287
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VOLUME 16 SEPTEMBER 1955 NUMBER 3
ORIGINAL
ARTICLES
HERMAPHRODITISM:
CLASSIFICATION,
DIAGNOSIS,
SELECTION
OF
SEX AND
TREATMENT
By Lawson Wilkins, M.D.,* Melvin M. Grumbach, M.D.,t Juds#{243}nJ. Van Wyk, M.D.,t
Thomas H. Shepard, M.D., and Constantine Papadatos, M.D.
T
HEITE is a great deal of confusioncon-cerning the methods of diagnosing and
treating individuals with ambisexual
de-velopment, and a lack of understanding of
the principles by which the sex of rearing should be selected. Often the choice of sex is postponed or reversed from time to time.
The parent regards the child as “half-boy and half-girl” and anticipates that morbid sexual perversions will ensue. Uncertainty, protective secrecy or social ostracism make
it difficult for the child to adjust properly. Frequently the sex of rearing is chosen un-wisely because of the traditional belief that
the sex chromosomal pattern, the gonads or
the hormones which they produce are
inev-itably intrinsic determinants of an
individ-ual’s psychosexual development and
inch-From the Department of Pediatrics, Johns Hop-kins University School of Medicine and the Harriet Lane home, Johns Hopkins Hospital.
This work WaS made possible by a Grant-in-Aid from the American Cancer Society upon recom-niendation of the Conimittee on Growth of the National Research Council, and by a research grant from the Division of Research, Grants and
Fellow-ships of the National Institutes of Health, U.S. Public health Service.
(Submitted April 29, accepted May 10, 1955.)
0 ADDRESS: Johns Hopkins Hospital, Baltimore 5,
Maryland.
Fellow of the National Foundation for Infantile Paralysis.
nations. This article is written in the hope
that better understanding of the problems
of diagnosis, treatment and psychosexual
determination will aid physicians to avoid some of the errors of the past. It is based
on studies made on 70 cases in our clinic
and an extensive review of the literature. The subjects of homosexuality and
trans-vestism, which are dependent upon
psy-chologic rather than physical abnormalities
will not be considered.
CLASSIFICATION
AND
ANATOMY
Although many schemes of
terminol-ogy#{176}-3have been suggested for describing individuals with ambisexual development,
the classification shown in Table I lends
itself best to a consideration of the clinical
problems of diagnosis and treatment. This
table divides the cases into 2 groups with different etiologies and shows the discrep-ancies between the morphologic structure of the gonads and the sex differentiation of
the external genitalia and/or the genital
ducts.#{176}
From the standpoint of etiology and
WITH CONGENITAL ADRENAL HYPERPLASIA
tINTER SEX”
WH0UT ADRENAL DISORDER
(OCCASIONALLY DUE TO
VIRILIZATION BY MATERNAL
A RRHENOBLASTOMA)
B FIG. 1. Female pseudohermaphrodites.
TABLE I
TYPES OF AMBISEXUAI. DEVELOPMENT
GONADS PHALLUS LABIAL FUSION
GENITAL
DUCTS
SECONDARY
SEX DEVELOP
A. CON( ADRENAL HYPERPLASIA
OVAR I ES LARGE + + +- 0 FEMALE
MALE PRECOCIOUS FEMALE PSEUDOHERMAPHR.
B. INTERSEXES
I. TRUE HERMAPHRODI TES
MIXED VARIABLE VARIABLE MIXED
MALE
OR
FEMALE
U. MALE PSEUDOHERMAPHR. A. EXTERNAL GENITALIA
SIMULATING MALE OR AMBIGUOUS
0
B EXTERNAL GENITALIA SIMULATING FEMALE
#{174}
.
TESTES
(ABOOM NAL OR
INGUINAL)
LARGE TO MEDIUM
++-‘+++
D
PREDOM. FEMALE
‘-USUALLY
MALE
PREDOM. MALE
(PEMAI.E VC5TII)
OR FEMALE
SMALL 0
.
PREDOM. FEMALE
UTERUS U$UAI.LY ABSENT
(MALE VEST lOtS)
USUALLY
FEMALE
m.FEMALE PSEUDOHERMAPHR. 0
OVARIES MAYLARGEHAVE
PENILE URETHRA
+ + + FEMALE FEMALE
0 PHALLUS RESEMBLES PENIS’ USUALLY HYPOSPADIAS AND CRYPTORCHIDISM; OCCASIONALLY PENILE URETHRA. SEPARATE VAGINAL ORIFICE OR UROGENITAL SINUS.
(j) PHALLUS RESEMBLES CLITORIS; WELL FORMED VULVA; USUALLY SEPARATE VAGINA ENDING BLINDLY; MAY OCCASIONALLY HAVE PARTLY DEVELOPED UTERUS.
FEMALE PSEUDOHERMAPHRODITISM SOMETIMES DUE To VIRTLIZATION BY MATERNAL A*RHENOBLASTOMA, ETC.
treatment, it is of paramount importance
to differentiate between (A) female
pseu-dohermaphroditism due to congenital
ad-renal hyperplasia and (B) ambisexual
development which is not associated with
an adrenal disorder. To emphasize this
A
distinction the term iiUersex has been
ap-plied to cases of the latter group.
It is necessary to describe briefly the
different groups of cases in order that the
289
A. Female Pseudohermaphroditism with
Congenital Adrenal Hyperplasia
Virilizing adrenal hyperplasia is caused
by an abnormality in the synthesis of
ad-renocortical steroids which leads to the se-cretion of excessive amounts of androgenic
hormones. It is probable that the frequent occurrence of the adreno-genital syndrome
in siblings is due to the inheritance of a re-cessive trait.5 When the disorder occurs pre-natally in females it causes the external genitalia to develop more or less along the male pattern after the m#{252}llerian ducts have
undergone female differentiation to form a
vagina, uterus and tubes (Fig. la). The
ovaries are normal and in the usual position.
The appearance of the external genitalia
varies considerably depending upon the
de-gree of enlargement of the phallus and the
extent of fusion of the labial folds. The
phallus is always definitely enlarged at birth
and in some cases resembles a more or less
well-developed penis with hypospadias and
bound in position of chordee. Several cases
have been described in which there was a
penile urethra. When there is little or no
fusion of the labial folds there may be a
vulva-like introitus with separate urethral
and vaginal orifices (Fig. 2c). More
com-monly there is partial fusion of the labial
folds posteriorly so as to form a urogenital sinus within which the orifices of the vagina
and urethra are situated. One then finds a
slit-like groove extending backward from
the base of the phallus and extending pos-teriorly in a funnel-shaped opening into the urogenital sinus (Fig. 2b). Sometimes there is a more complete fusion of the labial folds
to form a medial raphe on which there is a
small round or slit-like orifice of the
urogeni-tal sinus resembling the meatus of the
urethra in a patient with hypospadias
(Fig. 2a).
