Low Testosterone Levels Linked to Chromosome Damage in Men With IPF

The protective tips of chromosomes, called telomeres, are shorter in men with idiopathic pulmonary fibrosis (IPF) than age-matched peers, and these changes seem to be linked to lower blood levels of the male hormone testosterone, a study reported.

Further research is needed to determine if hormonal treatment might slow telomere loss, which increases the risk of age-related diseases like IPF, in male patients. 

The study, “Relation between sex hormones and leucocyte telomere length in men with idiopathic pulmonary fibrosis,” was published in the journal Respirology. 

Telomeres are structures made of DNA and protein located at the ends of chromosomes. They protect the genome from degradation, playing a vital role in preserving genetic information. 

Each time a cell divides, a small portion of telomeric DNA is lost. For this reason, telomere length can serve as a biological clock to determine the lifespan of a cell, or organism. 

Studies have suggested that people with IPF have shorter telomeres in leukocytes — white blood cells of the immune system — than do healthy individuals. Genetic mutations that impact telomere length have been identified in some IPF patients, but the mutations found in some do not fully explain the short leucocyte telomere length (LTL) seen in others. 

Considerable evidence suggests that sex hormones regulate an enzyme, called telomerase, that maintains telomere length. Blood levels of a precursor of the male sex hormone testosterone, known as dehydroepiandrosterone (DHEA), are also significantly lower in male IPF patients. 

However, studies into sex hormones and their associations with leucocyte telomere length in IPF is limited. 

Researchers at Peking Union Medical College in China explored a possible association between sex hormones and leucocyte telomere length in men with IPF, and whether they interact with genes essential for maintaining telomere length. 

A total of 101 male patients, with an average age of about 63, were selected for the study. For controls, 51 healthy subjects matched in age and smoking status were also included. 

Blood samples were collected from all participants. The sex hormones testosterone and DHEA were measured along with two metabolites of testosterone, dihydrotestosterone (DHT), and estradiol (E2). 

Male IPF patients had significantly lower testosterone and DHT levels in their blood compared with controls. The levels of DHEA and E2 were generally lower in the IPF group, but this difference was not statistically significant.

DNA was then extracted from leukocytes, and the lengths of telomeres were measured. Patients had significantly shorter telomere length than did healthy subjects. 

DNA sequencing of telomerase-related genes associated with maintaining telomere length found mutations in 11 of the 101 patients (10.9%), and none of the controls. 

An initial analysis accounting for patients’ age (a modifier of telomere length) found that higher blood levels of testosterone and DHT were associated with longer telomeres, while other sex hormones were not. But after accounting for mutation status in telomerase-related genes in addition to age, only testosterone remained significantly linked with leucocyte telomere length.

No evidence supported the association between testosterone and leucocyte telomere length being caused by mutations in telomerase-related genes. 

“These findings imply that in addition to rare variants in telomerase complex genes, lower [testosterone] might be a potential factor accounting for shorter LTL in male IPF patients,” the researchers wrote.

Finally, the team investigated  if an association between male sex hormones and single nucleotide polymorphisms (SNPs) in genes involved in male hormone synthesis and metabolism existed.

SNPs are the most common type of genetic variation and happen when a single nucleotide in the sequence of a gene is replaced by a different nucleotide . Despite finding one SNP common to people in Eastern Asia, none of the identified 13 SNPs was significantly associated with testosterone levels in the blood.

“Our study suggests that lower level of [testosterone] might play a role in the shorter LTL in male IPF patients apart from rare variants in telomerase‐related genes,” the investigators wrote. 

“Future research is needed to examine whether hormonal interventions might retard telomere loss in male IPF patients and whether such retardation is associated with clinically important outcomes,” they concluded.