Estradiol is a naturally occurring estrogen hormone and common medication used in various hormone treatments, such as menopausal hormone therapy and birth control. Previous studies by this research team found giving estradiol replacement in a rat model of menopause caused the rats to consume more of an offered sugar solution.

Highly palatable foods

Because the opioid system is known to contribute to overindulgence of highly palatable foods;l the researchers decided to examine its role in estradiol’s impact on sugar intake. Rats are assign to either estradiol treatment or a control. Researchers then continuously infused rats with either naltrexone, which blocks opioid receptors, or saline.

In a second experiment, the research team injected naltrexone or DAMGO; a synthetic compound that stimulates the opioid system, into an area of the brain associated with reward. In the first experiment; naltrexone treatment reversed the estradiol-related increase in sugar consumption. Injection of DAMGO stimulated sugar intake in both treated and control rats, but the effect was smaller in estradiol-treated rats than in control rats.

Opioid receptors

These suggests that the opioid system plays a role in the estrogen-induced enhancement of sugar intake, but opioid receptors in the nucleus accumbens is not likely to be directly involved in the estrogen-induced enhancement of sugar intake. Lead author Kurumi Iida noted that these findings suggest that extra sugar intake caused by estradiol “is possibly mediated by the opioid system.” However; a potential site of the action for this phenomenon remains unknown.

Alzheimer’s Disease (AD) is important for UK women as it is now the commonest cause of death; having surpassed heart disease; which remains the main cause of death in men. While it is establish that the hippocampus is the seat of the patho-physiology of AD; there are no definitive interventions to prevent or treat this awful pandemic; and any publication on AD will attract public attention and has the potential to modify behavior.

We are therefore concerned that in their recent paper in the BMJ, Savolainen-Peltonen; seem to make claims that are misleading to the scientific community and the public. The objective of their study was clearly specified: to compare the use of hormone therapy between Finnish postmenopausal women with and without a diagnosis of AD. Yet they have ended up reporting that the use of systemic hormone therapy was associated with a 9-17% increased risk of AD.

Hormone treatment

The design of a retrospective case-control study such as this allows the authors to conclude on the association between AD and exposure to hormone treatment in their past; but any claim on the odds or risk of AD is misleading, and raises epidemiological suspicion of the other findings.
The odds; as used in horse racing and betting; and odds ratio; as used in science; are completely different from each other. Each is completely different from measures of effect use to measure risk of an event like AD; such as relative risk, risk ratio or risk rate. To clarify; in science one can only measure the risk of developing an event.
Although there have been numerous publications in the past; it has always been senseless to measure the risk of using HRT; since in reality what is often being measure is exposure. Especially in a retrospective analysis; it makes more sense to measure the odds or odds ratio of using HRT in women who have a disease such as AD. Thus Tables 2 and 3 that report on the odds ratio of AD are scientifically misleading because they can only measure the exposure; that is; the odds ratio of exposure to HRT.