Hormone Levels In Postmenopausal Women Research Articles

The association between blood heavy metals level and sex hormones among postmenopausal women in the US.

Environmental pollutants could be implicated in female endocrine setting Q6 beyond traditional factors. Until now, few study has focused on the association of environmental exposure to heavy metals with sex hormones in postmenopausal women. This study intended to investigate whether serum levels of heavy metals(i.e., Cd, Pb, Hg, Mn, Se) would influence sex hormones in postmenopausal women. A cross-sectional study was performed on 614 nationally representative participants from 2013-2016 National Health and Nutrition Examination Survey (NHANES) in the US. Multivariate linear regression models and restricted cubic spline plots revealed cadmium(Cd) had linear positive association with TT(β=3.25, 95%CI= 1.12, 5.38), bioavailable TT(β=1.78, 95%CI=0.36,3.21) and TT/E2(β=0.76, 95%CI=0.28,1.24), which was more apparent in natural menopausal and obese women. Lead(Pb) had linear positive association with SHBG(β=12.84, 95%CI= 6.77,18.91), which was apparent in nearly all subgroups except in normal BMI group, and TT/E2 (β=0.69, 95%CI 0.134,1.25), which was apparent in natural menopausal and normal BMI women. Manganese(Mn) had non-linear association with SHBG, which was more apparent in natural menopausal and obese women, and TT/E2, which was more apparent in natural menopausal and normal BMI women. Selenium(Se) had U shaped non-linear association with TT, which was more apparent in hysterectomy, overweight and obese women, and SHBG, which was apparent in nearly all subgroups except in normal BMI group. In summary, this cross-sectional study indicates a possible role that various degree of environmental exposure to heavy metals plays in the disruption of sex Q5 hormone levels in postmenopausal women. Further experiments are needed to elucidate the underlying mechanisms.

Estimated Ovulatory Years Prior to Menopause and Postmenopausal Endogenous Hormone Levels.

Lifetime ovulatory years (LOY) is estimated by the difference between ages at menopause and menarche subtracting time for events interrupting ovulation. We tested whether LOY influences sex hormone levels in postmenopausal women with at least one intact ovary not using hormones. Estradiol, estrone, estrone sulfate, total testosterone, dehydroepiandrostendione sulfate, prolactin, and sex hormone binding globulin were measured in 1,976 postmenopausal women from the Nurses' Health Study. Associations of age, body mass index (BMI), smoking, alcohol use, and other factors on hormones were assessed by t tests and ANOVA. Linear regression was used to assess multivariable adjusted associations between LOY and hormones and trends in hormone levels per 5-year increases in LOY were estimated. Women averaged 61.4 years old, 11.0 years since menopause, with BMI of 25.8 kg/m2. A total of 13.6% had irregular cycles, 17.5% hysterectomy, 6.4% unilateral oophorectomy, and 13.8% were current smokers. Variables associated with one or more hormone levels were included as covariates. Each 5-year increase in LOY was significantly associated with a 5.2% increase in testosterone in women with BMI < 25 kg/m2 and a 7.4% increase in testosterone and 7.3% increase in estradiol in women with above-average BMI. This is the first study to show that greater LOY is associated with higher testosterone in postmenopausal women and higher estradiol in those with elevated BMI, suggesting accumulation of functioning stromal and thecal cells from repeated ovulations and peripheral conversion of testosterone. A possible explanation for why greater LOY increases risk for breast, endometrial, and ovarian cancer is offered.

Resistance training reduced luteinising hormone levels in postmenopausal women in a substudy of a randomised controlled clinical trial: A clue to how resistance training reduced vasomotor symptoms.

BackgroundVasomotor symptoms (VMS) are common around menopause. Menopausal hormone therapy is the most effective treatment for VMS. Physical exercise has been proposed as an alternative treatment since physically active women have previously been found to experience fewer VMS than inactive women. In our randomised controlled trial on resistance training to treat VMS, sympoms were reduced by 50% in the intervention group compared with the control group.ObjectivesTo propose a mechanism to explain how resistance training reduced VMS and to assess if luteinizing hormone (LH) and follicle stimulating hormone (FSH) were affected in accordance with the proposed mechanism.Trial design and methodsA substudy of a randomized controlled trial on 65 postmenopausal women with VMS and low physical activity who were randomised to 15 weeks of resistance training three times per week (n = 33) or to a control group (n = 32). To be regarded compliant to the intervention we predecided a mean of two training sessions per week. The daily number of VMS were registered before and during the 15 weeks. Blood samples were drawn for analysis of LH and FSH at baseline and after 15 weeks.ResultsLH decreased significantly in the compliant intervention group compared with the control group (-4.0±10.6 versus 2.9±9.0, p = 0.028 with Mann-Whitney U test). FSH also decreased in the compliant intervention group compared with the control group, however not enough to reach statistical significance (-3.5±16.3 versus 3.2±18.2, p = 0.063 with Mann-Whitney U test). As previously published the number of hot flushes decreased significantly more in the intervention group than in the control group but there was no association between change in LH or FSH and in number of VMS.ConclusionsWe propose that endogenous opiods such as β-endorphin or dynorphin produced during resistance training decreased VMS by stimulating KNDγ-neurons to release neurokinin B to the hypothalamic thermoregulatory centre. Through effects on KNDγ-neurons, β-endorphin could also inhibit GnRH and thereby decrease the production of LH and FSH. The significanty decreased LH in the compliant intervention group compared with the control group was in accordance with the proposed mechanism.