Unless treatment is instituted, the
andro-genie effects of adrenal hyperplasia are not
confined to the fetal period but result in
progressive virilization after birth. There is excessive growth and accelerated
epiphys-eal development. Male secondary sexual
characteristics develop precociously with
the appearance of sexual hair between the
ages of 1 and 4 years, followed later by
pro-gressive hirsutism, acne and deepening of
the voice.
Fortunately the abnormal androgenic
activity of the adrenal can be suppressed with relatively small doses of cortisone
and progressive virilization can be
pre-vented.4’6’7 Accordingly it is important to
establish the diagnosis and institute therapy as early as possible. The differential diag-nosis and treatment will be discussed later.
B. Intersexes
Various theories have been offered to ex-plain the occurrence of ambisexual develop-ment in individuals who do not have viriliz-ing adrenal hyperplasia. Recently consider-able clarification of the subject has resulted
from experiments in which young animal
embryos have been castrated8 and from the
study of chromosomal patterns in human
hemaphrodites.#{176}
It should be pointed out that a large pro-portion of the patients described formerly
as having the “syndrome of ovarian agenesis
and stunted growth” have male
chromo-somal patterns but entirely female sex
dif-ferentiation. Accordingly these patients
must be regarded as male pseudohermaph-rodites and the syndrome should be referred
to as “gonadal dysgenesis.” In the present
paper, however, we shall restrict the term intersex to male pseudohermaphrodites
whose gonads are morphologically testes
but whose external genitalia and/or genital
ducts show varying degrees of female
di.f-ferentation, true hermaphrodites with
mixed gonads and ambisexual differentia-tion of the sex organs, and female pseudo-hermaphrodites who do not have virilizing adrenal hyperpla$ia.
All types of intersexes can be
distin-guished from patients with the
adreno-genital syndrome by the fact that their sec-ondary sexual characteristics do not develop
until the usual age of puberty, 10 to 17
years, and that only normal childhood levels
of androgens or estrogen can be
demon-strated before this time.
I. TRUE HERMAPHRODITES. In rare
in-stance the gonad on one side is a testis
and that on the other side an ovary.
In these cases the differentiation of the
genital duct on each side follows the sex of
the adjacent gonad. More commonly 1 or
both gonads are ovotestes containing both
ovarian and testicular structures. In true
hermaphrodites there are innumerable
vari-ations in the degree of male and female
differentiation of both the external genitalia
and the genital duct structures (Fig. 3). It
is impossible to predict with certainty
whether at puberty the secondary sexual
development will be predominantly male
or female.
II. MAUi PSEUDOHERMAPHEODITES. These
patients have gonads which are
morpho-logically testes. They may be situated either
inside the abdomen where they are usually
found in the position of the ovary, in the
inguinal canal or in the labioscrotal folds, The tubules generally appear immature,
composed of undifferentiated germinal cells
but after puberty Sertoli cells may
pre-dominate and numerous Leydig cells in
large clumps are often found.
For practical purposes male
pseudoher-maphrodites may be divided into 2 main
groups: (A) those with external genitalia
which simulate the male or are of
geni-FIG. 3. True hermaphrodites.
talia simulating the female.
A. Male pseudohermaphrodites with ex-ternal genitalia which are ambiguous or re-semble the male have varying degrees of
phallic development and labioscrotal
fusion. In some instances the phallus
re-sembles a well-developed penis with
hypo-spadias and the scrotal folds are well fused,
the urinary meatus being situated on the
median raphe near the base of the phallus.
Such a patient can be mistaken for a
cryp-torchid male with hypospadias unless
stud-ies are made to determine whether any
female structures are situated internally. In other instances the phallus is only
moder-ately developed and the labioscrotal folds
are unfused or only partially fused leaving
a vulva-like slit or depression between. In
this depression there is usually a single
orifice through which the patient voids but
occasionally one can see a small vaginal
orifice adjacent to it. To demonstrate
whether there are female structures arising
from the mflllerian ducts and to determine
the extent of their development it is neces-sary to resort to urethroscopy and
explora-tory laparotomy. In some instances there is
extensive development of the female genital
ducts with a vagina opening into the
uro-genital sinus and normally formed uterus
and tubes. Anatomically these subjects are
identical to female pseudohermaphrodites
having congenital adrenal hyperplasia
ex-cept that they have testes instead of ovaries (Fig. 4, Al). In other cases the uterus is less
completely developed and 1 or both of the
fallopian tubes may be missing. Paradoxi-cally enough the male pseudohermaphro-dites who have predominantly female devel-opment of the internal genital ducts usually
develop masculine secondary sex character-istics at puberty (Table I, group B II, Al).
On the other hand, some of the male
geni-SIMULATING
MALES
(TESTIS MAYBE EITHER INTRAABDOMINALOR INGUINAL)
SIMULATING
FEMALES
(TESTIS MAY BE.EITHER INGUINALOR INTRAABDOMINAL)
B.1 B.2 B.3
FIG. 4. Male pseudohermaphrodites.
talia which are ambiguous or resemble the
male but show very little female
develop-ment of the genital ducts may develop
sex-ually as either males or females (Table I,
group B II, A2). In these individuals there may be a small vaginal pouch
communicat-ing with the urogenital sinus (Fig. 4, AS)
or a blind vaginal pouch opening separately between the labioscrotal folds (Fig. 4, A2). The vasa deferentia may be well developed
and open into the posterior urethra.
B. Male pseudohermaphrodites with ex-ternal genitalia simulating the female. This is a most interesting group of patients who
are often mistaken for normal females. The
external genitalia are entirely feminine. The clitoris is not enlarged or only slightly so.
The vulva is normally formed usually with
separate urethra and vagina, although
oc-casionally there is a urogenital sinus with a
communicating vaginal pouch (Fig. 4, Bl).
The testes may be in the inguinal canals or
labial folds or they may be situated in the
abdomen in the position of the ovaries.
When a separate vagina is present it is of
relatively normal size but usually terminates
blindly; and no cervix or uterus is present. In these cases there may be m#{252}llerian duct structures about the size of round ligaments
arising from the vault of the vagina and
terminating in bulbous ends containing
smooth muscle resembling myometrium
(Fig. 4, B2). These may be situated in the
pelvis in the position of fallopian tubes or they may be prolapsed into inguinal hernias
along with the testes. On section of the
adjacent rudiments of wolffian duct
strisc-tures (vasa deferentia and epididymal
tu-bules) may be found as well as rudimentary
fallopian tubes. Occasionally there is a
poorly formed uterus with 1 or both
fal-lopian tubes (Fig. 4, B3). The testes remain
immature even in adults. The tubules are
composed mostly of Sertoli cells and
un-differentiated epithelium. Large clumps of
At puberty the male
pseudohermaphro-dites with female external genitalia
practi-cally always develop feminine secondary
sexual characteristics. 1 The general
habi-tus, features and body contours are
mark-cdlv feminine. The breasts develop normally
and the vaginal mucosa becomes estrinized.
