From the Research
There is no established direct relationship between testosterone levels and malignant hyperthermia, and testosterone therapy can be administered safely in patients with a history of malignant hyperthermia or family history of this condition, as it does not act as a trigger for malignant hyperthermia episodes. Malignant hyperthermia is a rare, life-threatening genetic disorder triggered primarily by certain anesthetic agents, such as halogenated anesthetics or succinylcholine, and not by testosterone levels 1. The genetic predisposition to malignant hyperthermia involves mutations in the ryanodine receptor gene (RYR1) or less commonly the CACNA1S gene, which regulate calcium release in skeletal muscle. These mutations cause abnormal calcium regulation when exposed to triggering agents, leading to hypermetabolism, muscle rigidity, and hyperthermia. Testosterone, which affects the endocrine system primarily through androgen receptors, works through different physiological pathways and does not interact with the calcium channel mechanisms involved in malignant hyperthermia.
Some studies have investigated the use of dantrolene, a therapeutic agent for malignant hyperthermia, in various conditions, including catecholaminergic polymorphic ventricular tachycardia 2 and heart failure 3. However, these studies do not provide evidence for a direct relationship between testosterone levels and malignant hyperthermia.
In terms of testosterone replacement therapy, it is used to improve symptoms and signs of testosterone deficiency, including decreased libido, erectile dysfunction, and loss of muscle and bone mass 4. While there are benefits to testosterone replacement therapy, there are also potential risks, and clinicians must consider the unique characteristics of each patient and make the necessary adjustments in the management of late-onset hypogonadism to provide the safest and most beneficial results.
Patients with malignant hyperthermia should always inform all healthcare providers about their condition, carry medical alert identification, and ensure proper anesthetic protocols are followed during surgical procedures, but testosterone therapy itself does not require special precautions related to malignant hyperthermia. The most recent and highest quality study on the topic of malignant hyperthermia and its treatment is from 2025, which reports a successful management of malignant hyperthermia without dantrolene 5. However, this study does not provide evidence for a direct relationship between testosterone levels and malignant hyperthermia.
In summary, testosterone therapy can be administered safely in patients with a history of malignant hyperthermia or family history of this condition, without requiring special precautions related to malignant hyperthermia, as the genetic predisposition to malignant hyperthermia involves mutations in the ryanodine receptor gene or less commonly the CACNA1S gene, and testosterone works through different physiological pathways that do not interact with the calcium channel mechanisms involved in malignant hyperthermia.