46,XY Intersex Individuals: Phenotypic and
Etiologic Classification, Knowledge of Condition, and Satisfaction With
Knowledge in Adulthood
PEDIATRICS
Vol. 110 No. 3 September 2002, pp. e32
Abstract Full Text PDF
Introduction
Objectives. The objective of this study was to identify and study adults who have a 46,XY karyotype and presented as infants or children with variable degrees of undermasculinization of their genitalia (female genitalia, ambiguous genitalia, or micropenis). Participants’ knowledge of their condition, satisfaction with their knowledge, and desire for additional education about their intersex condition were assessed.
Methods. Participants were classified according to the cause underlying their intersex condition based on review of medical and surgical records. Knowledge of medical condition, satisfaction with that knowledge, and desire for additional education were assessed with a written questionnaire and a semistructured interview.
Results. Patients were ineligible for recruitment because of death (9%), because of developmental delay (12%), or because they were not located (27%). Among the 96 eligible patients, 78% participated. Approximately half of the men (53%) and women (54%) exhibited a good understanding of their history. Fewer women who have a 46,XY chromosome complement and were born with female genitalia were informed about their intersex condition (36% with complete androgen insensitivity syndrome) than were women who were born with masculinized genitalia such as micropenis (80%) or ambiguous genitalia (72%). More women (66%) than men (38%) were satisfied with their knowledge of their medical and surgical history.
Conclusions. Almost half of the patients, reared male or female, were neither well informed about their medical and surgical history nor satisfied with their knowledge.
Abbreviations: CAIS, complete androgen insensitivity syndrome
• CGD, complete gonadal dysgenesis • LH, luteinizing hormone • FSH, follicle-stimulating hormone • AR, androgen receptor • PAIS, partial androgen insensitivity syndrome • 17ß-HSD-3, 17ß-hydroxysteroid dehydrogenase-3 • PGD, partial gonadal dysgenesis • MIS, müllerian inhibiting substance
Full Text
In the mid-1940s, Lawson Wilkins established the
world’s first pediatric endocrine clinic at the Harriet Lane Home
of the Johns Hopkins Hospital, and he has thus been considered
the founder of pediatric endocrinology. Wilkins’s interest in
the study of sex differentiation, coupled with those of his
surgical, and psychological, colleagues, established
Johns Hopkins as a referral center for intersex patients.
Statements from patient activist groups (www.isna.org)
and research studies6 have suggested
that adults who are affected by syndromes of abnormal sex
differentiation are often poorly informed about their medical and
surgical histories by their physicians and parents. Furthermore,
some of these individuals express dissatisfaction with how little
they understand about their medical condition.
The goals of the present investigation were
to identify and study adults who have a 46,XY karyotype and
presented to the Johns Hopkins Pediatric Endocrine Clinic as
infants or children with variable degrees of undermasculinization
of their genitalia. On the basis of the appearance of their
external genitalia at birth, patients were classified into 3
groups: 1) external genitalia with a normal female appearance, 2)
micropenis without hypospadias, or 3) ambiguous genitalia with
perineoscrotal hypospadias. Verification of diagnosis was performed
for patients whose condition had previously been diagnosed, and an
attempt was made to identify the cause underlying abnormal sex
differentiation for patients for whom no diagnosis had previously
been established. Current gender at the time of study participation
was assessed with a written questionnaire. In addition, patients’
knowledge of their condition, satisfaction with their level of
knowledge, and their desire for additional services from our clinic
were assessed. The study of this group of patients is of particular
importance because of the lack of knowledge about long-term gender
development and sexual function in adults who are affected by
syndromes of abnormal sex differentiation.
METHODS
This research was approved by the Joint
Committee on Clinical Investigation of the Johns Hopkins University
School of Medicine (Baltimore, MD). Written, informed consent was
obtained from all patients before participation. Participants were
asked to complete a written questionnaire and to visit the Johns
Hopkins Clinical Research Center to participate in semistructured
interviews about their medical/surgical history and to assess their
knowledge regarding their clinical condition. Participants were
also questioned about their satisfaction with the amount of
information they had obtained relating to their condition, as well
as their current desire to obtain additional services offered by
our clinic. Physical examinations and laboratory tests were
conducted, and these results appear elsewhere.
