Hum Genet (1981) 58:117-122

© Springer-Verlag t981

The Gonads of Human True Hermaphrodites

Willem A. van Niekerk a n d Andries E. Retief

Tygerberg Hospital and Faculty of Medicine, University of Stellenbosch, RO. Box 63, Tygerberg, 7505, Republic of South Africa

Summary. G o n a d a l distribution in 409 cases of h u m a n true Table 1. Gonadal distribution in 409 true hermaphrodites
h e r m a p h r o d i t i s m is reviewed. A n ovary was f o u n d on the left
Type of gonadal distribution Number of cases Percentage
side of the b o d y in 62.8% of the cases a n d the testis o n the right
side in 59.5%. The ovotestis is the most c o m m o n g o n a d o f the Ovary--testis 121 29.6%
true h e r m a p h r o d i t e ; a m o n g s t 806 gonads in 406 cases it was Ovotestis--ovary 119 29.1%
f o u n d in 44.3%. In this p a p e r we give a detailed description of the Ovotestis--ovotestis 85 20.8%
m o r p h o l o g y of ovotestis, testis a n d ovary in the true h e r m a p h - Ovotestis-- testis 45 11%
rodite. In a d d i t i o n we discuss the effects of fetal a n d r o g e n s a n d Ovotestis--unknown 16 3.9%
Mtillerian inhibiting factor on the Wolffian a n d Mfillerian ducts. Other combinations 23 5.6%
Correlations between c h r o m o s o m a l c o m p l e m e n t a n d g o n a d a l
d i s t r i b u t i o n are presented. True h e r m a p h r o d i t e s with a 46,XX Total 409 100%
karyotype m o s t c o m m o n l y have a n ovary on one side a n d an
ovotestis on the o t h e r side; those with a Y - c h r o m o s o m e have a
testis in 61% of cases. A n analysis of the ratio of ovarian a n d Table 2. Gonadal distribution in 406 true hermaphrodites
testicular tissue within ovotestes showed a c o n t i n u u m from very
little ovarian tissue to a small p o r t i o n of testicular tissue. Each Gonad Left Right Total
type of tissue was clearly demarcated. Hypotheses for g o n a d a l
Ovary 169 (62.8%) 100 (37.2%) 269
induction in the true h e r m a p h r o d i t e should take cognizance of
Testis 73 (40.5%) 107 (59.5%) 180
these facts. True h e r m a p h r o d i t e s with a 46,XX c h r o m o s o m a l
Ovotestis 151 (42.3%) 306 (57.7%) 357
c o m p l e m e n t were characterized by a male p h e n o t y p e in 54% of
cases. This g r o u p m a y suggest a greater testicular i n d u c t i o n 806
ability in the g e n o m e as c o m p a r e d to the 46% with a female
phenotype.

seen t h a t the ovary was f o u n d on the left side in 62.8% a n d o n the

In order to classify a n individual as a true h e r m a p h r o d i t e , b o t h
ovarian a n d testicular tissue must be present. The histological
e x a m i n a t i o n of the testicular tissue should d e m o n s t r a t e distinct
tubules, whilst the ovarian tissue should contain follicles. This
report is based on 27 true h e r m a p h r o d i t e s who were investi-
gated by the a u t h o r s (Van Niekerk 1974, 1976) a n d 382 cases
which were reported in the literature, bringing the total n u m b e r
of cases in this analysis to 409.
Gonadal Distribution
In Table 1 the g o n a d a l distribution in 409 cases of true h e r m a p h -
roditism is shown. Lateral true h e r m a p h r o d i t i s m (an ovary on
the one side a n d a testis o n the other side) occurred in 29.6% of
cases. Unilateral true h e r m a p h r o d i t i s m (with a n ovotestis on the
one side a n d a n ovary on the o t h e r side) occurred in 29.1% of
cases. The next c o m m o n f o r m is bilateral true h e r m a p h r o d i t i s m
(with ovotestes on b o t h sides) which occurred in 20.8%. The
c o m b i n a t i o n of a n ovotestis on the one side with a testis on the
other side is m u c h less c o m m o n occurring in only 11% of cases.
In 406 true h e r m a p h r o d i t e s the side of the b o d y where a
particular g o n a d was f o u n d was recorded. In Table 2 it can be
Offprint requests to: W. A. van Niekerk
right side in 37.2%. As far as the testes are concerned, it was
f o u n d o n the left side in 40.5% a n d o n the right side in 59.5%. The
ovotestis was present on the right side in 57.7% a n d on the left
side in 42.3%. F r o m these data it is evident that the ovary occurs
most c o m m o n l y on the left side whilst testicular tissue, either as a
testis or as a n ovotestis, has a greater tendency to occur on the
right side of the body.
The Ovotestis
The ovotestis is the g o n a d most c o m m o n l y f o u n d in the true
h e r m a p h r o d i t e . In an analysis of 806 gonads in 406 cases of true
h e r m a p h r o d i t i s m , the ovotestis occurred in 44.3% of gonads,
an ovary in 33.4% a n d a testis in 22.3%.
The position where the ovotestes were found, is of interest.
Adding those cases where the position was m e n t i o n e d in the
literature, to o u r own, data are available on 116 ovotestes as far
as this aspect is concerned. A m o n g s t these, 47% are located in
the ovarian position, 26% in a labioscrotal fold a n d 24% in the
inguinal canal. F o u r per cent were f o u n d just inside the internal
inguinal ring. The p r o p o r t i o n a l c o m p o s i t i o n of testicular a n d
ovarian tissue in the ovotestis has an influence on the descent of
the ovotestis a n d eventually o n the position in which that
particular ovotestis will be found. Twenty-three ovotestes from

