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Hormone replacement therapy once seemed like a wonderful means to help women age gracefully. By dosing menopausal women with estrogen and progesterone as their bodies began to produce decreased amounts of those hormones, doctors believed they could help fend off heart disease, osteoporosis and cancer.

But those beliefs collapsed in 2002, when researchers pulled the plug three years early on the Women’s Health Initiative, a large-scale, federally funded study of hormone replacement therapy (HRT). They had found that the therapy produced an increased risk of breast cancer, heart attack, stroke and blood clots. HRT has been pretty much taboo ever since.

Or has it?

Several studies released in the past year have revealed ways in which HRT might still be beneficial. Under certain conditions and with the right timing, they found, some women could be helped by the therapy.

Despite these findings, experts with the American Cancer Society and the American Heart Association say there’s scant chance there will be any revision on the position on HRT in the United States anytime in the near future.

“In an effort to decrease hot flashes, it’s hard to tell someone to take the breast cancer risk and the heart and stroke risk shown in other studies,” said Dr. Vincent Bufalino, a spokesman for the American Heart Association and president and chief executive of Midwest Heart Specialists, in Naperville, Ill. “If you can put up with the menopausal symptoms, you’re better off doing that than taking the risks related to hormone replacement therapy.”

Research that has shown the more positive side of HRT has included:
A report on a Mayo Clinic study that found a lower rate of colorectal cancer among older women taking HRT.
A report by American Cancer Society epidemiologists that found that women could use an estrogen-progesterone combination for less than two years with no increased risk of breast cancer. It also found that cancer risk increased dramatically after three or more years of hormone therapy and that increased risk disappeared two years after stopping HRT.
A Danish study that found an increased risk of heart attack in women 51 to 54 years old who took hormone replacement therapy, especially those who’d taken it for a long time. But it found no correlation between hormone therapy and elevated heart attack risk in older women.
A Canadian study that found women who have a genetic predisposition to breast cancer actually reduced their breast cancer risk after taking HRT.

The American and Danish studies also found that HRT involving just estrogen was far safer than HRT that included a combination of estrogen and progesterone.

Based on research like this, Canadian doctors are revising their guidelines on hormone replacement therapy.

But Bufalino and Susan M. Gapstur, vice president of epidemiology for the American Cancer Society, said that the studies do not provide enough evidence to sway current medical thinking in the United States.

“I would not say the philosophy is changing,” Gapstur said. “The critical question becomes, there’s this balance between the long-term risk of chronic diseases versus immediate concerns of hot flashes and quality of life around the postmenopausal period.”

Short-term use of hormone replacement therapy might be helpful in alleviating menopause symptoms, she said, but more study is needed to fully assess the impact of that therapy — particularly because the younger women who might benefit most from such therapy appear to be most at risk.

“What we thought we knew about hormone replacement therapy and cardiovascular disease might not be true for older women, but I think there are still a lot of questions about the risks and benefits of hormone replacement therapy for younger women,” Gapstur said. “That’s where we need to focus our attention.”

Bufalino agrees, arguing there’s little point in pushing such therapy when there’s so much downside and so little benefit.

“There are some small subgroups inside the groups that show some statistical benefit, but I think we would all be cautious at this time based on this report,” Bufalino said of the American Cancer Society research. “If you just look at it on the surface, it’s not clearly definitive.”

And perhaps adding fuel to the fire of doubts, reports emerged Aug. 5 that a pharmaceutical company that makes HRT had paid a medical communications firm to help produce 26 studies supporting its use. Those studies were published in 18 medical journals between 1998 and 2005, according to a report first published by the New York Times.

The drug maker, Wyeth, contends that the studies were scientifically accurate. None of the papers disclosed Wyeth’s role in initiating and funding the work.

Dr Michael Craig of the Institute of Psychiatry at London’s King’s College Hospital, and may have profound implications for doctors, researchers and the criminal justice system.

“These were particular serious offenders with psychopathy and without any other mental illnesses,” he told Reuters in an interview.

“Essentially what we found is that the connections in the psychopaths were not as good as the connections in the non-psychopaths. I would describe them as roads between the two areas — and we found that in the psychopaths, the roads had potholes and weren’t very well maintained.”

TIMING IS KEY

The scientists cautioned against suggestions the study could lead to screening of potential psychopathic criminals before they are able to commit crimes, saying their findings had not established how, when or why the brain links were damaged.

“The most exciting question now…is when do the potholes come — are people born with them, do they develop early in life, or are they a consequence of something else?”

Psychopathic extremes have been portrayed in Hollywood blockbusters by characters like the serial killer and cannibal Hannibal Lecter. Psychopaths often violate social norms, are manipulative, impulsive and sensation-seeking, and appear to feel no empathy or remorse.

Craig, who conducted the study, published in the journal Molecular Psychiatry with colleagues Declan Murphy and Dr Marco Catani, stressed that the numbers in brain scan study were small, with only nine psychopaths analyzed and compared with nine non-psychopaths.

“Trying to get people of this particular type to take part in a study, and also then deal with all the security you need to get them into a brain scanner, is not an easy feat,” he said.

The study used a new brain imaging technology to further analyze psychopaths’ brains after previous studies found that the amygdala part of the brain, which processes emotions, and orbitofrontal cortex, which handles impulses and decisions, are structurally and functionally different in psychopaths.

“Up until recently the technology hasn’t been available to look at the connections between those two brain areas in any meaningful way,” Craig said.

But a new technique, called diffusion tensor magnetic resonance imaging (DT-MRI), allowed the researchers to look at the white matter tract linking the two key brain areas.

As well as finding clear structural deficits in the tract in psychopathic brains, they also found the degree of abnormality was significantly linked to the degree of psychopathy.

“As for the moral significance for society, and how society wants to deal with these things, that is a little premature,” said Craig. “This is a small study and the important thing it raises is that more research needs to be done.”

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