scholarly journals Oestradiol Contributes to Differential Antitumour Effects of Adjuvant Zoledronic Acid Observed Between Pre- and Post-Menopausal Women

2021 ◽  
Vol 12 ◽  
Author(s):  
Victor G. Canuas-Landero ◽  
Christopher N. George ◽  
Diane V. Lefley ◽  
Hannah Corness ◽  
Munitta Muthana ◽  
...  

Clinical trials have demonstrated that adding zoledronic acid (Zol) to (neo)adjuvant standard of care has differential antitumour effects in pre- and post-menopausal women: Both benefit from reduced recurrence in bone; however, while postmenopausal women also incur survival benefit, none is seen in premenopausal women treated with adjuvant bisphosphonates. In the current study, we have used mouse models to investigate the role of oestradiol in modulating potential antitumour effects of Zol. Pre-, peri-, and post-menopausal concentrations of oestradiol were modelled in BALB/c wild-type, BALB/c nude, and C57BL/6 mice by ovariectomy followed by supplementation with oestradiol. Mice also received 40 mg/kg/day goserelin to prevent ovariectomy-induced increases in follicle-stimulating hormone (FSH). Metastasis was modelled following injection of MDA-MB-231, 4T1, or E0771 cells after ovariectomy and saline or 100 μg/kg Zol administered weekly. Supplementing ovariectomised mice with 12.5 mg/ml, 1.38 mg/ml, and 0 ng/ml oestradiol, in the presence of goserelin, resulted in serum concentrations of 153.16 ± 18.10 pg/ml, 48.64 ± 18.44 pg/ml, and 1.00 ± 0.27 pg/ml oestradiol, which are equivalent to concentrations found in pre-, peri-, and post-menopausal humans. Osteoclast activity was increased 1.5–1.8-fold with peri- and post-menopausal compared with premenopausal oestradiol, resulting in a 1.34–1.69-fold reduction in trabecular bone. Zol increased trabecular bone in all groups but did not restore bone to volumes observed under premenopausal conditions. In tumour-bearing mice, Zol reduced bone metastases in BALB/c (wild-type and nude), with greatest effects seen under pre- and post-menopausal concentrations of oestradiol. Zol did not affect soft tissue metastases in immunocompetent BALB/c mice but increased metastases 3.95-fold in C57BL/6 mice under premenopausal concentrations of oestradiol. In contrast, Zol significantly reduced soft tissue metastases 2.07 and 4.69-fold in immunocompetent BALB/c and C57BL/6 mice under postmenopausal oestradiol, mirroring the results of the clinical trials of (neo)adjuvant bisphosphonates. No effects on soft tissue metastases were observed in immunocompromised mice, and differences in antitumour response did not correlate with musculoaponeurotic fibrosarcoma (MAF), macrophage capping protein (CAPG), or PDZ domain containing protein GIPC1 (GIPC1) expression. In conclusion, oestradiol contributes to altered antitumour effects of Zol observed between pre- and post-menopausal women. However, other immunological/microenvironmental factors are also likely to contribute to this phenomenon.

2018 ◽  
Vol 9 (1) ◽  
pp. 44-49 ◽  
Author(s):  
Sadia Khanduker ◽  
Rumana Ahmed ◽  
Mafruha Nazneen ◽  
Anawarul Alam ◽  
Farhana Khondokar

Background: Menopausal health in our environment has received little attention. As a independent risk factor for dyslipidemia, the degree and pattern of derangement, though difficult to assess may adversely affect the cardiovascular health of our women.Objectives: To estimate the serum lipid profile and the atherogenic index of plasma among the pre and post- menopausal women.Materials and Methods: After an overnight fasting blood samples were collected from a group of 339 women, 140 premenopausal aged between 25-50 years and 199 postmenopausal aged between 51-70 years. Serum total cholesterol (TC), triglycerides (TG) and HDL-cholesterol were estimated by enzymatic methods and LDL-cholesterol by established mathematical methods. Atherogenic index of plasma (AIP) were calculated by using the formula (logTG/HDL-C). Statistical analysis was carried out in the two groups using the unpaired t test. Results were expressed as mean±SD. P values <0.05 were considered to be statistically significant.Results: There were statistically significant increase in serum TC (191.21±45.50 mg/dl), TG (185.83± 111.83 mg/dl) and LDL-C (118.71±38.48 mg/dl) in post-menopausal women. Their HDL-C level (38.67±10.00mg/dl) was significantly decreased. The calculated atherogenic index of plasma (AIP) was significantly higher (0.63±0.27) in post-menopausal women as compared to that in premenopausal women (0.50±0.29).Conclusion: Menopause leads to changes in lipid profile. By elevating LDL and the reduction of cardioprotective HDL is an indication that menopause is an independent risk factor for developing cardiovascular disease. These changes are caused by loss of cardio-protective effect of oestrogen.Anwer Khan Modern Medical College Journal Vol. 9, No. 1: Jan 2018, P 44-49


