Sunday, August 24, 2008

Gender differences in medical care and mortality

Chronic obstructive pulmonary disease (COPD) is a growing global epidemic, as described by a great PLoS article. It is associated with smoking and is a major cause of disability. In 1990, it was the 6th leading cause of death worldwide. It is projected to climb to Bronze (in the Olympics of Morbidity and Mortality) by 2020. To put it in prospective, it is currently being beaten out by heart attacks, strokes, and AIDS. While we have been better able treat and prolong life with these other diseases, COPD is actually on the rise. It affects 10% of the global population--not a small chunk of people by any means. Of smokers 25% of them will develop COPD and despite the public and medical bias, the rates between men and women are equal according to a 25 year study published in 2006 in Thorax. Importantly, the rate is rising faster in women.

About COPD:
According to the Global Initiative for Chronic Obstructive Lung Disease COPD is “a preventable and treatable disease.‥characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases”.

There are two variants of COPD. With the chronic bronchitis subtype, you slowly lose the ability to breathe because your windpipes fill with mucus and plug up. With emphysema, your smallest airsacs, where the essential transfer of oxygen to the blood occurs, begin to dissolve. We measure the decline by following the forced expiratory volume (FEV1), which is the amount of air you can force out in 1 second. People with COPD lose 50-100 mililiters of volume each year. 'Normal' people only decline by less than 30 mililiters per year.

According to another great article in PLoS, while life expectancy has been steadily on the rise (7 years for men, 6 years for women), this increase is not distributed equally across socio-economic groups. The figure below is from that article. The darker the green, the higher the life expectancy compared to the national average, where as the darker the red, the lower. As you can see by the map in the lower right, women are doing worse as a whole (i.e. the map is more red).

Women are also more likely to die from COPD. Why?

Women are less likely to be properly diagnosed as having COPD. Below is an excerpt from "Gender and Chronic Obstructive Pulmonary Disease":
A 2001 study [Chapman K, Tashkin D, Pye D. Chest] that sampled 200 primary care physicians in North America presented two hypothetical cases of cough and dyspnea in smokers, one male and the other female. Physicians were then asked for provisional diagnosis and initial diagnostic steps. COPD was given as the most probable diagnosis significantly more often for the male case scenario than for the female case scenario (64.6 vs. 49%).
Women are more likely thought to just have asthma. A similar study was conducted in Spain with similar results, so it's not just us in the US. If a doctor is less likely to think a [female] patient has COPD, that doctor is less likely to order the proper tests and make the right diagnosis.

Women are more susceptible to tobacco. It is not clear why, but the same amount of smoking is more damaging to female lungs. Women also tend to decline more quickly once they do develop COPD. As described by Gan et al., women have an accelerated rate of decline of FEV1 as compared to men.
Women are more symptomatic. Women are more likely to have severe shortness of breath (dyspnea) with less pack year (number of cigarette packs smoked per day x number of years). Additionally, FEV1 (the above mentioned marker of disease progression) correlates significantly better with male disease and death.

Women are differently biologically. Sex hormones may affect the way the body deals with smoking. Just as children are NOT little adults; women are NOT men. We need specifically tailored drug and clinical trials. Women have smaller lungs, increased airway responsiveness, and hormones which modulate the body's response to irritants like smoke. From Han et al. :
It is interesting to note that chronic bronchitis is more prevalent in women, whereas emphysema is more prevalent in men. Gender dimorphism in COPD was first suggested by Burrows and colleagues in 1987.
Women are socially disadvantaged. As women have a lower socio-economic station, they have less access to health care and early intervention. Globally, particularly in poor countries, women have increased exposure to indoor toxins from burning dung, charcoal, and wood indoors for fuel for cooking and heating. This has led to increased rates of COPD in even non-smoking females.

Women choose to smoke more dangerous cigarettes. Cigarettes marketed towards women as "light" or "low tar" are typically lower in nicotine. The other toxins, however, are still in the same concentration. The low nicotine content results in a deeper and longer inhalation and thus more contact between the toxins and the lung surfaces.

COPD is a real threat towards women and the inequalities which exist are unacceptable. We need better education of the public and medical communities. We need better recognition of the disease in women and ultimately better treatments.
This post was inspired by a great lecture by a female physician.


Habladora said...

Wow, interesting post. Why do you think that women are more likely to be misdiagnosed? The same is true for heart disease, right? Why are women being assumed to have less serious diseases? And what is going on in the South East to shorten women's lives?

Another Anonymous Poster said...

Awesome post, Loup.

If anyone has an historical bent, check out this link to Stanford University's medical library site. If you click on "targeting women" on the left, they've got a summary of the tobacco companies' efforts to market to women from the 1920s on, as well as images of old ads (like the one that Loup included).

Then, to be truly horrified, click on "infants and children".

frau sally benz said...

The post was great, but I also wanted to comment on the ad: WOW, that's kind of crazy. I always think that gendered ads for gender neutral items are so weird. It's as if you can see the wheels turning in their heads "how can we make this a product geared towards men/women?!" Often, they fail miserably, IMO.

Le Loup-garou said...

The ad is incredibly sexist, too. You can imagine a room full of male ad executives scheming on how to sell to women.

daedalus2u said...

I think it is nitric oxide. Estrogen activates the estrogen receptor which causes activation of nitric oxide synthase and makes NO. People are pretty sure that that contributes to the reduced incidence of heart disease in pre-menopausal women. That is probably the mechanism for a lot of the reduced incidence of many diseases in pre-menopausal women. The loss of that NO is what causes osteoporosis, probably what causes other things too.

I think it is too much bathing in the South East.

Anonymous said...

Daed--that is a grossly over-simplified view of the mechanisms of disease. As a basic player in cell signaling NO may play some role, it is not going to be the only/primary instigator.

Another Anonymous Poster said...

Actually, current data suggest that it's not nitric oxide (at least not directly), but rather the CYP 450 system that's involved. The toxins are metabolized in a 2-step process: first oxidized by the cytochrome system, then conjugated by aldehyde oxidase. Elimination requires both steps, but estrogen upregulates only the first. The problem is that the oxidized crud builds up and causes all sorts of DNA damage, inflammation, and direct damage to the alveoli.

Maybe nitric oxide is involved, but it's not a direct effect. It's downstream.

For the reference, check out Sin et al. Proc Am Thorac Soc. 2007 Dec;4(8):671-4.

daedalus2u said...

You are right, it is a gross simplification.

NO inhibits the cytochrome P450 enzymes and is how physiology regulates them. Low NO disinhibits them, which is why the P450 enzymes are pretty uncoupled, that is they produce a lot of superoxide, which pulls down the NO level and disinhibits them so they "do their thing" somewhat faster.

NO causes expression of the phase II systems (by activating Nrf2) and NO is also an excellent antioxidant (~3,000 times faster then vitamin E).

NO is also an anti-inflammatory because it inhibits NFkB.

It does a lot of other stuff too.