Hormonal Aspects of OSA
Dr A K Simonds
Royal Brompton Hospital
Hormones are chemical substances produced by glands in the body with the purpose of regulating cellular activity. A correct hormonal balance is essential to life, as shown by various diseases which are caused by underproduction or overproduction of hormones.
The relationship between hormone levels and sleep is complex and not yet fully understood. However, it is clear that hormonal influences play an important part in breathing disorders during sleep. Overall, four main observations are relevant and these can be summarised as follows:
- Characteristic trends in hormone secretion are seen during sleep. These may be disrupted by sleep apnoea producing adverse effects.
- Obstructive sleep apnoea (OSA) is more common in males than females, and prevalence may increase following the menopause in females. This highlights the significant role of the sex hormones testosterone, oestrogen and progesterone in the cause of OSA.
- Medical conditions such as hypothyroidism (underactive thyroid gland) and acromegaly (abnormal growth hormone secretion from the pituitary gland) can predispose individuals to OSA. Care should always be taken to exclude these conditions, as they require specific treatment.
- The above information suggests the interesting possibility that hormonal manipulation may have a role in the treatment of OSA.
It is helpful to explore the evidence behind these observations in detail:
Levels of hormones from the pituitary gland in the brain show unique secretory profiles which are linked to sleep pattern. In particular growth hormone (vital in adults for protein synthesis and tissue repair, as well as for growth in children) and prolactin both show peaks at the onset of sleep. Testosterone secretion rises as sleep begins and continues to increase throughout the night. Most hormone peaks occur in non rapid eye movement sleep. Cortisol (the body's natural steroid) production is also tied to the 24 hour body clock, but in the short term cortisol profile is maintained if sleep pattern is altered (e.g., by shift work).
Obstructive sleep apnoea produces sleep fragmentation and may also produce falls in arterial oxygen level (hypoxia). Both sleep fragmentation and hypoxia cause abnormalities in hormone production, in particular a reduction in growth hormone and sex hormones, and a rise in the adrenaline level. As a result children with OSA may fail to grow normally. In adults, low sex hormones during sleep can produce diminished libido and impotence.
The effects of hypoxia on hormone profile have been confirmed in studies of patients with chronic bronchitis, in whom the arterial oxygen level is low, but sleep quality reasonably preserved. It is clear that there is likely to be an important interaction between sleep fragmentation and hypoxia in sleep apnoea patients.
A further compounding factor is obesity. In the vast majority of obese individuals there is no 'glandular' cause for weight gain - the problem is due to overeating/lack of exercise. However, obesity in its own right leads to a number of secondary changes in hormone function.
Male predominance of OSA
A striking and consistent observation in prevalence studies of OSA is the strong male preponderance. Early estimates of a male to female ratio of 10:1 are now seen to be exaggerated, but in a large USA cohort of middle aged patients 4% of men and 2% of women had OSA associated with daytime somnolence.
It has been suggested that oestrogen and progestogen levels in premenopausal women protect them from OSA, and that females after the menopause are at greater risk. Interestingly in premenopausal females with OSA, menstrual irregularities are common. This feature is seen in women who are of normal weight as well as in obese subjects. Several studies have shown higher levels of androgen (male hormone) in females with OSA, but care is needed in the interpretation of the results as obese females have higher androgen levels than non-obese patients.
Associated medical conditions
Hypothyroidism and acromegaly are well known disorders in which OSA is relatively common. Hypothyroidism is characterised by a low level of thyroid hormone which may cause abnormal soft tissue thickening (myxoedema) in the upper airway, a reduction in breathing control and weakness of the muscles that determine upper airway patency.
Some features of hypothyroidism (fatigue, general slowing down) are similar to symptoms of OSA, so it is crucial that the possible coexistence of the two conditions is considered. Although treatment with thyroid replacement therapy will normalise hormone levels and reduce symptoms, OSA often persists and requires continued therapy.
At least 20% of acromegaly patients have OSA, but it is important to note that in this group obesity is not a predisposing factor as would be expected in the general population. There is little correlation between the severity of OSA and growth hormone levels, but central apnoea appears more common with high circulating growth hormone levels. As with hypothyroidism, treatment for acromegaly may improve OSA, but specific measures such as CPAP may still be required.
Considering that OSA is commoner in males and there is evidence that testosterone therapy may worsen apnoeas, it is logical to assess the effects of testosterone inhibition as a therapy for OSA. The drug flutamide which blocks testosterone action has been used in a small study of males with OSA. Disappointingly this produced no change in breathing disorders during sleep.
Hormone replacement therapy (HRT) has been tried in postmenopausal females with OSA and snoring. This may be helpful in mild OSA, but has not been successful in reversing more severe cases. However there are many other good reasons for prescribing HRT in the menopausal period including reduction in cardiovascular risk, so that a trial of HRT is usually worthwhile.
Taking into account the results of the above studies it has been argued that one of the main reasons for the difference in OSA between the sexes, is the variation in upper airway configuration and function in males and females. Upper airway development is governed by a number of hormonal and genetic influences, so that further work in this area will be interesting.
Continuous positive airway pressure (CPAP) is, of course, the gold standard treatment for OSA. The good news here is that effective CPAP helps improve hormone profiles during sleep and is usually associated with an improvement in libido. It is also possible that restoration of normal growth hormone levels will facilitate fat breakdown and therefore help weight reduction in obese individuals.
What can we conclude?
Hormonal derangements lead to an increased incidence of OSA, while abnormalities of breathing during sleep lead to altered hormone profiles in their own right. These findings provide a fertile area for research which is not only likely to improve our understanding of the causes of OSA, but may lead to advances in therapy.