2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S55-S55
Author(s):  
Lisa M Troy ◽  
Sarah Witkowski

Abstract After menopause, women are at increased risk of diabetes and cardiovascular disease. A contributing factor to increased risk may be weight gain, especially visceral adiposity. Diet plays a role in maintaining weight at all ages but less is known about the specific contributions of a healthful dietary pattern after menopause. Therefore, we evaluated associations between diet and WC as a measure of visceral adiposity. We compared 869 pre- (aged 35-45 years) and 353 post-menopausal (aged 40-65 years) women from NHANES III (1988-94). Women were pre-menopausal if they self-reported menses in the past 2 months and postmenopausal if they reported no menses in past 12 months and were aged &gt; 40 years. Compared to premenopausal women, postmenopausal women consumed fewer Calories (-200 kcal/d) and had a higher mean waist circumference (+4.43 cm, p=0.007), after adjusting for age, race-ethnicity, height, physical activity, and smoking. Higher intakes of dark green vegetables (p=0.03) and lower intakes of potatoes (p=0.03), refined grains (p=0.001), and meats (p=0.04) were associated with lower WC for all women. Higher intakes of nuts and seeds and fish high in Omega-3 fatty acids were associated with smaller WC while higher intakes of poultry and dairy products were associated with higher WC in post- but not pre-menopausal women. Our findings generally support a diet high in nuts and seeds, dark green vegetables, and fish, and low in potatoes, refined grains, and meats. After menopause it may be important to incorporate fatty fish, nuts and seeds into the diet for lower visceral adiposity.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6588-6588
Author(s):  
B. M. Harris ◽  
A. C. Broxson ◽  
L. A. Anderson ◽  
J. G. Engelbrink ◽  
M. A. Zalewski ◽  
...  

6588 Background: Antiestrogen therapy has dramatically improved breast cancer survival rates but weight gain may be problematic. Studies evaluating antiestrogen therapy-related weight gain have yielded mixed results. Our primary objective was to evaluate weight changes in female breast cancer survivors (BCS) who received adjuvant anti-estrogen therapy for stage 0-III breast cancer. Methods: A retrospective chart review was conducted to evaluate weight changes in female chemo naive BCS receiving anti-estrogen therapy. Weights at initiation of hormonal therapy and at 6, 12, 24, and 36 months of follow-up were recorded. Median weight changes were calculated and were compared with Wilcoxon's signed rank test or the Kurskall-Wallis test. Results: A total of 622 women were included. The majority were white (77%), had stage I disease (78%), and were postmenopausal (82%). The median age at diagnosis was 59 years (range, 26–87). Median weight at initiation of hormonal therapy among premenopausal women was 65 kg (range 45.4–122.9). Median weight gain in this group was 0.4 kg (p = 0.009), 0.7 kg (p = 0.013), 1.9 kg (p = 0.0001), and 2.4 kg (p < 0.0001) at 6, 12, 24, and 36 months respectively. Among post-menopausal women, median weight at initiation of therapy was 71.7 kg (range 41.5–152.0) and median weight gain was 0.5 kg (p < 0.0001), 1 kg (p < 0.0001), 0.85 kg (p = 0.001), and 0.85 kg (p = 0.004) at 6, 12, 24, and 36 months respectively. Premenopausal patients had significantly more weight gain at 24 (p = 0.041) and 36 months (p = 0.005), as compared to postmenopausal patients. Among premenopausal women, 110/111 were treated with tamoxifen. Among post-menopausal women (n = 510), hormonal therapy was as follows: unknown n = 28 patients, tamoxifen n = 312, and AI n = 170. Overall, BCS treated with tamoxifen vs an AI had significantly more weight gain at 24 (p = 0.003) and 36 months (p = 0.009). Conclusions: Premenopausal patients are at higher risk for weight gain than postmenopausal patients. Further prospective research is warranted examining weight gain as a long-term side effect of anti-estrogen therapy in BCS. No significant financial relationships to disclose.