Participants
Participants who were recruited for the current study had a 46,XY
chromosomal complement and were affected by abnormal sex differentiation
that resulted in the following phenotypes at birth: 1) normal
female external genitalia, 2) micropenis without hypospadias, or 3)
ambiguous external genitalia with perineoscrotal hypospadias.
Karyotyping became available to our clinic in 1960; from 1953 to
1960, Barr body analysis was performed. Karyotyping was used to
confirm the genetic sex of participants when originally based on
Barr bodies. All participants were 21 years of age or older and had
formerly been treated at the Johns Hopkins Pediatric Endocrine
Clinic.
Etiologic Diagnosis
Criteria for Etiologic Diagnosis of 46,XY Participants With Normal
Female External Genitalia
Participants with normal female external genitalia consisted of 2
distinct conditions: complete androgen insensitivity syndrome (CAIS)
and complete gonadal dysgenesis (CGD). The latter condition is also
referred to as Swyer’s syndrome.
In the case of CAIS, elements of diagnosis
included the presence of testes and spontaneous breast development
at puberty when the gonads remained intact but without menses and
absent or sparse axillary and pubic hair. These individuals
presented with normal to high levels of testosterone and elevated
levels of luteinizing hormone (LH) and follicle-stimulating hormone
(FSH). An androgen receptor (AR) gene mutation was identified for
all of the women who had CAIS in our clinic and participated in
this study.
Patients with CGD presented with an absence
of breast development and primary amenorrhea at puberty. All of
these women in the current study had well-developed müllerian
ducts, including a normal uterus and fallopian tubes. In all cases,
bilateral streak gonads were removed to prevent malignancy. On
administration of estrogen treatment, all women with CGD
experienced menses, and 1 successfully carried pregnancies after in
vitro fertilization with donated eggs. Some of these women had an
SRY gene mutation. CGD can also be attributable to a mutation of 1
of several transcription factors required for the formation of a
gonadal anlagen and their differentiation into testes. These
factors exert multiple functions; therefore, their mutations result
in abnormalities beyond CGD. For example, steroidogenic factor 1
mutations are accompanied by adrenal insufficiency and central
nervous system lesions, WT-1 mutations result in the WAGR syndrome,
SOX-9 mutations are associated with camptomelic dysplasia, and
DAX-1 duplication leads to ambiguous genitalia. None of our
patients who had CGD and participated in the present study were
affected by these additional malformations.
Criteria for Etiologic Diagnosis of
46,XY Participants With Congenital Micropenis
The specific causes of micropenis included hypogonadotropic hypogonadism
(Kallmann’s syndrome, panhypopituitarism, various degrees of
septo-optic dysplasia), hypergonadotropic hypogonadism, and
idiopathic cases. Congenital micropenis, as opposed to a small
phallus (or microphallus), refers to a penis with a male-typical
urethral opening at the tip. Stretched length of a micropenis at
birth was <1.9 cm (2.5 standard deviations below the normal
mean) for affected individuals. Causes underlying micropenis of
participants for the current study appear elsewhere.8
Criteria for Etiologic Diagnosis of
46,XY Participants With Ambiguous External Genitalia Including Perineoscrotal
Hypospadias
Participants with ambiguous external genitalia were selected for
both a small phallus and perineoscrotal hypospadias. Participants with
hypospadias on the shaft or glans of the penis were excluded from
the present study. Although the phenotype for ambiguous genitalia
was similar for all participants, causes underlying their condition
varied. In a number of cases, information was insufficient to
establish a definitive diagnosis.
For participants who are affected by partial
androgen insensitivity syndrome (PAIS), androgen production was
normal with often mildly elevated testosterone and
dihydrotestosterone levels and a normal testosterone/dihydrotestosterone
ratio during the neonatal period.18 The presence
of a utriculovaginal pouch ending blindly without a uterus was
observed. Limited müllerian ducts, usually remnants of fallopian
tubes, were observed at laparotomy or laparoscopy in some of the
participants with PAIS.
PAIS, like CAIS, is transmitted as an
X-linked trait. This type of X-linkage proved helpful in the
diagnosis of some participants’ conditions. The gold standard for
diagnosis of PAIS should be the demonstration of an AR gene
mutation. However, such mutations were not identified in some of
our patients despite the observation of abnormal AR binding
properties (low Bmax and/or high Kd) in
studies of cultured sex skin fibroblasts.19
Perhaps candidate proteins believed to be important for the
biological activity of the AR may be impaired, resulting in partial
expression of androgen responsive genes for these participants.
