Adrenoleukodystrophy (ALD)
https://www.sciencedirect.com/science/article/pii/S0003426625007838
This study examines how the rare genetic disorder X‑linked adrenoleukodystrophy (ALD) may affect male hormone production, specifically the function of the testes and hormonal control of male characteristics, known as hypogonadism. ALD is caused by mutations in the gene ABCD1, which disrupts the body’s ability to break down very-long-chain fatty acids (VLCFAs). These fatty acids accumulate in several organs, including the adrenal glands, nervous system and testes. The researchers focused on adult males with ALD and assessed whether they develop low testosterone or other hormone system abnormalities. They found that men with ALD are at higher risk than the general population for two kinds of hormonal problems: central hypogonadism and compensated primary hypogonadism. This means that while some men may still have normal testosterone levels, their hormone signalling is abnormal, and the testes are working harder than normal. Out of 56 adult males with X-linked ALD, 7 men (13%) had central hypogonadism. Among the subset of adults with normal total testosterone in retrospective testing (49 men), 5 (10%) displayed elevated luteinising hormone but normal testosterone, consistent with compensated primary testicular dysfunction. Erectile dysfunction was reported in 25 of the adult men who had normal testosterone levels, representing 51% of that subgroup. Adolescents and infants showed no evidence of testicular dysfunction, with normal anti-Müllerian hormone and inhibin levels. The findings suggest that hypogonadism in ALD may develop quietly, without obvious symptoms. Since hormone problems in ALD could affect fertility, libido, sexual health and general wellbeing, the researchers recommend that adult males with ALD should be monitored for gonadal/hormonal function as part of their routine care. Early recognition might allow timely hormone replacement or supportive intervention.