Women are from Earth

Men are from Mars, Women are from Venus –remember that book? It was published in 1992, and although it was really talking about relationship issues between the sexes, it seems to hint at other, more physiological differences that underpin the disparity -differences that have sometimes been overlooked, or perhaps ignored, in many pharmaceutical drug studies. http://www.cbc.ca/news/health/sport-exercise-menstrual-cycle-1.3618140

The justifications seem reasonable at first glance. There are cyclic changes in women –alterations in the hormonal milieu that make it difficult to standardize conditions for studying the drug in question. For example, progesterone is only found in women after ovulation, and this might alter the metabolism or effect of the drug being studied. Or estrogen –the quintessential female hormone- might alter the effects of the study drug differently than the testosterone milieu of men. Might alter the risks. Indeed, the CBC article quotes Georgie Bruinvels, the lead author of a paper in the British Journal of Sports Medicine: “Evidence actually suggests that women are almost twice as likely to have an adverse reaction to a drug than a male counterpart,” she said. In fact, a U.S. accountability study found “80 per cent of drugs there are withdrawn from the market due to unacceptable side-effects on women.”

And then, of course, there is the risk of inadvertent exposure of an unexpected fetus to the study drug. So why take the chance? Well, for a start, except for pregnancy of course, the sexes share most of the same problems: heart disease, hypertension, diabetes, strokes, arthritis, pain… to name just a few. But if the drugs created to combat these conditions are only tested on men, the information obtained may not apply to women. At the very least, doses may have to be altered. For example, ‘In 2013, the U.S. Food and Drug Administration released a safety announcement about the sleep aid, zolpidem, also known as Ambien. It recommended the bedtime dose be lowered for men and women. It also warned that women are more susceptible to risks associated with the medication because they metabolize the drug at a slower rate than men.’

In Canada, there is an attempt to rectify the gender bias in studies: ‘[…] a policy of the Canadian Institutes of Health Research requires researchers to say how they are dealing with sex and gender when applying for research grants.’

But the issue of sex biased research applies not only to human studies, believe it or not. It can even apply to animal surrogates studied to provide drug data –laboratory mice: http://www.cbc.ca/news/technology/mouse-sex-studies-1.3545486 The same reason -hormonal cycles- is the reason given for choosing male mice as subjects, although the validity of this justification has been questioned. And the results of using male mice has had similar, if not more severe, repercussions: ‘A stomach drug called cisapride that was sold in the 1990s under the name Prepulsid was withdrawn by Health Canada in 2000 because it sometimes caused irregular heartbeat and sudden death “in women only”.’

Or, take Jeffrey Mogil, a neuroscientist and pain specialist at McGill University who ‘estimates that in pain research, 80 per cent of published studies use male mice or rats, even though 70 per cent of people with chronic pain are women.’ And further, ‘Published studies on male mice showed that blocking immune cells called glial cells could block pain. When Mogil repeated the studies on mice of both sexes, he found they worked in male mice, but not females.’

There has been an attempt to rectify this bias: ‘The Canadian Institutes of Health Research, the main federal funding agency for health and medical research, has been trying to address the sex bias in rodent research. Since 2010, researchers have been required to answer questions about whether they will account for sex in their studies.’

Given the need for drug data on both sexes before the resulting medication or therapy is safely released to the general public, what can be done? Well, in most well-designed studies, there are two groups: the group given the medication, and a ‘control’ group who is, as much as possible, identical to the studied group. The general idea is to decrease the number of variables to a minimum, so that the only difference in the study group is the drug.

So, to start with, the study could be partitioned according to the menstrual cycle in women –with the use of a simple blood test to check for progesterone if there is any doubt, or if the menstrual cycle is sufficiently irregular or unpredictable. Thus, after controlling for such things as weight, other medications, health, and past history (as one would do anyway to establish control groups) three arms to the study could be included to address the disparities: 1. Men –knowing that they would have minimal estrogen on board; 2. Women –a). pre-ovulatory (i.e. no progesterone in blood) and b). post-ovulatory women (progesterone in blood). Of course, given that there would also have to be matching controls, this would add extra costs –and probably time- to complete the study. But I would imagine these would be counterbalanced by the costs of developing a drug that might have to be withdrawn from the market for unexpected side effects -on women, say– not to mention any resulting law-suits or ethical considerations held against the company.

And what about inadvertent pregnancy exposures to the drug? Oral contraceptives themselves may interfere with the study drug metabolism so either women on this type of contraception could be added to the study as yet another arm or, more feasibly, women using other reliable, non hormonal contraceptives could be enrolled, including women who have had a surgical sterilization procedure (e.g. tubal ligation).

All of these permutations and combinations may seem daunting, and yet surely the validity and applicability of the study results are what count in the end. As Mahatma Gandhi once said: ‘It is health that is real wealth, and not pieces of gold and silver.’ I just wish he’d said it louder.