Alternatively, it is possible that some participants were affected
by 17ß-hydroxysteroid dehydrogenase-3 (17ß-HSD-3) deficiency,
which bears close resemblance to PAIS at initial presentation. This
possibility was recently suggested by a study of subjects with
genital ambiguity in The Netherlands, in which the incidence of 17ß-HSD-3
deficiency was found to be 0.65 times that of AIS.
Partial gonadal dysgenesis (PGD) was defined
as an abnormality of the testicular gonads that involved both
Leydig and Sertoli cell function. Dual abnormality in the
production of testosterone and müllerian inhibiting substance
(MIS) results in ambiguous genitalia coupled with incomplete
suppression of müllerian duct formation. Individuals who are
affected by PGD and participated in this study had a fully or
partially formed uterus. In the neonatal period, low levels of
androgens and all androgen precursors were evident in affected
individuals. Measuring MIS has recently been shown to distinguish
successfully between GD and AIS. CGD and PGD are associated with
low levels of MIS, whereas CAIS and PAIS are associated with normal
to high levels. Unfortunately, because participants in our study
came to medical attention 20 or more years ago, measurements for
MIS were unavailable. It is probable that PGD, like CGD, results
from mutations of transcription factors necessary for early gonad
formation.
Numerous additional causes underlying
ambiguous genitalia were detected in our study population.
Steroidogenic enzyme defect was one, which results from a
deficiency of any 1 of the enzymes necessary to produce
testosterone or dihydrotestosterone from cholesterol, thus leading
to ambiguous external genitalia. This diagnosis required the study
of the final androgen products testosterone and dihydrotestosterone
and also of their precursors (pregnenolone, 17-hydroxypregnenolone,
dehydroepiandrosterone, 17-hydroxyprogesterone, and androstenedione).
A decrease of any of these steroids along with accumulation of
precursors indicated abnormal enzymatic activity at a specific
point in this biosynthetic pathway. All of the genes involved in
this pathway are now known. Studies of gene mutations could confirm
the specific biosynthetic abnormality for affected individuals; however,
such mutation studies are time-consuming and expensive at this
time.
Another cause of ambiguous genitalia was
Leydig cell hypoplasia; a decreased number of Leydig cells caused
decreased androgen secretion and partial masculinization of the
genitalia. It is possible that the low number of Leydig cells in
some patients resulted from LH receptor mutations. It would be
expected that normal Sertoli cell function was maintained, but this
was not always the case and some participants who presented with
signs of MIS deficiency similar to PGD.
True hermaphroditism is a condition in which
normally functioning follicles develop along with tubules and
Leydig cells in the gonads of an individual. The degree of
masculinization of the genitalia is related to the number of
functioning Leydig cells, whereas the degree of müllerian duct
formation is related to the extent of Sertoli cell function. More
than half of the participants with true hermaphroditism possess a
46,XX karyotype; approximately 10% are 46,XY or 46,XX/46,XY
chimeras, and a few are 45,X0/46,XY mosaics. True hermaphroditism
can be determined only by microscopic examination of the gonads and
may be a variant of GD.
We have described a condition termed
"timing defect." In such cases we postulated that the
production of testosterone by the Leydig cells was delayed past the
normal fetal onset of masculinization of the external genitalia in
males. When masculinization occurred late in fetal life, fusion of
the labioscrotal folds and development of a full penile urethra was
not possible. At puberty, affected individuals produced and
responded to androgens in a male-typical manner.
Abnormalities of sex differentiation can
occur in association with multiple congenital anomalies. Among
these are the CHARGE syndrome, Vater syndrome, and
exstrophy-epispadias complex.
Patient Chart Review
Each patient who was evaluated in the Pediatric Endocrine Clinic had
a patient identification card on file that included his or her
Johns Hopkins history number, date of birth, last known address,
parent contact information, date of initial visit, and address of
referring physician. When known, the clinical diagnosis was listed
on the patient identification cards. All identification cards in
our clinic were examined to determine those patients who were
appropriate for recruitment (46,XY with an intersex condition
described earlier, 21 years of age or older, and a past patient at
the Johns Hopkins University Pediatric Endocrine Clinic). Since
Wilkins’s initiation of the Johns Hopkins Pediatric Endocrine
Clinic, medical charts were kept on the premises for all patients
who were examined. Complete medical and surgical charts from the
Johns Hopkins Medical Records Department were also reviewed for
each patient who consented to study participation.
