Sex Hormones in Older Women Study (The SHOW Study)
Sex Hormones in Older Women Study
(The SHOW Study)
Funded by the National Health and Medical Research Council (NHMRC)
The SHOW study commenced in 2016 as a sub study of the ASPREE (ASPirin in Reducing Events in the Elderly) Study. ASPREE is a placebo-controlled randomised clinical trial of daily low dose aspirin versus placebo in older people, free of cardiovascular events, with unimpaired cognition at recruitment. The large sample of women aged 70-94 years at recruitment in this cohort has enabled us to:
1 | Measure sex hormones in women aged 70-94 years with precision and, for the first time, establish age-specific reference ranges for each of the main sex steroids for community-dwelling women aged 70 years and older (70+). |
2 | Examine the associations between sex hormones (estrogen and androgens) and number of health outcomes in older women. |
Major findings from the SHOW Study
July 2023
1 | Sex hormones in older womenSex hormone reference ranges were established using a precise method (LCMS) in 5,326 women aged 70-95 not using medication that might influence blood sex hormone levels.
Change with age was confirmed in a separate analysis of women who had blood drawn at baseline and 3 years later. |
2 | What estrogen to measure in older womenAfter menopause, estrogen is made in fat from hormones from the adrenal glands. The main estrogen in the blood is estrone which can be converted to estradiol in cells. 66% of women had blood estradiol concentrations below the assay limit of detection. We examined what was the main indicator of blood estradiol concentrations, taking into account age and body weight. We found that blood estrone alone explained ~ 20% of the variation in estradiol and is a robust indicator of estradiol in older women. |
3 | Testosterone and DHEA concentrations above the lowest quartile in older women are associated with a reduced risk of a first ever major adverse cardiovascular event (MACE)Associations between hormones and MACE and all-cause mortality were examined with adjustment for age, body mass index (BMI), smoking status, alcohol consumption, diabetes, hypertension, dyslipidaemia, impaired renal function and treatment allocation (aspirin or placebo) in 5535 women not using medication that affected hormone levels. During 4.4 years of follow-up (24,553 person-years) 144 women experienced a MACE; incidence rate of 5.9/1,000 person-years. There were 200 deaths. In the fully adjusted models, testosterone levels in the upper 50% and DHEA in the upper 75% were associated with a lower risk of MACE (~ 40% risk reduction) compared with having a testosterone in the lowest 25%. Divergence in risk between women with higher versus low testosterone/DHEA emerged early and low levels were statistically significantly different from the higher quartiles by year 3. No association was seen between any hormone or SHBG and all-cause mortality. |
4 | Sex hormones and cognitive functionAssociations between sex hormones, sex hormone binding globulin (SHBG) and cognitive performance were examined in women aged at least 70 years, without dementia and not using medications that influence sex hormones. Linear and generalized linear regression models included age, body mass index, education, smoking, alcohol, living circumstances, diabetes, hypertension, depression and impaired renal function. The included 5,511 women had a median (interquartile range) age of 73.9 (71.6–77.6) years. No associations were found for estrone, estradiol, testosterone or dehydroepiandrosterone and cognitive performance. SHBG concentrations above quartile 1 (Q1) were significantly inversely associated with processing speed. Conclusions: Sex hormones were not associated with cognitive performance. The finding that low SHBG is associated with better processing speed warrants further investigation. The null findings for the sex hormones establish a firm baseline to confidently explore the association between sex hormones and longitudinal cognitive performance in this population |
Publications from the SHOW Study
- Davis SR, Bell RJ, Robinson PJ, Handelsman DJ, Gilbert T, Phung J, Desai R, Lockery JE, Woods RL, Wolfe RS, Reid CM, Nelson MR, Murray AM, McNeil JJ; ASPREE Investigator Group. Testosterone and estrone Increase From the Age of 70 Years: Findings From the Sex Hormones in Older Women Study. J Clin Endocrinol Metab. 2019 Dec 1;104(12):6291-6300. doi: 10.1210/jc.2019-00743.
- Davis SR, Martinez-Garcia A, Robinson PJ, Handelsman DJ, Desai R, Wolfe R, Bell RJ; ASPREE Investigator Group. Estrone Is a strong predictor of circulating estradiol in women age 70 years and older. J Clin Endocrinol Metab. 2020 Sep 1;105(9):e3348–54. doi: 10.1210/clinem/dgaa429.
- Handelsman DJ, Gibson E, Davis S, Golebiowski B, Walters KA, Desai R. Ultrasensitive Serum Estradiol Measurement by Liquid Chromatography-Mass Spectrometry in Postmenopausal Women and Mice. J Endocr Soc. 2020 Jul 10;4(9):bvaa086. doi: 10.1210/jendso/bvaa086.
- Islam RM, Bell RJ, Handelsman DJ, Robinson PJ, Wolfe R, Davis SR; ASPREE Investigator Group. Longitudinal changes over three years in sex steroid hormone levels in women aged 70 years and over. Clin Endocrinol (Oxf). 2021 Mar;94(3):443-448. doi: 10.1111/cen.14401.
- Islam RM, Bell RJ, Handelsman DJ, McNeil JJ, Nelson MR, Reid CM, Tonkin AM, Wolfe RS, Woods RL, Davis SR. Associations between blood sex steroid concentrations and risk of major adverse cardiovascular events in healthy older women in Australia: a prospective cohort substudy of the ASPREE trial. Lancet Healthy Longev. 2022 Feb;3(2):e109-e118. doi: 10.1016/S2666-7568(22)00001-0.
- Azene ZN, Davis SR, McNeil JJ, Tonkin AM, Handelsman DJ, Islam RM. Estrone, sex hormone binding globulin and lipid profiles in older women: an observational study. Climacteric. 2023 Apr;26(2):114-120. doi: 10.1080/13697137.2023.2165908.
- Sultana F, Davis SR, Murray AM, Woods RL, McNeil JJ, Islam RM. Sex hormones, SHBG and cognitive performance among older Australian women: an observational study. Climacteric. 2023 Apr;26(2):121-128. doi: 10.1080/13697137.2023.2166824.