Cardiometabolic Risk Factors and Endogenous Sex Hormones in Postmenopausal Women: A Cross-Sectional Study.

ContextIt is uncertain which cardiovascular risk factors are associated with sex hormone levels in postmenopausal women.ObjectiveThis work aimed to investigate the association between cardiometabolic risk factors and sex hormones in a cross-sectional, observational population study.MethodsIn this Swedish population study, participants were physically examined from 2002 to 2004, and endogenous sex hormones were analyzed by liquid chromatography–tandem mass spectrometry. Women aged 55 years or older with estradiol levels below 20 pg/mL and not using any hormonal therapy were eligible for inclusion in the study (N = 146). Variable selection and bootstrap stability analyses were performed and linear regression models presented, with each of the 8 hormones as outcome variables.ResultsBody mass index (BMI) was positively associated with estradiol (β = 0.054, P < .001), but negatively associated with 17-α-hydroxyprogesterone (β = –0.023, P = .028). Waist-to-hip ratio (WHR) was negatively associated with dihydrotestosterone (β = –2.195, P = .002) and testosterone (β = –1.541, P = .004). The homeostatic model assessment of insulin resistance was positively associated with androstenedione (β = 0.071, P = .032), estradiol (β = 0.091, P = .009), estrone (β = 0.075, P = 0.009), and 17-α-hydroxyprogesterone (β = 0.157, P = .001). Age was positively associated with testosterone (β = 0.017, P = .042). C-reactive protein showed an inverse association with progesterone (β = –0.028, P = .037). Lower low-density lipoprotein cholesterol was associated with higher estradiol levels (β = –0.093, P = .049), whereas lower triglycerides were associated with higher concentrations of dihydrotestosterone (β = –0.208, P = .016).ConclusionIn postmenopausal women, WHR was strongly inversely associated with androgens, while BMI was positively associated with estrogens.

Effect of risk-reducing salpingo-oophorectomy on sex steroid hormone serum levels among postmenopausal women: an NRG Oncology/Gynecologic Oncology Group study

Risk-reducing salpingo-oophorectomy is an effective ovarian cancer risk reduction strategy. However, bilateral oophorectomy has also been associated with increased long-term nonneoplastic sequelae, effects suggested to be mediated through reductions in systemic sex steroid hormone levels. Currently, it is unclear whether the postmenopausal ovary contributes to the systemic hormonal milieu or whether postmenopausal ovarian volume or other factors, such as body mass index and age, affect systemic hormone levels. We examined the impact of oophorectomy on sex steroid hormone levels in postmenopausal women. Furthermore, we explored how well ovarian volume measured by transvaginal ultrasound correlated with direct ovarian measures obtained during surgical pathology evaluation and investigated the association between hormone levels and ovarian volumes. Postmenopausal women who underwent risk-reducing salpingo-oophorectomy (180 cases) or ovarian cancer screening (38 controls) enrolled in an international, prospective study of risk-reducing salpingo-oophorectomy and risk of ovarian cancer algorithm-based screening among women at increased risk of ovarian cancer (Gynecologic Oncology Group-0199) were included in this analysis. Controls were frequency matched to the cases on age at menopause, age at study entry, and time interval between blood draws. Ovarian volume was calculated using measurements obtained from transvaginal ultrasound in both cases and controls and measurements recorded in surgical pathology reports from cases. Serum hormone levels of testosterone, androstenedione, androstenediol, dihydrotestosterone, androsterone, dehydroepiandrosterone, estrone, estradiol, and sex hormone-binding globulin were measured at baseline and follow-up. Spearman correlation coefficients were used to compare ovarian volumes as measured on transvaginal ultrasound and pathology examinations. Correlations between ovarian volumes by transvaginal ultrasound and measured hormone levels were examined using linear regression models. All models were adjusted for age. Paired t tests were performed to evaluate individual differences in hormone levels before and after risk-reducing salpingo-oophorectomy. Ovarian volumes measured by transvaginal ultrasound were only moderately correlated with those reported on pathology reports (Spearman rho [ρ]=0.42). The median time interval between risk-reducing salpingo-oophorectomy and follow-up for the cases was 13.3 months (range, 6.0-19.3), and the median time interval between baseline and follow-up for the controls was 12.7 months (range, 8.7-13.4). Sex steroid levels decreased with age but were not correlated with transvaginal ultrasound ovarian volume, body mass index, or time since menopause. Estradiol levels were significantly lower after risk-reducing salpingo-oophorectomy (percentage change,-61.9 post-risk-reducing salpingo-oophorectomy vs+15.2 in controls; P=.02), but no significant differences were seen for the other hormones. Ovarian volumes measured by transvaginal ultrasound were moderately correlated with volumes directly measured on pathology specimens and were not correlated with sex steroid hormone levels in postmenopausal women. Estradiol was the only hormone that declined significantly after risk-reducing salpingo-oophorectomy. Thus, it remains unclear whether the limited post-risk-reducing salpingo-oophorectomy changes in sex steroid hormones among postmenopausal women impact long-term adverse outcomes.