\‘lenstniation does not occur. The patient
may marry and have normal intercourse.
The female development is remarkable in
view of the fact that the testes contain
abundant Leydig cells and in our
experi-ence histologically do not differ appreciably from those of male pseudohermaphrodites
who masculinize. Furthermore, it has been
shown in some cases that the 17-ketoste-roids are elevated to levels of 20 to 30 mgI
day. In several cases which we studied it
was demonstrated that in addition to
an-drogen the testes were secreting estrogens in
amounts normal for adult females and that
after gonadectomy the estrogens
dis-appeared and urinary gonadotropins rose to
menopausal levels.1
In many but not all of the cases of male
pseudohermaphroditism “of feminine type,”
sexual hair has been entirely lacking.1#{176} In 1 patient studied by us even the administra-tion of relatively large doses of
methyltestos-terone (50 mg. daily) caused no growth of
hair.
III. FEMALE PSEUDOHERMAPHRODITES
WITHOUT ADRENAL HYPERPLASIA. This is the
rarest type of intersex and the one most
difficult to explain. Only 9
well-authenti-cated cases have been recorded of which
we have studied 1.110 In our case the
phallus was well developed, resembling a
penis with hypospadias and the
labio-scrotal folds were fused to resemble a
scro-tum. In 3 other cases there was a penile
urethra and an auxiliary urethral meatus
opening into the vagina. No gonads were
pallable in the canal or in the labia.
Ac-cordingly, before puberty, such patients are
* Recently Papadatos and Klein12 have described 2 other cases and Perloff et aL” 1case. In these pa-tients there was only slight clitoral enlargement and partial fusion of the labia.
often mistaken for cryptorchid males with
hypospadias. The genital tract is identical
anatomically with that of female
pseudo-hermaphrodites with congenital adrenal
by-perplasia. There is either a vagina opening into the urogenital sinus or a separate vagi-nal orifice. The uterus and fallopian tubes
are normally formed. The ovaries are
lo-cated in the usual position in the broad liga-ments (Fig. 1, B).
Unlike females with congenital adrenal
hyperplasia these intersexes show no mani-festations of androgen secretion or any de-velopment of secondary sexual character-istics until the usual age of puberty. At this
time the breasts develop and pubic and
axillary hair begins to grow. Later, bleeding
may take place through the urinary meatus and recur periodically. Normally developed uterus and tubes are found at laparotomy. The ovaries are mature and show evidences of ovulation with corpora lutea formation. There are reports4”5 of 2 female
pseudo-hermaphrodites of the type described who
were born to mothers who were proved to
have arrhenoblastomas during gestation. In
these cases it would seem that
masculiniza-tion of the female fetus was caused by
an-drogen secreted by the arrhenoblastoma. The cause of fetal virilization in the other cases is not known.
RELATIVE FREQUENCY OF DIFFERENT
TYPES
OF
HERMAPHRODITISM
Table II shows 298 cases of
hermaphrG-ditism culled by Dr. John Money16 from the
literature. All cases reported in the English
language between 1895 and 1950 are
in-cluded except 15 cases in which the data
were not adequate to permit a satisfactory
classification according to the scheme
de-scribed above. The table also shows, in
comparison, 70 cases studied at the Johns
Hopkins Hospital between 1936 and 1954.
It seems probable that female
pseudoher-maphroditism due to congenital adrenal
hyperplasia and the various types of
inter-sexuality may occur with about equal
fre-quency. The predominance of the
STUDIED AT H.L.H. 1936-1954
A. CONG. ADRENAL HYPERPLASIA
122
- 122 - 46 - 46 - $68
FEMALE PSEUDOHERMAPHR.
B. INTERSEXES
I. TRUE HERMAPHRODITES
2. MALE PSEUDOHERMAPHR.
3. FEMALE PSEUDOHERMAPHR.
TOTAL
39
$29
8
22 10 7
42 87
-0 6
-I
22
I
0 I
-7 9 6
0 I -40
151
9
176 64 105 7 24 7 II 6 200
TOTAL 298 64 227 7 70 7 57 6 368
294
in the adreno-genital syndrome and in some
TABLE II
NUMBERS AND TYPES OF CASES OF AMBISEXUALITY
COLLECTED FROM
LITERATURE BY MONEY 1895-1950
TOTAL SIMULATING TOTAL SIMULATING
due to our interest in its treatment with
cortisone. Among 200 patients with
ambi-sexual development not due to adrenal
dis-order, there were 151 male
pseudoherma-phrodites, 40 true hermaphrodites, and only
9 female pseudohermaphrodites. It is of
interest that in Aoney’s group of male
pseudohermaphrodites, one-third had
ex-ternal genitalia of female type and the same proportion occurred in our group. Morris10
has recently emphasized the frequency of
feminization in male pseudohermaphrodites
by collecting from the literature 82 cases in
adults. In 20 of these it is recorded that
pubic and axillary hair was absent and in
33 “scantY.”
DIAGNOSIS
It is most important to establish as early
in life as possible the differential diagnosis between female pseudohermaphroditism
due to congenital adrenal hyperplasia and
non-hormonal forms of ambisexual develop-ment. This cannot be based on the anatomy
of the external genitalia or the genital duct structures because these may be identical
types of “intersexuality.” The diagnosis of
the adreno-genital syndrome depends upon
the demonstration of increased secretion of
adrenal androgens.’6’’ lib This manifests
itself by the early appearance of sexual
hair, excessive growth in stature during
early childhood and greatly accelerated epi-physeal ossifications. In the congenital form
of virilizing adrenal hyperplasia these signs
are usually apparent by the age of 1 to 4
years, but sometimes they do not appear
until later. It is important that the
condi-tion should not be confused with benign
variations of sexual development which we
have termed “premature pubarche.”T In
this syndrome there is an early but not an
excessive secretion of adrenal androgen,
causing precocious growth of sexual hair,
but there is no progressive virilization.
These patients show no abnormalities of
their sex organs.
Fortunately the diagnosis of the
adreno-genital syndrome can be made long before
the appearance of hirsutism and
in-creased to 2 to 5 mg/day, compared to the
normal level of less than 0.5 467
In cases where there may be ambiguous
values of 1 to 2.5 mg/day, the
demonstra-tion of urinary pregnanetriol confirms the
diagnosis.4’ 6, 18 After the first year or two of
life the 17-ketosteroid excretion is generally
increased to levels of 6 to 15 mg./day and
by adolescent years reaches 25 to 80 mg./
day.
