I. Kyvernitakis

Effects of Exemestane and Tamoxifen Treatment on Bone Texture Analysis Assessed by TBS in Comparison With Bone Mineral Density Assessed by DXA in Women With Breast Cancer

We performed an analysis of a substudy of the randomized Tamoxifen Exemestane Adjuvant Multinational trial to determine the effects of exemestane (EXE) and tamoxifen (TAM) adjuvant treatment on bone mineral density (BMD) measured by dual-energy X-ray absorptiometry compared with the trabecular bone score, a novel grey-level texture measurement that correlates with 3-dimensional parameters of bone texture in postmenopausal women with hormone receptor-positive breast cancer for the first time. In total, 36 women were randomized to receive TAM (n = 17) or EXE (n = 19). Patients receiving TAM showed a mean increase of BMD in lumbar spine from baseline of 1.0%, 1.5%, and 1.9% and in trabecular bone score of 2.2%, 3.5%, and 3.3% at 6-, 12-, and 24-mo treatment, respectively. Conversely, patients receiving EXE showed a mean decrease from baseline in lumbar spine BMD of -2.3%, -3.6%, and -5.3% and in trabecular bone score of -0.9%, -1.7%, and -2.3% at 6-, 12-, and 24-mo treatment, respectively. Changes in trabecular bone score from baseline at spine were also significantly different between EXE and TAM: p = 0.05, 0.007, and 0.006 at 6, 12, and 24 mo, respectively. TAM induced an increase in BMD and bone texture analysis, whereas EXE resulted in decreases. The results were independent from each other.

Prevalence of menopausal symptoms and their influence on adherence in women with breast cancer.

Abstract Objectives The use of aromatase inhibitors for the adjuvant treatment of breast cancer may affect the quality of life of patients, as well as adherence to treatment. Methods Here we report the 2-year results of the 180 patients in the COMPAS study. This is the first randomized, controlled study reporting on menopausal symptoms under endocrine treatment with aromatase inhibitors in breast cancer patients, based on the Menopause Rating Scale. We analyzed the prevalence of menopausal symptoms as well as their associations with patient adherence. Results Baseline characteristics showed no significant differences among the control and the intervention groups. The majority of women experienced the symptoms at various severities. Overall, we found an increase in the prevalence of hot flushes, sleep disorders, bladder problems, dryness of the vagina as well as of joint and muscular discomfort between the 12- and 24-month visits. In compliant patients, all symptoms except for vaginal dryness improved between the 12- and 24-month visits while, in non-compliant women, hot flushes, irritability, dryness of the vagina as well as joint and muscular discomfort deteriorated. When comparing compliant and non-compliant patients, we found a significant difference only for anxiety (p = 0.028) in the 12-month analysis, as well as a large but non-significant difference for heart discomfort (p = 0.089) in the 24-month visit. Conclusions Our results indicate that the majority of women treated with aromatase inhibitors are experiencing menopausal symptoms at various severities. We showed that the mean symptom values in compliant patients improve with longer therapy duration. Furthermore, anxiety correlates with better compliance, while heart discomfort may lead to therapy discontinuation.

The Effect of Age, Sex Hormones, and Bone Turnover Markers on Calcaneal Quantitative Ultrasonometry in Healthy German Men

The aim of this cross-sectional study was to determine the age-dependent variations of calcaneal quantitative ultrasonometry (QUS) and the association with sex hormones and biochemical bone turnover markers in a large sample of unselected healthy German men. Bone measurements are expected to behave differently among men and women. The speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index (SI) of the os calcaneus were measured in 506 German men aged 20-79 yr (mean age: 45.7 yr). Additionally, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin, testosterone, dehydroepiandrosterone sulfate (DHEA-S), sex hormone-binding globulin (SHBG) as well as N-terminal propeptide of human procollagen type I (PINP), C-terminal telopeptide of type I collagen (ICTP), osteocalcin, bone-specific alkaline phosphatase, and CrossLaps were measured with standardized essays and correlated with the QUS results. The QUS results comprised an overall change of 12.4%, 3.2%, and 23.2% for BUA, SOS, and SI, respectively, between the 20-29 and 70-79 yr age groups (p ≤ 0.001). The annual rate of the age-related differences was 0.33% (standard deviation [SD]: 0.31), 0.06% (SD: 0.08), and 0.53% (SD: 0.56) for BUA, SOS, and SI, respectively. Testosterone and DHEA-S were significantly associated with QUS parameters and increasing age, whereas SHBG showed an age-related increase and was inversely related with QUS values (p < 0.05). Bone turnover markers present lower values gradually, and we found a significant correlation between carboxy-terminal collagen crosslinks (CTX), osteocalcin (OC), bone alkaline phosphatase (BAP), and QUS variables (p < 0.05).