Perfluoroalkyl substances and sex hormones in postmenopausal women: NHANES 2013–2016

BackgroundAlthough an alteration in sex hormones has been linked to perfluoroalkyl substances (PFAS) in premenopausal women and girls, whether such associations exist in postmenopausal women remains uncertain. ObjectsTo examine the associations between serum PFAS concentrations and sex hormone levels in postmenopausal women. MethodsData from the National Health and Nutrition Examination Survey (NHANES) 2013–2016 waves were used. A total of 706 postmenopausal women with information on serum PFAS [perfluorohexane sulfonic acid (PFHxS), pefluorodecanoic acid (PFDA); perfluorononanoic acid (PFNA); linear perfluorooctanoate (n-PFOA); linear perfluorooctane sulfonate (n-PFOS); monomethyl branched isomers of PFOS (Sm-PFOS)], sex hormones indicators [e.g., total testosterone (TT), estradiol (E2) and sex hormone binding globulin (SHBG)] as well as selected covariates were included. An indicator of circulating free testosterone (FT), and ratio of TT to E2 (TT/E2) were generated. Multiple linear regression accounting for the primary sampling unit, strata, and environmental sampling weights of PFAS was used for association analyses. Effect modification by obesity and type of menopause was explored via stratified analyses as well as the testing of interaction terms. Principal component analysis (PCA) and Bayesian kernel machine regression (BKMR) were conducted to assess these relationships in a multiple PFAS exposure setting. ResultsAfter adjusting for potential confounders, total perfluorooctanoate (TPFOA: n-PFOA + Sb-PFOA) and total perfluorooctane sulfonate (TPFOS: n-PFOS + Sm-PFOS), and their linear and branched isomers were positively associated with two androgen indicators (i.e., TT and FT). PCA results revealed that the principal component (PC) composed of n-PFOA was positively associated with ln (TT) [β = 0.09, 95% confidential interval (CI): 0.02, 0.16; per ln-ng/mL increase in exposure], and ln (FT) (β = 0.12, 95% CI: 0.05, 0.2) in overweight/obese [body mass index (BMI) ≥ 25 kg/m2] women, but not in those with BMI < 25 kg/m2. Additionally, among overweight/obese women, PFHxS was positively associated with androgens and negatively with ln (SHBG) (β = -0.06, 95% CI: −0.12, −0.01). The PC composed of Sm-PFOS, n-PFOS, and PFHxS was positively associated with ln (TT) levels among overweight/obese women. Results from BKMR also confirmed the findings on n-PFOA and PFHxS. ConclusionsOur study indicates that n-PFOA and PFHxS were positively associated with levels of several androgen indicators in postmenopausal women, particularly among overweight/obese ones. Given the higher risk of cardiometabolic diseases associated with elevated levels of androgens in postmenopausal women, future studies are needed to explore the potential underlying mechanisms.

Abstract PO029: Oral contraceptive use and postmenopausal sex steroid hormone metabolism

Abstract OBJECTIVE: Oral contraceptive (OC) use is common in the United States and high-profile articles have renewed research interest in OC use and cancer risk. Several mechanisms have been proposed to explain how OC use influences postmenopausal cancer risk; one of the leading hypotheses is that OC use fundamentally alters feedback in the hypothalamic-pituitary-gonad axis, leading to long term changes in sex steroid hormone metabolism. However, women who use OCs are also unique with respect to factors that may affect both hormone metabolism and cancer risk. No studies have comprehensively commented on hormone levels in postmenopausal women who did and did not use OCs. DESIGN: We examined differences in circulating markers of sex steroid hormone metabolism associated with prior use of OCs among a subcohort of postmenopausal women from the Women’s Health Initiative Observational Study (983 women with at least one intact ovary and not currently using menopausal hormone therapy). MATERIALS AND METHODS: Using highly sensitive liquid chromatography–tandem mass spectrometry assays, we measured over 30 markers of estrogen and androgen metabolism in study serum samples. We used linear regression (adjusted and weighted) to estimate geometric mean hormone levels, which were then converted into relative percent differences. We controlled for potential confounders and stratified by: lifetime ovulatory cycles, body mass index, and parity (the focus of this abstract). RESULTS: Women with a history of OC use (n=346) had lower levels of estrogen metabolites than women who never used OCs (n=637), particularly when limiting this comparison among parous women (n=158 nulliparous women, n=825 parous women). In parous women, OC use was associated with reductions in total estrone (-18.5%, 95% confidence interval [CI] -31.1, -3.7%) and in estrogen metabolism overall: 2-hydroxylation metabolites were reduced by -18.5% (CI -28.2, -7.7%), 4-hydroxylation metabolites by -19.9% (CI -29.4, -9.1%), and 16-alpha-hydroxylation metabolites by -24.0% (CI -34.2, -12.2%). Hormone differences associated with OC use among nulliparous women were imprecise. When we made comparisons to nulliparous women who did not use OCs, women who both used OCs and were parous had lower testosterone (-21.2%, CI -33.1, -7.2%) and higher dihydrotestosterone relative to testosterone (its metabolic precursor; 16.5%, CI% -0.6, 36.6). However, aside from lower total estrone (-25.5%, CI -44.6, 0.2%), estrogen metabolism was not different between these groups. CONCLUSIONS: We saw evidence suggesting estrogen metabolism, as reflected in circulating markers, may be lower in postmenopausal women who previously used OCs. These effects were strongest among parous women, likely due to sufficient sample size, rather than any synergistic effect attributable to both using OCs and giving birth. These results support the idea that OC users have lower estrogen levels, but this should be evaluated in other age groups, as differences in hormone metabolism early in the lifecourse may lead women to use OCs. Citation Format: Kara A. Michels, Sally B. Coburn, Garnet Anderson, Louise A. Brinton, Chu Chen, Roni T. Falk, Margery L. Gass, Ashley M. Geczik, JoAnn E. Manson, Ruth M. Pfeiffer, Kerryn Reding, Gloria E. Sarto, Nicolas Wentzensen, Robert A. Wild, Xia Xu, Britton Trabert. Oral contraceptive use and postmenopausal sex steroid hormone metabolism [abstract]. In: Proceedings of the AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; 2020 Nov 9-10. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(3_Suppl):Abstract nr PO029.

