Compensated Hypogonadism Identified in Males with Cluster Headache: A Prospective Case-Controlled Study

Area of Science:

• Neurology
• Endocrinology
• Genetics

Background:

• Cluster headache exhibits a significant male predominance, suggesting a potential role for androgens in its pathophysiology.
• Previous research has not definitively established whether androgen levels are altered in individuals with cluster headache.

Purpose of the Study:

• To investigate potential alterations in androgen levels in male patients with cluster headache.
• To explore the relationship between cluster headache and testosterone concentrations, including genetic factors.

Main Methods:

• A prospective, case-controlled study involving 180 adult males: 60 with episodic cluster headache, 60 with chronic cluster headache, and 60 healthy controls.
• Sera were analyzed for testosterone, luteinizing hormone (LH), and sex hormone-binding globulin; calculated free testosterone (fT) using the Vermeulen equation.
• Genetic analysis was performed to identify shared risk variants between cluster headache and testosterone concentrations.

Main Results:

• Patients with chronic and episodic cluster headache exhibited significantly reduced free testosterone/LH ratios compared to controls, even after adjusting for confounding factors.
• Androgen concentrations did not vary between cluster headache bouts and remission periods.
• A shared genetic risk allele (rs112572874) within the MAPT gene was identified, potentially linking fT and cluster headache.

Conclusions:

• The male endocrine system in cluster headache patients displays a state of compensated hypogonadism, independent of sleep or acute medication use.
• The observed hormonal alterations and shared genetic risk allele suggest a potential pathophysiological connection between cluster headache and free testosterone levels.