The Problem of Puberty

Puberty is alchemy, don’t you think? Like the chrysalis of a butterfly, the girl emerges from the pupal case of her childhood into an adolescent -an almost-woman- with hormones ablaze. It is a magic time of change, both in growth and physiology, but also in cognitive development. It is a time of evolving expectations, but more slowly developing judgement –the brain, too, is undergoing renovations. Hence our oft-aggrandized memories of the time –not deceptions, exactly, but distortions. To paraphrase Napoleon: history is the version of past events that I have decided to agree upon.

Many of the manifestations we see of puberty are the confusion of autonomies –the challenges to the boundaries that society imposes. I think Wikipedia has summarized the issues quite succinctly: ‘Psychologists have identified three main types of autonomy: emotional independence, behavioral autonomy, and cognitive autonomy. Emotional autonomy is defined in terms of an adolescent’s relationships with others, and often includes the development of more mature emotional connections with adults and peers. Behavioral autonomy encompasses an adolescent’s developing ability to regulate his or her own behavior, to act on personal decisions, and to self-govern. Cultural differences are especially visible in this category because it concerns issues of dating, social time with peers, and time-management decisions. Cognitive autonomy describes the capacity for an adolescent to partake in processes of independent reasoning and decision-making without excessive reliance on social validation.’ It is obviously a special and bewildering, albeit a magical  time. A time for planting the crop that is to come…

Because there are so many physiological processes involved, the actual start of puberty has always been approximate. Genes no doubt play a major role in its onset, but nutrition and general health are obviously involved as well because puberty is changing –it’s starting earlier. As an article from BBC news reports: The age of puberty is changing around the world. In the UK it is currently starting about one month earlier every decade. In China it is more than four months earlier every decade.

Of course, we have an almost obsessive need to analyze every change –to match every nuance with some overly reductionist, albeit plausible, explanation. Meat, for example. Yes, I’m serious:  Although it’s an older study, and Vegan-unreferenced, I have to wonder if they could have equally successfully used milk consumption, or perhaps eggs, or even Starbucks coffee… 

But whatever the causes of earlier puberty, that very change may have unexpected –and perhaps unwanted- ramifications as the MRC Epidemiology Unit  at the University of Cambridge recently published using the data of almost half a million people from the UK Biobank:

Doesn’t it seem strange that improving health and nutrition could have untoward, unintended consequences, although somewhat removed in time and maturity? Perhaps targetable with preventive interventions to be sure, as the authors point out in their abstract, but nonetheless ironic –the Red Queen needing to run faster and faster to stay in the same spot…

The most convincing evidence of the effect of an earlier puberty, apparently, is in its association with higher risks for type 2 diabetes and cardiovascular disease in women. A simple reasoned path to the type 2 diabetes (and its well known association with obesity) might be that: ‘early childhood rapid growth and overweight precede early puberty timing in both sexes, but in turn early puberty timing leads to subsequent rapid gains in weight and adiposity during adolescence and early adulthood’, but this may be an over-simplification of one of many factors that may be contributing –longer exposure to hormones, say, or life-style decisions altered by earlier maturation than peers: ‘environmental stressors may precede early puberty, but in turn early puberty leads to more risk taking behaviours and poor school performance.’ Intriguing, but speculative to say the least.

And on the more optimistic side of changing pubertal age? Well… there is a trend towards a lower risk for breast cancer in those with a later onset of puberty –although in fairness, this is likely related to a decreased time of exposure to hormones, so I’m not sure if it isn’t just a bit of trade-off… And anyway, trend is often what you call something that is not statistically significant (and yet perhaps lends credence to your hypothesis?).

