Sex Hormone in Males Linked to Slower Biological Aging in New Study

A person’s levels of sex hormones, like testosterone and estrogen, have impacts on characteristics ranging from “male menopause” to shopping habits. Now, new research shows these hormones also seem to have an impact on the aging process — particularly in men.

In a presentation on Monday at the Endocrine Society’s conference in New Orleans, the authors of a study published in Clinical Endocrinology show that sex hormone levels have powerful impacts on how quickly the body deteriorates due to age.

A well-studied branch of aging research focuses on telomeres, the tiny caps at the ends of chromosomes. They shorten over time, so their length is often used as a marker of “biological age” — or how well the body is holding up. This study, performed on 2,913 men, shows an association between sex hormone levels and telomere lengths normally associated with people 3.6 years younger. The relationship could potentially lead to hormone-based therapies for aging in the future

“This study is the largest to date, confirms our previous study, and extends its findings to older men,” lead study author Bu Yeap, Ph.D., a professor at Western Australia Medical School, tells Inverse, referring to his team’s previous work connecting the presence of certain sex hormones to telomere length. “Sex hormone exposure appears to be related to a lower biological age in men.”

In particular, the study focuses on a lesser-known but very important male sex hormone known as estradiol (the dominant form of estrogen). It’s usually associated with women but is naturally present to some degree in men, and it’s previously been linked to male sexual function.

In Yeap’s study, men who had estradiol levels that were one standard deviation above the average had telomere lengths associated with being 3.6 years younger than they actually were. The men involved with the study were 77 years old on average.

Seeking evidence that sex hormones are related to telomere length in general — that is, they are linked to both shortening and lengthening — Yeap and his team also looked at testosterone and SHBG (sex hormone binding globulin), a protein that binds to sex hormones. High levels of SHBG were associated with shorter telomeres, but testosterone was not associated with telomere length.

Though testosterone patterns were not the main focus of this study, Yeap points out that estradiol in men is manufactured from testosterone. And so, he says, investigating the relationship between both hormones will be crucial to understanding their effect on telomere length down the line.

“This is an observational study,” he says. “We would need to do a randomized, controlled trial of testosterone in men, measure how much is converted to estradiol, and see whether this treatment preserves telomere length.”

For now, Yeap’s study shows how different levels of sex hormones impact telomere length naturally. He’s studying this with the hope that scientists can someday use these patterns to figure out how to manipulate telomere length using hormones, thereby potentially lengthening a biological lifespan.

We already know that telomere length can be influenced by certain behaviors. For instance, endurance exercise lengthens them and stress shortens them. The question is whether estradiol is another intervention that could potentially help lengthen telomeres, too.

Given his team’s current results, Yeap says it’s still “too early to speculate about anti-aging treatments.” Though there are some crucial gaps that still need to be filled, the evidence for the connection between hormones, telomeres, and aging is getting stronger.

Partial Abstract:

Methods: We aimed to clarify associations of sex hormones with LTL in a cohort of 2,913 community-dwelling men aged 70-89 years. Early morning blood samples were assayed for T, DHT and E2 using mass spectrometry, and for sex hormone-binding globulin (SHBG) using immunoassay. LTL was measured using a multiplex quantitative PCR method and expressed as the amount of telomeric DNA relative to beta-globin, a single copy control gene (T/S ratio). Cross-sectional analyses utilised multivariable linear regression. Mean (±SD) age was 76.7±3.2 years. The average difference per decade of age was T -0.46 nmol/L, DHT -0.11 nmol/L, E2 -7.5 pmol/L, SHBG +10.2 nmol/L, and LTL (T/S ratio) -0.065. E2 correlated with T/S ratio (r=0.038, p=0.039).

Results: Results: After excluding highest and lowest 1% of values, the correlation between E2 and T/S ratio was largely unchanged (r=0.039, p=0.037). SHBG was inversely correlated with T/S ratio (r=-0.053, p=0.004), also unchanged in the trimmed analysis (r=-0.055, p=0.004.) After adjusting for age, BMI, cardiovascular disease, diabetes, alcohol, smoking, physical activity, lipids and hypertension, E2 remained associated with T/S ratio (per 1 SD increase E2: coefficient 0.011, p=0.043). When E2 and SHBG were simultaneously included in the multivariate model, E2 remained positively associated with T/S ratio (coefficient 0.014, p=0.014) and SHBG inversely associated (coefficient -0.013, p=0.037). The magnitude of increase in T/S ratio associated with a 1 SD higher plasma E2 concentration was comparable with having a BMI 3.6 kg/m2 lower, and two thirds that associated with being 3.6 years younger. T, DHT and LH were not associated with LTL in multivariate analyses.

Conclusions: To conclude, in older men, neither T nor DHT are associated with LTL while E2 is independently associated with LTL and SHBG is inversely associated. These findings associate activity of the gonadal axis with lower biological age in older men. However, causality cannot be inferred from an observational, cross-sectional study, thus additional research is necessary to determine whether sex hormone exposure modulates male biological aging.