0340-6717/81/0058/0117/$01.20
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our own series were analyzed in this respect and added to 20 cases
in the literature where these data were recorded. Amongst these
43 ovotestes, 14 had an equal proportional composition of
testicular and ovarian tissue, 16 had more testicular than ovarian
tissue and 13 more ovarian than testicular tissue. It was inter-
esting that when analyzing the position of these 3 groups,
amongst the 13 ovotestes with more ovarian than testicular
tissue, 10 were found in the ovarian position and 3 in the inguinal
ring area. Amongst the 16 ovotestes with more testicular than
ovarian tissue, 8 were found in the labioscrotal folds, 6 in the
inguinal region, 1 in the internal ring and 1 in the ovarian
position. Amongst the 14 cases with an equal distribution of
these two types of tissue, 7 were found in the ovarian position, 3
at the internal ring, 1 in the inguinal area and another 3 in the
labioscrotal area. It is evident, therefore, that the more ovarian
tissue that is present in the ovary, the greater the possibility that
the gonad will be in an ovarian position. The more testicular
tissue present, the greater the possibility that the gonad will be in
the labioscrotal area. No particular pattern was evident for those
ovotestes which contained equal amounts of ovarian and
testicular tissue.
An ovotestis usually has a diagnostic macroscopic appear-
ance, In 80% of cases the ovarian and testicular tissue were
arranged in an end-to-end fashion. In 20% the testicular tissue
may occur the hilar region of the gonad where a macroscopic
diagnosis of an ovotestis is more difficult. The ovarian portion of
an ovotestis has a convoluted surface while the testicular portion
has a smooth, glistening, yellow appearance. These macroscopic
features become more evident when the gonad is bissected. There
is usually a distinct line of demarcation on histological
examination between these 2 types of tissue. The fact that the
ovarian tissue is firm on palpation and the testicular tissue soft is
a valuable clinical sign previously described (Van Niekerk 1974).
This sign is extremely useful in palpating the gonad of a newborn
baby with ambisexual external genitalia. An ovotestis may be
diagnosed clinically in this way.
The histological appearance of the ovarian portion of an
ovotestis is usually normal. Data available on 86 ovotestes
including our own cases, revealed that in 77% the ovarian
portion was histologically normal while in 23% it was con-
sidered to be abnormal. A reduction in the amount of primordial
follicles in the ovotestis in infants was the most common ab-
normality found. It is of interest that 50% of the ovotestes
showed evidence of ovulation. In comparison the testicular
portion of an ovotestis is histologically usually abnormal. In
only 2 of our own 24 specimens of ovotestes the testicular
histology showed a near normal appearance. Spermatogonia
and spermatogenesis were never observed. In patients over the
age of 15 years tubular sclerosis was observed in 15% of cases.
One third of our group of patients showed signs of Leydig cell
hyperplasia in the testicular portion of the ovotestis. Another
feature frequently observed, is the abundance of Sertoli cells in
the lumen of the seminiferous tubules. This is reminiscent of an
infantile testis.
The ratio of testicular to ovarian tissue in the ovotestes is of
some interest. In those cases where the testicular tissue occurs in
the hilar region, it is usually a very small area of testicular tissue.
In the end-to-end arrangement it varies between a small ovarian
portion with a ratio of ovarian to testicular tissue of 1 : 4 to a 4 : 1
ratio where most of the gonad consists of ovarian tissue and just
a small testicular portion is present. It is a continuum, therefore,
of distribution from a normal ovary to less and less ovarian tissue
until a normal testis is found.
The Ovary
An ovary is the second most common gonad of the human true
hermaphrodite, Amongst 806 gonads in 406 true hermaph-
rodites the ovary occurred in 269 instances with a percentage of
33.4%.
The ovary is most commonly situated in the normal ovarian
position in the true hermaphrodite. When a gonad with the
macroscopic features of an ovary is situated in the inguinal canal
or in the labioscrotal fold, the possibility of that particular gonad
being an ovotestis should be seriously considered.
Amongst 19 ovaries of true hermaphrodites we have investi-
gated, the histological examination showed that all those 15
years of age and older had either a corpus luteum or a corpus
albicans. Definite ovae were observed in 3 patients. These figures
are in agreement with those gleaned from the literature. The
macroscopic appearance of the ovary in true hermaphrodites
was specifically mentioned in the literature in connection with
88 ovaries; 58 appeared normal, 17 were described as being
smaller than normal and 10 were cystic and 3 were thought to
be larger than normal.
Most of the ovaries found in true hermaphrodites do show
signs of ovulation. Ovulatory peaks as far as LH is concerned,
were found in 3 of our own patients. Three true hermaphrodites
became pregnant (Narita et al. 1975; Mayou et al. 1978; Kim et
al. 1979). All three pregnancies terminated in a premature labour
which could be expected because of the abnormal uterine devel-
opment in the true hermaphrodite. All 3 children were normal
males with normal male appearing external genitalia. Unfortun-
ately no chromosomal analysis was performed on these children.
The normal oestrogen production is evident in the well
developed breasts which occurred in 70% of 89 true hermaph-
rodites, past puberty, reported in the literature. Another 18%
had what the authors called poorly developed breasts and only
6% were considered by the authors as not having any breast
development at all. The reason for the latter group's apparent
lack of oestrogen response, or production, is discussed else-
where (Van Niekerk 1974). All our cases past puberty showed
normal breast development.
The Testis
Amongst 806 gonads in 406 true hermaphrodites a testis occur-
red in 108 instances giving a percentage of 22.3%. It is evident
that this is the least common gonad found in the human true
hermaphrodite. Amongst 162 testes which occurred in human
true hermaphrodites the majority (63%) occurred in the scrotum,
22% were found in a normal ovarian position and a further 14%
were found in the inguinal region with 1% in the internal inguinal
ring. The size of the testis was documented in 40 patients of
which 26 were considered to be smaller than normal whilst 14
were of normal size.
On histological examination most of these testes showed a
histological pattern similar to the testicular portion of an
ovotestis. The usual appearance is that of immature testis with
the lumen of the tubules filled with Sertoli cells. Leydig cell
hyperplasia occurred in 19% of 57 testes reported in the
literature. It is interesting that spermatogenesis was present in
only 12% of cases.
Gonadal Tumours
Tumours with a malignant potential occurred in 2.6% of true
hermaphrodites. Two cases of gonadoblastoma in true hermaph-

