The prospect of a hormonal male contraceptive is no longer distant. Data on the potential impact of this improvement in contraceptive provision, however, is limited, particularly between different cultures. We have therefore carried out a multi-centre study to assess men's attitudes to proposed novel hormonal methods. Questionnaire-based structured interviews were administered to men in Edinburgh, Cape Town, Shanghai and Hong Kong. Approximately 450 men were interviewed in Edinburgh, Shanghai and Hong Kong, and a slightly larger group (n = 493) in Cape Town to give samples (n > 150) of black, coloured and white men. Knowledge of existing male and female methods of contraception was high in all centres and groups. The majority of men welcomed a new hormonal method of contraception, 44-83% stating that they would use a male contraceptive pill. Overall, a pill was more acceptable than an injectable form (most popularly given at 3-6 month intervals); long-acting implants were least so except in Shanghai. Familiarity with comparable female methods appeared to influence acceptability, for both oral and injectable methods. Hong Kong was the only centre where a male method (condom) was currently the most commonly used; men there appeared to rate the convenience of condoms highly while being least likely to think that they provided effective protection against pregnancy compared to other centres, and were least enthusiastic about novel male methods. The acceptability of potential male hormonal methods of contraception was high in some groups but showed wide variability, determining factors including cultural background and current contraceptive usage. These results suggest that the emerging emphasis that men should have greater involvement in family planning will be substantiated when appropriate contraceptive methods become available.

Several lines of recent evidence indicate that the amyloid precursor protein-derived C-terminal fragments (APP-CTFs) could correspond to an etiological trigger of Alzheimer’s disease (AD) pathology. Altered mitochondrial homeostasis is considered an early event in AD development. However, the specific contribution of APP-CTFs to mitochondrial structure, function, and mitophagy defects remains to be established. Here, we demonstrate in neuroblastoma SH-SY5Y cells expressing either APP Swedish mutations, or the β-secretase-derived APP-CTF fragment (C99) combined with β- and γ-secretase inhibition, that APP-CTFs accumulation independently of Aβ triggers excessive mitochondrial morphology alteration (i.e., size alteration and cristae disorganization) associated with enhanced mitochondrial reactive oxygen species production. APP-CTFs accumulation also elicit basal mitophagy failure illustrated by enhanced conversion of LC3, accumulation of LC3-I and/or LC3-II, non-degradation of SQSTM1/p62, inconsistent Parkin and PINK1 recruitment to mitochondria, enhanced levels of membrane and matrix mitochondrial proteins, and deficient fusion of mitochondria with lysosomes. We confirm the contribution of APP-CTFs accumulation to morphological mitochondria alteration and impaired basal mitophagy in vivo in young 3xTgAD transgenic mice treated with γ-secretase inhibitor as well as in adeno-associated-virus-C99 injected mice. Comparison of aged 2xTgAD and 3xTgAD mice indicates that, besides APP-CTFs, an additional contribution of Aβ to late-stage mitophagy activation occurs. Importantly, we report on mitochondrial accumulation of APP-CTFs in human post-mortem sporadic AD brains correlating with mitophagy failure molecular signature. Since defective mitochondria homeostasis plays a pivotal role in AD pathogenesis, targeting mitochondrial dysfunctions and/or mitophagy by counteracting early APP-CTFs accumulation may represent relevant therapeutic interventions in AD.

Despite a renewed interest in the development of hormonal contraceptives for men, many discussions about the potential acceptability of a 'male pill' end by speculating whether women would trust their partners to use the method reliably. To determine the views of women, we undertook a survey of 1894 women attending family planning clinics in Scotland (450), China (900) and South Africa (544). In all centres over 65% of women thought that the responsibility for contraception falls too much on women. More than 90% in South Africa and Scotland thought that a 'male pill' was a good idea, with Chinese women (71% in Hong Kong and 87% in Shanghai) only slightly less positive. Only 13% of the total sample did not think that hormonal male contraception was a good idea and only 36 women (2% of the total) said that they would not trust their partner to use it. 78% of Scottish women, 71% of Shanghai women, and 78% of white women and 40% of black and coloured women in Cape Town thought that they would use the method. This survey should dispel the myth that women would not trust their partners to use a 'male pill' reliably and illustrates the potential market for the method.