Menopause depression: Under recognised and poorly treated.

Menopause is a biological process experienced by all people assigned female at birth. A significant number of women experience mental ill health related to the major brain gonadal hormone shifts that occur in their midlife. There is poor understanding and management of the complex mental ill health issues, with the biological brain hormone changes receiving little formal attention. The current treatment advice is to manage this special type of mental ill health in the same way that all mental ill health is managed. This leads to poor outcomes for women and their families. Many women leave the workforce earlier than expected due to menopause-related depression and anxiety, with subsequent loss of salary and superannuation. Others describe being unable to adequately parent or maintain meaningful relationships - all ending in a poor quality of life. We are a large and diverse group of national and international clinicians, lived experience and social community advocates, all working together to innovate the current approaches available for women with menopausal mental ill health. Above all, true innovation is only possible when the woman with lived experience of menopause is front and centre of this debate.

A dose-escalation phase I trial of nimotuzumab, an antibody against the epidermal growth factor receptor, in patients with advanced solid malignancies.

PURPOSE: Nimotuzumab is a humanized monoclonal antibody which inhibits the ligand-dependent activation of epidermal growth factor receptor (EGFR). We conducted a phase I trial to assess the pharmacodynamic (PD) effects of escalating doses of nimotuzumab administered alone in patients with advanced solid cancers patients. EXPERIMENTAL DESIGN: Patients were treated with escalating doses of weekly intravenous nimotuzumab at doses ranging between 100 and 800 mg. Tumor and skin biopsies were done before start of treatment and repeated 3 weeks after to assess immunohistochemical expression of EGFR and its downstream components. RESULTS: Seventeen patients were enrolled, including 1 patient never treated. Although 1 dose-limiting-toxicity (DLT) was observed at 100 mg (grade 3 fatigue), nimotuzumab dose was escalated to 800 mg with no other DLT. No grade 4 toxicity was observed. Only 3 patients developed a grade 1 acneiform rash (18.7%). One patient achieved a partial response (6.2%) and 8 patients had stable disease (50.0%). The median TTP was 2.4 months. No significant changes in EGFR, AKT, ERK and Ki67 immuno-stainings were observed between pre- and on-treatment tumor or skin biopsies. CONCLUSION: Nimotuzumab could be safety administered up to 800 mg with manageable toxicity. No relationships were found between pharmacodynamic effects on EGFR downstream signaling pathways and drug efficacy or toxicity.