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Mouse model for neurodegenerative disorders
SCIENCE AND MEDICINE
NEWS Oestrogen fails to halt Alzheimer’s disease progression for women taking placebo. There was also no significant difference between the groups in measures of mood, memory, attention, language skills, motor function, or activities of daily living. Nonetheless, note the authors, “numerous publications with broadbased distribution” are supporting the use of oestrogen in women with Alzheimer’s disease to improve cognition and delay disease progression. “Such clinical practice, begun in advance of rigorous clinical trials, could be detrimental to patient outcomes”, they warn (JAMA 2000; 283: 1007–15). “The results are clear and unequivocal, but they really relate only to that specific group of women who are about 75 years of age and already have the disease”, comments Bennett Shaywitz (Yale University School of Medicine, New Haven, CT, USA). “The notion that oestrogen can improve Mouse model for neurodegenerative disorders cognition is still a very Scientists have bred a transgenic mouse strain that tenable hypothesis, and might help elucidate the earliest events in neurohas been shown in other degenerative diseases such as Alzheimer’s and studies”, he insists. “It Parkinson’s disease. The mice overexpress human might still be important ␣-synuclein, a protein originally isolated from plaques in improving cognition in brains of people with Alzheimer’s disease. The in women in midlife or mice developed intranuclear and cytoplasmic in older women without inclusions, lost dopaminergic termini in the basal Alzheimer’s disease.” ganglia, and developed motor defects. These results, And, adds Mulnard, says co-author Lennart Mucke (University of California women who have at San Francisco, CA, USA), “suggest that blocking Alzheimer’s disease the accumulation of ␣-synuclein might help prevent or should not be prevented treat Parkinson’s and related conditions” (Science from receiving oestro2000; 287: 1265–69). Jane Bradbury gen. “We know oestro-
estrogen replacement therapy neither improves cognition nor halts the decline of women with Alzheimer’s disease, report US researchers. “We were surprised and quite disappointed”, says lead author Ruth Mulnard (University of California, Irvine, CA, USA). “Given the early evidence and the epidemiological data, we thought oestrogen would really become part of the armamentarium for treating women with Alzheimer’s disease.” Mulnard and co-workers in the Alzheimer’s Disease Cooperative Study studied 97 women with mildto-moderate Alzheimer’s disease who were assigned low-dose (0·625 mg) or high-dose (1·25 mg) oestrogen or placebo daily. After 1 year, the average score on the 7-point Clinical Global Impression of Change (CGIC) scale for women receiving oestrogen was 5·1, compared with 5·0
O
gen has benefits for other body systems. If it is beneficial for a woman’s heart, bone, bladder or whatever is
Ensuring a mentally fit old age?
being treated, then it should not be withheld simply because it won’t help cognitively”, she stresses. Mulnard also remains hopeful that a US trial underway in women at high risk for Alzheimer’s disease will show that oestrogen can prevent disease onset. But Thomas Chase of the US National Institute of Neurological Disorders and Stroke (Bethesda, MD, USA) argues that “it is time to move on to other things”. Past studies that suggested that oestrogen was beneficial in Alzheimer’s disease “were fairly slender, and doing a quick trial in small numbers of patients can often give funny results that are hard to reproduce”, he says. So what about the ongoing prevention trials? “This impressive negative study limits their prospects and raises the probability that they will not find a positive result”, he concludes. Marilynn Larkin
Male contraceptive pill would be acceptable to men and women
T
wo multicentre surveys reveal that most men would welcome a hormonal method of male contraception. And, contrary to popular belief, most women would “trust their partners to use a ‘male pill’”. These findings, says researcher Richard Anderson (Centre for Reproductive Biology, University of Edinburgh, UK), “should encourage more drug-company involvement in male-pill development”.