Techniques Used for Locating Eligible
Participants
Eligible participants were located via a variety of tracking methods.
First, we checked the active patient lists at Johns Hopkins
Hospital to determine whether individuals were currently receiving
care at our medical institution. If not listed in the active files,
then individuals were located with Internet search engines for a
current mailing address, telephone number, and/or e-mail address.
For cases in which Internet searches proved unsuccessful, the Motor
Vehicle Administration in the state where the patient was known to
reside last was contacted.
Once located, patients were mailed an
invitation to participate in the study. This letter stated that the
purpose of our study was to determine the long-term outcome of
former patients who were treated for various endocrine conditions.
Former patients, not their parents, were contacted directly because
they were adults at the time of study. Individuals were asked to
indicate whether they desired to participate, desired more
information before deciding to participate, or did not wish to be
contacted further. When individuals chose the last option, no
additional contact was made, as requested by the Johns Hopkins
Joint Committee on Clinical Investigation.
Study Protocol
After the receipt of informed consent, participants were mailed a
written questionnaire that asked about their knowledge of their
condition. Participants’ evaluation of their level of
understanding of medical history included knowledge of karyotype, genital
ambiguity at birth if relevant, gonadal development, cause of
condition, gender reassignment if relevant, genital reconstructive
surgeries if relevant, and level of understanding of endocrine
treatment in adulthood. To be considered as having good knowledge
of their history, participants needed to be informed about all of
these aspects of their condition. Participants were also asked
about their degree of satisfaction with their amount of knowledge
with the following yes/no question: Are you presently satisfied
with how much you understand about your medical history? Finally,
participants were asked whether they desired additional services
from our clinic in the form of 1) talking one-to-one with someone
about problems concerning gender and sexuality and/or 2) attending
an organized meeting to discuss issues of gender and sexuality for
adults with similar endocrine conditions. All participants were
asked whether they desired additional education about their
particular condition and treatment history. Educational material
about normal sex differentiation and the syndromes of abnormal sex
differentiation was made available to participants in a
semistructured interview by providing them with our web site on
syndromes of abnormal sex differentiation (www.hopkinsmedicine.org/pediatricendocrinology/intersex).
Finally, contact information for male and female counselors was
provided to participants who desired such services.
Participants were given the option of
completing the written questionnaire during the course of a
telephone conversation. This was then followed by a semistructured
interview to verify their original written questionnaire responses
or to elaborate on unclear responses during the visit to the Johns
Hopkins Clinical Research Center.
Statistical Analysis
Descriptive statistics and the 
2
test of association were performed. For the 2,
an 
= 0.95 was used and P
< .05 was considered statistically significant.
RESULTS
Sample Selection
Among the 183 eligible patients who were on file in our clinic and
are presently 21 years of age or older, 50 (27%) were not located
despite multiple searching strategies . Patients who were not
located did not differ among the 3 genital phenotypes at birth
(female, ambiguous, micropenis; P > .05) or current gender
(P > .05). Of the remaining 133 individuals, 37 were unavailable
for study because of developmental delay or death .
Patients With Developmental Delay
Twenty-one patients (12%) were affected by developmental delay as
indicated by their medical chart. These individuals were institutionalized
and/or delayed in their development to the extent that
communication was limited and thus completion of the questionnaire
was not possible. The proportion of patients with delay was highest
in the men and women with congenital micropenis (2
= 7.72; P < .05).
Developmental delay is known to occur in
individuals with congenital micropenis. Patients from our clinic
with both congenital micropenis and developmental delay were
affected by CHARGE syndrome (n = 1), septo-optic dysplasia
with variable brain abnormalities (n = 6), Prader-Willi
syndrome (n = 1), Rudd syndrome (n = 1), and
occipital encephalocele (n = 2).
Developmental delay can also be associated
with ambiguous genitalia. Patients in our clinic with both
ambiguous genitalia and developmental delay were affected by
Kennedy syndrome (n = 2), an unnamed syndrome described by
Urban et al (n = 2), CHARGE syndrome (n = 1), Walker-Warburg
syndrome (n = 1), cerebral palsy (n = 1), septo-optic
dysplasia (n = 1), and psychomotor delay of unknown origin (n
= 2). We had no evidence for developmental delay among patients who
were born with unambiguously female genitalia.