The finding of increased 17-ketosteroid
excretion (and the demonstration of
preg-nanetriol) is diagnostic of the adreno-genital syndrome. Marked suppression of
17-keto-steroid excretion by the administration of
cortisone proves that the disorder is due to bilateral virilizing adrenal hyperplasia and
net to an adrenocortical tumor.6’7 Under
these circumstances it is neither necessary nor desirable to resort to surgical explora-tion of the adrenals or the pelvic organs since the anatomic findings are uniform and well known. It is desirable, however, when
anatomic correction of the external
geni-talia is contemplated, to make a urethro-scopic examination of the urogenital sinus
to determine the relations of the communi-cating vagina.
When the adreno-genital syndrome has
been excluded by the absence of increased l7-ketosteroids, it is necessary to carry out
more extensive studies of the anatomy in
every case of abnormal sexual development.
This applies to individuals who have
de-formities of the external genitalia, to
sub-jects who appear to be cryptorchids with
hypospadias, and to those who have female external genitalia but palpable firm bodies
in the groins or labia. The first procedure is
to make a careful urethroscopic
examina-tion to determine whether there is a vagina joining the urethra to form a urogenital
sinus and whether a cervix can be
visual-ized at the end of the vagina. In some cases
when urethroscopic examination fails to
demonstrate a vagina, a lateral
roentgeno-gram taken after the injection of lipiodal
into the urinary meatus may demonstrate a
communicating vagina or pouchhlc but at
times there is no communication. Following
this a surgical exploration should be made
to examine the pelvic organs and, if
mdi-cated, the contents of the inguinal canals.
Biopsies should be made of both gonads
and examined at the time of the operation. Recently it has been shown19 that the sex
chromosomal pattern can be determined by
studying the nuclear chromatin in skin
bi-opsies prepared with proper fixative. The
sex chromosomal pattern of
pseudoher-maphrodites corresponds to the type of
go-nad. Dr. Murray Barr has found the female pattern in 8 and the male pattern in 4 true hermaphrodites (personal communication).
The study of skin biopsies is of interest and may be of help in the diagnosis of
pseudo-hermaphrodites. However, surgical explora-tion is important in determining the exact anatomy of the genital organs and deciding upon corrective procedures.
SELECTION DURING INFANCY OF THE
SEX OF REARING
Congenital Adrenal Hyperplasia
Not infrequently the decision in regard
to the sex in which the newborn child is to
be reared is made by the parents or
phy-sician solely on the appearance of the
ex-ternal genitalia without further study. This can be a grave error if the patient is a fe-male pseudohermaphrodite with congenital adrenal hyperplasia. It has been shown4’6’7 that with the administration of cortisone in
small doses the virilizing activity of the
adrenals is suppressed, and the patient will
grow and develop as a normal female,
ma-turing at puberty into a normal adult with
ovulatory menstrual cycles. Accordingly, when an infant is born with hypospadias
and an enlarged phallus either with or
without labial fusion, the 24-hour excretion
of 17-ketosteroids in the urine should be
measured as soon after birth as possible and
the decision in regard to sex reserved until
the results are known. If the excretion of
17-ketosteroids is elevated, cortisone
ther-apy should be instituted immediately
ac-cording to the methods described4’6’7 and
the child should be reared as a girl. As
stated previously surgical exploration is not
potas-sium and sodium should also be estimated
to determine whether the adrenal
hyper-plasia is accompanied by a defect of
elec-trolyte regulation. Patients of this type may
die suddenly of an adrenal crisis unless
treated with sodium chloride and
desoxy-corticosterone in addition to cortisone.4’ 6, 7, 20
It is usually best to postpone the decision
concerning clitorectomy until the child is
2 to 4 years of age. If the clitoris is enlarged
sufficiently to attract attention and arouse the curiosity of other children or neighbors it is best to remove it. A plastic operation to separate the labial fusion and expose the vaginal orifice can readily be performed at the same time according to the technique of Jones.2’
Intersexes
In the case of patients in whom the possi-bility of congenital adrenal hyperplasia has
been excluded by steroid studies there has
been considerable confusion in regard to
the basis for the selection of the sex of rear-ing. It is the writers’ emphatic opinion that
in male pseudohermaphrodites and true
hermaphrodites the decision should be
made according to the anatomy of the
ex-ternal genitalia, particularly the size of the
phallus or the presence of a serviceable vagina, without regard to the type of gonad, the chromosomal pattern or the structure of the internal genital tract. It is obvious that unless there is a fairly well-developed
phallus the patient cannot function as a
male and will be subjected to constant
hu-miliation and embarrassment throughout
life. In patients with testes, if the phallus is
sufficiently large it can be lengthened by correction of the chordee so that coitus may
be possible, and a penile urethra can be
constructed. The labial separation can be
closed and internal female structures
re-moved. On the other hand, the male
pseu-dohermaphrodite with a very small phallus or with external genitalia of entirely female
type cannot be altered surgically to
re-semble a male. Furthermore, those with
fe-male external genitalia practically always
feminize at puberty under the influence of
estrogen secreted by the testes. They often
marry and lead normal sexual lives in spite
of the fact that they do not menstruate and
are 16 is tragic, and unnecessary,
to condemn such patients to live as males
without any masculine equipment solely on
the basis of finding gonads which
histo-logically are testes.
An exception should be made to the rule
for selecting the sex of rearing according to the morphology of the external genitalia, in
the rare cases of female
pseudoherma-phroditism without adrenal hyperplasia (as
well as those with adrenal hyperplasia), provided the diagnosis is made in early
in-fancy. Unfortunately these patients often
are mistaken for cryptorchid males with hy-pospadias. If the diagnosis can be estab-lished early the phallus should be excised and the urogenital sinus corrected to form a
separate vagina. The ovaries mature
nor-mally at puberty so that menstruation and
ovulation occur.
The selection of the sex of rearing accord-ing to the external genitalia rather than the
chromosomal pattern or the morphology of
the gonads can be justified only if there is substantial evidence that this course does not lead to abnormalities in psychosexual
orientation and development. Extensive
studies carried out in this clinic by Money,
Hampson, and Hampson22 have led to the
conclusion that the gender in which a child
is reared is the predominant factor in
de-termining the future sexual orientation. The hair cut, the style of clothing, the name and
gender of personal pronouns applied, the
toys and type of play, in addition to the
anatomy of the external genitals, are all im-portant influences in establishing in early life the child’s conviction as to whether he or she is a boy or a girl, provided there is
not an attitude of contusion or uncertainty
on the part of the parents. As adolescence approaches the whispered talk, fantasies,
and rumination about sex matters in the
group of girls or of boys of which she or he is a part serve further to orient and direct the pathway of sexual inclination.