Breast cancer and bone mineral density: the Marburg Breast Cancer and Osteoporosis Trial (MABOT II).

Objectives The current case–control study is the first to examine the relationship between bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) and quantitative ultrasonometry (QUS) in pre- as well as postmenopausal women with breast cancer compared to healthy matched controls. Methods Among 1422 women (premenopausal, n = 238, postmenopausal, n = 1184), BMD and QUS were measured. In total, 541 of the women had an incident diagnosis of breast cancer (122 premenopausal, 419 postmenopausal) without prior breast cancer treatment. Because of significant intergroup differences in multiple risk factors, a matched-pair analysis (88 premenopausal and 402 postmenopausal women with and without breast cancer) was performed. Additionally, a multiple linear regression analysis was undertaken, odds ratios were determined and subjects grouped according to quartiles of DXA and QUS results. Results DXA results (except the L1–L4 Z-score) were significantly higher in postmenopausal women with breast cancer even after a matched-pair analysis was performed (p < 0.05). In premenopausal women, we observed no significant differences in DXA results between the groups. QUS results in pre- and postmenopausal women with breast cancer were significantly higher compared with their matched controls (p < 0.001 for all, except for speed of sound in premenopausal patients, p < 0.05). Odds ratios for breast cancer risk in the second, third and fourth quartiles compared with the lowest quartile were significantly different for a number of variables. Conclusions Our results showed significantly higher BMD irrespective of the method and site of measurement in postmenopausal women with breast cancer compared to controls, even after matching for possible confounders for the first time.

Comparison of dual-energy X-ray absorptiometry with six quantitative ultrasonometry devices in women with hip fractures

Abstract Objectives Dual-energy X-ray absorptiometry (DXA) is the gold standard for assessment of bone mineral density, an important risk factor for osteoporotic fractures. Recent reports suggest that quantitative ultrasonometry (QUS) is able to predict fractures; however, only limited data in women with hip fractures are available. Methods We examined 91 postmenopausal women who had sustained an osteoporosis-related hip fracture within the past 7 days using DXA and six different QUS devices and compared them with 91 healthy age-matched controls. Results Femoral neck (FN), total hip (TH) and lumbar spine (LS) T-scores were lower in women with hip fractures compared to matched controls: − 2.38 vs. − 1.64 (p < 0.001), − 2.36 vs. − 1.44 (p < 0.001) and − 2.05 vs. − 1.50 (p = 0.41), respectively. The T-scores of the Achilles, Sahara, InSight and Omnisence QUS devices were also lower in patients with hip fractures compared to matched controls: − 3.20 vs. − 2.36 (p < 0.001), − 2.196 vs. − 1.761 (p = 0.005), − 2.631 vs. − 1.849 (p < 0.001), − 3.707 vs. − 3.030 (p = 0.032), respectively. However, the T-scores of the DBM and QUS-2 did not differ between the two groups: − 4.543 vs. − 4.324 (p = 0.352) and − 1.7 vs. − 2.0 (p = 0.465), respectively. Compared to DXA (hip), the odds ratios of the Achilles, InSight and Sahara were comparable, while the odds ratios of the DBM, Omnisence and QUS-2 were significantly lower (p ≤ 0.05). Conclusions Compared to DXA, the Achilles, Sahara and InSight QUS devices showed similar hip fracture discrimination while the DBM, Omnisence and QUS-2 did not. Therefore, some QUS devices are able to identify a clinically meaningful risk factor in women at high risk of hip fracture.