Deceased Patients
Sixteen patients (9%) were deceased. The proportion of deceased patients
was highest in the group of men who were born with ambiguous
genitalia (2 =
15.9, P < .05). The death of 1 man with congenital
micropenis was attributed to cardiac disease. All deaths among
women who were born with genital ambiguity were the result of renal
disease associated with Wilms tumors (n = 5). Deaths among
men who were born with genital ambiguity were attributed to renal
disease associated with Wilms tumors (n = 2), suicide (n
= 2), lactic acidosis (n = 1), adverse reaction to
medication (n = 1), and unknown cause (n = 4).
Patients Who Participated in the
Present Study
Seventy-five (78%) of the 96 eligible patients who were located and
invited to participate in the study consented to and completed study
participation. The remaining 21 individuals (22%) either declined
to participate or did not complete their participation in the study
after providing informed consent . Individuals who chose not to
participate did not differ by genital phenotype at birth (female,
ambiguous, micropenis; P > .05) or current gender (P
> .05).
Knowledge of Medical/Surgical History
Eighteen (53%) of the 34 men who participated in our follow-up studies
exhibited a good understanding of their medical and surgical
history, whereas the remaining 16 men (47%) demonstrated a poor
understanding . Knowledge of medical/surgical history did not
differ for men who were born with a micropenis versus those who
were born with ambiguous genitalia (P > .05).
Twenty-two (54%) of the 41 women who participated in our follow-up studies
exhibited a good understanding of their medical/surgical history,
whereas 18 women (44%) exhibited knowledge of their genital
ambiguity but were unaware of their karyotype or gonadal development.
One woman (2%) was uncomfortable with discussing her history;
therefore, the extent of her knowledge could not be determined .
Women who were born with female genitalia (CAIS and CGD) exhibited
a poorer understanding of their history than did women who were
born with a micropenis or ambiguous genitalia (2
= 9.08; P < .05).
Participants did not differ by their current
gender regarding knowledge of their medical/surgical history (P
> .05). It is impossible to know whether patients who were
poorly informed about their condition were never provided with this
knowledge or this information was provided but then forgotten or
denied.
Satisfaction With Knowledge Received
About Medical/Surgical History
Thirteen men (38%) were satisfied with their knowledge of their medical/surgical
history. Satisfaction did not differ for men according to their
genital appearance (ambiguous or micropenis) at birth (P
> .05). Seventeen men (50%) were dissatisfied with their
understanding of their condition, and 4 men (12%) did not respond
to this question.
Among men who were satisfied with their
knowledge, 10 (77%) were considered to have good knowledge of their
medical/surgical history and 3 (23%) exhibited poor knowledge of
their history. Among men who were dissatisfied with their
knowledge, 5 (29%) were well informed and 12 (71%) were not.
Twenty-seven women (66%) were satisfied with
their knowledge of their medical/surgical history. Satisfaction did
not differ for women according to their genital appearance (female,
ambiguous, micropenis) at birth (P > .05). Twelve women
(29%) were dissatisfied with their understanding of their
condition, and 2 women (5%) did not respond to this question.
Among 27 women who were satisfied with their
knowledge, 17 (63%) were considered to have good knowledge of their
medical/surgical history and 10 (37%) exhibited poor knowledge of
their history. Among 12 women who were dissatisfied with their
knowledge, 5 (42%) were well informed about their condition and 7
(58%) were not .
Participants differed by sex of rearing
regarding their satisfaction with knowledge of their
medical/surgical history (2
= 4.55; P < .05), with more women than men reporting
satisfaction. In addition, amount of knowledge corresponded to
satisfaction for men (2
= 6.6; P < .05) but not for women (P > .05). Men
with greater knowledge reported more satisfaction with that knowledge.
However, no such relationship was observed for women.
Desire for Additional Services
Some of the men reported a desire for additional services, such as
speaking to a person one-to-one (47%) and attending a meeting with
other individuals who are affected by syndromes of abnormal sex
differentiation to discuss gender issues (26%). Similarly, some of
the women reported a desire to talk one-to-one (44%) and attend a
meeting (39%). The desire for additional services did not differ
for participants according to their current gender (P >
.05).