Contrary to popular belief sexual
per-versions and bisexual or ambisexual
her-maphrodites who have been reared
stead-fastly since infancy in a gender contrary to
the chromosomes, the gonads, or the
hor-mones. For example before the introduction of cortisone the female
pseudohermaphro-dites with adrenal hyperplasia became
equally well oriented psychosexually as
fe-males or males according to the gender in
which they had become accepted and reared
by their parents. Conversely male pseudo-hermaphrodites with female genitalia
.
fre-quently are reared as women, marry, have
normal coitus and libido without ever
sus-pecting that they have testes.
SHOULD SEX EVER BE ALTERED AFTER
EARLY CHILDHOOD?
Fortunately the sex which is assigned
to hermaphrodites at birth often agrees
with the predominant characteristics of the external genitalia. This is correct provided the necessary studies are made to exclude
female pseudohermaphroditism. However,
when the external genitalia are of doubtful nature the physician often refuses to make a
definite decision and postpones surgical
exploration and other diagnostic procedures until later life, leaving the parents in a
con-fused state with much mental anguish. Not
infrequently these children are changed
back and forth from one sex to the other.
At times when an individual, who has been
raised as a girl because of ambiguous geni-talia, begins to masculinize at puberty and
is found to have testes, conversion to the
male sex is ill-advisedly urged by some
physicians. It is even less justifiable to ad-vocate a change of sex for a male
pseudo-hermaphrodite who has female genitalia
when “she” is discovered to have testes in
the groins or abdomen. Psychologic studies
made in our clinic22 indicate strongly that
alterations in the sex of rearing after the
age of 18 months to 2 years, except for the
rare exceptions of post-adolescent requests
for change of sex, invariably leave the
pa-tient utterly confused and perplexed and
result ultimately in psychologic disasters.
After this age, even when the original
se-lection of sex was grossly erroneous,
altera-tion should not be contemplated during
childhood but surgical and hormonal
meas-ures should be instituted to enable the pa-tient to conform as well as possible to the sex in which he has been reared. If the
pa-tient has already reached mature years and
voluntarily requests a change of sex there should be no objection to this.
THE PROBLEMS OF GONADECTOMY AND
HORMONAL THERAPY
In true hermaphrodites who have a testis
on one side and an ovary on the other it
seems rational and desirable to remove the
gonad and
the
internal organs which donot correspond to the type of external
geni-talia. The remaining gonad at puberty will
probably lead to secondary sexual
develop-ment, corresponding to the external
geni-talia. (We have seen 1 patient raised as a
male in whom the results were excellent.)
In patients with ovotestes it may be
pos-sible in some cases to remove the male or
the female portions of the gonads accord-ing to the sex selected, but this is unlikely.
The advisability of orchidectomy must be
considered whenever it is elected to raise
a male pseudohermaphrodite as a female.
There is abundant evidencebo,16 that in the
male pseudohermaphrodites who have
fe-male external genitalia (Table I, group B
II, B) feminization invariably occurs at
puberty due to estrogen secreted by the
testes. It is not necessary, therefore, to
orchidectomize these patients for fear of
masculinization. The only reason for remov-ing the testes is the possibility that they
may become malignant in later life.
Morris10 and Gilbert23 have emphasized the
increased incidence of malignant testicular
tumors, particularly seminomas, among
male pseudohermaphrodites. One must
weigh the possible hazard of malignancy against the fact that if the patient is
orchi-dectomized it will be necessary to give
estrogens throughout adult life to maintain normal female characteristics.
In male pseudohermaphrodites who have
external genitalia of predominately male or of ambiguous structure, the type of
second-ary sexual development cannot be
the patients who have internal genital
structures which are predominantly
fe-male usually masculinize (Table I, group
B II, Al) while those with only vestiges of internal female organs (Table I, group B II,
A2) may either masculinize or feminize. If
it is elected in early childhood to raise a
male pseudohermaphrodite belonging to
one of these groups as a female because
the phallus is too small, one may either re-move the testes to avoid any risk of
mascu-linization or leave them until puberty to
determine whether masculinization or
fem-inization occurs. It seems to the writers that
in such cases when it has been firmly
de-cided that it is best to raise the child as a girl, it is often justifiable to perform a
go-nadectomy in early infancy at the time of
the original surgical exploration in order to
relieve the parents of the constant fear
of possible masculinization and to avoid
further operations at a later age.
As stated previously, after the age of 18 months to 2 years, a change of sex should
rarely if ever be considered. Plastic
opera-tions should be undertaken to make the
genitalia conform as nearly as possible to
the sex of rearing. If secondary sexual de-velopment begins along a pattern contrary to the sex of rearing, a gonadectomy should be performed promptly.
Whenever gonadectomies are performed
it is most important to inform the parents
of the necessity of keeping the patient
un-der observation and to plan at the age of
puberty to give hormonal therapy as
indi-cated by the sex selected.
The writers are aware of the objections
which might be raised to the criteria
dis-cussed for the selection of sex and to the
indications for gonadectomy. The
objec-tions are based upon traditional but
dis-proven beliefs that the chromosomal and
gonadal structures are the sole
determin-ants of the sexual development and the
psychosexual orientation. The removal of
the gonads under the indications
dis-cussed cannot be condemned on the
basis that this deprives the patient of
fertility since testes of male
pseudoher-maphrodites almost never show any
sper-matogenesis; on the contrary this procedure
with the subsequent use of sex hormone
may enable a patient to play a reasonably
normal role in society and save him from
a life of misery and psychologic confusion.
SUMMARY AND CONCLUSIONS
The different types of ambisexual
de-velopment have been described. It is most
important in earliest infancy to differenti-ate, on the basis of the 17-ketosteroid
excre-tion, female pseudohermaphroditism due to
congenital adrenal hyperplasia from other
forms of ambisexual development. The
fe-male pseudohermaphrodites should be
reared as girls and treated with cortisone
according to the methods described.
Surgi-cal exploration is not indicated. If the
clitoris is enlarged it should be removed
before school age and the urogenital sinus
corrected to form a separate vagina. With
cortisone therapy continued normal female
development can be assured.
When the adreno-genital syndrome has
been excluded, all patients with ambiguous
genitalia should be submitted to careful
urethroscopic study and exploratory
laparot-omy. This applies also to individuals who
appear to be cryptorchid males with
hypo-spadias and those resembling females with
gonads in the groins or labia. These
pro-cedures should be carried out in the earliest months of life and a definite decision made
as to the sex in which the child is to be
reared.
