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Higher testosterone level may confer ‘survival advantage’ in older women
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Sex steroid levels, particularly levels of estrone and testosterone, vary widely among older women, with higher levels of testosterone possibly indicating lower risk for disease, according to findings published in The Journal of Clinical Endocrinology & Metabolism.
“Estrone is the major source of circulating estrogen in older women and must be measured in any study seeking to determine the association between estrogens and health outcomes in older women,” Susan Davis, MBBS, FRACP, PhD, FAHMS, a professor in the School of Public Health and Preventive Medicine at Monash University, Australia, told Endocrine Today. “Consistent with previous studies, there are some older women with surprisingly high estrone levels, and this needs to be better understood. This study establishes that women beyond the age of 70 years have similar blood testosterone concentrations to those seen in healthy premenopausal women.”
In a cross-sectional study, Davis and colleagues analyzed sex steroid data from 6,392 women aged at least 70 years participating in ASPREE, a randomized controlled trial assessing the effect of low-dose aspirin vs. placebo on older adults without cardiovascular disease or impaired cognition at recruitment (98% European ancestry; mean BMI, 28 kg/m²). Researchers assessed sex steroids and sex hormone-binding globulin levels using liquid chromatography-tandem mass spectrometry.
“Until now, the available data have been limited by small sample sizes and/or the use of direct immunoassays, which lack sensitivity and specificity for the measurement of testosterone at the concentrations occurring in women, compared with the higher levels seen in men,” the researchers wrote.
A reference group to establish sex steroid, age-specific reference ranges (n = 5,326) excluded women using systemic or topical sex steroids, antiandrogen or glucocorticoid therapy or diabetes medications (mean age, 75 years).
Among the reference group population, median estrone level was 181.2 pmol/L, median testosterone level was 0.38 nmol/L, median dehydroepiandrosterone (DHEA) level was 2.6 nmol/L and median SHBG level was 41.6 nmol/L. Estradiol and dihydrotestosterone (DHT) levels were below the sensitivity of the assay method in 66.1% and 72.7% of women, respectively.
“There were a number of outliers for each steroid in each age group,” the researchers wrote. “We examined whether any of the measured variables (BMI, weight, waist circumference, smoking) and any reported medication use predicted extreme outliers for any of the steroids, but could not identify a common explanation for the outliers.”
Researchers found that women aged 80 to 84 years had estrone levels that were on average 9.2% higher vs. women aged 70 to 74 years (P = .001); women aged at least 85 years had estrone levels that were on average 11.7% higher vs. women aged 70 to 74 years (P = .01). When stratified by BMI, excess weight further influenced sex steroid levels, the researchers wrote, noting that older women with obesity had estrone levels that were on average 34.1% higher vs. women with normal weight (P < .001).
Similarly, women aged 80 to 84 years had testosterone levels that were on average 9.3% higher vs. women aged 70 to 74 years; that percentage rose to 11.3% for women aged at least 85 years (P = .02). Older women with overweight and obesity had higher testosterone levels vs. women with normal weight.
Researchers also found that, compared with women aged 70 to 74 years, SHBG levels were on average 5.6% higher among women aged 75 to 79 years, 13.6% higher in women aged 80 to 84 years and 22.7% higher in women aged at least 85 years (P < .001 for all). Obesity, however, was associated with a 27% lower SHBG level (P < .001).
“The increasing proportion of women with unmeasurable [estradiol] in the older groups most likely reflects different effects of age on the enzymatic pathways essential for the biosynthesis of these hormones,” the researchers wrote. “Regardless, a key message from the findings is that studies investigating the association between estrogens and diseases of aging in postmenopausal women must measure [estrone] in order to provide meaningful findings.”
The researchers noted that that the high androgen levels observed in some women in the cohort reaffirm the “wide range of normality” within a community-based population and support the representativeness of the study sample.
“The study suggests that higher testosterone may confer a survival advantage, particularly considering that between the ages of 70 to 95 years, older women have higher testosterone levels in this age group,” Davis said. – by Regina Schaffer
For more information:
Susan R. Davis, MBBS, can be reached at the Women’s Health Research Program, Monash University School of Public Health and Preventive Medicine, 553 St. Kilda Road, Melbourne 3004, Australia; email: susan.davis@monach.edu.
Disclosures: The authors report no relevant financial disclosures.
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Sharon Parish, MD
This is new information, and it provides a starting point for better understanding the association between sex steroids and some of what we study related to androgens in women.
There is a widely held belief that declining testosterone levels are responsible for changes in sexual function in women as they age. Additionally, there is a lot of discussion about how useful it is to measure testosterone or other androgens to assess or appraise sexual function. What follows is whether measuring androgens confers a predictive value as to whether women will benefit from supplementation, and whether androgen levels are perhaps biomarkers for longevity.
This study provides more complexity, but also more information, about whether this question of whether testosterone decline with age has a relationship to sexual function. What is striking here is that we now have good measurements providing age-specific data, which we did not have before, suggesting that testosterone levels went up and were higher among women as they age.
The authors are not commenting about the relationship between these measurements and global sexual function, so I would like to see how this fits into the schema of what we understand about sexual function. The other interesting finding here is that testosterone and estrone levels go up as DHEA declines. We need to understand how that influences some of the clinical issues related to androgen levels.
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