Breathing During Sleep in Menopause: A Randomized, Controlled, Crossover Trial With Estrogen Therapy

OBJECTIVE To evaluate the prevalence of different types of nocturnal breathing abnormalities in postmenopausal women and the effect of estrogen replacement therapy (ERT) on nocturnal breathing. METHODS A prospective, randomized, placebo-controlled, double-blind, crossover study was completed by 62 of 71 recruited healthy women. The first 3-month treatment period with either estrogen or placebo was followed by placebo washout for a month and then by a second treatment period with crossover to either estrogen or placebo. On a night after each treatment period, sleep was monitored with polysomnography, and breathing was assessed with a static-charge-sensitive bed and oximeter. For the respiratory variables, a sample size of 48 subjects was sufficient to give statistical power of 85% with a significance level of P < .05. RESULTS The occurrence of obstructive sleep apnea in all women was low (1.6%), but partial upper airway obstruction, manifesting as an increased respiratory resistance pattern, was more common (17.7%). Estrogen replacement therapy decreased the occurrence (P = .047) and frequency (P = .049) of sleep apnea but had no effect on partial upper airway obstruction or arterial oxyhemoglobin saturation. CONCLUSION Partial upper airway obstruction is the most prevalent form of sleep-disordered breathing, occurring ten times more frequently than sleep apnea in postmenopausal women. Unopposed estrogen replacement therapy has only a minor effect on sleep apnea and has no effect on partial airway obstruction.

[1]  A. Porath,et al.  Sub-clinical worsening of bronchial asthma during estrogen replacement therapy in asthmatic post-menopausal women. , 1995, Maturitas.

[2]  M. Tafti,et al.  Why don't all heavy snorers have obstructive sleep apnea? , 1991, The American review of respiratory disease.

[3]  R. Heller,et al.  Coronary heart disease in relation to age, sex, and the menopause. , 1978, British medical journal.

[4]  L. Moore,et al.  Progestin and estrogen reduce sleep-disordered breathing in postmenopausal women. , 1989, Journal of applied physiology.

[5]  A J Block,et al.  Menopause, medroxyprogesterone and breathing during sleep. , 1981, The American journal of medicine.

[6]  M Partinen,et al.  Women and the obstructive sleep apnea syndrome. , 1988, Chest.

[7]  P. Polo-Kantola,et al.  When does estrogen replacement therapy improve sleep quality? , 1998, American journal of obstetrics and gynecology.

[8]  J. Dempsey,et al.  Ventilatory response to medroxyprogesterone acetate in normal subjects: time course and mechanism. , 1978, Journal of applied physiology: respiratory, environmental and exercise physiology.

[9]  O. Polo,et al.  Partial upper airway obstruction during sleep. Studies with the static charge-sensitive bed (SCSB). , 1992, Acta physiologica Scandinavica. Supplementum.

[10]  A. Lanthier,et al.  Sex steroids and 5-en-3 beta-hydroxysteroids in specific regions of the human brain and cranial nerves. , 1986, Journal of steroid biochemistry.

[11]  M Partinen,et al.  Daytime sleepiness and vascular morbidity at seven-year follow-up in obstructive sleep apnea patients. , 1990, Chest.

[12]  J. Y. Lee,et al.  Tissue distribution of estrogen receptors alpha (ER-alpha) and beta (ER-beta) mRNA in the midgestational human fetus. , 1997, The Journal of clinical endocrinology and metabolism.

[13]  S. Rooney,et al.  Stimulation of fetal lung surfactant production by administration of 17beta-estradiol to the maternal rabbit. , 1979, American journal of obstetrics and gynecology.

[14]  T. Gislason,et al.  Snoring, hypertension, and the sleep apnea syndrome. An epidemiologic survey of middle-aged women. , 1993, Chest.

[15]  T. Young,et al.  The occurrence of sleep-disordered breathing among middle-aged adults. , 1993, The New England journal of medicine.

[16]  S. Campbell,et al.  Pulsatility index in internal carotid artery in relation to transdermal oestradiol and time since menopause , 1991, The Lancet.

[17]  L. Moore,et al.  Progesterone receptors and ventilatory stimulation by progestin. , 1986, Journal of applied physiology.

[18]  W. Wiest,et al.  Progesterone "receptor" in rabbit uterus. I. Characterization and estradiol-17beta augmentation. , 1973, Endocrinology.

[19]  O. Polo,et al.  Detection of periodic leg movements with a static‐charge‐sensitive bed , 1996, Journal of sleep research.

[20]  D. Pfaff,et al.  Actions of estrogens and progestins on nerve cells. , 1983, Science.

[21]  B. Ettinger,et al.  Reduced Mortality Associated With Long‐Term Postmenopausal Estrogen Therapy , 1996, Obstetrics and gynecology.

[22]  P. Cistulli,et al.  Effect of short-term hormone replacement in the treatment of obstructive sleep apnoea in postmenopausal women. , 1994, Thorax.

[23]  L. Moore,et al.  Combined effects of female hormones and metabolic rate on ventilatory drives in women. , 1989, Journal of applied physiology.

[24]  A J Block,et al.  Sleep apnea, hypopnea and oxygen desaturation in normal subjects. A strong male predominance. , 1979, The New England journal of medicine.

[25]  P. Polo-Kantola,et al.  Respiratory insufficiency in postmenopausal women: sustained improvement of gas exchange with short-term medroxyprogesterone acetate. , 1999, Chest.

[26]  A. Peiris,et al.  Bronchospasm secondary to replacement estrogen therapy. , 1993, Chest.

[27]  J. Alihanka,et al.  A new method for long-term monitoring of the ballistocardiogram, heart rate, and respiration. , 1981, The American journal of physiology.

[28]  M. Kenward,et al.  Design and Analysis of Cross-Over Trials , 1989 .