Abundant evidence has been
accumu-lated that an individual’s gender role and
erotic orientation are established through
the cumulative experiences of years of
living as a boy or a girl. Irrespective of
chromosomes, gonads or hormones, the
child who from earliest infancy has been
steadfastly accepted as a girl or as a boy,
particularly if the external genitals have
been altered to conform to this sex, will not
question his own gender and will conform
to the habits and behavior of the sex of
rearing. When there is prolonged doubt and
uncertainty on the part of the parents or
when a change of sex is imposed after an
child will be confused and perplexed and psychologic difficulties result. Accordingly,
every effort should be made in early
in-fancy to decide the sex of rearing and the parents should be given support, guidance
and reassurance. Necessary corrective
op-erations should be undertaken as early in
life as possible. No change from the original
decision should be made in later childhood.
It is advisable to select the sex of
rear-ing according to the anatomic structure of
the external genitalia rather than the type
of gonads or the sex chromosomal pattern. To attempt to make a boy of an individual
who does not have a fairly well-developed
phallus is unwise and condemns the
pa-tient to a life of misery. Male
pseudoher-maphrodites who have external genitalia of
female configuration invariably feminize at
puberty, so that orchidectomy is not neces-sary to prevent masculinization. Its only in-dication might be to avoid the possible risk
of testicular malignancy. Male
pseudoher-maphrodites whose genitalia resemble the
male or are ambiguous may either
mascu-linize or feminize at puberty. If it is
de-cided to raise such a child as a female be-cause of the small size of the phallus,
orchi-dectomy may be performed in infancy to
avoid the risk of masculinization or it may
be postponed until masculinization begins. The former course often seems preferable.
At puberty estrogen should be given in
doses adequate to develop female sex
char-acteristics. In these cases gonadectomy can-not be considered a mutilating operation or one which deprives the patient of fertility. On the contrary it is one which enables the patient to continue as a reasonably normal individual in the sex in which he has been reared and prevents the disastrous psycho-logic upheaval of a sex reversal.
REFERENCES
1. Young, H. H.: Genital Abnormalities,
Her-maphroditism and Related Adrenal
Dis-eases. Baltimore, Williams & Wilkins,
1937.
2. Greene, R. R.: Embryology of sexual
struc-ture and hermaphroditism.
J.
Clin.Endocrinol., 4:335, 1944.
3. Meicow, M. M., and Cahill, C. F. : The
role of the adrenal cortex in somato-sexual disturbanes in infants and chil-dren: a clinicopathologic analysis.
J.
Clin. Endocrinol. & Metab., 10:24, 1950. 4. Wilkins, L., Bongiovanni, A. M., Clayton,
C. W., Grumbach, M. M., and Van
Wyk,
J. J.
: Virilizing AdrenalHyper-plasia: Its Treatment with Cortisone and The Nature of the Steroid Abnormalities. The Human Adrenal Cortex. Ciba Foun-dation Colloquia on Endocrinology, 8: 460. Boston, Little, Brown & Co., 1955.
5. Childs, B., Grumbach, M. M., and Van
Wyk,
J. J.
: Virilizing adrenalhyper-plasia: a genetic and hormonal study. To be published.
6. Wilkins, L.: The diagnosis of the adreno-genital syndrome and its treatment with
cortisone.
J.
Pediat., 41:860, 1952.7. Wilkins, L., Bongiovanni, A. M., Clayton,
G. W., Grumbach, M. M., and Van
Wyk,
J. J.:
The Present Status of theTreatment of Virilizing Adrenal
Hyper-plasia with Cortisone: Experience of
33 years. Modern Problems in Pediatrics.
Vol. I (Supplement to Annals of Pedi-atrics, Fasc. 58). Basel, New York, S.
Karger, 1954.
8. Jost, A.: Problems of Fetal Endocrinology:
The Gonadal and Hypophyseal
Hor-mones. Recent Progress in Hormone
Research, 8:379. New York, Academic
Press, Inc., 1953.
9. Grumbach, M. M., Van Wyk,
J. J.,
andWilkins, L.: Chromosomal sex in gonadal dysgenesis (so called ‘ovarian agenesis’): Relationship to male
pseudohermaphro-ditism and the theories of human sex
differentiation.
J.
Clin. Endocrinol. & Metab., in press.10. Morris,
J.
MeL.: The syndrome of testicular feminization in male pseudohermaphro-dites. Am.J.
Obst. & Gynec., 65:1192,1953.
11. Wilkins, L.: The Diagnosis and Treatment of Endocrine Disorders in Childhood and Adolescence. Springfield, Thomas, 1950, (a) p. 278, (b) p. 277, (c) p. 262.
12. Papadatos, C., and Klein, R.: Nonadrenal
female pseudohermaphroditism.
J.
Pediat., 45:662, 1954.
13. Perloff, W., Conger, K. B., and Levy, L. M.:
Female pseudohermaphroditism.
J.
Clin. Endocrinol. & Metab., 13:783, 1953.14. Brentnall, C. P.: A case of arrhenoblastoma
complicating pregnancy.
J.
Obst. & Gynaec. Brit Emp., 52:235, 1945. 15. Javert, C. T., and Finn, W. F.:300
sterility,and to treatment. Cancer, 4:60, 1951.
16. Money,
J.:
Hermaphroditism: An Inquiry into the Nature of a Human Paradox.Doctoral Thesis, Harvard University Library, 1952.
17. Silverman, S. H., Migeon, C., Rosemberg, E., and Wilkins, L.: Precocious growth of sexual hair without other secondary sex-ual development; “premature pubarche,” a constitutional variation of adolescence.
PEDIATRICS, 10:426, 1952.
18. Bongiovanni, A. M. and Clayton, G. W.,
Jr.: A simplified method for the routine determination of pregnanediol and preg-nanetriol in urine. Bull. Johns Hopkins Hosp., 94:180, 1954.
19. Moore, K., Graham, M., and Barr, M.:
The detection of chromosomal sex in
hermaphrodites from a skin biopsy. Surg., Gvnec. & Obst., 96:641, 1953. 20. Crigler,
J.
F., Silverman, S. H., andWil-kiiis, L.: Further studies on the treat-ment of congenital adrenal hyperplasia
with cortisone. PEDIATRICS, 10:397,
1952.
21. Jones, H. W., Jr., and Jones, G. E. S.: The gynecological aspects of adrenal hyperplasia and allied disorders. Am.
J.
Obst. & Gynec., 68:1330, 1954. 22. Money,
J.,
Hampson,J.
C., and Hampson,J.
L.: Hermaphroditism: Recommenda-tions concerning assignment of sex, change of sex, and psychologicmanage-ment. Bull. Johns Hopkins Hosp., in
print, 1955.
23. Gilbert,
J.
B., and Hamilton,J.
B.: Studiesin malignant testis tumors. III. Incidence and nature of tumors in ectopic testes. Surg., Gynec. & Obst., 71:731, 1940.