But are we simply treading water in storm-tossed seas?  At risk of drowning in the details of semi-focused data swirling around us –most of which, at least in this case, was dependent on self reported medical histories and events that happened years before? Admittedly, the age of the first period is probably recalled with fair accuracy by most women –it is an event like few others- but aren’t researchers as seduced by this form of reasoning as the rest of us: the development of diabetes just begging for a scapegoat? So, choose the goat, widen the parameters, and voila…

An illustrative example of how easy it is to be led astray: many years ago, before we knew very much about the causal agent for cancer of the cervix (it is now known to be the human papilloma virus) but had pretty well decided it was something infectious –something sexually transmitted at any rate- the herpes virus came under scrutiny. It was infectious; many women exhibiting it also had abnormal pap smears suggesting precursor lesions for cervix cancer; and it was obvious –women who developed herpes were almost always aware of it. Herpes was easy to blame, because it was fairly straightforward to date the pap smear problem to some time after the event of acquisition. Everything fit –except it was not the cause. Not only did people who had never experienced herpes also develop abnormal pap smears, but similarly, not all people with herpes developed pap smear changes. The recall was an easy data point -something to blame- it’s just that it was the wrong thing.

My point is, it can be misleading to attribute cause merely based on recallable events. We all require explanations -something to blame. But, Post hoc ergo propter hoc? Well, the Latin may sound authoritative but not in Medicine. It is a logical fallacy…

This is all unfair to the study I know; I don’t mean to cast aspersions on either the researchers or their methodology, and yet I can’t help but worry about reports of this kind. Huge data bases are tempting geologies for data mining. But association is not necessarily causation.

As the humorist James Thurber once wrote: ‘Well, if I called the wrong number, why did you answer the phone?’ –just in case, I guess…


The Body’s Clock

Scientists –well, all of us- have been suspicious about the health risks of shift work for a long time now. Perhaps there is a reason buried somewhere in our genes that suggests night is for sleeping and daytime for working. Originally, no doubt, it was because it was difficult to see things in the dark and lighting, even when it became available, wasn’t very good.

But there is another reason: the Circadian Rhythm (from the Latin circa –around, and dies –day) which is often defined as physical, mental and behavioral changes that follow a roughly 24-hour cycle, responding primarily to light and darkness in an organism’s environment. The body clock, in other words. And there’s the clue: light and darkness. These are not just elements in our environment that we have come to expect, they actually have a biological meaning for us although this is, to a certain extent, entrainable. Malleable. As Wikipedia (sorry!) puts it: The rhythm can be reset by exposure to external stimuli (such as light and heat), a process called entrainment. The external stimulus used to entrain a rhythm is called the Zeitgeber, or “time giver”. But it can take a while to adjust –think of jetlag, or sleep disturbance after starting a new shift at a different time.

The body can adapt to many things, no doubt; the problems seem to arise when the pattern keeps changing. As folk wisdom attests, we are inherently creatures of habit –acquired behaviour patterns that are repeated so frequently they can become almost involuntary. As no less an observer of folkways than Samuel Johnson once said: “The chains of habit are too weak to be felt until they are too strong to be broken.” So one might ask why we –and many other animals- seem prone to develop these routines, these almost unconscious ceremonies. Is it simply a need for predictability? Or is it something deeper, something tied to our evolutionary past..?

In our evolutionary development we obviously experienced disruption of light/dark cycles –they occur as we travel through the seasons- but these are gradual and steadily progressive; shift work –especially rotational shift work- is not. And only recently has it become more obvious that there may be a price to pay. There have been several studies that have looked at this in various ways, but ‘Although epidemiological studies in shift workers and flight attendants have associated chronic circadian rhythm disturbance (CRD) with increased breast cancer risk, causal evidence for this association is lacking’ as the abstract of a paper published in Current Biology noted. I saw this in a July 2015 article in BBC News reporting on a study co-authored by Dr. Kirsten Van Dycke which suggested that the chronic need to re-entrain the circadian rhythm because of changing light/dark cycles can increase the risk for both obesity and breast cancer! Now, admittedly, the study was done on mice who were prone to develop breast cancers anyway, but when the light/dark cycles were switched over a long period of time (‘Mice prone to developing breast cancer had their body clock delayed by 12 hours every week for a year’) they developed them sooner.

Humans are obviously not mice, but it is difficult to control for possible contributing factors in the average human study: ‘Several scenarios have been proposed to contribute to the shift work-cancer connection: (1) internal desynchronization, (2) light at night (resulting in melatonin suppression), (3) sleep disruption, (4) lifestyle disturbances, and (5) decreased vitamin D levels due to lack of sunlight. The confounders inherent in human field studies are less problematic in animal studies, which are therefore a good approach to assess the causal relation between circadian disturbance and cancer.’