Ultraviolet radiation as a predictor of sex hormone levels in postmenopausal women: A European multi-center study (ECRHS)

BackgroundSolar ultraviolet radiation (UVR) affects the body through pathways that exhibit positive as well as negative health effects such as immunoregulation and vitamin D production. Different vitamin D metabolites are associated with higher or lower concentrations of estrogens and may thus alter the female sex hormone balance. ObjectiveTo study whether exposure to UVR, as a modifiable lifestyle factor, is associated with levels of sex hormones (17β-estradiol, estrone, estrone 3-sulfate, testosterone, dehydroepiandrosterone sulfate), gonadotropins (follicle stimulating hormone, luteinizing hormone) as well as sex hormone binding globulin in postmenopausal women, and thus investigate whether managing UVR exposure can influence the hormone balance, with potential benefits for the biological aging process. MethodsThe study included 580 postmenopausal women from six European countries, participating in the European Community Respiratory Health Survey (2010–2014). Average UVR exposure during the month before blood sampling was estimated based on personal sun behavior and ambient levels. Hormone concentrations were measured in serum using state-of-the-art methods. Subsequently we applied linear mixed-effects models, including center as random intercept, hormone concentrations (one at a time) as outcome and UVR, age, skin type, body mass index, vitamin D from dietary sources, smoking, age at completed full-time education and season of blood sampling as fixed-effect predictors. ResultsOne interquartile range increase in UVR exposure was associated with decreased levels of 17β-estradiol (-15.6 pmol/L, 95 % Confidence Interval (CI): -27.69, -3.51) and estrone (-13.36 pmol/L, 95 % CI: -26.04, -0.68) and increased levels of follicle stimulating hormone (9.34IU/L, 95 % CI: 2.91, 15.77) and luteinizing hormone (13.86 IU/daL, 95 % CI: 2.48, 25.25). ConclusionsExposure to UVR is associated with decreased estrogens and increased gonadotropins in postmenopausal women, a status associated with osteoporosis, lung function decline and other adverse health effects. This study indicates that managing UVR exposure has potential to influence the hormone balance and counteract adverse health conditions after menopause.

Associations between Polymorphisms in Phase II Enzymes and Circulating Sex-Steroid Hormones in White Postmenopausal Women.

ObjectivesThe purpose of this cross-sectional study was to examine whether single nucleotide polymorphisms (SNPs) in enzymes that metabolize sex steroid hormones were associated with the blood levels of these hormones in postmenopausal women and if the use of menopausal hormone therapy (MHT) could modify this association.MethodsBaseline data were collected from 932 postmenopausal women enrolled in the Minnesota Green Tea Trial. Participants filled out a questionnaire about their demographics, lifestyle factors, and medical and reproductive history. Free, bioavailable, and total serum levels of reproductive hormones were measured through liquid chromatography/tandem mass spectrometry. For genotyping of UGT1A1 (rs10928303), UGT1A4 (rs10929301, rs11673726), UGT1A6 (rs1105879, rs2070959, rs6759892), UGT1A8 (rs10167119), UGT2B7 (rs7439366), and SULT1A1 (rs9282861, rs1968752), mass spectrometry based on multiplex methods and TaqMan assays were performed. Adjusted linear models were fit to assess the associations between SNPs and blood hormones using age, body mass index (BMI), and MHT as covariates.ResultsThe mean age was 59.8 years, and the mean BMI was 25.1 kg/m2. Past or recent use of MHT was reported by 41.2% of the participants. SNPs in SULT1A1 (rs1968752 and rs9282861) and UGT1A4 (rs11673726) genes were significantly associated with estrone levels, whereas SNPs in UGT1A6 (rs6759892) and UGT1A8 (rs10167119) genes were significantly associated with bioavailable estradiol levels.ConclusionsThere was no evidence that MHT use modified the association between SNPs and sex-steroid hormone levels; however, further studies are needed to establish the potential clinical significance of UGT1A4 (rs11673726), UGT1A6 (rs6759892), and UGT1A8 (rs10167119) SNPs and the modulation of hormone levels in postmenopausal women.

Hypothyroidism is associated with higher testosterone levels in postmenopausal women with Hashimoto's thyroiditis.