SPANISH ABSTRACT
Hermafroditismo: Clasificaci#{243}n, Diagn#{243}stico,
Selecci#{243}ndel
Sexo y Tratamiento
Debido a Ia gran confusion sobre m#{233}todos de diagnOstico y tratamiento de seres con de-sarrollo ambisexual y a Ia incomprensi#{243}n de los principios para selecciOn del sexo y edu-caci#{243}nposterior, los autores publican este
tra-bajo esperando aclarar los rroblemas
diag-n#{243}sticos, terapCuticos y de determinaci#{243}n psico-sexual para avuda de los medicos en evitar
algunos errores del pasado. Se hasa en 70 casos de su servicio y en una extensa revision dc Ia literatura.
En Ia tabla I presentan in clasificaciOn de los problemas clInicos, diagn#{243}sticos y terap#{233}uticos;
los casos se dividen en dos grupos con etiologla
diferente, y se yen las discrepancias
estruc-turales morfol#{243}gicas de las g#{243}nadas con la
diferenciaci#{243}n sexual de los genitales externos
y/#{243}los conductos genitales.
Desde el punto de vista de Ia etiologIa y del
tratamiento, importa diferenciar el
pseudo-hermafroditismo femenino por hiperplasia
con-g#{233}nita suprarrenal del desarrollo ambisexual no asociado a trastorno suprarrenal los autores
le asignan a este grupo el t#{233}rmino de inter-sexo).
A) Pseudo-hermafroditismo femenino con
hiperplasia cong#{233}nita suprarrenal.-La
hiper-plasia suprarrenal virilizante se debe a una
anormalidad en Ia smntesis de los esteroides
adrenocorticales que Ileva a una hipersecreci#{243}n
de hormonas androg#{233}nicas; cuando es prenatal
en las ni#{241}as,los genitales externos se
desarro-ilan m#{225}so menos de acuerdo con el patron
masculino despu#{233}s de que los conductos de
Muller se han diferenciado para formar In
vagina, la matriz y las trompas; los ovarios son normales y en posiciOn normal; si los pliegues
labiales son peque#{241}os o no se han unido pre-sentan el aspecto de vulva con orificios uretral
y vaginal separados, pero frecuentemente se
fusionan formando un seno uretral en el que se encuentran ambos orificios. Al no tratarse estos casos, los efectos androg#{233}nicos producen yin-lizaci#{243}n progresiva despu#{233}s del nacimiento; afortunadamente Ia actividad androg#{233}nica anormal puede suprimirse con pequeflas dosis de cortisona y en esta forma evitarse Ia yin-lizaci#{243}n.
B) Intersexos.-El desarrollo ambisexual sin hiperplasia virilizante presente tres grandes
grupos: 1) Pseudo-hermafroditas masculinos,
cuyas gOnadas con morfol#{243}gicamente testiculos pero con genitales externos y/#{243}conductos geni-tales de diversos grados de diferenciaciOn fe-menina; para fines pr#{225}cticos se subdividen en: a)
Con genitales externos simulando los m#{225}sculinos o de sexo ambiguo y b) Con genitales externos simulando los femeninos. 2) Verdaderos
herma-froditas con g#{243}nadas mixtas y diferenciaci#{243}n
ambisexual de los #{243}rganos sexuales; ocasional-mente presentan Ia estructura de un testiculo en un lado y de un ovanio en el otno; m#{225}s
fre-cuentemente una o ambas gOnadas son
ORIGINAL ARTICLES
grupo m#{225}sraro y difIcil de desenibir.
La frecuencia relativa de los diferentes tipos (IC henmafroditismo se pnesenta en Ia tabla II.
De capital importancia es definir lo m#{225}s
tem-pranamente posible el diagnOstico entre el
pseudo-hermafroditismo femenino y las formas no hormonales del desarrollo ambisexual; como no es posible hacenlo bas#{225}ndose en la anatomla de los genitales externos y las estructuras de los conductos genitales (porque pueden ser id#{233}nti-cas en todas estas formas clmnicas) el
diag-nOstico difenencial debe realizarse con la
demonstraciOn de hipensecreci#{243}n de
andr#{243}ge-1105 suprarrenales; afortunadamente antes de que se pueda hacer cilnicamente por la apani-ciOn de hirsutismo y vinilizaci#{243}n progresiva, el estudio de los 17-ketosteroides ayuda decisiva-mente: Ia hipensecreci#{243}mn (2 a 4 mgrs. diarios)
se ye en el sIndrome adrenogenital, que se
confirma, ante cifras ambiguas (Ia 2.5 mgrs. diarios), con Ia pnesencia de pregnanetniol un-naro.
Los pseudo-hermafroditas femeninos deben educarse como ni#{241}asy tratarse con cortisona sin necesidad de necunnir a exploraciOn qui-rdrgica; sin embargo, si el clitoris est#{225} hiper-trofiado debe eliminanse antes de Ia edad
esco-Ian ‘v corregirse el seno urogenital para formar una vagina separada. El desarrollo femenino normal se asegura al conservarse el tratamiento con cortisona.
Si se ha excluldo el sIndrome adrenogenital par ausencia de hipersecreciOn de los
17-ketos-teroidea, es necesario recurnin a mayores
estudios anatOmicos de 1 anormal desarnollo sex-ual, pues los pacientes pueden tener deformi-dades de los genitales externos, hipospadias, criptorquidia, genitales externos femeninos y grupos cavernosos en las ingles y labios, etc.; asI como sujetar a los pacientes a estudios
cuidadosos uretroscOpicos y laparatomia ex-ploradora a Ia mayor brevedad posible en los primeros meses de Ia vida para definir el sexo en que deben educanse.
Se supone que el papel sexual y Ia orienta-ciOn erOtica de los individuos se establecen con las experiencias acumuladas en los aflos de vida como nina o ni#{241}o;independientemente de las gOnadas, hormonas o cromosomas, el ni#{241}oque desde so m#{225}stemprana infancia se ha sentido niiio o nina, en particular si los genitales
ex-ternos se han modificado para conformanse a
su sexo, no dudar#{225} de su pnopio sexo y se adap-tar#{225}a los h#{225}bitos y Ia conducta del sexo en el
que se ha educado. Ante Ia duda e inquietud de
los padres o cuando se realiza un cambio de sexo despu#{233}sde temprana edad pero antes de
la adolescencia tardIa, el ni#{241}ose sentir#{225}
per-plejo y confundido y terminar#{225} con senios pro-blemas psicol#{243}gicos; por lo tanto debe definirse
tempranamente el sexo en el que se eduquen, los padres recibir ayuda, gula y seguridad de
parte del medico, practicarse las operaciones
correctoras necesanias y no alterar Ia decisiOn original posteriormente.
