SummaryObjectives Elevated circulating androgens are risk factors for several chronic, metabolic and reproductive disorders. Metformin is an insulin-sensitizing agent that may lower androgen levels. To evaluate the effects of metformin on endogenous androgens and SHBG levels in women, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing metformin with placebo or no treatment. Data source We used OVID to search MEDLINE, EMBASE and CENTRAL until March 2007. Review methods Two reviewers independently extracted data on methodological quality, participants, interventions and outcomes of interest. Our a priori primary outcome was post-treatment measurements. In a secondary analysis, we evaluated the difference between the pre-and post-treatment levels. We computed the weighted mean difference (WMD) as a measure of effect for each outcome using the DerSimonian-Laird random effects method. We used the I 2 statistic to assess heterogeneity and explored its causes in subgroup analyses of features related to participants' characteristics and study design. Based on a regression model, we conducted sensitivity analyses by investigating the use of placebo as a predictor of effect size. Results Twenty RCTs fulfilled the inclusion criteria. Pooled WMDs in post-treatment levels between the metformin and control group were -0·31 nmol/l (95% CI -0·65 to 0·03) for total testosterone (TT), 0·10 pmol/l (95% CI -0·89 to 1·10) for free testosterone (FT), 0·14 μ mol/l (95% CI -0·34 to 0·62) for dehydroepiandrosteronesulfate (DHEAS), -0·60 nmol/l (95% CI -1·67 to 0·46) for androstenedione (AND) and 5·88 nmol/l (95% CI 2·01-9·75) for SHBG. Pooled WMDs of the pre-to post-treatment differences (i.e. with adjustment for baseline hormone levels) were -0·38 (95% CI -0·51 to -0·25) for TT, -2·71 (95% CI -10·35 to 4·93) for FT, -0·50 (95% CI -0·83 to -0·16) for DHEAS, -1·39 (95% CI -2·30 to -0·49) for AND and 6·63 (95% CI 2·32-10·94) for SHBG. In subgroup analyses, features related to the administered treatment (i.e. metformin as a single agent or as part of combined regimens) partly explained the heterogeneity. Sensitivity analyses of studies using placebo showed similar results to those not using placebo. Conclusions Our systematic review and meta-analysis provides evidence of metformin-induced changes in circulating androgens and SHBG levels in women but the quality of evidence is not high. However, there are no data from RCTs regarding these effects in postmenopausal women or healthy premenopausal women. Highquality RCTs are required to evaluate whether metformin has effects on surrogate markers and patient-important outcomes in these patient groups.

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Purpose Our objective was to determine what vial sharing techniques and other strategies were being used globally to reduce wastage from partially used single-use drug vials, what barriers are preventing these strategies being employed, and what savings are being achieved. Methods A survey, comprising 19 questions, was distributed to the membership of the International Society of Oncology Pharmacy Practitioners and British Oncology Pharmacy Association. Questions asked included how parenteral cancer drugs are obtained and prepared, what vial sharing strategies are used, what means are employed to extend stability, how prepared products are reused and what cost savings are achieved. Results In all, 74 responses were received from 20 countries, most from the United Kingdom. Some manufacturing is done by 60.8% of institution, with 41.9% making all products. Vial sharing strategies, for frequently used drugs, were employed in 53% of cases. Barriers preventing vial sharing being used included government legislation, USP 797 guidelines, and health insurance companies. Extension of stability was possible for 70.2% of centres. Most respondents reported reduction in cytotoxic and biological waste, and alleviation of drug shortages from vial sharing utilisation. Cost savings were achieved in 74% of cases and was significant in one third. Conclusions The survey has determined that drug vial wastage and expenditure can be reduced, and vial sharing facilitates this. International collaboration plus the assistance of governments and the pharmaceutical industry is vital in achieving this aim. These findings can hopefully guide oncology pharmacy in establishing appropriate strategies to reduce wastage internationally.

Gel formulation of chlormethine (CG) has gained a preeminent role among therapies available for mycosis fungoides (MF). To evaluate the frequency of use of CG for MF treatment and to determine the limits and potentialities of CG in a real-world setting.A systematic review of articles published prior to October 2021 was performed. Articles were included in the review if a full-text English version was available. MEDLINE (PubMed), Scopus, and Web of Science were each queried from their date of inception with the following terms: "mechlorethamine gel", "chlormethine gel", and "mycosis fungoides". The reference lists of the studies retrieved were searched manually. Moreover, this study included all consecutive patients with different stages of MF (from IA to IIB) who started treatment with CG gel between July 2020 and May 2021. Data of the literature were compared to our single-center real-life experience.Of the surveyed literature, 11 publications were included in the final analysis describing a total of 548 patients with MF. Eleven patients with a median (standard deviation) age of 66 years (15.1) were enrolled and followed up, receiving CG (0.02% chlormethine HCl). Response to treatment resulted higher (90.1%) in our study population than in other real-world experiences published in literature. This systematic review supports the role of CG for MF treatment, showing its limits and potentialities. Our single-center real-life experience revealed an elevated percentage of clinical response with high safety and tolerance, demonstrating its versatile use with dose and application rate adaptability. K E Y W O R D S drug-related side effects and adverse reactions, lymphoma, mechlorethamine, mycosis fungoides, nitrogen mustard compounds, cutaneous T-cell lymphoma Primary cutaneous T-cell lymphomas (CTCLs) represent a heterogeneous group of lymphoproliferative disorders involving almost exclusively the skin. 1 Mycosis fungoides (MF) is the most common entity, consisting in