rodites were reported (Park et al. 11972; M c D o n o u g h et al. 1975).
Both had a 46,XY karyotype. Other tumours described were a
seminoma and 2 cases of embryonal carcinoma and a seminoma
in the same gonad (Stirling 1946; Kustrup 1969; Aiman et al.
1978). There were 5 cases of dysgerminomas described amongst
384 human true hermaphrodites, giving a prevalence of 1.3%
(Daube 1919; Weyeneth 1936; Botella-Llusia 1960; Kustrup
1969; Van Niekerk 1974).
The Gonads of the True Hermaphrodite
and the Development of Miillerian and Wolffian Ducts
It is believed that the stabilization of the Wolffian ducts and
subsequent differentiation of epididymis are androgen depend-
ant. In all animal species the presence of an embryonic testis
seems to be necessary to induce sexual differentiation of this duct
and to ensure its retention in a mammalian embryo. In the true
hermaphrodite a vas deferens and epididymis are invariably
present next to a testis. There are 3 patients citedin the literature
where the duct next to the testis was described as being a
Fallopian tube, but the nature of the gonads was not confirmed
by histological examination. The 3 gonads might well have been
ovotestes (Schwiebinger and Hodges 1955; Gobrial and Girgis
1962; Brogger and Aargenaes 1965). We are particularly inter-
ested in the duct next to an ovotestis. An epididymis was present
in 17 out of 22 ovotestes from whom information was available.
We have personally examined the duct adjacent to 26
ovotestes. All of them had only one duct adjacent to this gonad.
Another feature was that the macroscopic appearance of this
duct could be misleading. In a number of cases the appearance
was that of a hypoplastic Fallopian tube, but on histological
examination on cross section, the picture of a vas deferens was
revealed. Of 22 patients in the literature in whom the histology of
the duct adjacent to an ovotestis was available for examination,
it was found that 15 had the histological picture of a Fallopian
robe. In 7 the histology was similar to that of a vas deferens.
When our own figures are added to that gleaned from the
literature, information becomes available on the histological
picture of ducts adjacent to 48 ovotestes. The ducts showed the
appearance of a Fallopian tube in 65% and that o f a vas deferens
in 35% of the cases.
In an analysis of our own cases preliminary evidence shows
that the more testicular tissue present in an ovotestis, the more
likely the adjacent duct will be a vas deferens. It is noteworthy,
however, th~it in none of these cases both a Fallopian tube as well
as a vas deferens was detected. As was stated previously (Van
Niekerk 1976) the development of the vas deferens and the
Fallopian tube might be more interdependant than is realized at
the present time.
In 20 Fallopian tubes next to an ovotestis which were
examined, 18 were found to be closed at the osteal end. This
closure was congenital because there were no histological signs
of infection or endometriosis. In those where the osteal end was
open the fimbriae were distinctly normal.
Experimental and clinical findings indicate that the regres-
sion of the Mfillerian ducts is due to the secretion by the fetal
testis of a specific Mtillerian inhibiting factor which is not an
androgen (Jost 1947; Josso 1977) and which mediates its effect
locally. A striking example of this effect can be seen in the lateral
true hermaphrodite with a testis on the one side and an ovary on
the other side. In these cases a vas deferens is always found next
to the testis and a Fallopian tube next to the ovary on the contra-
119
lateral side. A unicornuate uterus is most commonly found in the
lateral true hermaphrodite with an absent horn on the side of the
testis. The Mtillerian inhibiting substance may also be the cause
of the abnormal fimbrial end of the Fallopian tube adjacent to an