Los autores aconsejan definir el sexo de
acuerdo con la estructura anatOmica de los
genitales extemos y no con el tipo de gOnadas 0 el patron sexual de los cromosomas. Es
in-justo tratar de hacer hombre a un paciente sin
pene bien desarrollado, pues esto lo condena a una vida de misenia. Los pseudo-hermafroditas masculinos con genitales externos femeninos invaniablemente se feminizan en Ia pubertad y por lo tanto no es necesanio recurrir a Ia orqui-dectomla para evitar la masculinizaciOn,
orqui-dectomla cuya Onica indicaci#{243}n seria en todo caso evitar el riesgo de malignizaciOn testicular. Los pseudo-hermafroditas masculinos con geni-tales masculinos ambiguos pueden masculini-zarse o feminizarse en Ia pubertad; si debido al peque#{241}o tamaflo del pene se decide educar a este paciente como nifla, puede recurnirse a Ia
orquidectomIa en la infancia para prevenir el
riesgo de la masculinizaciOn o posponerse hasta que #{233}stase anuncie (es de recomendarse Ia
pnimera sugestiOn); ya en Ia pubertad se ad-ministrar#{225}n estr#{243}genos en dosis adecuadas para desarrollar los caracteres sexuales femeninos; en estos casos no debe considerarse Ia
gonadec-tomia como mutilante ni tampoo operaciOn
que pnive al paciente de su fertilidad; por el contranio, capacita a los pacientes para con-tinuar como un individuo razonablemente nor-mal dentro del sexo en que se ha educado y le
evita el desastre psicolOgico de una reversiOn sexual.
INTERLINGUA ABSTRACT
Hermaphroditismo:
Classification,
Diagnose, Selection
del
Sexo,
e
Tractamento
Ii existe multe confusion concernente le
methodos diagnostic e therapeutic applicabile a individuos de disveloppamento ambisexual.
Correspondentemente il ha pauc comprension del principios que debe governar le selection
302
un meliorate appreciation del problemas de diagnose, tractamento, e determination psycho-sexual va adjutar le medicos a evitan le errores del passato. Le articulo es basate super studios de 70 casos vidite per nos al Hospital Johns
Hopkins a Baltimore, Maryland, insimul con
Un extense revista del litteratura pertinente. Le material es presentate e discutite sub duo major categorias: (A) Casos de pseudoherma-phroditismo feminin con adrenohyperplasia congenite e (B) casos de disveloppamento am-bisexual non associate con ulle disordine adrenal. Pro sublinear Ic importantia de iste distinction, le termino “intersexo” es usate pro designar casos del secunde categonia. Iste cate-goria del cases de intersexo es subdividite in ver hermaphroditos, pseudohermaphroditos
mascule, e pseudohermaphroditos feminin sin
hyperplasia adrenal. Inter Ic pseudohermaphro-ditos mascule nos distingue le casos con externe genitales ambigue o masculeide e Ie casos con externe genitales femininoide.
Nos considera como importantissime que
studios del excretion de 17-cetosteroides sia utilisate pro differentiar in le primissime periodo neonatal inter pseudohermaphroditos feminin cuje condition es causate per congenite hyper-plasia adrenal e casos de intersexo. Le pseudo-hermaphroditos feminin deberea esser trainate como pueras e deherea reciper le correspon-dente tractamento a cortisona. Explorationes chirurgic non es indicate in iste casos. Si le clitoris es allargate, illo deberea esser excidite ante le etate scholar. Le sino urogenital es a corniger pro formar on separate vagina. Si le therapia a cortisona es continuate, on normal disveloppamento feminin pote esser assecurate in iste casos.
Omne patientes in qui le absentia del syn-drome adrenogenital ha definitivemente essite demonstrate debe esser subjicite a tin precise studio urethroscopic e a laparotomia explora-tori. Isto vale etiam pro individuos qui pare esser masculos cryptorchidic con hypospadias e ro ifl(Iividuos qui resimila femininas con
gonades in Ic inguine o in le labios. Iste in-vestigationes debe esser executate durante le prime menses del vita, e super br base on debe establir tindefinitive decision in re be sexo in ciiie le infante va esser trainate.
II existe abundante observationes a supportar le assertion que le conducta social como mascule o feminin e be orientation erotic del individuo es determinate per Ic experientias cumulative
de annos de existentia in Ic rob de puero o
puera. Sin reguardo a chromosomas, gonades,
0 hormones, le individuo qui ab be dies de su
prime infantia es consequentemente acceptate per su gruppo social como puero o puera-spe-cialmente Si be externe genitales es alterate a corresponder al sexo sebigite-va nunquam ques-tionar su rob mascule o feminin e va conformar
se al habitudes e al conducta del sexo in que ille o illa es trainate. Si be parentes exhibi pro-longate dubita o incertitude in re be sexo in que illes va trainar br infante o si un alteration de
su rob como puero o puera es imponite post
su pnimissime etate, le effecto super le mdi-viduo es que ille deveni confuse e perplexe e disveloppa omne genere de difficultates
psycho-logic. Post que un decision ha essite attingite in re be sexo in que le infante debe esser
trai-nate, iste decision non debe unquam esser cam-biate a un peniodo plus avantiate in be infantia del individuo.
Ii es recommendabile que be sexo in que be
individuo va esser trainate sia seligite de ac-condo con be externe genitales plus tosto que de accordo con be typo de su gonades o be con-figuration de su chromosomas sexual. Le tenta-tiva de trainar como puero un individuo qui non possede Un satis ben disveloppate phalbo es
pauco sage e condemna be patiente a un vita de miseria. Pseudohermaphroditos mascule con
externe genitales de configuration feminin se femininisa invariabilemente al etate pubere, e
in iste casos nulle orchidectomia es necessari pro prevenir masculinisation. Le sob valor de
orchidectomia es que ibbo evita be nisco de un
possibile disveboppamento de malignitate tes-ticular.
Pseudohermaphroditos mascule con externe genitales ambigue o mascuboide pote mascu-linisar o femininisar se al etate pubere. Si Ie minute dimensiones del phabbo de un
mdi-viduo in iste gruppo induce be decision de
trainar be como puera, abora orchidectomia in infantia es indicate pro evitar be nisco de mascu-binisation. On etiam pote postponer le orchidec-tomia usque be masculinisation comencia mani-festar se. Le prime de iste duo methodos es pre-feribibe. Al etate pubere le administration de
estrogeno es indicate in doses adequate pro dis-veboppar charactenisticas sexual feminin. In iste
casos gonadectomia non pote essen considerate
como un operation mutibante o como un opera-tion que pniva Ic patiente de fertilitate. Al
con-trario, ilbo es un operation que rende be
mdi-viduo capace a viver un vita rationabibemente
normal in le sexo in que ilbo esseva trainate. Le operation preveni be disastrose disturbation
