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Endogenous Circulating Sex Hormone Concentrations and Colon Cancer Risk in Postmenopausal Women: A Prospective Study and Meta-Analysis.
Mori, N, Keski-Rahkonen, P, Gicquiau, A, Rinaldi, S, Dimou, N, Harlid, S, Harbs, J, Van Guelpen, B, Aune, D, Cross, AJ, et al
JNCI cancer spectrum. 2021;(6)
Abstract
BACKGROUND Observational studies have consistently reported that postmenopausal hormone therapy use is associated with lower colon cancer risk, but epidemiologic studies examining the associations between circulating concentrations of endogenous estrogens and colorectal cancer have reported inconsistent results. METHODS We investigated the associations between circulating concentrations of estrone, estradiol, free estradiol, testosterone, free testosterone, androstenedione, dehydroepiandrosterone (DHEA), progesterone, and sex hormone-binding globulin (SHBG) with colon cancer risk in a nested case-control study of 1028 postmenopausal European women (512 colon cancer cases, 516 matched controls) who were noncurrent users of exogenous hormones at blood collection. Multivariable conditional logistic regression models were used to compute odds ratios and 95% confidence intervals to evaluate the association between circulating sex hormones and colon cancer risk. We also conducted a dose-response meta-analysis of prospective studies of circulating estrone and estradiol with colorectal, colon, and rectal cancer risk in postmenopausal women. All statistical tests were 2-sided. RESULTS In the multivariable model, a nonstatistically significantly positive relationship was found between circulating estrone and colon cancer risk (odds ratio per log2 1-unit increment = 1.17 [95% confidence interval = 1.00 to 1.38]; odds ratioquartile4-quartile1 = 1.33 [95% confidence interval = 0.89 to 1.97], P trend = .20). Circulating concentrations of estradiol, free estradiol, testosterone, free testosterone, androstenedione, DHEA, progesterone, and SHBG were not associated with colon cancer risk. In the dose-response meta-analysis, no clear evidence of associations were found between circulating estradiol and estrone concentrations with colorectal, colon, and rectal cancer risk. CONCLUSION Our observational and meta-analysis results do not support an association between circulating concentrations of endogenous sex hormones and colon or rectal cancer in postmenopausal women.
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Associations between endogenous sex hormones and MRI structural changes in patients with symptomatic knee osteoarthritis.
Jin, X, Wang, BH, Wang, X, Antony, B, Zhu, Z, Han, W, Cicuttini, F, Wluka, AE, Winzenberg, T, Blizzard, L, et al
Osteoarthritis and cartilage. 2017;(7):1100-1106
Abstract
OBJECTIVE To investigate the longitudinal association between endogenous sex hormones and knee osteoarthritis (OA) structures and pain. METHOD We examined 200 participants (mean age 63.0 ± 7.3 years) from a clinical trial of vitamin D supplement for symptomatic knee OA. Serum levels of estradiol, progesterone, testosterone and sex hormone binding globulin (SHBG) were analyzed at baseline and 24 months later. Magnetic resonance imaging (MRI) scans of selected knee were obtained at both baseline and follow-up for the measurement of cartilage volume, cartilage defects, bone marrow lesions (BMLs) and effusion-synovitis volume. Knee pain was assessed using a 100 mm visual analogue scale (VAS). Longitudinal data were analyzed using linear mixed-effects model. RESULTS One hundred and seven males and 93 females were included in this study. For females, after adjustment for age, body mass index (BMI), and vitamin D level, progesterone was positively associated with cartilage volume (β = 0.12 mm3 per quartile, P < 0.01). Estradiol levels were associated with lower grades of BMLs (β = -0.46 per quartile, P = 0.03), while estradiol (β = -1.28 per quartile, P = 0.04), progesterone (β = -1.56 per quartile, P < 0.01) and testosterone (β = -1.51 per quartile, P = 0.01) were inversely associated with effusion-synovitis volume. Testosterone was inversely associated with knee pain. No consistent associations were observed for males. CONCLUSION In women but not men, low serum levels of endogenous estradiol, progesterone and testosterone are associated with increased knee effusion-synovitis and possibly other OA-related structural changes. This may contribute to observed sex differences in knee OA.
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Complex Influence of Gonadotropins and Sex Steroid Hormones on QT Interval Duration.