And the conclusion from this study? ‘Animals exposed to the weekly LD [light/dark] inversions showed a decrease in tumor suppression. In addition, these animals showed an increase in body weight. Importantly, this study provides the first experimental proof that CRD [Circadian Rhythm Disturbance] increases breast cancer development. Finally, our data suggest internal desynchronization and sleep disturbance as mechanisms linking shift work with cancer development and obesity’.

This is worrisome, to say the least. One could certainly argue that a woman with an increased risk for breast cancer –say a heditarily aquired BRCA1/2 mutation- would be best to avoid jobs involving chronic irregular body clock disturbance such as flight attendants, commercial pilots, and so on. But I’m not sure the risk is confined to that population. What about others –especially if they have additional life-style risks such as smoking, diabetes, alcohol issues?

And what about men? If –as the study suggests- a chronic body clock disruption may cause a decrease in tumour suppression, would that not suggest a similarly increased risk? The disruption also seems to have an additional risk for increased weight gain –obesity. Is the risk for type 2 diabetes therefore also increased? Clearly this is an area requiring much more research -further elucidation of the mechanisms involved and mitigation strategies at the very least. Sleep is so important –regular sleeping patterns…

I can’t help but remember the words of Shakespeare’s Macbeth talking to his wife after he has killed Duncan, the king:

Methought I heard a voice cry, “Sleep no more!

Macbeth does murder sleep”—the innocent sleep,

Sleep that knits up the raveled sleave of care,

The death of each day’s life, sore labor’s bath,

Balm of hurt minds, great nature’s second course,

Chief nourisher in life’s feast.

Art, once again, anticipating Science…

Pelvic Exams

Medicine has been my life, and over the years I have seen my specialty of obstetrics and gynaecology break free of many of the traditions that shackled it to the past. Obstetrics was once a superstition-clad field -a world unto itself; gynaecology was mired in taboo and cultural sensitivities that often precluded open-minded and unbiased research and therapy.

To a variable extent, both managed to disentangle themselves from the constraining mesh of gendered folklore and even sexual politics by embracing a non-discriminatory and objective multidisciplinary approach to the problems surrounding each domain: what a pregnant woman had in common with her non-pregnant counterpart, for example. A recognition that gestational diabetes, say, could be engendered by the stresses of pregnancy and that its diagnosis and management had much in common with type 2 diabetes in both sexes. That not only did conditions -diseases, anomalies, medical and surgical abnormalities- have an effect on pregnancy, but that pregnancy had an effect on them as well. Treatment had to be contextualized. Tailored.

An awareness that one of the most common and devastating cancers of women had preliminary and treatable forms that could be detected by scraping the surface cells of the uterine cervix led to the development by Papanicolau of his eponymous pap smear in the early part of the last century. This mainstay of Women’s Health required some education, of course: although readily accessible physically, the cervix occupied an understandably personal and intimate region hitherto guarded by powerful societal norms -not to mention feminine propriety.

And yet, despite the obvious progress and benefits accruing to this approach, there remain other elements equally important to success. To ignore these, is to forget that there is more to personhood than meets the eye. We are more than the sum total of our parts.

I can’t help but feel that Medicine has sometimes capitulated to the Scientific Method -surrendered its mandate. Forgotten its purpose: to help and reassure. Even my own specialty, despite its undeniable progress, occasionally mistakes a valuable stand of trees for a forest and seems to be in a hurry to log them all to ground level -to the bottom, if you’ll pardon the mixed metaphor- in its haste to discover what might be hidden. There are tides of change that buffet us all, but are they sweeping baby, bathwater and flotsam out to some nebulous Sargasso place beyond the horizon? A place unreachable by the rest of us. Unusable. Unauditable. In our dash to embrace what has been called evidence-based care, have we thrown reality-based care overboard to lighten the load? The bureaucratic equivalent of jetsam: cargo thrown overboard to save the ship -a word derived from jettison.

We must be sensitive to changing times and evidence, of course; new data require new approaches. We must be aware of public opinion and evolving mores because sensibilities wander, expectations mutate. We are not the same people we were even a decade ago. We are an ever-simmering melange as new customs merge with established ones, and religions stir several pots at once.

