An understanding why women experience more stress-related mental disorders like depression and Post Traumatic Stress Disorder (PTSD) has eluded scientists but a new study in rat brains may help explain why women are more prone to mood and anxiety disorders than men.

In order to better understand this study, I found it helpful to look up a few key definitions:

• stressor:   a stimulus that causes stress, can be physical, emotional or social

• hormone:  a secretion of an endocrine gland that is transmitted by the blood to the tissue on which it has an effect

• neurotransmitter:   a chemical that transmits signals from a neuron (nerve system cell) to a cell across an empty space called a "synapse"

• receptor:   a protein molecule embedded in either the membrane or cytoplasm of a cell, to which one or more specific kinds of signaling molecules, such as a neurotransmitter or hormone may attach. Each cell typically has many receptors, of many different kinds.

Now, back to the study:

Corticotropin releasing factor (CRF), which acts as both a hormone and a neurotransmitter, is likely a key player.   In response to a stressor, CRF binds to receptors on cells in an alarm center deep in the brainstem, called the locus ceruleus.   This telegraphs heightened emotional arousal throughout the brain via the chemical messenger norepinephrine.   Such hyper-arousal can be adaptive for brief periods, but not if it becomes chronic.   Runaway CRF is a core feature of depression.

Previous studies suggested that this alarm system is more sensitive to CRF and stress in the female brain and researchers at Children's Hospital in Philadelphia developed an experiment to see how CRF receptors responded in male versus female rats, both unstressed and after exposure to a stressor (in this case, a swim).

Even in the absence of any stress, the researchers found the female stress signaling system to be more sensitive from the start.   CRF receptors had stronger connections or coupling in the female rats, so it took lower levels of CRF to activate proteins in the unstressed females compared to males.    CRF levels that had no effect in males turned on cells in female rats.

After stress, CRF receptors remained exposed on the neuronal membranes in the female rat, maintaining the CRF effect.   In the stressed male, the CRF receptors interacted with proteins in the cell that enabled some of the them to retreat and not be available to couple to the CRF.  This helped the male brain adapt its sensitivity to the stressor and thus the stress response was less than in the females.

What is the significance of this experiment?   Certain brain cells in females are more sensitive to CRF  and less able to adapt to too much CRF than male brain cells.

The next step is to examine the male and female CRF receptors for structural differences that might account for the functional differences (e.g., response to stress, depression).   Since most rodent models of mood and anxiety disorders use male animals exclusively, the new findings of sex differences in stress signaling mechanisms call for a more sex- and gender-balanced approach---especially for mental disorders that disproportionately affect females.   This sex-difference should also be factored in as medication treatments based on blocking CRF receptor are developed, say the researchers.

Source: Sex differences in corticotropin-releasing factor receptor signaling and trafficking:   potential role in female vulnerability to stress-related psychopathology.  Mol Psychiatry. 2010 Jun 15. (PMID:  20548297)

Women with the most serious type of angina are three times as likely as men with the same condition to develop severe coronary artery disease (CAD), researchers have found.

In the study, Canadian researchers analyzed the medical records of 23,771 patients referred for a first diagnostic angiography. They found that women over age 60 with the most serious type of angina (Class IV) had a 21 percent higher absolute risk of developing CAD than did men. Women younger than 60 had an 11 percent greater risk of CAD than men in the same age group.

When the researchers factored in other variables commonly associated with CAD -- such as diabetes, high blood pressure, high cholesterol, smoking and age -- they found that Class IV angina increased the risk of CAD by 82 percent in women and 28 percent in men.

The study also found that men were more likely to have severe CAD than women (37 percent versus 22 percent) and that women with severe CAD tended to be significantly older than men with severe CAD (70 years versus 66 years).

The study findings are published in the July issue of the Journal of Internal Medicine.

"CAD is the leading cause of ill health and death in men and women in the western world, accounting for over a third of deaths. In fact, more women die from CAD than breast disease every year. Despite this, there is still a persistent perception that CAD is a man's disease," lead author Catherine Kreatsoulas, of the department of clinical epidemiology and biostatistics at McMaster University in Hamilton, Ontario, said in a news release from the journal's publisher.

However, the university's research found that women who have what the Canadian Cardiovascular Society defines as Class IV angina -- which means they are unable to perform any activity without symptoms and even suffer angina at rest -- "are significantly more likely to develop severe CAD than men with the same condition," Kreatsoulas added.

The findings are crucial for doctors deciding which patients should be referred for coronary angiography, Kreatsoulas said.

SOURCE: Journal of Internal Medicine, news release, July 8, 2010.

Copyright (c) 2010 HealthDay. All rights reserved.

No, you did not open the wrong page.   Yes, this blog is posted by the Institute for Women's Health Research at Northwestern. As an advocate for better  sex and gender based research, we support all avenues that increase our knowledge about sex differences and that includes  a better understanding of  hormone changes in women AND MEN.

Furthermore, women are generally the source of health information for their families and that includes their male partners! So, women and men, read on!

Low testosterone levels to blame for low libido, fatigue and weight gain

While most frequently associated with women’s health, age-related hormone changes, often dubbed menopause, can occur in men as well, causing symptoms of fatigue, mood swings, decreased desire for sex, hair loss, lack of concentration and weight gain. Experts estimate that more than 5 million men are affected, yet worry the number may be considerably higher since symptoms are frequently ignored.  Male hypogonadism, as it’s referred to in the medical community, occurs when the testicles do not produce enough testosterone, the hormone that plays a key role in masculine growth and development. When hormone levels drop, men can experience significant mental and physical changes.

