Graziani, A., Grande, G., & Ferlin, A. (2023). The complex relation between obstructive sleep apnoea syndrome, hypogonadism and testosterone replacement therapy. Frontiers in reproductive health. https://doi.org/10.3389/frph.2023.1219239
Graziani A, Grande G, Ferlin A. The complex relation between obstructive sleep apnoea syndrome, hypogonadism and testosterone replacement therapy. Frontiers in reproductive health. 2023. doi:10.3389/frph.2023.1219239
Graziani, Andrea, et al. "The complex relation between obstructive sleep apnoea syndrome, hypogonadism and testosterone replacement therapy." Frontiers in reproductive health, 2023.
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Sleep apnea is tied to low testosterone in men, and TRT data are thin
Men with obstructive sleep apnea tend to have lower testosterone than other men. This narrative review describes 7 clinical studies of testosterone replacement therapy (TRT) in these men. The studies were found in PubMed through December 2022. Four of the seven were randomized, placebo-controlled trials.
Key Findings
A meta-analysis of 24 case-control studies, with 1,268 male patients and 745 male controls, found significantly lower serum testosterone in men with obstructive sleep apnea syndrome (OSAS).
A second meta-analysis pooled 18 studies: 1,823 patients in all, split into 1,119 with OSAS and 704 controls. Lower testosterone tracked with OSAS, independent of BMI and age.
The review's PubMed search ended with 7 clinical studies of TRT that reported OSAS severity or sleep changes. Four of the seven were randomized placebo-controlled trials.
One retrospective study reported a 2-year risk of OSAS of 16.5% in the TRT group versus 12.7% in the control group.
In 67 obese men with severe OSAS, TRT might mildly worsen sleep-disordered breathing at 7 weeks. At 18 weeks, TRT did not alter ODI or O2 saturation compared with placebo.
Interpretation
This review summarizes the included studies without statistically pooling their results. Sleep apnea may lower testosterone by reducing LH, the pituitary signal that drives testosterone production. Low testosterone may in turn disturb sleep. The authors note that the TRT evidence is low quality. The findings support larger, controlled trials of TRT in men with obstructive sleep apnea.
RRM Context
The paper defines male hypogonadism as testes failing to make normal testosterone or sperm. OSAS may be an upstream cause of low testosterone, through lower LH, the pituitary signal that drives testosterone. Restorative reproductive medicine looks for causes like this in the man as well as the woman. The studies it reviews measured sleep and breathing outcomes.
Our editorial summary of this paper, not the article's abstract.
Abstract
Obstructive sleep apnoea syndrome (OSAS) is an under-recognized medical disease. The main risk factors for OSAS are male sex, older age, obesity, and metabolic syndrome, that are also associated with male hypogonadism (MH). Therefore, obesity has been classically identified as the most evident link between OSAS and MH. However, OSAS is per se linked to the development of MH by a combined effect of hypoxia, increased night-time awakenings, reduced sleep efficiency and fragmented sleep. Similarly, MH might represent a risk factor for OSAS, mainly related to sleep disturbances that are frequently associated with low testosterone. Data on testosterone replacement therapy (TRT) in patients with OSAS are limited. Nevertheless, TRT is generally contraindicated by guidelines in the presence of untreated or severe OSAS. TRT might in fact worse OSAS symptoms in different ways. Furthermore, OSAS has been proposed to be a risk factor for secondary polycythaemia and TRT might exacerbate polycythaemia. Therefore, TRT in hypogonadal men affected by untreated OSAS or severe OSAS should be considered with caution and in a personalised way. Nevertheless, the type and dosage of TRT should be considered, as short-term high-dose TRT might worsen OSAS, whereas long-term lower doses could eventually determine a clinical improvement of symptoms of OSAS. Here we reviewed the data on the association between OSAS, MH and TRT, including the opportunity of assessment of patients who develop signs and symptoms of OSAS during TRT by polysomnography.
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