Effect of adjuvant endocrine therapy on hormonal levels in premenopausal women with breast cancer: the ProBONE II study.

Endocrine therapy (ET) is a key treatment modality in hormone receptor positive (HR+) early breast cancer (BC) patients. Although the anticancer activity of adjuvant ET + zoledronic acid (ZOL) has been investigated, the potential effects of ET ± ZOL on endocrine hormones in premenopausal women with HR+ early BC are not well understood. ProBONE II was prospective, double-blind, randomized controlled trial. Premenopausal patients with histologically confirmed invasive BC with no evidence of metastases and a T score >-2.5 received ET ± ZOL 4 mg every 3 months for 2 years. Serum levels of estradiol (E2), follicle-stimulating hormone, anti-muellerian hormone (AMH), inhibins A and B, sex hormone-binding globulin, parathyroid hormone, total testosterone, and vitamin D were evaluated at baseline and at every scheduled visit. Of 71 women enrolled, 70 were evaluable (n = 34, ZOL; n = 36, placebo). No statistically significant differences were observed in hormone levels, except E2 and AMH, which showed minor differences. These included decreases in serum E2 levels, which reached a nadir after 3 and 9 months in placebo and ZOL groups, respectively, and decrease in serum AMH levels throughout the study with ZOL, but remained constant with placebo after 6 months. Adverse events in ZOL-treated group were influenza-like illness (32.4 %), bone pain (32.4 %), chills (20.6 %), and nausea (23.5 %). ET ± ZOL was well tolerated. This study showed no influence of ZOL on hormonal level changes that accompany ET, supporting inclusion of ZOL in adjuvant therapy for premenopausal women with HR + BC.

Use of antidiabetic agents in the treatment of gestational diabetes mellitus in Germany, 2008-2012.

AIM: Adequate blood glucose control during pregnancy is important because gestational diabetes mellitus (GDM) is known to have adverse effects on the mother and child. Due to an increasing prevalence of GDM in recent years, more information on the use of different antidiabetic agents is required, which was the aim of the present study. MATERIAL AND METHODS: Data from 32 diabetic practices in Germany were collected from January 2008 to December 2012 and analyzed using the Disease Analyzer Database. All women with International Classification of Diseases diagnosis O24 (that is, GDM) participated, except for patients with known type I or II diabetes mellitus, who were excluded. Analysis focused on the proportion of women requiring drug treatment in general. Thereafter, subanalysis was performed with a focus on the administration of different antidiabetic agents, namely insulin, metformin, and sulfonylurea. RESULTS: Within the given timeframe, medication-based treatment for GDM significantly rose to reach 30.8% of all women with GDM. Both the administration of insulin and metformin grew considerably within the 5-year period with metformin being increasingly used without supplemental insulin and at lower dosages. Within the insulin treatment arm, insulin analogues became increasingly important. The proportion of sulfonylurea remained stable (0.2%). CONCLUSIONS: GDM is more often treated with antidiabetic agents and, due to the fact that metformin is more frequently prescribed, it can be assumed that it is increasingly regarded as a safe and effective alternative to insulin.

Effects of a low-dose oral estrogen only treatment on bone mineral density and quantitative ultrasonometry in postmenopausal women.

INTRODUCTION: The aim of this study was to evaluate an oral low-dose estrogen therapy on bone mineral density (BMD) and quantitative ultrasonometry (QUS) in osteopenic postmenopausal women. MATERIAL AND METHODS: This prospective, open-label cohort study investigated 120 postmenopausal hysterectomized women. Forty-seven women had been treated with 0.3 mg conjugated equine estrogen daily (ET). Primary end point was the change in BMD at the spine after 24 months. Secondary end points were among other changes in QUS at the os calcis and phalanges. RESULTS: After matching 42 participants in the ET group, 42 controls were analyzed. The change in BMD differed significantly after 24 months (p = 0.019). Women on ET showed significant increase of spine and hip Z-score, whereas controls showed significant decreases in spine and total hip BMD. In QUS of the os calcis and the phalanges, a number of variables showed a significant improvements with ET. CONCLUSION: Our results comprised a positive effect of an oral low-dose estrogen therapy on BMD. Limitations of the study are the small sample size and the open-label, non-randomized cohort study design. The findings are in accordance to the common literature and support the use of ET in the primary prevention of postmenopausal bone loss.

