Higher dementia risk in women with prolonged fertility

September 17, 2020

Science Daily/University of Gothenburg

Women with a longer reproductive period had an elevated risk for dementia in old age, compared with those who were fertile for a shorter period, a population-based study from the University of Gothenburg shows.

"Our results may explain why women have a higher risk of developing dementia and Alzheimer's disease than men after age 85, and provide further support for the hypothesis that estrogen affect the risk of dementia among women," says Jenna Najar, a medical doctor and doctoral student at Sahlgrenska Academy who also works at AgeCap, the Centre for Ageing and Health at the University of Gothenburg.

The study, now published in the journal Alzheimer's & Dementia, covers 1,364 women who were followed between 1968 and 2012 in the population studies collectively known as the "Prospective Population-based Study of Women in Gothenburg" (PPSW) and the "Gothenburg H70 Birth Cohort Studies in Sweden" (the H70 studies). The "reproduction period" spans the years between menarche (onset of menstruation) and menopause, when menstruation ceases.

Of the women studied with a shorter reproductive period (32.6 years or less), 16 percent (53 of 333 individuals) developed dementia. In the group of women who were fertile a longer period (38 years or more), 24 percent (88 of 364) developed dementia. The difference was thus 8 percentage points.

The study shows that risk for dementia and Alzheimer's disease increases successively for every additional year that the woman remains fertile. The association was strongest for those with dementia onset after age 85, and the effect was most strongly associated with age at menopause.

These results persisted after adjustment for other factors with an influence, such as educational attainment, physical activity, BMI, smoking, and cardiovascular disease. On the other hand, no association was found between dementia risk and age at menarche, number of pregnancies, duration of breastfeeding, or exogenous estrogen taken in the form of hormonal replacement therapy (HRT) or oral contraceptives.

Several studies have investigated how estrogen in the form of HRT affects dementia risk. Some studies show that dementia risk falls and others that it rises, especially in women who take estrogen late in life.

In the current study Jenna Najar has, instead, investigated the long-term association between factors related to endogenous estrogen and dementia.

"What's novel about this study, too, is that we've had access to information about several events in a woman's life that can affect her estrogen levels. Examples are pregnancies, births, and breastfeeding. Being pregnant boosts estrogen levels tremendously; then they decline once the baby is born, and if women breastfeed the levels fall to extremely low levels. The more indicators we capture, the more reliable our results are," Najar says.

Ingmar Skoog, professor of psychiatry at Sahlgrenska Academy, University of Gothenburg and head of AgeCap, led the study.

"The varying results for estrogen may be due to it having a protective effect early in life but being potentially harmful once the disease has begun."

At the same time, Skoog points out that the duration of women's fertile periods is one risk factor for dementia among many.

Most women whose menopause is delayed do not develop dementia because of this factor alone. However, the study may provide a clue as to why women are at higher risk than men for dementia after age 85, the most common age of onset. Alzheimer's disease, on the other hand, starts developing some 20 years before symptoms of the disorder become apparent.

"Most people affected are over 80 and female," Najar says.

"As a result of global ageing, the number of people affected by dementia will increase. To be able to implement preventive strategies, we need to identify people with an elevated risk of dementia."

https://www.sciencedaily.com/releases/2020/09/200917105419.htm

Early puberty in girls may be 'big bang theory' for migraine

July 11, 2019

Science Daily/University of Cincinnati

Adolescent girls who reach puberty at an earlier age may also have a greater chance of developing migraine headaches, according to new research from investigators at the University of Cincinnati (UC) College of Medicine.

"We know that the percentage of girls and boys who have migraine is pretty much the same until menstruation begins," says Vincent Martin, MD, professor in the Division of General Internal Medicine and director of the Headache and Facial Pain Center at the UC Gardner Neuroscience Institute. "When the menstrual period starts in girls, the prevalence goes way up, but what our data suggests is that it occurs even before that."

The findings will be presented by Martin at the American Headache Society 61st Annual Scientific Meeting Saturday, July 13, in Philadelphia.

Nationally, about 10 percent of school age children suffer from migraine, according to the Migraine Research Foundation (MRF). As adolescence approaches, the incidence of migraine increases rapidly in girls, and by age 17, about 8 percent of boys and 23 percent of girls have experienced migraine, the MRF reports.

Martin and a team of researchers were part of a longitudinal study looking at 761 adolescent girls from sites in Cincinnati, New York and the San Francisco Bay area. The girls ranged in age from 8 to 20 and study took place over a 10-year period beginning in 2004. Girls enrolled in the study at age 8-10 were examined during study visit every six to 12 months. Researchers determined when they showed initial signs of thelarche (breast development), pubarche (pubic hair growth) and menarche (start of menstrual periods).

Girls answered a headache questionnaire to find out if they suffered from migraine headache, no migraine or probable migraine -- the latter is defined as meeting all the diagnostic criteria for migraine except one. The average age at which they completed the survey was 16.

Of those surveyed, 85 girls (11 percent) were diagnosed with migraine headache while 53 (7%) had probable migraine and 623 (82%) had no migraine, according to Martin, also a UC Health physician specializing in migraine.

Researchers found that girls with migraine had an earlier age of thelarche (breast development) and the onset of menarche (menstrual periods) than those with no migraine. On average breast development occurred four months earlier in those with migraine while menstruation started five months earlier. There was no difference in the age of pubarche (pubic hair development) between those with migraine and no migraine.

"There was a 25 percent increase in the chance of having migraine for each year earlier that a girl experienced either thelarche or menarche," says Susan Pinney, PhD, professor in the UC Department of Environmental Health and lead investigator on the study. "This suggests a strong relationship between early puberty and the development of migraine in adolescent girls."

The age of onset of thelarche, pubarche or menarche did not differ between those with probable migraine and no migraine, says Pinney.

Previous research suggests that migraine often starts with the onset of menstrual cycles during menarche in adolescent girls. But this study looks at earlier stages of puberty such as thelarche and pubarche, explains Martin.

"To suggest the origins of migraine may occur actually before menstrual periods begin is pretty novel," says Martin. "At each of these stages, different hormones are starting to appear in girls. During pubarche, testosterone and androgens are present, and during thelarche, there is the very first exposure to estrogen. Menarche is when a more mature hormonal pattern emerges. Our study implies that the very first exposure to estrogen could be the starting point for migraine in some adolescent girls. It may be the Big Bang Theory of migraine."

So is there anything that one can do to prevent an early puberty?

"Studies suggest that childhood obesity is associated with early puberty," says Martin, who is also president of the National Headache Foundation. "Keeping your weight down might prevent the early onset of puberty. Future studies will need to be done to determine if strategy will decrease also the likelihood of developing migraine."

https://www.sciencedaily.com/releases/2019/07/190711122700.htm