“This is a highly prevalent disorder,” said Robert Brannigan, MD, urologist at Northwestern Memorial Hospital. “Unfortunately, we estimate that 95 percent of cases are undiagnosed and therefore untreated. When ignored, symptoms can seriously disrupt one’s quality of life.”

Brannigan explains hormone variations are a normal aspect of getting older. “In females, ovulation comes to an end and hormone production declines in a relatively quick period of time, whereas men experience hormone shifts more slowly, with testosterone levels dropping around one percent each year beginning in a man’s late thirties,” adds Brannigan. He goes on to explain that by age seventy, the reduction in a male’s testosterone level could be as high as fifty percent or more compared to baseline levels, but notes that aging men are not the only ones at risk. A number of genetic causes can impact males from birth and are usually diagnosed with failure to progress normally through puberty during the teenage years.

Treatment options for male hypogonadism include hormone replacement therapy (HRT) via absorbable pellet implants, topical gels, patches, and injections. Through HRT, doctors can restore sexual function and muscle strength. In addition, men often experience an increase in energy and an improved overall sense of well-being.

“We are seeing more men affected by male hypogonadism than we saw ten years ago,” said Brannigan. “However, many men continue to suffer in silence due to a lack of awareness surrounding the disorder. Because male hypogonadism can significantly impact the quality of one’s life, it’s important that men pay attention to their body and openly discuss symptoms with their physician in order to prevent overlooking the cause and avoid missing an opportunity for appropriate therapy.”

Although research to determine the exact association continues, doctors also warn that male hypogonadism has been linked to chronic medical conditions such as high cholesterol, diabetes and cardiovascular disease. It’s also closely associated with infertility.

“This disorder is not something that should be ignored,” said Brannigan, who is working to educate patients and physicians about the symptoms and treatments available in order to ensure therapies are made available to men in need.

Male hypogonadism is most commonly diagnosed through a simple blood test. Brannigan notes hormone replacement therapy is not appropriate for all patients especially those with history of prostate and breast cancer and men trying to conceive. He suggests consulting your doctor if you are experiencing symptoms.

Postmenopausal women have an increased risk of hypertension (high blood pressure), and among older adults, more women than men have hypertension.   As with many other health issues, hypertension research has been conducted predominately in males, and little is known about how women's bodies manage blood flow.   Research conducted by Heidi A. Kluess at the University of Arkansas is focusing on a  better understanding of hypertension in women by using a new technique to examine the release of a neurotransmitter in small blood vessels.

Kluess, an exercise scientist, believes the answer seems to be in the "synapse".  The synapse is the space between the nerve and the vascular smooth muscle, the place where the nerve and blood vessel interact.   A neurotransmitter crosses the "synapse" to activate a receptor, which then causes the artery to constrict.   "There's been a little evidence to say that some of the neurotransmitter breakdown is different in women.   It suggests that when we've been looking at receptors on the smooth muscle, we may have been missing a big part of the story, particularly in women," Kluess said.

The team measured the neurotransmitter adenosine triphosphate (ATP) coming from the small blood vessels (arterioles).  ATP plays a key role in controlling blood flow and blood pressure by causing the diameter of blood vessels to change.   Thus, the constriction of veins associated with hypertension could be related to relatively high levels of ATP in arterioles. So this raises the questions:   Where is the ATP coming from, what tissues are releasing it and how does this change with aging?

To study this,the researchers had to overcome the difficulty of working with very small blood vessels that produced minute amounts of ATP.   A biosensor that was only previously used in brain researcher was utilized that uses a set of enzymes to indirectly measure ATP as it is released.

The research findings suggest that ATP from small arterioles can be measured and that the arteriole wall plays an important role in release and management of ATP. The researchers found that ATP is released mostly from the sympathetic nerves in the arteriole wall and that only a small part comes from the smooth muscle. Considerable research suggests that having a lot of ATP floating around in the blood vessels is not a good thing. The upside of this finding is that the nerve releases ATP in response to nerve signals. However, the mechanisms involved in the release of ATP by smooth muscles are less well understood, Kluess explained, and may result in chronically high ATP release.

The researchers found that the ATP overflow varied considerably with age. Because ATP is associated with vascular growth, it is important during early development when blood vessels are growing, but levels generally decline when people reach their twenties. Elevated levels can be a bad sign during aging when the body is no longer growing and may be a predictor of vascular changes that can be detected years before hypertension is a problem.

Some previous research had suggested that the endothelium – the outer layer of the smooth muscle – produced ATP. However, Kluess’ research showed that the endothelial tissue did not produce ATP. Rather, it decreased levels of ATP and potentially plays a positive role in controlling ATP levels.

“That’s an interesting finding because we know that as people age or develop disease that their endothelium doesn’t work as well,” Kluess said. “That may be a way that ATP increases during aging because the endothelium doesn’t function as well and so can’t buffer ATP quite as well.”

More research is needed to investigate the factors that control ATP overflow and metabolism to reveal the mechanisms associated with age-related change. “We are very much at the beginning of this story,” Kluess said.

Source:   University of Arkansas

Kluess HA, Stone AJ, Evanson KW. ATP overflow in skeletal muscle 1A arterioles. J Physiol.