How does obstructive sleep apnea affect testosterone levels in men?

How Sleep Apnea Affects Testosterone in Men

Obstructive sleep apnea (OSA) causes decreased testosterone levels in men through central suppression of the pituitary-gonadal axis, driven primarily by sleep fragmentation and hypoxia, though obesity is the dominant confounder that explains most of the testosterone reduction seen in clinical practice. 1, 2

Mechanisms of Testosterone Suppression

OSA reduces testosterone through multiple pathways that affect the hypothalamic-pituitary-gonadal axis:

Primary Mechanisms

• Sleep fragmentation is the most significant factor causing central suppression of nocturnal testosterone secretion, independent of obesity and age 2, 3
• Nocturnal hypoxemia contributes to reduced testosterone production, though to a lesser degree than sleep disruption 2, 3
• Reduced LH secretion occurs in OSA patients, with significantly lower mean levels and area under the curve compared to controls (24.9 vs. 43.4 IU/L·h), indicating pituitary dysfunction 2
• Decreased testosterone pulsatility manifests as fewer testosterone pulses with longer interpulse duration in OSA patients compared to healthy controls 3

The Obesity Confounding Effect

Critical caveat: The relationship between OSA and low testosterone is heavily confounded by obesity, which is itself a major cause of hypogonadism 1, 4:

• When controlling for BMI in multivariate analysis, the independent effect of OSA on testosterone becomes minimal or disappears entirely 1
• Obesity is present in approximately 70% of OSA patients and independently suppresses testosterone through increased aromatase activity in adipose tissue 5
• Men with altered testosterone levels have significantly higher BMI compared to those with normal levels, even within OSA populations 4

Clinical Manifestations

Hormonal Changes

• Nocturnal testosterone suppression shows mean testosterone levels of 67.2 nmol/L·h in OSA patients versus 113.3 nmol/L·h in controls during sleep 2
• Morning testosterone levels may fall into the hypogonadal range (40% of OSA patients in one study had morning levels below normal) 2
• LH levels are concordantly reduced, confirming central (hypothalamic-pituitary) rather than primary testicular dysfunction 2, 3

Severity Correlation

• There is a negative correlation between respiratory distress index (RDI) and testosterone secretion after controlling for BMI, indicating that OSA severity independently affects hormone levels 2
• The degree of nocturnal hypoxemia (time with O₂ saturation <90%) correlates with testosterone suppression, though less strongly than sleep fragmentation 6, 2

Effect of OSA Treatment on Testosterone

CPAP Therapy Benefits

• Chronic CPAP treatment partially corrects testosterone suppression, with increases in both mean and integrated (AUC) values of testosterone and LH after 9 months of therapy 6
• CPAP normalizes respiratory parameters (RDI and oxygen saturation) and improves pituitary-gonadal axis function 6
• However, the magnitude of testosterone increase with CPAP is limited, suggesting that obesity and other factors remain dominant 1

Weight Loss vs. CPAP

• Weight loss has a graded, more substantial effect on testosterone levels compared to CPAP therapy alone 1
• This finding reinforces that obesity management is the primary intervention for improving testosterone in men with OSA and hypogonadism 1

Bidirectional Relationship: Testosterone Worsens OSA

Important clinical pitfall: While OSA lowers testosterone, testosterone replacement therapy can worsen OSA 5, 7:

• Testosterone administration increases the apnea-hypopnea index (AHI) and prolongs hypoxemia time in men without prior sleep apnea history 5
• Testosterone increases time spent with oxygen saturation <90%, worsening sleep-disordered breathing 5
• This detrimental effect is consistent with the higher OSA prevalence in men versus women 5

Clinical Implications for Testosterone Therapy

• Screen for OSA before initiating testosterone replacement in men with risk factors (obesity, snoring, witnessed apneas, hypertension, excessive daytime sleepiness) 7
• Polysomnography should be performed before starting testosterone therapy in high-risk patients 7
• CPAP therapy should be initiated before or concurrently with testosterone replacement in men with diagnosed OSA 7
• Untreated severe OSA is no longer considered an absolute contraindication to testosterone therapy, but OSA must be adequately treated first 7

Practical Clinical Algorithm

Step 1: Assess for Hypogonadism

• Measure morning total testosterone using an accurate assay in men with symptoms (decreased libido, erectile dysfunction, fatigue) 5
• Check sex hormone-binding globulin (SHBG) if total testosterone is borderline, as SHBG is often low in diabetes and obesity 5
• Measure LH and FSH to distinguish primary from secondary hypogonadism 5

Step 2: Screen for OSA

• Evaluate for OSA symptoms: snoring, witnessed apneas, excessive daytime sleepiness, morning headaches 5, 7
• Assess risk factors: obesity (especially central), hypertension, neck circumference >17 inches 5
• Order polysomnography if symptoms or risk factors are present 7

Step 3: Prioritize Interventions

• Weight loss is the primary intervention for men with obesity, low testosterone, and OSA, as it addresses both conditions most effectively 1
• Initiate CPAP therapy for diagnosed OSA before considering testosterone replacement 7, 6
• Monitor testosterone levels after 9 months of CPAP treatment, as partial correction may occur 6

Step 4: Consider Testosterone Replacement

• Testosterone therapy may be initiated in men with adequately treated OSA (compliant with CPAP) and persistent symptomatic hypogonadism 7
• Avoid testosterone replacement in untreated OSA due to risk of worsening sleep-disordered breathing and cardiovascular complications 7
• Re-evaluate sleep quality after starting testosterone, as worsening OSA may occur even in treated patients 7

Key Clinical Pitfalls to Avoid

• Do not attribute low testosterone solely to OSA without addressing obesity, which is the dominant factor 1
• Do not start testosterone therapy without OSA screening in high-risk patients, as testosterone worsens sleep apnea 7
• Do not overlook weight management, as it provides greater testosterone improvement than CPAP alone 1
• Do not assume CPAP will fully normalize testosterone—it provides partial correction at best 6, 1
• Do not ignore cardiovascular risk—the combination of OSA, low testosterone, and testosterone therapy increases cardiovascular morbidity 7