Abehsira, G, Bachelot, A, Badilini, F, Koehl, L, Lebot, M, Favet, C, Touraine, P, Funck-Brentano, C, Salem, JE
The Journal of clinical endocrinology and metabolism. 2016;(7):2776-84
Abstract
CONTEXT QT interval duration is longer in women than in men. Sex steroid hormones have inconsistently been suggested to explain this difference. The implication of gonadotropins has never been studied. OBJECTIVE We report here the combined influence of sex steroid hormones and gonadotropins on QT interval duration in healthy subjects and patients with congenital adrenal hyperplasia (CAH) as a model of T and progesterone overexpression. DESIGN AND PATIENTS Eighty-four CAH patients (58 women) and 84 healthy subjects matched and paired for sex and age were prospectively included. Circulating concentrations of 17-OH-progesterone, progesterone, T, estradiol, FSH, and LH were measured concomitantly to the recording of a digitized electrocardiogram. RESULTS QTcFridericia (QTcF) was shorter in women with CAH than in control women (404 ± 2 vs 413 ± 2.1 milliseconds; P ≤ .001). 17-OH-progesterone, progesterone, the progesterone/estradiol ratio, and total T were higher in women with CAH than in female controls (P < .05), whereas FSH was lower (P ≤ .05). According to multivariable analysis in all women, the progesterone/estradiol ratio (β = -0.33) and FSH levels (β = 0.34) were related to QTcF (r = 0.5; P < .0001), with no influence of CAH or healthy status. QTcF was not different between CAH (404.7 ± 3.7 milliseconds) or healthy men (396 ± 2.8 milliseconds). For men, QTcF (r = 0.48; P < .01) was negatively related to free T (β = -0.29) and positively to FSH levels (β = 0.34). CONCLUSION Cardiac repolarization is influenced by complex interactions between sex steroid hormones and gonadotropins, depending on gender. Our results indicate that the progesterone/estradiol ratio in women, T in men, and FSH in both genders are major determinants of ventricular repolarization with opposite effects on QTc interval.
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Association of sex hormones with carotid artery distensibility in men and postmenopausal women: multi-ethnic study of atherosclerosis.
Vaidya, D, Golden, SH, Haq, N, Heckbert, SR, Liu, K, Ouyang, P
Hypertension (Dallas, Tex. : 1979). 2015;(5):1020-5
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Abstract
The decline in carotid distensibility with age is steeper in women than in men, however, the correlates of this sex difference are not known. We examined the association of bioavailable testosterone, estradiol, dehydroepiandrosterone, and sex hormone-binding globulin, in 2783 postmenopausal women and 2987 men aged 45 to 84 years at the Multi-Ethnic Study of Atherosclerosis baseline examination. Carotid artery lumen diameters by ultrasound and brachial artery blood pressures were measured at systole and diastole. Regression models to determine the association of carotid distensibility coefficient and lumen diameter with sex-specific quartiles of sex hormones were adjusted for age, race, height, weight, diabetes mellitus, current smoking, antihypertensive medication use, total and high-density lipoprotein cholesterol levels, and hormone replacement therapy in women. A higher DC indicates a more distensible vessel. In women, higher dehydroepiandrosterone (P=0.008) and lower sex hormone-binding globulin (P=0.039) were associated with lower distensibility; higher dehydroepiandrosterone and lower estradiol were associated with smaller carotid diameters. In men, higher Bio-T (P=0.009) and lower estradiol (P=0.007) were associated with greater distensibility and also with smaller diameters (P=0.012 and 0.002, respectively). An androgenic internal milieu is associated with lesser carotid distensibility and diameter remodeling in women, but the opposite is true for men. Higher levels of estradiol are associated with smaller carotid diameters in both the sexes. Future longitudinal and experimental studies are needed to reveal the mechanism and clinical consequences of these associations.
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Graft function, cardiovascular risk factors, and sex hormones in renal transplant recipients on an immunosuppressive regimen of everolimus, reduced dose of cyclosporine, and basiliximab.
Krämer, BK, Neumayer, HH, Stahl, R, Pietrzyk, M, Krüger, B, Pfalzer, B, Bourbigot, B, Campbell, S, Whelchel, J, Eris, J, et al
Transplantation proceedings. 2005;(3):1601-4
Abstract
A prospective, randomized trial evaluated the combination of everolimus of 1.5 or 3 mg/d with steroids, basiliximab, and low-dose cyclosporine (CsA) adjusted by C2 monitoring in 256 renal transplant recipients. CsA C2 target levels, initially set at 600 ng/mL, were tapered over time posttransplant. The median serum creatinine concentrations were 130 mumol/L in both sirolimus groups (1.5 and 3 mg/d) at 6 months. Biopsy-proven acute rejection (BPAR) occurred in 13.7% and 15.1% of patients in the 1.5 and 3 mg/d groups, respectively. The incidence of BPAR was significantly higher among patients with everolimus trough levels < 3 ng/mL. Posttransplant diabetes mellitus occurred rarely, and blood pressure control appeared favorable; however, serum cholesterol levels were increased by approximately 50%, and serum triglycerides by approximately 100%. Serum testosterone concentrations increased after renal transplantation in both everolimus groups. Concentration-controlled everolimus therapy combined with low-dose CsA provides effective protection against rejection with good renal function and safety profiles.