So there is no one center around which things revolve; we are many circles, each overlapping. We are a stochastic society: a kaleidoscopic stew of boiling colours and tastes.

But just because there are many variables that resist easy classification, this does not necessitate ill-considered solutions. Some things in Medicine are important -worth preserving even if they require more work than in the past. More patience. More understanding.

Think, for example, of vaccinations. Who would have thought there would be any resistance to these life-saving measures a generation ago when polio, smallpox, diphtheria, tetanus –even measles- were reeking havoc across the world? Nowadays it’s not the doctors who are suspicious, but the public: ‘Why vaccinate my child and subject her to risks of side effects for something that nobody gets anymore?’

I hear this occasionally from my pregnant patients. So, I have to make the time to counsel them and attempt to answer their pre-printed Google inquiries. And by and large they understand. What they have been seeking is not so much a detailed data-ridden explication with appended references, but an empathetic hearing and discussion of their concerns. People are sensible, by and large. They simply want what’s best for themselves and their families. They want to be participants in health related issues –and why not?

But to come to the point of this essay:

Some patients have readily discoverable problems -an enlarging mole on their skin that worries them, say. But some areas are hidden –both from the world and the person herself. The vagina was not designed as a shop window, and what hides at its end in the pelvis –like the uterus, ovaries, Fallopian tubes, for example- are not subject to casual interrogation. Tests like ultrasounds or CT scans are only done when symptoms arise –and like everything else, that is often too late. This is a worry.

Most women are resigned to interval pap smears (and soon, no doubt, to interval HPV testing from the same area). It seems to be accepted by most people in the community that pap smears can detect abnormal cells arising on the surface of the cervix long before –years before- any noticeable symptoms appear. And the fact that the rest of the pelvis can be assessed at the same time as the pap smear is reassuring to most women. Expected, actually -especially since their doctor is already focussed on the area. In the neighbourhood, as it were.

So it came as a surprise to me that a recent guideline from the American College of Physicians suggested that a pelvic exam should not be done routinely with pap smears. Only if symptoms arise that are suggestive of pelvic pathology could one justify its performance… Where’s the reassurance in that?

There are harms associated with it apparently. Evaluated harms ‘included fear, anxiety, embarrassment, pain, and discomfort. Physical harms may include urinary tract infections, and symptoms such as dysuria, and frequent urination.’ Wow! I wonder who is doing the pelvic exams for their studies.

And I wonder if any of the examiners actually discussed the examination with the patient beforehand. Or, more importantly, asked her permission. Her arrival at the office for the pap smear was voluntary (one hopes) and so she must be an active and willing participant in any medical investigations performed on her –including a pelvic examination, obviously. If possible, she should be able to choose her examiner –a female doctor, for example, or someone she trusts and with whom she feels at ease. As for my part, if she should choose not to be examined at the time of the pap, I certainly do not object; but I always ask.

Sometimes, there are cultural differences where the patient would feel awkward being examined by a male and if I suspect that is the case, I do not insist or make her feel uncomfortable about having to make a choice. I also offer to have another woman (her friend, my secretary, or her husband if she so chooses) to be present in the examination room.

Examination is as much for her reassurance as to discover something. The choice is hers, not mine. But there is usually an expectation that it will be done –or at least offered. I don’t think that we should make a big production about it. I don’t enjoy going to the dentist –childhood memories of pain and discomfort, I suppose- but when I do go, I expect her to check more in my mouth than just my teeth. Even if it is just my regular dental checkup I am willing to have my tongue palpated and my gums poked and prodded… especially if it is just a check up. I want to prevent problems as well as solve them. And the more thorough the examination, the more reassured I feel when it is normal. Am I alone in this?

Let’s face it, there are some things that, like it or not, we need to do for our own benefit. In the long march of Time, they might not amount to much, but nonetheless we may put them off in anticipation of discomfort or embarrassment. Autonomy –choice- is paramount.

But let me paraphrase (para-sex) Shakespeare:

She that outlives this day, and comes safe home,                                                                         

Will stand a’ tiptoe when this day is named.

Kind of makes one proud to have participated, don’t you think..?