 %-units (IQR 4.9; 95% CI 0.06, 18.7) higher than at baseline. Increases in SaO2 mean and SaO2 nadir during sleep with MPA were inversely associated with baseline SaO2 mean (r = -0.70, p = 0.032) and baseline SaO2 nadir (r = -0.77, p = 0.008), respectively. Treatment response in SaO2 mean, SaO2 nadir and tcCO2 levels did not associate with pack-years smoked, age, BMI, spirometric results or sleep variables.

Conclusion: MPA-induced respiratory improvement in postmenopausal women seems to be consistent and prolonged. The improvement was greater in patients with lower baseline SaO2 values. Long-term studies in females are warranted.

Figure 1

Study design. Both placebo (PL) and medroxyprogesterone acetate (MPA) periods lasted for 14 days. Arrows indicate the timing of sleep studies, dashed line the timing and duration of the placebo period and solid line thetiming and duration of the MPA period.

Figure 2

Changes of SaO₂ nadir, SaO₂ mean, and tcCO₂ median during sleep with MPA and after a 3- and a 6-week follow-up. Changes are absolute percentage values. MPA = medroxyprogesterone acetate, SaO₂ = arterial oxygen saturation, tcCO₂ = transcutaneous partial carbon dioxide tension. The error bars of SaO₂ mean and tcCO₂ median represent standard deviation and those of SaO2 nadir represent interquartile ranges. P-values are corrected with Bonferroni method. ** = p < 0.01, * = p < 0.05.

Figure 3

Changes of SaO₂ nadir during different sleep stages with MPA and after a 3- and a 6-week follow-up. Changes are absolute percentage values. MPA = medroxyprogesterone acetate, SaO₂ = arterial oxygen saturation. The error bars of SaO₂ nadir represent interquartile ranges. P-values are corrected with Bonferroni method. ** = p < 0.01.

Figure 4

Changes of SaO₂ mean during different sleep stages with MPA and after a 3- and a 6-week follow-up. Changes are absolute percentage values. MPA = medroxyprogesterone acetate, SaO₂ = arterial oxygen saturation. The error bars of SaO₂ mean represent standard deviation. P-values are corrected with Bonferroni method.

Figure 5

Changes of the mean of tcCO₂ median during different sleep stages with MPA and after a 3- and a 6-week follow-up. Changes are absolute percentage values. MPA = medroxyprogesterone acetate, tcCO₂ = transcutaneous partial carbon dioxide tension. The error bars of tcCO₂ represent standard deviation. P-values are corrected with Bonferroni method. ** = p < 0.01, * = p < 0.05.