Relugolix and Cholesterol Levels
Direct Answer
Yes, relugolix can affect cholesterol levels, specifically causing increases in triglycerides (TG) based on preclinical safety data. 1
Evidence of Lipid Effects
Preclinical studies in male Beagle dogs demonstrated statistically significant increases in triglyceride (TG) levels following relugolix administration, suggesting potential concerns regarding lipid metabolism abnormalities. 1 This represents the most direct evidence available linking relugolix to cholesterol/lipid parameter changes.
Mechanism and Clinical Context
Relugolix is an oral GnRH receptor antagonist that suppresses testosterone production in men and estradiol/progesterone production in women by competitively binding to GnRH receptors and preventing FSH and LH release. 2, 3
The drug achieves rapid and sustained castration levels of sex hormones, which can have downstream metabolic effects including alterations in lipid metabolism. 3, 4
Sex hormone suppression is known to affect lipid profiles, as testosterone and estrogen play roles in lipid metabolism regulation. 1
Clinical Monitoring Recommendations
Given the preclinical evidence of triglyceride elevation, baseline lipid panels should be obtained before initiating relugolix therapy, with periodic monitoring during treatment, particularly in patients with preexisting dyslipidemia or cardiovascular risk factors. 1
This is especially important since cardiovascular safety is a major concern in patients receiving androgen deprivation therapy for prostate cancer. 3, 4
The HERO trial demonstrated improved cardiovascular safety compared to LHRH agonists, but lipid-specific outcomes were not the primary focus of cardiovascular event analysis. 3, 4
Management Approach
If triglyceride elevations occur during relugolix therapy, standard lipid-lowering therapies can be initiated according to established guidelines for dyslipidemia management. 5
Ezetimibe (18% LDL-C reduction) or PCSK9 inhibitors can be considered for patients requiring lipid management while on relugolix. 5
Statins remain the first-line therapy for most patients with elevated cholesterol and can be safely used in combination with relugolix, as no significant drug-drug interactions have been identified between relugolix and lipid-lowering agents. 5, 6
Important Caveats
The lipid effects of relugolix have primarily been documented in preclinical animal studies; large-scale human data specifically examining lipid parameters as a primary outcome are limited. 1
The clinical significance of triglyceride elevations observed in animal models requires validation through larger human studies and longer-term follow-up data. 1
Patients with preexisting cardiovascular disease or metabolic syndrome warrant closer lipid monitoring given their baseline elevated risk. 3, 7