DISCUSSION
Limitations of Etiologic Diagnosis
One of the major limitations encountered in our study was the inability
to make an etiologic diagnosis for all patients. This problem was
unique to patients with ambiguous genitalia. Patients who were
classified as having PAIS on the basis of studies of sex skin
fibroblasts had no identifiable AR gene mutation. These same
individuals also did not have 1 of the 4 most common mutations of
the 17ß-HSD-3 gene.
It was less difficult to classify patients
with ambiguous genitalia into the PGD category as patients who
present with well-developed müllerian ducts fit this diagnosis. In
the area of abnormal steroid biosynthetic pathways, patients’
conditions were diagnosed on the basis of steroid studies at the
appropriate time of life (before 4 months of age or at puberty when
the gonads remained intact).
Genitalia as a Bioassay for Androgen
Action
It is widely accepted that masculinization of the genitalia requires
adequate effects of androgens. A simple corollary is that the
degree of undermasculinization will be proportional to the degree
of deficiency of androgen effects. This is true regardless of cause
(failure to produce androgens or failure to respond to androgens).
We can conclude that regardless of whether
fetal exposure to androgens masculinizes the human central nervous
system, patients with undermasculinized genitalia were exposed to
androgen effects below the normal male range. Thus, regardless of
whether this is important to psychosexual development, degree of
decreased prenatal androgen exposure can be assessed by the
appearance of the genitalia at birth. On this principle, we believe
that whatever the cause of genital ambiguity in a 46,XY patients,
the most feminized patients would benefit from female sex of rearing
and the most masculinized patients would optimally respond to male
sex of rearing. In addition, our follow-up studies have shown that
the number and difficulty of surgical procedures necessary for
either sex of rearing should be discussed when assigning gender.
Reproduction
Among 46,XY intersex patients, the only conditions with potential for
fertility are 5-reductase
deficiency and timing defect In cases of CGD and PGD, there exists
the potential for in vitro fertilization in patients who are reared
female.
Intersex and Transsexualism
In retrospective follow-up studies of self-defined patient samples, it
is possible to recruit accidentally patients who are postoperative transsexuals.
Because of this potential confound, we included in our studies only
patients whose conditions were diagnosed and treated in the Johns
Hopkins University Pediatric Endocrine Clinic.
Patients Not Located
Fifty individuals (27%) were not located, and failure to locate these
patients may be attributed to the length of time since they were
last seen at Johns Hopkins. The tendency of people to relocate for
education and work opportunities is well established in our
society; therefore, it is not surprising that 27% of the original
group of patients spanning a period of 50 years were not located.
Patients who were not located did not cluster according to age.
Before study initiation, we had anticipated greater difficulty in
finding patients who were reared female because of their likelihood
for name change on marriage. This was not the case, however, as our
ability to contact patients did not differ according to their
current gender.
Developmental Delay
The incidence of developmental delay was highest for individuals who
were born with a micropenis followed by those who were born with
ambiguous genitalia, and this observation is consistent with
previous reports.27–29
Somewhat surprising was the number of patients who had profound
developmental delay and were assigned to the female gender. As this
group seems to have obstacles far greater than a small phallus for
sexual intercourse, this decision seems questionable. However, for
some of these patients, the extent of developmental delay may not
have been evident until after a female gender assignment had been
made.
Deaths
The incidence of death was highest among patients who were born with
ambiguous external genitalia, and several of these deaths were
attributed to Wilms tumors known to be malignant. It is difficult
to determine the relationship between suicide and endocrine
condition in the 2 men for whom this information is known, as these
deaths occurred before study initiation. Considering the enormous
impact that having ambiguous genitalia exerts on patients, it is
possible that their intersex conditions contributed to the suicide
of these men.
Refusal to Participate
Among the patients who were eligible for study participation, 78%
participated in all aspects of the study. Among the 21 patients who
did not participate, 3 had consented to study participation but
never returned a completed questionnaire or completed a physical
examination. We had anticipated greater nonparticipation rates from
women because of their desire for confidentiality regarding their
karyotype. This was not the case, and nonparticipants did not
differ according to current gender or phenotype at birth. It is
unfortunate that we were unable to determine the reason for refusal
of these patients. As previously noted, our research protocol did
not permit us to contact individuals who chose not to participate.
