Menstrual Cycle Influences Concussion Outcomes

Researchers found that women injured during the two weeks leading up to their period (the premenstrual phase) had a slower recovery and poorer health one month after injury compared to women injured during the two weeks directly after their period or women taking birth control pills.

The University of Rochester study was published today in the Journal of Head Trauma Rehabilitation. If confirmed in subsequent research, the findings could alter the treatment and prognosis of women who suffer head injuries from sports, falls, car accidents or combat.

Several recent studies have confirmed what women and their physicians anecdotally have known for years: Women experience greater cognitive decline, poorer reaction times, more headaches, extended periods of depression, longer hospital stays and delayed return-to-work compared to men following head injury. Such results are particularly pronounced in women of childbearing age; girls who have not started their period and post-menopausal women have outcomes similar to men.

Few studies have explored why such differences occur, but senior author Jeffrey J. Bazarian, M.D., M.P.H. says it stands to reason that sex hormones such as estrogen and progesterone, which are highest in women of childbearing age, may play a role.

“I don’t think doctors consider menstrual history when evaluating a patient after a concussion, but maybe we should,” noted Bazarian, associate professor of Emergency Medicine at the University of Rochester School of Medicine and Dentistry who treats patients and conducts research on traumatic brain injury and long-term outcomes among athletes. “By taking into account the stage of their cycle at the time of injury we could better identify patients who might need more aggressive monitoring or treatment. It would also allow us to counsel women that they’re more – or less – likely to feel poorly because of their menstrual phase.”

Although media coverage tends to focus on concussions in male professional athletes, studies suggest that women have a higher incidence of head injuries than men playing sports with similar rules, such as ice hockey, soccer and basketball. Bazarian estimates that 70 percent of the patients he treats in the URMC Sport Concussion Clinic are young women. He believes the number is so high because they often need more follow-up care. In his experience, soccer is the most common sport leading to head injuries in women, but lacrosse, field hockey, cheerleading, volleyball and basketball can lead to injuries as well.

Sex hormone levels often change after a head injury, as women who have suffered a concussion and subsequently missed one or more periods can attest. According to Kathleen M. Hoeger, M.D., M.P.H., study co-author and professor of Obstetrics and Gynecology at the University of Rochester School of Medicine and Dentistry, any stressful event, like a hit to the head, can shut down the pituitary gland in the brain, which is the body’s hormone generator. If the pituitary doesn’t work, the level of estrogen and progesterone would drop quickly.  

According to Bazarian, progesterone is known to have a calming effect on the brain and on mood. Knowing this, his team came up with the “withdrawal hypothesis”: If a woman suffers a concussion in the premenstrual phase when progesterone levels are naturally high, an abrupt drop in progesterone after injury produces a kind of withdrawal which either contributes to or worsens post concussive symptoms like headache, nausea, dizziness and trouble concentrating. This may be why women recover differently than men, who have low pre-injury levels of the hormone.     

Hoeger and Bazarian tested their theory by recruiting144 women ages 18 to 60 who arrived within four hours of a head hit at five emergency departments in upstate New York and one in Pennsylvania. Participants gave blood within six hours of injury and progesterone level determined the menstrual cycle phase at the time of injury. Based on the results, participants fell into three groups: 37 in the premenstrual/high progesterone group; 72 in the low progesterone group (progesterone is low in the two weeks directly after a period); and 35 in the birth control group based on self-reported use.

One month later, women in the premenstrual/high progesterone group were twice as likely to score in a worse percentile on standardized tests that measure concussion recovery and quality of life – as defined by mobility, self-care, usual activity, pain and emotional health – compared to women in the low progesterone group. Women in the premenstrual/high progesterone group also scored the lowest (average 65) on a health rating scale that went from 0, being the worst health imaginable, to 100, being the best. Women in the birth control group had the highest scores (average 77).

“If you get hit when progesterone is high and you experience a steep drop in the hormone, this is what makes you feel lousy and causes symptoms to linger,” said Bazarian. “But, if you are injured when progesterone is already low, a hit to the head can’t lower it any further, so there is less change in the way you feel.”

The team suspected that women taking birth control pills, which contain synthetic hormones that mimic the action of progesterone, would have similar outcomes to women injured in the low progesterone phase of their cycle. As expected, there was no clear difference between these groups, as women taking birth control pills have a constant stream of sex hormones and don’t experience a drop following a head hit, so long as they continue to take the pill.    

“Women who are very athletic get several benefits from the pill; it protects their bones and keeps their periods predictable,” noted Hoeger. “If larger studies confirm our data, this could be one more way in which the pill is helpful in athletic women, especially women who participate in sports like soccer that present lots of opportunities for head injuries.”