Trends and patterns of hormonal contraceptive prescribing for adolescents in primary care in the U.K.

BACKGROUND: Hormonal contraceptives are the most common method used worldwide by teenagers to prevent unwanted pregnancies. To date there are limited data about such use by teenagers in the UK. This study investigated trends and patterns of hormonal contraceptive prescribing to adolescents aged 12-18 years in UK primary care between 2002 and 2011. METHODS: A retrospective cohort study using the IMS Disease Analyzer database was conducted. All females aged 12-18 years with ≥1 prescription for a contraceptive drug between 1 January 2002 and 31 December 2011 were included. Annual prevalence of contraceptive drug prescribing was calculated, and indications for prescribing, and types of contraceptive drug prescribed, were examined. RESULTS: In 2002, 13.7% (6135/44 532) of female adolescents received prescriptions for hormonal contraceptives, compared to 19.0% (6597/34 676) in 2011. The majority of female adolescents [2002: 76.2% (4676/6135); 2011: 65.7% (4334/6597)] received a contraceptive drug for 'contraceptive management'. The combined oral contraceptive (COC), 'progestogen+estrogen', was the most commonly prescribed. Although use of progestogen-only contraceptives was lower than COCs, the number of patients who received desogestrel pills and etonogestrel implants increased during the study period; levonorgestrel pill use declined. Only one injectable progestogen, long-acting depot medroxyprogesterone acetate, was prescribed. CONCLUSIONS: Use of hormonal contraceptives among adolescents increased between 2002 and 2011, and COC usage was dominant. The increasing use of hormonal contraceptives in adolescents, especially in younger adolescents, warrants further investigation, including research into the long-term safety of these medicines in this age group.

Evaluation of efficacy, safety and effects on symptoms of androgenization of a generic oral contraceptive containing chlormadinone acetate 2 mg/ethinylestradiol 0.03 mg.

BACKGROUND: This prospective noninterventional study assessed the contraceptive efficacy, safety and the effects on signs of androgenization of the generic oral contraceptive containing 2 mg chlormadinone acetate/0.03 mg ethinylestradiol (CMA/EE) in a real-world setting. STUDY DESIGN: A total of 1440 women were investigated during a six-cycle period by 229 gynecological practices throughout Germany. RESULTS: The adjusted Pearl index was 0.136 (unadjusted: 0.271). Of 463 patients with cycle irregularities at baseline, 83.4% had regular cycles after six cycles. Likewise, 74.1% of 162 patients with spotting or breakthrough bleeding at baseline were free from these symptoms at the end of study. The percentage of patients with dysmenorrhea decreased significantly from baseline (36.5%) to visit 3 after six cycles (12.3%; p=.0001), with a significant reduction in the use of pain medication (p<.0001). Additionally, the number of patients with skin and hair problems was significantly reduced (skin: 56.3% at baseline, 19.6% after six cycles; hair: 45.7% at baseline, 13.4% after six cycles; p=.001). CMA/EE was well tolerated by the patients, and 89.44% of the gynecologists were satisfied with the treatment. CONCLUSION: Generic CMA/EE exhibits very good contraceptive efficacy, cycle control and dysmenorrhea reduction. Furthermore, treatment with generic CMA/EE led to a favorable reduction of skin and hair problems in our study.

The ZOTECT study: Effect of zoledronic acid on bone metabolism in patients with bone metastases from prostate or breast cancer.