2019 ◽  
Vol 4 (2) ◽  
pp. 1-10
Author(s):  
Amrilmaen Badawi

The prevalence of breast cancer is still very high among women, in particular post-menopausal women. There are many factors contributed to the diseases, including diabetes. Recently, it has been emerged that metformin, an antidiabetic agent, is capable of reducing the risk of developing breast cancer among post-menopausal women, and act as aromatase inhibitors (AIs) which inhibits the production of estrogen. In this review, we focus in discussing the possible work mechanism of metformin as AIs and what is in the pipeline on clinical trials.


Author(s):  
Ricardo Costeira ◽  
Karla A Lee ◽  
Benjamin Murray ◽  
Colette Christiansen ◽  
Juan Castillo-Fernandez ◽  
...  

Background: Men and older women have been shown to be at higher risk of adverse COVID-19 outcomes. Animal model studies of SARS-CoV and MERS suggest that the age and sex difference in COVID-19 symptom severity may be due to a protective effect of the female sex hormone estrogen. Females have shown an ability to mount a stronger immune response to a variety of viral infections because of more robust humoral and cellular immune responses. Objectives: We sought to determine whether COVID-19 positivity increases in women entering menopause. We also aimed to identify whether premenopausal women taking exogenous hormones in the form of the combined oral contraceptive pill (COCP) and post-menopausal women taking hormone replacement therapy (HRT) have lower predicted rates of COVID-19, using our published symptom-based model. Design: The COVID Symptom Study developed by Kings College London and Zoe Global Limited was launched in the UK on 24th March 2020. It captured self-reported information related to COVID-19 symptoms. Data used for this study included records collected between 7th May - 15th June 2020. Main outcome measures: We investigated links between COVID-19 rates and 1) menopausal status, 2) COCP use and 3) HRT use, using symptom-based predicted COVID-19, tested COVID-19, and disease severity based on requirement for hospital attendance or respiratory support. Participants: Female users of the COVID Symptom Tracker Application in the UK, including 152,637 women for menopause status, 295,689 for COCP use, and 151,193 for HRT use. Analyses were adjusted for age, smoking and BMI. Results: Post-menopausal women aged 40-60 years had a higher rate of predicted COVID (P=0.003) and a corresponding range of symptoms, with consistent, but not significant trends observed for tested COVID-19 and disease severity. Women aged 18-45 years taking COCP had a significantly lower predicted COVID-19 (P=8.03E-05), with a reduction in hospital attendance (P=0.023). Post-menopausal women using HRT or hormonal therapies did not exhibit consistent associations, including increased rates of predicted COVID-19 (P=2.22E-05) for HRT users alone. Conclusions: Our findings support a protective effect of estrogen on COVID-19, based on positive association between predicted COVID-19 and menopausal status, and a negative association with COCP use. HRT use was positively associated with COVID-19 symptoms; however, the results should be considered with caution due to lack of data on HRT type, route of administration, duration of treatment, and potential comorbidities. Trial registration: The App Ethics has been approved by KCL ethics Committee REMAS ID 18210, review reference LRS-19/20-18210


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 556-556
Author(s):  
R. Aft ◽  
M. Naughton ◽  
K. Trinkuas ◽  
M. Watson ◽  
K. Weilbaecher