Discontinuation rates of menopausal hormone therapy among postmenopausal women in the post-WHI study era

Abstract Objectives Many women are reluctant to take menopausal hormone therapy (MHT) and discontinue the treatment within 12 months. The aim of this study was to investigate the persistence rates of combined MHT in the last decade, reflecting changes in the post-Women’s Health Initiative era. Methods We analyzed 17 020 patients receiving combined MHT from 2004 to 2013 using the Disease Analyzer database. Results After 12 months of follow-up, 44.6% and 33.5% of patients receiving 1 mg and 2 mg, respectively, of oral combined MHT were still on treatment (p < 0.0001). The persistence rate of patients receiving < 50 μg of transdermal MHT was 39.1% after 1 year of treatment and presented no differences compared to patients receiving ≥ 50 μg of transdermal MHT with a persistence rate of 38.2%. MHT start in the years 2007–2009 was associated with higher discontinuation rates (hazard ratio 1.04, p = 0.0709) than MHT start in the years 2010–2013 (hazard ratio 0.90, p = 0.0001). Conclusions Our results indicate that patients beginning their treatments in the years 2010–2013 were more treatment-persistent than patients beginning with MHT in the early years after publication of the Women’s Health Initiative study (2004–2009). Administration of low-dose oral MHT and transdermal MHT is associated with increased persistency compared to higher doses of oral MHT.

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

Abstract 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.

Persistency with estrogen replacement therapy among hysterectomized women after the Women’s Health Initiative study

ABSTRACT Objectives Many women are reluctant to undergo estrogen replacement therapy (ERT) and discontinue the treatment within 12 months. The aim of this study was to investigate the persistence rates of ERT in hysterectomized women over the past decade, reflecting changes in the post-Womens Health Initiative (WHI) era. Methods We analyzed 8045 patients receiving ERT from 2004 to 2013 using the Disease Analyzer database. Results After 12 months of follow-up, only 24.6% of patients receiving 1 mg and 24.5% of patients receiving 2 mg of oral ERT were still on treatment (p < 0.0001). The persistency rate of patients receiving <50 μg of transdermal ERT was 28.6% compared to 33.5% for patients receiving >50 μg within the 12 months of follow-up. ERT that began in 2007–2009 was associated with a higher discontinuation rate (hazard ratio 1.06, p = 0.0660) than ERT that began in 2010–2013 (hazard ratio 0.88, p = 0.0001). Conclusions Our results indicate low persistency rates in women on ERT irrespective of the dose as well as the route of administration. However, a decrease in discontinuation rates was found when comparing women in the early vs. late post WHI era.

Comparison of combined low-dose hormone therapy vs. tibolone in the prevention of bone loss

Abstract Objectives: To compare the effects on bone mineral density (BMD) measured by dual-energy X-ray absorptiometry at the lumbar spine, the femoral neck and the total hip following 2 years of treatment with a low-dose combined hormone therapy (HT) comprised of 1 mg estradiol and 0.5 mg norethisterone acetate (E2/NETA) versus 2.5 mg tibolone in postmenopausal women. Additionally, quantitative ultrasonometry (QUS) of the os calcaneus and of the phalanges was performed. Methods: Changes in BMD, QUS and side-effects were assessed at baseline, 6, 12 and 24 months in 50 postmenopausal women who received either E2/NETA (n = 26) or tibolone (n = 24) for 2 years. Results: Compared to women on tibolone, women receiving E2/NETA showed a significant increase in BMD from baseline to 12 and 24 months at the lumbar spine (3.07%, 3.86%; p < 0.01 vs. 1.13%, 2.23%; p < 0.05), and at the total hip (1.33%, 1.69%; p < 0.01 vs. 0.76%, 0.70%) and at the femoral neck from baseline to 24 months (1.10%; p < 0.05). QUS indices only showed a significant change with the ultrasound bone profile index with E2/NETA at 6 months (-2.32%; p < 0.001). Conclusions: Low-dose E2/NETA showed a significantly higher increase in BMD compared to tibolone. QUS measurement was not considered to comprise beneficial effects in monitoring drug-induced bone changes.