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Interrelationships among lipoprotein levels, sex hormones, anthropometric parameters, and age in hypogonadal men treated for 1 year with a permeation-enhanced testosterone transdermal system.
Dobs, AS, Bachorik, PS, Arver, S, Meikle, AW, Sanders, SW, Caramelli, KE, Mazer, NA
The Journal of clinical endocrinology and metabolism. 2001;(3):1026-33
Abstract
Serum lipoproteins and cardiovascular risk are affected by endogenous and exogenous sex hormones. As part of a multicenter evaluation of a permeation-enhanced testosterone transdermal system (TTD), the interrelationships among serum lipoproteins, hormone levels, anthropometric parameters, and age were investigated in 29 hypogonadal men. Subjects (aged 21-65 yr) were first studied during prior treatment with im testosterone esters (IM-T), then during an 8-week period of androgen withdrawal resulting in a hypogonadal state (HG), and finally during a 1-yr treatment period with the TTD. Compared with treatment with IM-T, the HG period produced increases in high density lipoprotein [HDL; 12.0 +/- 1.6% (+/-SEM); P<0.001] and total cholesterol (4.2 +/- 1.9%; P: = 0.02) and a decrease in the cholesterol/HDL ratio (-9.7 +/- 2.8%; P = 0.02). Compared with the HG period, TTD treatment produced decreases in HDL (-7.6 +/- 2.5%; P = 0.002) and increases in the cholesterol/HDL ratio (9.0 +/- 2.5%; P = 0.01) and triglycerides (20.7 +/- 6.4%; P: = 0.03). Small decreases in total cholesterol (-1.2 +/- 1.8%; P: = 0.1) and low density lipoprotein (-0.8 +/- 2.6%; P = 0.07) were also observed during TTD, but did not reach statistical significance. Likewise, there were no significant differences between the IM-T and TTD treatments. Serum HDL levels showed a strong negative correlation with body mass index and other obesity parameters in all three study periods (r < -0.45; P < 0.02). During treatment with TTD, serum testosterone levels also correlated negatively with body mass index (r = -0.621; P < 0.001). As a consequence of these relationships, a positive trend was observed between HDL and testosterone levels during TTD treatment (r = 0.336; P = 0.07). Interestingly, the changes in lipoprotein levels during TTD treatment indicated a more favorable profile (decrease in cholesterol and low density lipoprotein levels) with increasing age of the patients. In hypogonadal men the effects of transdermal testosterone replacement on serum lipoproteins appear consistent with the physiological effects of testosterone in eugonadal men.
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Population frequency distributions of HDL, HDL(2), and HDL(3) cholesterol and apolipoproteins A-I and B in healthy men and women and associations with age, gender, hormonal status, and sex hormone use: the Stanford Five City Project.
Gardner, CD, Tribble, DL, Young, DR, Ahn, D, Fortmann, SP
Preventive medicine. 2000;(4):335-45
Abstract
BACKGROUND The purpose of this study is to present population-based frequency distribution data for several lipoprotein-related variables and to examine their associations with gender, age, menopausal status, and sex hormone use. METHODS High-density lipoprotein cholesterol (HDL-C), HDL(2)-C, HDL(3)-C, apolipoprotein (Apo) A-I, and Apo B were measured in a population-based sample of 1, 027 healthy adults from four California cities who participated in the 1989-1990 survey of the Stanford Five City Project. These data were examined cross-sectionally with sociodemographic and other related variables. RESULTS Relative to men, all of the HDL-related parameters-HDL-C, HDL(2)-C, HDL(3)-C, Apo A-I-were significantly higher and Apo B levels were significantly lower among women (P < 0. 001). Menopausal status was not associated with HDL-related parameters, but Apo B levels were higher in post- versus premenopausal women (P < 0.001). Among women, HDL-C and Apo A-I levels were higher in oral contraceptive and estrogen replacement therapy users (P = 0.003). Most of the significant findings remained statistically significant after adjusting for age, body mass index, smoking, energy expenditure, and alcohol intake. CONCLUSIONS These population-based data indicate that gender, menopausal status, and the use of sex hormones among women are associated with differential levels of one or more of HDL-C, HDL(2)-C, HDL(3)-C, Apo A-I, and Apo B, independent of age and a broad set of lifestyle factors.