Sarah Berga, et. al. presented a paper at
European Society of Human Reproduction and Embryology conference in
Prague, about the use of cognitive-behavioral therapy for treatment of
infertility. It this post, I elaborate on some of the details
that the mainstream media left out. I end by speculating
about what it might mean about our society, that such a simple solution
could have been overlooked for so long.
From a report on the Times Online:
how to beat stress could be the best fertility treatment
by Mark Henderson, Science Editor
June 21, 2006
A study into the effects of therapy offers new hope to
thousands of women
STRESS may be one of the main causes of female infertility, preventing
thousands of otherwise healthy women in Britain from starting a family.
Many women who struggle to conceive could increase their chances
greatly by learning to cope more effectively with the stress of daily
life, scientists said yesterday.
Research in the United States has shown that psychological treatment
designed to relieve stress can achieve spectacular results, restoring
fertility to women who do not ovulate or menstruate. […]
In Professor Berga’s study, 16 women aged between 20 and 35
stress-related amenorrhea, none of whom had had a period for at least
six months, were split into two groups. One group was observed but not
treated, while the other eight women were given a 20-week course of
cognitive behavioural therapy, a “talking
which strategies for coping with stress are taught.
“A staggering 80 per cent of the women who received CBT
to ovulate again, as opposed to only 25 per cent of those randomised to
observation,” Professor Berga said.
The study had a small sample size, not unusual for a paper of this
sort, but still it is a factor that limits the generalizability.
Perhaps more importantly, the study only involved women with
“stress-related amenorrhea.” Presumably, this refers to functional
hypothalamic amenorrhea, a condition in which the normal
release of GnRH
is disrupted, often with an apparent stressful antecedent.
structure of GnRH
What this means, is that the study may not apply to the majority
women with infertility, but it could turn out to apply to a
sizable fraction. About 10% of women are infertile
(from all causes combined) at any single point in time, and about 5% of
women develop functional hypothalamic amenorrhea at some point in their
lives. From an earlier article
about Dr. Berga’s work:
Called functional hypothalamic amenorrhea (FHA), the
condition affects some 5 percent of women in their reproductive years.
It is characterized by wildly irregular or absent periods — often for
as long as two years or more.
As I mentioned before, FHA often involves a disruption in the normal
pulsatile release of GnRH. This means that all of the
components of the reproductive system are working, in that all the
reproductive organs are intact, and all of the tissues that are
supposed to secrete hormones are capable of doing so. The
only problem is that the clock that determines when a key hormone is
supposed to be released, is not working right. It is a very
subtle problem, but it has significant consequences.
The regulation of GnRH secretion is complex. The following is
from an online endocrinology
textbook. Skip it unless you are fascinated by the
subject, or unless you are a medical student, in which case you are
expected to memorize everything:
As with most neurosecretory hormones, the GnRH pulse
generator localized in the arcuate nucleus is modulated by input from
other neuronal systems. Animal studies have shown that neurotransmitter
agents such as dopamine, norepinephrine, and serotonin can regulate
GnRH or LH secretion. These studies suggest that activation of the
noradrenergic system is associated with increased release of GnRH
whereas dopaminergic or serotonergic activation can either inhibit or
stimulate GnRH release , . These observations can explain in part the
CNS-associated disruption of normal menstrual cycles in patients who
take phenothiazines (dopamine receptor antagonists), stimulants,
antidepressants, and sedatives on a chronic basis.
Excitatory amino acids such as glutamate and aspartate have recently
been shown to be localized to the arcuate nucleus in the media basal
hypothalamus adjacent to GnRH neurons and have been implicated in a
regulatory role for GnRH secretion primarily during pubertal maturation
. These two amino acids appear to activate GnRH secretion during
puberty in monkeys.
Endogenous opiates peptides such as endorphins, enkephalins, and
dynorphins appear to play largely an inhibitory role in GnRH and LH
secretion. In patients with hypothalamic amenorrhea, blockade of
endogenous opiate receptors with receptor antagonists such as naloxone
or naltrexone will induce an increase in pulsatile release of GnRH and
LH . Long term treatment of hypothalamic amenorrhea patients with
naltrexone can result in return of normal menstrual cycles in some
individuals. These findings indirectly suggest that endogenous opiate
activity is suppressing GnRH secretion.
In case you skipped the technical stuff, I’ll summarize:
regulation of the main hormones that control the menstrual
cycle comes from the pituitary. The pituitary is controlled
by the hypothalamus, which is part of the brain. The
hypothalamus is controlled by input from a variety of sources.
The transmitters involved include dopamine, serotonin,
norepinephrine, endorphins, glutamate, and aspartate.
It follows that a profound dysfunction in any of those transmitter
systems can have an effect on fertility. Stress, of course,
can affect many of those transmitter systems. So it would not
be terribly surprising to find that stress can have a negative effect
One irony here, is that infertility is often treated by massive doses
of hormones. That in itself can be stressful. (If
that is not obvious, take my word for it, or better yet, talk to
someone who’s been through it.) So in a way, hormone
treatment is inherently an uphill battle. You may succeed in
forcing some on the hormones to do what the textbook says they should
do, but in so doing, you actually add to the stress that probably is
the root of the problem to begin with.
So, I do not know how what the response rate would be, if
cognitive-behavioral therapy were tried for the entire population of
women with FHA, but it sure would be nice if it turned out that a
simple, elegant, and inexpensive treatment could eliminate the need for
much of the expensive and stressful hormone treatment that currently is
I know from prior experience working in an eating disorder clinic, that
some women with eating disorders have difficulty attaining pregnancy,
and some undergo hormone treatment. It always seemed obvious
to me that such treatment was not only unnecessary, but it was
unnecessarily risky. What the person needed to do, was to eat
properly, manage stress, and back off on the compulsive exercise, not
take a ton of hormones. Those were extreme cases.
What Berga’s work shows, is that the same can be true for
less extreme cases as well.
Looking at it from another angle, it could be interesting to figure
out what it is about our society that led us to pursue a complex,
invasive, high-tech solution, when a simpler and less intrusive
solution was right there to begin with. You don’t suppose it
could have anything to do with a paternalistic attitude among
physicians, do you?