Dr. Ron’s Research Review – January 19, 2011

This week’s research review contains information on testosterone and women.

Low testosterone levels predict all-cause mortality and cardiovascular events in women in a prospective cohort study in German primary care patients. (Sievers, Klotsche et al. 2010)

Premenopausal women with elevated serum testosterone levels are at an increased risk of breast cancer. (Dorgan, Stanczyk et al. 2010)

Low serum testosterone levels were independently associated with frailty in the elderly Taiwanese. (Wu, Lin et al. 2010)

Dr. Ron


Articles

Prospective case-control study of premenopausal serum estradiol and testosterone levels and breast cancer risk

            (Dorgan, Stanczyk et al. 2010) Download

ABSTRACT: INTRODUCTION: Breast cancer is frequently a hormonally dependent cancer, and associations of circulating estrogens and androgens with subsequent breast cancer risk are well established in postmenopausal women. Associations of serum estrogens and androgens with breast cancer risk in premenopausal women are less well studied. The objective of this study was to determine whether estradiol and testosterone levels in serum collected before menopause are associated with subsequent breast cancer risk. METHODS: We conducted a prospective case-control study of 266 participants who were registered in the Columbia, Missouri, Serum Bank and not using exogenous hormones at the time of blood collection. Each of 98 in situ or invasive breast cancer cases with prediagnostic serum collected before menopause was matched to two controls by age, date, menstrual cycle day, and time of day of blood collection. Estradiol and testosterone concentrations were quantified by using specific radioimmunoassays, and sex hormone-binding globulin (SHBG) was quantified with a chemiluminescent immunoassay to allow calculation of the non-SHBG bound hormone fractions. Data were analyzed by using conditional logistic regression. All tests of statistical significance were two-sided. RESULTS: Serum testosterone was strongly and significantly associated with breast cancer risk. The relative odds (OR) for increasing quartiles of total testosterone were 1.0, 2.1 (95% confidence interval (CI) 0.9 to 4.8), 1.5 (95% CI, 0.6 to 3.4), and 3.3 (95% CI, 1.5 to 7.5, Ptrend = 0.006). Comparable ORs for the non-SHBG bound fraction of testosterone that is bioavailable were 1.0, 1.7 (95% CI, 0.7 to 4.2), 1.7 (95% CI, 0.7 to 4.0), and 4.2 (95% CI, 1.6 to 10.9, Ptrend = 0.002). Total and non-SHBG-bound estradiol were not associated with breast cancer, but extreme variation in levels across the menstrual cycle coupled with relatively small numbers, particularly for analyses stratified by cycle phase, limited the power to detect associations. CONCLUSIONS: Results suggest that premenopausal women with elevated serum testosterone levels are at an increased risk of breast cancer.

Low testosterone levels predict all-cause mortality and cardiovascular events in women: a prospective cohort study in German primary care patients

            (Sievers, Klotsche et al. 2010) Download

OBJECTIVE: Although associations between testosterone and cardiovascular (CV) morbidity in women have been proposed, no large prospective study has evaluated potential associations between testosterone and mortality in women. The objective was to determine whether baseline testosterone levels in women are associated with future overall or CV morbidity and mortality. DESIGN: Prospective cohort study with a 4.5-year follow-up period. METHODS: From a representative sample of German primary care practices, 2914 female patients between 18 and 75 years were analyzed for the main outcome measures: CV risk factors, CV diseases, and all-cause mortality. RESULTS: At baseline, the study population was aged 57.96+/-14.37 years with a mean body mass index of 26.71+/-5.17 kg/m(2). No predictive value of total testosterone for incident CV risk factors or CV diseases was observed in logistic regressions. Patients with total testosterone levels in the lowest quintile Q1, however, had a higher risk to die of any cause or to develop a CV event within the follow-up period compared to patients in the collapsed quintiles Q2-Q5 in crude and adjusted Cox regression models (all-cause mortality: Q2-Q5 versus Q1: crude hazard ratios (HR) 0.49, 95% confidence interval (CI) 0.33-0.74; adjusted HR 0.62, 95% CI 0.42-0.939; CV events: Q2-Q5 versus Q1: crude HR 0.54, 95% CI 0.38-0.77; adjusted HR 0.68, 95% CI 0.48-0.97). Kaplan-Meier curves revealed similar data. CONCLUSIONS: Low baseline testosterone in women is associated with increased all-cause mortality and incident CV events independent of traditional risk factors.

Low serum testosterone and frailty in older men and women

            (Wu, Lin et al. 2010) Download

BACKGROUND: Frail older persons are at high risk of morbidity and mortality, and are characterized by body composition alterations. Serum testosterone, which regulates body composition, declines with age. We investigated the relation between serum testosterone level and physiological frailty in both older men and women. METHODS: This was a cross-sectional study of 108 adults 65 years old or older. Frailty status was determined by hand-grip strength, weight change, walking speed, exhaustion, and activity levels, and was classified as frail (3 or more deficits), pre-frail (1 or 2 deficits), or robust (no deficit) according to the Fried criteria. Serum total testosterone (TT) and sex-hormone-binding globulin were measured while free testosterone (FT) was estimated. RESULTS: Median (range) TT and FT were lower in frail than in pre-frail and robust men (TT: (frail) 15.7 [2.4-26.9] vs. (pre-frail) 19.4 [7.2-39.9] and (robust) 25.9 [13.2-35.2] nmol/L, P=0.03; FT: 230.0 [35.9-299.0] vs. 272.0 [86.7-411.0] and 303.0 [267.0-396.0] pmol/L, P=0.02) and women (TT: 0.31 [0.10-0.51] vs. 0.47 [0.14-1.55] and 0.45 [0.36-1.25] nmol/L, P=0.02; FT: 4.59 [0.46-6.63] vs. 4.66 [1.57-15.10] and 6.65 [3.91-21.00] pmol/L, P=0.03). After adjusting for age, comorbidities, body mass index, and serum albumin in ordinal logistic regression model, odds ratios of being frail were significantly higher for those participants whose TT and FT levels were in the lowest tertile compared to the highest tertile in men (TT: odds ratio [OR] 3.29, 95% confidence interval [CI] 1.14-9.50; FT: OR 3.44, 95% CI 1.05-11.22) and in women (TT: OR 6.69, 95% CI 1.84-24.31; FT: OR 4.86, 95% CI 1.31-18.08). CONCLUSIONS: Low serum testosterone levels were independently associated with frailty in the elderly Taiwanese.


References

Dorgan, J. F., F. Z. Stanczyk, et al. (2010). "Prospective case-control study of premenopausal serum estradiol and testosterone levels and breast cancer risk." Breast Cancer Res 12(6): R98.

Sievers, C., J. Klotsche, et al. (2010). "Low testosterone levels predict all-cause mortality and cardiovascular events in women: a prospective cohort study in German primary care patients." Eur J Endocrinol 163(4): 699-708.

Wu, I. C., X. Z. Lin, et al. (2010). "Low serum testosterone and frailty in older men and women." Maturitas 67(4): 348-52.