556 Background: Ovarian failure secondary to adjuvant chemotherapy is known to have an adverse effect on bone mineral density and to increase bone turnover markers. The effects of chemotherapy with growth factor support in the absence of hormonal changes have not been described. The impact of zoledronic acid on these changes was also explored. Methods: We evaluated bone turnover markers in 82 women undergoing neoadjuvant chemotherapy for localized stage II/III breast cancer at initial diagnosis prior to treatment and after 4 cycles of epirubicin (75mg/m2)-docetaxel (75mg/m2) with pegylated G-CSF support with or without zoledronic acid. 47% of patients were post-menopausal and all groups were balanced for other variables. Women were randomized to receive zoledronic acid 4 mg IV every 3 weeks concurrently with chemotherapy (n=41) versus no bisphosphonate treatment (n=41). Bone turnover markers included: urinary N-telopeptide (NTx), serum bone specific alkaline phosphatase (BAP)and osteocalcin (OSTEO). Results: Women, regardless of menopausal status, who received no bisphosphonate had statistically significant increases in NTx, from baseline after 3 months of neoadjuvant chemotherapy using multivariable mixed repeated measures (p=0.0213). Women who received zoledronic acid concurrently with neoadjuvant chemotherapy had statistically significant decreases in NTx (p<0.0001), BAP (p<0.0001) and OSTEO (p=0.0295) from baseline. This is the first demonstration that anthracycline-taxane chemotherapy with growth factor support increased bone turnover markers in both post-menopausal and pre-menopausal women independent of hormone therapy, radiation therapy and surgery. Conclusions: Neoadjuvant chemotherapy with anthracycline- taxane and growth factor support increased bone resorption markers in both post-menopausal and pre-menopausal women. Zoledronic acid given concurrently with each cycle of chemotherapy reversed this increase in bone turnover markers. No significant financial relationships to disclose.


2008 ◽  
Vol 18 (2) ◽  
pp. 320-323 ◽  
Author(s):  
B.A. Siesky ◽  
A. Harris ◽  
C. Patel ◽  
C.L. Klaas ◽  
M. Harris ◽  
...  

Purpose The incidence of eye disease increases with age and can often be linked to worsening cardiovascular function and increasing intraocular pressure. Estrogen is known to have vasodilatory effects in the systemic circulation. Decreased estrogen levels during menopause may therefore complicate or contribute to ocular pathologies as estrogen receptors are found in both retinal and choroidal tissue. The purpose of this investigation was to determine the effects of menopause on visual function and cardiovascular and ocular hemodynamics. Methods Twelve premenopausal and 24 postmenopausal women were evaluated at the Indiana University School of Medicine during a single study visit. Vision screening and ocular blood flow evaluations were performed, including blood pressure, heart rate, visual acuity, contrast sensitivity, intraocular pressure, and retinal capillary and retrobulbar blood flow imaging. Vision and ocular hemodynamics were compared using unpaired Student t-tests with pp<0.05 regarded as statistically significant. Results The premenopausal group had significantly lower heart rate (-16.1 b/m, p=0.0001) and systolic blood pressure (-17.7 mmHg, p=0.003) than postmenopausal subjects. Contrast sensitivity was significantly higher (measured in log units) in premenopausal women in both the right (0.25, p=0.039; 0.16, p=0.039) and left (0.45, p=0.001; 0.27, p=0.032) eyes at 9 and 18 cycles per degree, respectively. Premenopausal women also had significantly lower intraocular pressure in both the right (-2.19 mmHg, p=0.024) and left (-1.74 mmHg, p=0.035) eyes. Total ocular perfusion was not significantly different between groups. Conclusions This pilot work suggests that postmenopausal women have lower contrast sensitivity detection and elevated intraocular pressures compared to premenopausal women. Premenopausal women have lower cardiovascular risk factors, while total ocular circulation was similar to post-menopausal women.


2017 ◽  
Vol 9 (3) ◽  
pp. 204
Author(s):  
Sameena Sultana

Chronic periodontitis and osteoporosis are two interconnected medical issues, which usually develops complications in the general public. However, public is mostly unaware of their periodontal status. The research study has aimed to understand the impact of periodontal status among pre and post-menopausal women, suffering from periodontitis and osteoporosis. A cross-section approach has been selected for data collection. 70 patients were selected from the outpatient department of SRM dental college in Chennai. SPSS version 20 has been used for statistical analysis. Postmenopausal women have shown statistically significant poor periodontal status as compared to premenopausal women. Similarly, it has also been evaluated that osteoporosis played a progressive role among postmenopausal women for developing periodontitis. The study leads to the conclusion that pre and post-menopausal women must undergo a periodontal assessment on a monthly basis for developing outcomes related to the risk of fractures. Parameters are closely connected with the levels of calcium according to the tests and assessments.


Bone ◽  
2010 ◽  
Vol 46 ◽  
pp. S54-S55
Author(s):  
Emanuela Mrak ◽  
Veroniquè Frattini ◽  
Isabella Villa ◽  
GianLuigi Moro ◽  
Gianfranco Fraschini ◽  
...  

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