In addition to determining menstrual cycle phase at the time of injury, Bazarian plans to scrutinize a woman’s cycles after injury to make sure they are not disrupted. If they are, the woman should make an appointment with her gynecologist to discuss the change.

Breastfeeding may reduce Alzheimer’s risk

A new study suggests that mothers who breastfeed run a lower risk of developing Alzheimer’s, with longer periods of breastfeeding further reducing the risk.

Mothers who breastfeed their children may have a lower risk of developing Alzheimer’s Disease, with longer periods of breastfeeding also lowering the overall risk, a new study suggests.

The report, newly published in the Journal of Alzheimer’s Disease, suggests that the link may be to do with certain biological effects of breastfeeding. For example, breastfeeding restores insulin tolerance which is significantly reduced during pregnancy, and Alzheimer’s is characterised by insulin resistance in the brain.

Although they used data gathered from a very small group of just 81 British women, the researchers observed a highly significant and consistent correlation between breastfeeding and Alzheimer’s risk. They argue that this was so strong that any potential sampling error was unlikely.

At the same time, however, the connection was much less pronounced in women who already had a history of dementia in their family. The research team hope that the study – which was intended merely as a pilot – will stimulate further research looking at the relationship between female reproductive history and disease risk.

The findings may point towards new directions for fighting the global Alzheimer’s epidemic – especially in developing countries where cheap, preventative measures are desperately needed.

More broadly, the study opens up new lines of enquiry in understanding what makes someone susceptible to Alzheimer’s in the first place. It may also act as an incentive for women to breastfeed, rather than bottle-feed – something which is already known to have wider health benefits for both mother and child.

Dr Molly Fox, from the Department of Biological Anthropology at the University of Cambridge, who led the study, said: “Alzheimer’s is the world’s most common cognitive disorder and it already affects 35.6 million people. In the future, we expect it to spread most in low and middle-income countries. So it is vital that we develop low-cost, large-scale strategies to protect people against this devastating disease.”

Previous studies have already established that breastfeeding can reduce a mother’s risk of certain other diseases, and research has also shown that there may be a link between breastfeeding and a woman’s general cognitive decline later in life. Until now, however, little has been done to examine the impact of breastfeeding duration on Alzheimer’s risk.

Fox and her colleagues – Professor Carlo Berzuini and Professor Leslie Knapp – interviewed 81 British women aged between 70 and 100. These included both women with, and without, Alzheimer’s. In addition, the team also spoke to relatives, spouses and carers.

Through these interviews, the researchers collected information about the women’s reproductive history, their breastfeeding history, and their dementia status. They also gathered information about other factors that might account for their dementia, for example, a past stroke, or brain tumour.

Dementia status itself was measured using a standard rating scale called the Clinical Dementia Rating (CDR). The researchers also developed a method for estimating the age of Alzheimer’s sufferers at the onset of their disease, using the CDR as a basis and taking into account their age and existing, known patterns of Alzheimer’s progression. All of this information was then compared with the participants’ breastfeeding history.

Despite the small number of participants, the study revealed a number of clear links between breastfeeding and Alzheimer’s. These were not affected when the researchers took into account other potential variables such as age, education history, the age when the woman first gave birth, her age at menopause, or her smoking and drinking history.

The researchers observed three main trends:

• Women who breastfed exhibited a reduced Alzheimer’s Disease risk compared with women who did not.

• Longer breastfeeding history was significantly associated with a lower Alzheimer’s Risk.

• Women who had a higher ratio of total months pregnant during their life to total months breastfeeding had a higher Alzheimer’s risk.

The trends were, however, far less pronounced for women who had a parent or sibling with dementia. In these cases, the impact of breastfeeding on Alzheimer’s risk appeared to be significantly lower, compared with women whose families had no history of dementia.

The study argues that there may be a number of biological reasons for the connection between Alzheimer’s and breastfeeding, all of which require further investigation.

One theory is that breastfeeding deprives the body of the hormone progesterone, compensating for high levels of progesterone which are produced during pregnancy. Progesterone is known to desensitize the brain’s oestrogen receptors, and oestrogen may play a role in protecting the brain against Alzheimer’s.

Another possibility is that breastfeeding increases a woman’s glucose tolerance by restoring her insulin sensitivity after pregnancy. Pregnancy itself induces a natural state of insulin resistance. This is significant because Alzheimer’s is characterised by a resistance to insulin in the brain (and therefore glucose intolerance) to the extent that it is even sometimes referred to as “Type 3 diabetes”.

“Women who spent more time pregnant without a compensatory phase of breastfeeding therefore may have more impaired glucose tolerance, which is consistent with our observation that those women have an increased risk of Alzheimer’s disease,” Fox added.