Over the past 15 years, there has been a growing chorus of voices
medical professionals, parents and affected adults calling for more
research into long-term effects of medical treatment of children with
differences of sex development.
After decades of treatment, two of the most commonly voiced concerns are
that we still lack evidence-based guidelines for making decisions about
elective genital surgery or about prenatal treatment with dexamethasone to
prevent genital virilization in girls with congenital adrenal hyperplasia. This
forces parents and physicians to make difficult decisions without needed
information about the long-term effects on personality development, sexual or
mental function, and overall quality of life.
As an advocate for children with differences of sex development (DSD)
and their families, I support these calls for research to support development
of patient-centered, evidence-based care. However, the idea of more research
also gives me a feeling of trepidation. History shows that medical research is
fraught with risks for the subjects, and that many of these hazards have only
been perceived with hindsight. I worry that a rush into research without
consideration of the specific needs of children with DSD may cause more harm
At the core of most ethical problems with research is that the
researcher has an inherent conflict of interest with the research subject. I am
not just talking about financial conflicts of interest, the effect of research
outcomes on the researchers career or the influence of ego in scientific
inquiry all well-documented moral hazards for researchers. Even when a
researcher has the noblest of intentions, the researchers goal is the
production of knowledge. This goal may not be congruent with the subjects
best interest. When the subject is also the researchers patient, the
conflict becomes more complex.
In the case of DSD, there has been such vociferous criticism of past
practices and such great need for more information that providers may feel an
urgent need to gather data. This can make it difficult for a researcher or
physician to maintain clinical judgment about what is best for the patient.
For this reason, the scientific community has developed special
protections that should apply whenever humans are the subjects of research.
Although we cannot cover the entire regulatory framework in this article, there
are some basic protections that are legally mandated in most cases and are
certainly ethically required any time human subjects are used. These include
requirements for enhanced informed consent, for assent when children are the
subjects of research that will not benefit them individually and for an
institutional review board (IRB) to approve the research plan.
This last requirement is arguably the most important because the IRB is
an independent body whose role is to examine the specific context of the
proposed research, ask probing questions about potential harms to subjects and
ensure that the rights of subjects are fully taken into account.
When is it necessary to consult with an IRB? One good answer is that if
you think it might be necessary, go ahead and consult. The IRB can tell you if
your work does not require its oversight.
Another sign that IRB consultation is needed is when the line is crossed
from treatment of a patient into research. If a physician undertakes an
intervention or examination with the intention of contributing to generalizable
knowledge, it is likely to be considered research. This is true whether or not
the patient stands to benefit from the procedure. So for example, genital exams
are sometimes necessary for patient care. But if a surgeon does follow-up exams
years after surgery on multiple DSD patients with the intention of aggregating
data to improve future surgical treatment, the activity is likely to require
Even diligent IRB oversight may not be enough to protect children with
DSD if the IRB is not educated about the special concerns affecting these
children. One of the tasks of the IRB is to assess the risk of harm that
proposed research poses to the subjects and weigh that against any potential
benefit. In most situations, for instance, an IRB might consider the risk of
harm from a single genital exam to be relatively low. But adults with DSD have
reported that they experienced such exams as deeply shaming and painful in
childhood, even if they did not protest.
Children with DSD are likely to have been exposed already to multiple
genital exams, and it is well-documented that these children can suffer
psychological harm from excessive genital exams. An IRB must be accurately
informed about the effect such procedures may have specifically for children
with DSD to accurately assess whether proposed research is ethically warranted,
construct procedures for meaningful patient assent and inform parents of the
risks involved in the research.
When proposed research involves innovative treatment, such as new
surgical techniques or off-label prescription, the IRB needs accurate
information about the knowns and unknowns of current treatment outcomes to
evaluate potential harms and benefits of innovative treatment. For example,
many treatment protocols for children with DSD assume that some surgical
intervention is necessary for genital ambiguity it is just a matter of
figuring out which surgical techniques are best. However, an IRB considering a
surgical protocol must know about the lack of evidence that any surgery is
necessary for healthy psychosocial development and about the potential to delay
surgical treatment until consent or assent is possible.
Given the many ethical questions about treatment of DSD, the IRB must
also be sure to independently consider whether the goals of treatment are
ethically justified. For example, many published studies on the use of
dexamethasone prenatally in 46,XX fetuses with congenital adrenal hyperplasia
have offered the possibility of a reduction in masculine behavior
as a possible benefit of this experimental treatment. However, the idea of
using prenatal interventions with the goal of changing nonpathological behavior
traits is ethically troubling. This outcome should not be considered a
potential benefit to be weighed against risk of harm in evaluating a proposed
Research is critically needed into outcomes of treatment for children
with DSD. I applaud the researchers and clinicians who are turning their
attention to this important matter. Remembering the mistakes of the past,
however, with clinical research and with treatment of DSD, I also beseech them
to proceed with caution.
Anne Tamar-Mattis, JD, is the Executive Director of Advocates for
Informed Choice, Cotati, Calif. She welcomes responses to this article at
For more information:
- Committee on Clinical Research Involving Children. The
Ethical Conduct of Clinical Research Involving Children. Washington,
D.C.: The National Academies Press; 2004.
- Consortium on Disorders of Sex Development. Clinical guidelines for
the management of disorders of sex development in childhood. Available at:
Accessed March 10, 2010.
- Sytsma SE. The ethics of using dexamethasone to prevent
virilization of female fetuses. In: Sytsma SE, ed. Ethics and
Intersex. Netherlands: Springer; 2006;29:241-258.