There are few data about possible interaction of sex hormones and thyroid autoimmunity and function in women with Hashimoto's thyroiditis (HT) after menopause. Therefore, our aim was to investigate sex hormone levels in euthyroid (EuHT) and hypothyroid (HypoHT) postmenopausal women with HT. We performed a prospective observational clinical study that included 55 women with HT (AllHT) and 18 healthy subjects (HS) after menopause matched by age, body mass index, follicle-stimulating hormone, and menopause duration. According to their thyrotropin (TSH) level, the AllHT patients were divided into two subgroups: EuHT with TSH in the range 0.35-5.5 mU/L and HypoHT with TSH above 5.5 mU/L. Total and free testosterone (T), sex hormone-binding globulin (SHBG), oestradiol (E2), and progesterone (P) were measured in all subjects. Values are presented as mean ± SD. The Mann-Whitney U test was used for comparison of values between the groups. Correlations were tested using Kendall's tau test. In the HypoHT group, significantly higher free T levels were found in comparison to the HS group (7.89 ± 3.55 pmol/L and 7.13 ± 3.03 pmol/L, p < 0.05). Furthermore, in HypoHT, free T was significantly higher than in EuHT (7.19 ± 5.65 pmol/L, p < 0.05). SHBG was significantly lower in HypoHT compared with HS (45.4 ± 17.4 nmol/L and 60.09 ± 19.51 nmol/L, p < 0.05). No significant correlation was found between sex hormone levels and thyroglobulin and thyroid peroxidase antibodies. We report significantly higher free and total T levels in hypothyroid postmenopausal women with HT. To our knowledge, this is the first study of sex hormone levels in postmenopausal women with HT.

Study on the Association of some Single Nucleotide Polymorphisms of CYP19A1 Gene with Breast Cancer in Vietnamese Women

The CYP19A1 gene encodes for aromatase P450, which is a key enzyme in estrogen metabolism, catalyzes the conversation of testosterone to estradiol and androstenedione to estrone. It is generally believed that polymorphisms in genes coding for key enzymes involved in these pathways could effect to the activity of enzymes, which can change the level of endogenous hormones. Therefore genetic polymorphisms in hormone-related genes could increase the breast cancer susceptibility. In this study, 60 blood samples of breast cancer women and 50 control populations were analyzed to identify the genotype frequency at SNP loci rs10046 C&gt;T and rs2236722 Trp39Arg (T&gt;C) on CYP19A1 using PCR-RFLP and PCR-CTPP respectively. The data were analyzed to determine the association between these polymorphism loci and susceptibility to breast cancer. The result showed that, the genotype frequencies at SNP rs10046 in the control as: CC (14%), CT (48%), TT (38%), in case group are CC (18.33%) , CT (58.33%) and TT (23.34%); at SNP rs2236722 in the control group: TT (94%), TC (6%), in case group TT (90%), TC (10%). The OR analyses for the gene carrying the CC and TC genotypes compared with TT genotype at both loci (OR=2.01; 95% CI=0.87–4.67 with rs10046 and OR = 1.74; 95% CI= 0.40 – 7.42 with rs2236722) indicated that these SNP loci in CYP19A1 have no effect on breast cancer susceptibility.&#x0D; Keywords&#x0D; Breast cancer, SNP, rs10046, rs2236722, CYP19A1 gene&#x0D; References&#x0D; 1. Bora M. T., Tülin Ö., Halil I. K., Sennur I., Calay Z., Oğuz Ö., Turgay I. (2010), “CYP17 (T-34C) and CYP19 (Trp39Arg) Polymorphisms and their Cooperative Effects on Breast Cancer Susceptibility”, In vivo, 24, pp.71–74.2. Chen C., Sakoda L. C., Doherty J. A., Loomis M. M., Fish S., Ray R. M. (2008), “Genetic variation in CYP19A1 and risk of breast cancer and brocystic breast conditions among women in Shanghai, China”, Cancer Epidemiology Biomarkers Prevention, 17(12), pp.3457–3466.3. Dunning A. M., Dowsett M., Healey C. S., Tee L., Luben R. N., Folkerd E., Novik K. L., Kelemen L., Ogata S., Pharoah P. D., Easton D. F., Day N. E., Ponder B. A. (2004), “Polymorphisms associated with circulating sex hormone levels in postmenopausal women”, J. Natl. Cancer Inst., 96(12), pp.936–945.4. Farzaneh F., Noghabaei G., Barouti E., Pouresmaili F., Jamshidi J., Fazeli A. (2016), “Analysis of CYP17, CYP19 and CYP1A1 gene polymorphisms in Iranian women with breast cancer”, Asian Pacific Journal of Cancer Prevention, 17, pp.23–26.5. Ghisari M., Eiberg H., Long M. (2014), “Polymorphisms in phase I and phase II genes and breast cancer risk and relations to persistent organic pollutant exposure: A case-control study in Inuit women”, Environmental Health, 13(1), pp.19.6. Henderson B. E., Ross R., Bernstein L. (1988), “Estrogens as a cause of human cancer: The Richard and Hinda Rosenthal Foundation award lecture”, Cancer Research, 48, pp.246–253.7. Hirose K., Matsuo K., Toyama T. (2004), “The CYP19 gene codon 39 Trp/Arg polymorphism increases breast cancer risk in subsets of premenopausal Japanese”, Cancer Epidemiol BiomarkPrev, 13, pp.1407–1411.8. Kristensen V. N., Harada N., Yoshimura N., Haraldsen E., Lonning P. E. (2000), “Genetic variants of CYP19 (aromatase) and breast cancer risk”, Oncogene, 19, pp.1329–1333.9. Lunardi G., Piccioli P., Bruzzi P., Notaro R., Lastraioli S., Serra M. (2013), “Plasma estrone sulfate concentrations and genetic variation at the CYP19A1 locus in postmenopausal women with early breast cancer treated with letrozole”, Breast Cancer Research and Treatment, 137(1), pp.167–174.10. Miyoshi Y., Iwao K., Ikeda N., Egawa C., Noguchi S., (2000), “Breast cancer risk associated with polymorphism in CYP19 in Japanese women”, Int J Cancer, 89, pp.325–328. 11. Pineda B., García-Pérez M.Á., Cano A., Lluch A., Eroles P. (2013), “Associations between Aromatase CYP19 rs10046 Polymorphism and Breast Cancer Risk: From a Case–Control to a Meta–Analysis of 20.098 Subjects”, PLos One, 8(1), pp.1–9.12. Ralph D. A., Zhao L. P., Aston C. E., Manjeshwar S., Pugh T. W. (2007), “Age-specific association of steroid hormone pathway gene polymorphisms with breast cancer risk”, Cancer, 109, pp.1940–1948.13. Samson M., Rama R., Swaminathan R., Sridevi V., Nancy K. N., Rajkumar T., (2009), “CYP17 (T-34C), CYP19 (Trp39Arg), and FGFR2 (C-906T) polymorphisms and the risk of breast cancer in South Indian women”, Asian Pacific J Cancer Prev, 10, pp.111–116.14. Yang L., Wang X. Y., Li Y. T., Wang H. L., Wu T., Wang B. (2015), “CYP19 gene polymorphisms and the susceptibility to breast cancer in Xinjiang Uigur women”, Genetics and Molecular Research, 14(3), pp.8473–8482.15. Yoshimoto N., Nishiyama T., Toyama T., Takahashi S., Shiraki N., Sugiura H., (2011), “Genetic and environmental predictors, endogenous hormones and growth factors, and risk of estrogen receptor positive breast cancer in Japanese women”, Cancer Science, 102(11), pp.2065–2072.16. Zins K., Mogg M., Schneeberger C., Abraham D., (2014), “Analysis of the rs10046 polymorphism of aromatase (CYP19) in premenopausal onset of human breast cancer”, International Journal of Molecular Sciences, 15(1), pp.712–724.