THE LANCET • Vol 355 • February 26, 2000
450 men in Edinburgh, Shanghai, and Hong Kong, and 493 men in Cape Town were asked about their attitudes to a male pill. Depending on the centre, 44–83% of men said that they would use a male contraceptive pill. Overall, a pill was more acceptable than an injection, which was more acceptable than an implant. Men, says Anderson, see hormonal contraception as a “longterm option, after they have had a
couple of children but before they are willing to be vasectomised”. In the second survey, a similar number of women were asked how they felt about a male pill. 65% of them thought contraception should be more evenly shared, and only 2% said they would not trust their partner to use a male pill (Hum Reprod 2000; 15: 637–45, 646–49). Jane Bradbury
727
NEWS Oestrogen fails to halt Alzheimer’s disease progression for women taking placebo. There was also no significant difference between the groups in measures of mood, memory, attention, language skills, motor function, or activities of daily living. Nonetheless, note the authors, “numerous publications with broadbased distribution” are supporting the use of oestrogen in women with Alzheimer’s disease to improve cognition and delay disease progression. “Such clinical practice, begun in advance of rigorous clinical trials, could be detrimental to patient outcomes”, they warn (JAMA 2000; 283: 1007–15). “The results are clear and unequivocal, but they really relate only to that specific group of women who are about 75 years of age and already have the disease”, comments Bennett Shaywitz (Yale University School of Medicine, New Haven, CT, USA). “The notion that oestrogen can improve Mouse model for neurodegenerative disorders cognition is still a very Scientists have bred a transgenic mouse strain that tenable hypothesis, and might help elucidate the earliest events in neurohas been shown in other degenerative diseases such as Alzheimer’s and studies”, he insists. “It Parkinson’s disease. The mice overexpress human might still be important ␣-synuclein, a protein originally isolated from plaques in improving cognition in brains of people with Alzheimer’s disease. The in women in midlife or mice developed intranuclear and cytoplasmic in older women without inclusions, lost dopaminergic termini in the basal Alzheimer’s disease.” ganglia, and developed motor defects. These results, And, adds Mulnard, says co-author Lennart Mucke (University of California women who have at San Francisco, CA, USA), “suggest that blocking Alzheimer’s disease the accumulation of ␣-synuclein might help prevent or should not be prevented treat Parkinson’s and related conditions” (Science from receiving oestro2000; 287: 1265–69). Jane Bradbury gen. “We know oestro-
estrogen replacement therapy neither improves cognition nor halts the decline of women with Alzheimer’s disease, report US researchers. “We were surprised and quite disappointed”, says lead author Ruth Mulnard (University of California, Irvine, CA, USA). “Given the early evidence and the epidemiological data, we thought oestrogen would really become part of the armamentarium for treating women with Alzheimer’s disease.” Mulnard and co-workers in the Alzheimer’s Disease Cooperative Study studied 97 women with mildto-moderate Alzheimer’s disease who were assigned low-dose (0·625 mg) or high-dose (1·25 mg) oestrogen or placebo daily. After 1 year, the average score on the 7-point Clinical Global Impression of Change (CGIC) scale for women receiving oestrogen was 5·1, compared with 5·0
O
gen has benefits for other body systems. If it is beneficial for a woman’s heart, bone, bladder or whatever is
Ensuring a mentally fit old age?
being treated, then it should not be withheld simply because it won’t help cognitively”, she stresses. Mulnard also remains hopeful that a US trial underway in women at high risk for Alzheimer’s disease will show that oestrogen can prevent disease onset. But Thomas Chase of the US National Institute of Neurological Disorders and Stroke (Bethesda, MD, USA) argues that “it is time to move on to other things”. Past studies that suggested that oestrogen was beneficial in Alzheimer’s disease “were fairly slender, and doing a quick trial in small numbers of patients can often give funny results that are hard to reproduce”, he says. So what about the ongoing prevention trials? “This impressive negative study limits their prospects and raises the probability that they will not find a positive result”, he concludes. Marilynn Larkin
Male contraceptive pill would be acceptable to men and women
T
wo multicentre surveys reveal that most men would welcome a hormonal method of male contraception. And, contrary to popular belief, most women would “trust their partners to use a ‘male pill’”. These findings, says researcher Richard Anderson (Centre for Reproductive Biology, University of Edinburgh, UK), “should encourage more drug-company involvement in male-pill development”.
THE LANCET • Vol 355 • February 26, 2000
450 men in Edinburgh, Shanghai, and Hong Kong, and 493 men in Cape Town were asked about their attitudes to a male pill. Depending on the centre, 44–83% of men said that they would use a male contraceptive pill. Overall, a pill was more acceptable than an injection, which was more acceptable than an implant. Men, says Anderson, see hormonal contraception as a “longterm option, after they have had a
couple of children but before they are willing to be vasectomised”. In the second survey, a similar number of women were asked how they felt about a male pill. 65% of them thought contraception should be more evenly shared, and only 2% said they would not trust their partner to use a male pill (Hum Reprod 2000; 15: 637–45, 646–49). Jane Bradbury
727