Knowledge of Medical/Surgical History
Approximately half of the patients who participated demonstrated a
good knowledge of their history, and this knowledge did not differ
according to their sex of rearing. Patients who were born with
ambiguous genitalia or micropenis and were reared female exhibited
better knowledge than those who were born with normal female
genitalia. We speculate that because women with CAIS and CGD had a
totally female phenotype, they required no or few surgical
procedures, thus leading to fewer opportunities to be informed of
their condition. In addition, these patients may not have requested
as much information as the women with ambiguous genitalia. Slijper
et al6 also reported a poor understanding of
diagnosis among 46,XY patients who were reared female. Their results
may be attributable to the fact that many patients were affected by
CAIS and thus had female genitalia. Our study indicates that
attempts to improve knowledge of their condition among intersex
patients needs to focus on patients with female genitalia (CAIS and
CGD) as well as those with ambiguous genitalia or a micropenis.
Satisfaction With Knowledge
More women (66%) than men (38%) were satisfied with how well they
understood their medical/surgical history. Cancer patient dissatisfaction
with their medical information has been attributed to limited time
for discussion, poor communication skills of medical staff, medical
staff’s withholding information, and patient inability to
remember information. It is reasonable to suspect that similar
reasons contributed to the dissatisfaction reported by intersex
patients in the present study. Resources designed to increase
satisfaction with the amount of medical information provided to
intersex patients would greatly serve this population.
Unfortunately, information provided to the patients through media
such as the Internet is currently unregulated and can be
misleading.
For men but not for women, satisfaction with
knowledge related to the patients’ understanding of their
history. Observations of patients with other disorders reveal that
some individuals prefer to know only partial information concerning
their condition, whereas others wish to know as many details as
possible. Women in the present study were more likely than men to
be satisfied with what the authors considered to be poor
medical/surgical knowledge. One interpretation is that some of
these women had a better understanding of their condition than they
indicated but were unwilling to discuss their diagnosis openly
because of concerns about confidentiality. In all of our dealings
with patients for follow-up studies, confidentiality was extremely
important to patients.
Additional Services
Roughly half of the men and women who participated desired additional services
for discussing issues of gender and sexuality. This observation,
taken with the fact that some patients were dissatisfied with the
knowledge provided to them concerning their condition, illustrates
the importance of offering education and counseling to patients and
their families. Although the present data identify groups of
patients for whom education would prove useful, the practical
questions of what information to provide and when to provide it
remain unresolved.
Future Studies
In addition to offering guidelines for educating patients and their
families, future studies of intersex patients could include information
about the impact of family members and friends on psychosexual
development in individuals who are affected by syndromes of
abnormal sex differentiation. For example, the degree of parents’
understanding of their child’s intersex condition may have a
major impact on later medical knowledge and satisfaction with
treatment by patients. In addition, if parents of children with
intersex conditions are themselves at an increased risk for
hardships such as divorce or substance abuse, then this could
translate into psychosexual difficulties for patients. We are
currently in the process of collecting such data from parents of
intersex patients.
ACKNOWLEDGMENTS
This work was supported by a grant from
the Genentech Foundation for Growth and Development (98-33C),
National Institutes of Health National Research Service Award
F32HD08544; and by National Institutes of Health, National Center
for Research Resources, General Clinical Research Center grant
RR-00052. It must be noted that many of the studies obtained on the
patients included in the present article were made possible by
National Institutes of Health grant 5-ROI-DK-00180 (1953–1987).
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Citation: Claude J. Migeon, MD*, Amy B. Wisniewski, PhD*, Terry R. Brown, PhD*,, John A. Rock, MD, Heino F. L. Meyer-Bahlburg, Dr. rer. nat.||, John Money, PhD¶ and Gary D. Berkovitz, MD#
* Department of Pediatrics, Division of Pediatric Endocrinology, Johns Hopkins University School of Medicine, Baltimore, Maryland
Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia
|| Department of Psychiatry, Division of Child Psychiatry and Program of Developmental Psychoendocrinology, Columbia University College of Physicians and Surgeons and New York State Psychiatric Institute, New York, New York
¶ Department of Medical Psychology and Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
# Department of Pediatrics, Division of Pediatric Endocrinology, University of Miami School of Medicine, Miami, Florida
Key Words: intersex hermaphrodite
gender androgen insensitivity gonadal dysgenesis micropenis
patient satisfaction patient knowledge