Menstruation and Sports

Okay, time to cross the line again. I’ve written about this before (see Menstrual Taboos  https://musingsonwomenshealth.wordpress.com/2014/11/26/menstrual-taboos/ ) but the issue keeps popping up. In the recent 2015 Australian Open, the top ranking female tennis player in Britain, Heather Watson, suffered a first round defeat. In the subsequent interview, as she was being grilled about what might have gone wrong, she reluctantly and perhaps somewhat timidly admitted that it could have been ‘girl things’. I didn’t get the impression that she was blaming them for her defeat, as much as conceding that her period may have been a contributing factor. http://www.bbc.com/sport/0/tennis/30926244#

But it seemed to have opened the old societal wound: the ‘She’s blaming it on her period. I knew she would!’ The age old reason for excluding women from activities that require stamina and perseverence –or at least considering them inferior as a group to men. The time-worn excuse for domination vindicated once again.

My first  instinct is to stand on a street corner and yell ‘Grow up, guys!’ If it weren’t for the physiology of menstruation none of us would even be here! The uterus has a lining of cells that cyclically prepares itself to receive and grow a fertilized egg, but if no egg arrives, it needs to cast off that old lining and renew itself for another try. Another egg. Another cycle…

There are many reasons why the very topic of menses, let alone its existential reality has engendered such discomfort in polite conversation and I have covered some of them in my previous essay. But what I am concerned about here is how menstruation may be misunderstood, mislabelled as an impediment, or assigned properties and attributes it doesn’t usually deserve. Not all periods are disruptive; not all periods –even in the same woman- are alike. Nor, unless she has developed an untreated iron deficiency anemia because of heavy menstrual loss, will the fact of periods necessarily interfere with performance.

And yes, they are surrounded by myth and euphemisms –just read Karen Houppert’s The Curse: Confronting the Last Unmentionable Taboo, Menstruation. There’s precious little good research addressing menstruation and sport except about ways to attempt to prevent menses altogether and to concede that there might  be an increased chance of injury because estrogen, for example, may render tendons and ligaments more lax. Pretty soft science, to say the least.

Now let’s be clear –I’m a male, and despite my training as a gyaecologist, I can never quite enter that other world. Some would go so far as to say that I can never even hope to understand it; that genes and physiology imprison me and afford only a poor approximation of what it would be like to be a woman; that there is an opaque curtain separating us, obscuring important details.

This argument reminds me of Plato’s allegory of the Cave –you know, where prisoners are chained inside a cave so they can only see shadows cast on the opposite wall from a fire burning behind them. It’s all they’ve ever known; they think they are seeing reality; that the shadows are all there is to it. Then one prisoner escapes and enters the sunlight outside and finally sees the real world and not just shadows. The Truth. Things as they actually are.

So, are we all just looking at shadows? All of us Homo Sapiens? Because if that’s the case, then both sexes are prisoners of the same misapprehensions. The same inability to judge the other… We’re both handicapped. We’re both deceived.

I cannot accept that; I will not. I may not know what its like to experience having a baby, for example, and yet I can understand the joy and suffering attending it. And I can experience, although once removed, the frustration and fatigue I see in my patients in the second stage of labour. Believe me, it is palpable anywhere in the delivery room. It is a human thing. Knowing another entails a melding of shadows. Seeing the same thing differently and yet comparibly. Empathetically.

No, I can never have menstrual periods; I can never truly experience what it must be like. But I do remember an incident in the office many years ago. A colleague from another hospital was away and I had agreed to see some of her patients for her. One of the patients had come in because of heavy and painful periods. All of the investigations –blood tests, ultrasounds, and even a D&C coupled with a laparoscopy to look directly into her abdomen under anaesthesia- were normal. She was not anemic, despite her heavy menses and was reluctant to take the birth control pill for fear of side effects. But she was desparate to talk to somebody about her periods.

I listened to her for a while before she stopped talking and stared at me. I looked sad, she said and reached out to touch my hand across the desk. I remember smiling, but even the smile looked pained, she said.

I suppose I was caught off guard, and responded with something lame like that her periods seemed awfully heavy and that it must be hard for her. I really did think she must be suffering.

Her face brightened and I could see her mood change right in front of me. “You know,” she said, hardly able to contain her enthusiasm, “I never felt I could go to a male doctor and talk about this sort of thing. I mean, how could you ever understand?”

I must have looked puzzled, because she added, “My other doctor didn’t seem to want to talk about it. When all of the investigations came back normal, and I expressed reservations about the options she’d offered, she just shrugged -as much as told me to suck it up. Deal with it.

“And yet, you listened, tried to hear what I was going through. Obviously you don’t have to be a woman to empathize.”  She shook her head slowly and carefully, as if she had just figured something out. Then, as I recall, she sighed rather theatrically. “Who says men will never understand women..?”

I don’t think Ms Watson was necessarily blaming her loss on her period, any more than a man would attempt to blame his poor performance on, for example, a headache. Once the initial shock of mentioning the unmentionable has worn off, I imagine there will be nobody that will believe that she was using a normal and incontrovertibly organic event as an excuse. But, even if she were, so what? Things happen. And anyway, I suspect that she may have helped to remove yet one more shadow –if only an edge- from the reality that we are, all of us, members of the genus Homo –human- and of the species sapiens –knowing. Intelligent. Wise. And both sexes share far more physiology than separate us. Lets face it, we need each other. And, except for a tiny Y chromosome, we are each other.

The ramparts are coming down.