Sex hormone levels and risk of primary open-angle glaucoma in postmenopausal women.

We evaluated the relation of prediagnostic sex hormone levels in postmenopausal women with primary open-angle glaucoma (POAG) and intraocular pressure (IOP). Among postmenopausal participants of the Nurses' Health Study, POAG cases (n = 189; diagnosed 1990-2008) and controls (n = 189) were matched on age, fasting status, and postmenopausal hormone use at blood draw (1989-1990). Plasma concentrations of estrone sulfate, estradiol, testosterone, sex hormone binding globulin, and dehydroepiandrosterone sulfate were assessed. The primary outcome was POAG; in secondary analyses, among cases only, we evaluated maximum untreated IOP at diagnosis. Multivariable-adjusted logistic/multiple linear regression models were used to evaluate tertiles (Ts) of biomarker levels and the two outcomes, adjusting for various potential confounders. We observed no significant associations of estrone, estradiol, sex hormone binding globulin, or dehydroepiandrosterone sulfate with POAG risk or with maximum IOP at glaucoma diagnosis among cases. Suggestive significant associations were observed with highest testosterone and POAG risk (T3 vs T1 multivariable-adjusted odds ratio 1.84; 95% confidence interval 1.02, 3.33; P trend 0.10). Similarly, for maximum IOP at diagnosis among cases only (mean 8 years after blood draw), higher testosterone was significantly associated with higher IOP (multivariable-adjusted difference in IOP T3 vs T1 2.17 mm Hg; 95% confidence interval 0.34, 3.99; P trend 0.02). Overall, plasma sex hormone levels in postmenopausal women were not associated with POAG risk; however, a trend of higher testosterone levels being associated with higher POAG risk and higher IOP at diagnosis was observed and needs confirmation.

Causes of elevated parathyroid hormone levels in postmenopausal women

Objective. In this study we aimed to investigate causes of hyperparathyroidism and related factors in postmenopausal women. Methods. The study was conducted on 156 postmenopausal women, 43 with normal serum parathyroid hormone (PTH) levels and 113 with elevated serum PTH levels. Serum levels of 25-OH vitamin D, calcium and phosphorus, 24-hour urine calcium, phosphorus and calcium/creatinine ratio were compared between study groups. Also, bone mineral density, age of menopause, educational level, occupation, clothing style, daylight exposure time and daily dietary calcium consumption of subjects and relationships of these parameters with parathyroid hormone levels were investigated. Results. Causes of elevated serum PTH level were vitamin D deficiency in 92.9% and primary hyperparathyroidism in 4.4% of study group. Serum PTH levels were significantly higher in housewives ( p <0.001), women with less than a high school graduates ( p =0.008), and the veiled women ( p =0.025). Serum 25-OH vitamin D levels were significantly lower in the veiled covered ( p =0.002) and participants with less than a high school graduate ( p =0.041). Significant negative correlation was detected between serum 25-OH vitamin D and the logarithmic value of serum PTH levels (r= -0.188; p =0.019). Conclusions. Vitamin D deficiency was common in all postmenopausal women but especially in those with lower education level and the veiled. Postmenopausal women should be screened for vitamin D deficiency and encouraged to benefit more from sunlight. Also, enriching foods in the markets with vitamin D may be helpful for decreasing hyperparathyroidism in this population.

Correlation between Reproductive Hormonal Level and Osteoporosis among Women in Mongolia.