PURPOSE: The ZOTECT study assesses the effect of zoledronic acid (ZOL) on bone-marker levels and potential correlations with disease outcomes in bisphosphonate-naive patients. METHODS: This prospective, single-arm, open-label study in bisphosphonate-naive (≥6 months) patients with bone metastases from prostate cancer (PC; n=301) or breast cancer (BC; n=99) enrolled at 98 German sites (May 2006 to July 2008) investigated the effect of ZOL (4 mg intravenously every 4 weeks×4 months, with a final follow-up at 12 months) on bone-marker levels. Secondary assessments: skeletal-related event (SRE) rate, pain, quality of life (QoL), and prostate-specific antigen levels. Endpoints were assessed using summary statistics by visit/tumor type and Kaplan-Meier analyses. RESULTS: ZOL treatment significantly decreased bone-marker levels (amino-terminal propeptide of type I collagen [P1NP], C-terminal cross-linking telopeptide of type I collagen [CTX]; P<0.0001), and this decrease was maintained through the final 1-year follow-up visit. Baseline P1NP and CTX levels correlated with extent of bone disease (P<0.0001, each) and on-treatment decreases in marker levels. Skeletal disease burden and bone-marker levels were similar between PC and BC patients, and ZOL did not significantly influence osteoprotegerin/receptor activator of nuclear factor-κB ligand levels. Only 13 SREs occurred in 11 patients, supporting the known ZOL-mediated reduction in SREs. On-treatment bone-marker level changes did not correlate with SRE rate, pain scores, or QoL. Generally, ZOL was well tolerated and adverse events were consistent with its known safety profile. CONCLUSIONS: This study confirms that ZOL therapy significantly reduces bone turnover (measured as P1NP and CTX levels) in patients with bone metastases from PC or BC.

The effect of exemestane and tamoxifen on bone health within the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial: a meta-analysis of the US, German, Netherlands, and Belgium sub-studies.

PURPOSE: We performed a meta-analysis of three sub-studies of the randomized Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial to determine the effects of exemestane and tamoxifen on bone health. METHODS: Patients received exemestane or tamoxifen as adjuvant therapy for hormone receptor-positive breast cancer. Bone mineral density (BMD) was assessed at baseline and after 12 and 24 months of treatment. Bone turnover markers were also measured. RESULTS: Patients receiving tamoxifen showed a mean increase from baseline in lumbar spine BMD of 1.2% at month 12 and 0.2% at month 24. Patients receiving exemestane showed a mean decrease from baseline of 2.6% after 12 months and 3.5% after 24 months. There were significant differences in the changes in lumbar spine BMD between treatment groups (P < 0.0001 at both time points). Changes in BMD from baseline at the total hip were also significantly different between exemestane and tamoxifen (P < 0.05 at both time points). Bone turnover markers decreased from baseline with tamoxifen and increased with exemestane. CONCLUSIONS: Exemestane resulted in decreases in BMD and increases in bone turnover markers. BMD increased and bone turnover markers decreased with tamoxifen.

The influence of chemotherapy on bone mineral density, quantitative ultrasonometry and bone turnover in pre-menopausal women with breast cancer.

INTRODUCTION: The effects of doxorubicin/cyclophosphamide (A/C; 6 cycles) chemotherapy on bone mineral density (BMD), quantitative ultrasonography (QUS) and bone turnover markers in pre-menopausal women with oestrogen receptor-negative breast cancer (BC) were compared with age-matched controls. METHODS: Among 106 women (BC=53, controls=53), BMD (spine and hip), QUS (calcaneus and phalanges) and bone marker levels were measured at baseline, 6 and 12 months. Correlations between parameters were determined by Spearman's rho. RESULTS: All BC patients became amenorrhoeic after chemotherapy and remained so for the duration of treatment. BC patients had significant bone loss at all sites (P.005) and significant increases in bone turnover (P.05). There were significant correlations between BMD, QUS and bone markers (P.05). CONCLUSIONS: Results confirm A/C's deleterious influence on bone health in pre-menopausal women with BC and established QUS's utility for monitoring bone effects. Large-scale longitudinal studies are needed to further understand and prevent bone changes following chemotherapy.