Background:Postmenopausal osteoporosis is the most common bone metabolic disease associated with low bone mineral density (BMD) and osteopathic fragility fractures, which can lead to significant morbidity. The objective of this study was to investigate the relationship between serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels and bone mineral density (BMD) across the stages of menopause in Mongolian women.Methods:Two hundred sixty participants aged 50.1±4.4 years were enrolled in the study. Blood samples were obtained from each participant and analyzed using ELISA. Data were first stratified and analyzed by bone mineral density status (osteoporotic, osteopenic, and normal) and then by menopause status. Between group differences were analyzed using t-tests, and correlations were assessed using the Spearman rank order test, with Bonferonni correction. The data were analyzed using Statistical Package Statistical Software version 20.0 (SPSS Inc., Chicago, IL). Significance was set at p<0.05.Results:The mean menopausal age was 48.4±3.4, which is comparable to the Mongolian population mean menopausal age. The mean serum estradiol level in the normal BMD group was 18.3±13.1 pg/ml and 15.8±10.7 pg/ml in the osteoporotic group. The mean serum FSH in the normal BMD group was 54.5±44.1 pg/ml and 81.3±34.2 pg/ml in the osteoporotic group. The mean serum LH level in the normal BMD group was 53.1±41.2 and 75.1±26.1 pg/ml in the osteoporotic group. The mean T and Z score were lower in the osteoporotic group. FSH and LH levels significantly differed across menopause stages in that those who were post-menopausal had higher levels compared to those who were pre- or peri-menopausal. Both hormones, FSH and LH, showed weak negative correlations with BMD level, but not E2. There were significant negative correlations between FSH and Speed of Sound (SOS) (r=−0.16; p<0.01), and between osteoporosis with age (r=−0.30, p<0.05) and number of childbirths (r=−0.14 p<0.05).Discussion:Osteoporosis is a significant problem with associations to hormone levels in post-menopausal women. In our study, mean serum estradiol levels decreased with age, and the mean FSH and LH levels were higher in women of later menopausal stage. Further study is warranted to investigate the bone related studies to establish better statistical references among Mongolian women.

Serum of 25-Hydroxyvitamin D and Intact Parathyroid Hormone Levels in Postmenopausal Women with Hip and Upper Limb Fractures.

To assess the serum of 25-hydroxyvitamin D (25(OH)D) and intact parathyroid hormone (iPTH) levels in postmenopausal women from northern China with hip and upper limb fractures. Case-control. Affiliated Hospital of Qingdao University. Postmenopausal women diagnosed with hip fracture (n = 335) and matched controls without fracture (n = 335). Between 2011 and 2013, fasting venous samples were analyzed for 25(OH)D, iPTH, alkaline phosphatase (ALP), calcium, and phosphorus. All women completed a standardized questionnaire designed to document putative risk factors for fractures. Eight percent of participants had vitamin D deficiency, and 66.0% had secondary hyperparathyroidism. Serum 25(OH)D levels were significantly (P < .001) lower in women with hip fracture than in controls. Multivariate logistic regression analysis adjusted for common risk factors showed that serum 25(OH)D of 20 ng/mL or less was an independent indicator of hip fracture (odds ratio (OR) = 2.98, 95% confidence interval (CI) = 2.11-4.20) and concomitant upper limb fracture in those with existing hip fractures (OR = 4.77, 95% CI = 1.60-10.12). The area under the receiver operating characteristic curve of 25(OH)D was 0.77 (95% CI = 0.68-0.84) for hip fracture and 0.80 (95% CI = 0.72-0.89) for hip and upper limb fractures. Vitamin D insufficiency and secondary hyperparathyroidism were a common problem in postmenopausal women who presented with concomitant hip and upper limb fractures, suggesting that they might contribute to the pathophysiology of fractures in postmenopausal women.

Abstract P3-07-22: RS1008805 polymorphism in CYP19A1 gene is related to the efficacy of hormone therapy in early breast cancer

Abstract Purpose It has been suggested that genetic polymorphisms in CYP19A1 gene were related to aromatase activity as well as circulating steroid hormone levels in postmenopausal women. Therefore, it is biologically reasonable that CYP19A1 rs1008805 (A/G) polymorphism may be associated with clinical outcome for hormone therapy. Methods Genotyping for CYP19A1 polymorphism rs1008805 was performed on 287 women with HR-positive early breast cancer. Associations were evaluated between CYP19A1 rs1008805 genotypes and disease-free survival (DFS). Results Based on the analysis of the whole cohort, no significant differences were observed between rs1008805 genotypes and DFS, 5-year DFS rate. However, in postmenopausal women, rs1008805 genotypes were significantly associated with DFS and 5-years DFS rate (AA versus AG versus GG: 89.2 months versus 58.2 versus 32.7 months; 55.9% versus 47.8% versus 0%; P = 0.019). In addition, when the population was subgrouped into two cohorts, women carrying GG variant have a poorer DFS, 5-years DFS rate (GG versus AA or AG: 32.7 months versus 70.6 months; 0% versus 52.1%; HR, 3.613; 95% CI,1.380-9.457; P = 0.005). Furthermore, being adjusted by patients features in multivariate analyses, GG genotype remained an independent prognostic factor for DFS (HR, 3.439; 95% CI, 1.251-9.456; P = 0.017). However, there was no significant differences in DFS and 5-years DFS rate between women harbor the minor allele and those with the homozygous common allele (AG or GG versus AA: 52.4 months versus 89.2 months; 41.0% versus 52.9%; HR, 1.288; 95% CI, 0.705-2.353; P = 0.408). In addition, there were no differences between rs1008805 polymorphisms and DFS among premenopausal women. Conclusions The homozygous minor allele (GG) of CYP19A1 rs1008805 is significantly associated with worse clinical outcome of hormone therapy in postmenopausal HR-positive early breast cancer patients. If confirmed, genotyping for CYP19A1 polymorphisms rs1008805 may provide predictive information for better selection of endocrine treatment. Citation Format: Wang X, Shao X, Zheng Y, Shi L, Huang Y. RS1008805 polymorphism in CYP19A1 gene is related to the efficacy of hormone therapy in early breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-22.

RS1008805 polymorphism in CYP19A1 gene in relation to the efficacy of hormone therapy in early breast cancer.

e11568 Background: It has been suggested that genetic polymorphisms in CYP19A1 gene were related to aromatase activity as well as circulating steroid hormone levels in postmenopausal women. Therefo...

Relationship of RS4646 polymorphism in CYP19A1 gene to the efficacy of hormone therapy in early breast cancer.

e11516 Background: Polymorphisms in the aromatase CYP19A1 gene have been shown to alter aromatase activity as well as circulating steroid hormone levels in postmenopausal women. The aim was to verify the potential association between CYP19A1 genetic polymorphisms and clinical outcome of hormone therapy in hormone receptor (HR) - positive early breast cancer. Methods: Genotyping for CYP19A1 rs4646 (C/A) polymorphism was performed on 287 Chinese women with HR-positive early breast cancer in Zhejiang Cancer Hospital. Associations were evaluated between CYP19A1 rs4646 genotypes and disease-free survival (DFS). Results: Overall, women with the minor allele (AA or AC) had an improved DFS when compared with those carrying the homozygous common allele (CC) (62.7 months versus 55.6 months; HR, 0.745; 95% CI, 0.562-0.988; p = 0.04). The difference was further demonstrated by multivariate analyses (HR, 0.681; 95 % CI, 0.506-0.917; p = 0.011). In premenopausal women, AA genotype was associated with a prolonged DFS (9...

The relationship between bilateral oophorectomy and plasma hormone levels in postmenopausal women.

Oophorectomy prior to natural menopause reduces breast cancer risk. We evaluated whether timing of oophorectomy (during premenopause vs. postmenopause) or hysterectomy was associated with hormone levels, specifically estradiol, estrone, estrone sulfate, testosterone, sex hormone binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), and prolactin, using data from the Nurses' Health Study. We included 2,251 postmenopausal women not using hormones who provided blood samples in 1989-1990 and/or 2000-2002, and who were controls in various nested case-control studies. We used multivariate linear mixed-effects models to assess geometric mean hormone levels by surgery status. Bilateral oophorectomy was associated with 25% lower testosterone levels versus women with natural menopause (20.8 vs. 15.5 ng/dL) (P < 0.0001) with no effect of timing of surgery (P = 0.80). SHBG levels were lower among women with a premenopausal oophorectomy (52.2 nmol/L) versus those with natural menopause (58.1 nmol/L) or a postmenopausal oophorectomy (62.0 nmol/L) (P = 0.02). There was no significant association of oophorectomy with estradiol, estrone, estrone sulfate, DHEAS, or prolactin levels (P ≥ 0.23). A simple hysterectomy was associated with a significant 8% lower testosterone (P = 0.03) and 14 % lower DHEAS (P = 0.02) levels compared with women with natural menopause but not with other hormone levels. Although limited by small numbers, our findings suggest no differential influence of timing of surgery on sex hormone levels. The reduction of testosterone levels in women with oophorectomy or hysterectomy suggests a possible role of this hormone in postmenopausal breast cancer development.

Effect of anastrozole on hormone levels in postmenopausal women with early breast cancer

Objectives The aim of this study was to investigate the influence of anastrozole on serum hormone levels in postmenopausal women with hormone receptor-positive breast cancer.Methods We prospectively determined serum levels of estradiol, testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), follicle stimulating hormone (FSH) and luteinizing hormone (LH) at screening, as well as after 12 and 24 months of treatment and studied the associations with markers of bone turnover and bone mineral density (BMD).Results Altogether, a full set of hormone levels was available for 70 patients. Anastrozole treatment led to decreases of 92.1% for estradiol and 11.1% for LH over the observation period (p < 0.001). Conversely, FSH, DHEAS and testosterone concentrations increased by 5.9%, 33.3% and 50%, respectively (p < 0.001). SHBG levels remained stable during the 24 months of treatment (p = 0.355). There were modest associations between FSH, SHBG, CrossLaps and N-terminal propeptide of human procollagen type I (p < 0.05). Moreover, SHBG correlated positively with the BMD of femoral neck, total hip, total hip T-score, lumbar spine and the lumbar spine T-score, whereas FSH and estradiol correlated with the lumbar spine T-score (p < 0.05).Conclusions During the 24 months of follow-up, treatment with anastrozole decreased the serum levels of estradiol and LH. Furthermore, we found notable increases of serum levels of FSH, DHEAS and testosterone in the first 12 months of treatment, stabilizing thereafter. Additionally, we were able to correlate hormone levels with markers of bone turnover and BMD for the first time in this regard.