ovotestis. The possibility that this effect may be caused by fetal
androgens cannot be excluded, however.
The effect of the Mfillerian inhibiting function of the fetal
testis can also be ascertained by analyzing the appearance of the
uterus in the true hermaphrodite. In 169 cases of true hermaph-
roditism the uterus was hypoplastic in 46%, the corpus uteri
alone was present in 14%, the uterus was totally absent in 13%
and a unicornuate uterus was found in 10%. In only 10% of cases
was the uterus considered to be completely normal. There is,
therefore, a profound effect, also on the lower end of the
Mt~llerian duct.
In one of our cases a prostate was palpable on rectal
examination. This does not preclude the presence of a rudimen-
tary prostate, however. In 50% of cases of true hermaphroditism
in the literature, it was mentioned to be present.
The development of the external genitalia is generally
believed to be an effect of dihydrotestosterone. This effect of the
fetal gonad is correlated with the fact that only 12% of patients
with true hermaphroditism cited in the literature had a penile
urethra. This indicates that most patients with true hermaphro-
ditism are deficient in fetal dihydrotestosterone production or
are insensitive to this hormone. The testicular tissue in the true
hermaphrodite seems to be capable of stabilizing the Wolffian
duct, but incapable of fully differentiating male type external
genitalia. It is significant however, that in 120 case reports of true
hermaphroditism in the literature the sex of rearing was
mentioned specifically. Amongst these, 73% were reared as male
and 27% as female. These data, added to our own cases, show
that approximately 75% of 146 true hermaphrodites have been
reared as male. The apparent reason for this is that most true
hermaphrodites have a phallus at birth. For this reason dihydro-
testosterone must have been produced during fetal life to such an
extent that 75% of true hermaphrodites are considered by the
parents a n d / o r obstetricians as being male. In the perusal of the
literature we found only 3 cases in which neither a large clitoris
nor a small phallus had been described in a true hermaphrodite.
These cases were reviewed previously (Van Niekerk 1974). Their
clinical features were remarkably similar to those produced by a
testicular feminization syndrome.
The majority of patients reported in the literature had a
phallus measured between 4 and 8 cm. In only a small number of
true hermaphrodites was the phallus found to be larger than
8 cm. Most of the patients showed chordee; this was specifically
mentioned as being absent in only 18 cases. Data are available on
160 cases in which the appearance of the external genitalia was
described in detail including our own cases. Amongst these, 63%
had labioscrotal folds, 17% a normal scrotum, 13% a hemi-
scrotum; normal labia majora were present in only 7% of
patients.
F r o m these data it is evident that enough dihydrotesto-
sterone must have been present (or enough receptors present) to
partially virilize the external genitalia of the true hermaphro-
dite.
Those cases which we have examined who showed signs of
ovulation with an L H peak, also had virilization of the external
genitalia. No influence from the fetal androgen on the hypo-
thalamic function of these true hermaphrodites is evident there-
fore.
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Table 3. Gonadal distribution and karyotype in 195 true hermaphrodites

Distribution 46,XX 46,XX/46,XY 46,XY 46,XY/47,XXY 45,X/46,XY Other Total

Ovary--testis
Ovary--ovotestis
Ovotestis--ovotestis
Ovotestis--testis
Ovotestis--unknown
23 10 13 5 4 5 60
43 7 3 3 1 2 59
33 6 2 2 0 2 45
12 2 5 0 1 2 22
5 0 1 I 1 1 9

Total 116 25 24 11 7 12 195

(59.5%) (12.8%) (12.3%) (5.6%) (3.5%) (6.2%)

The Correlation of the Karyotypes with Gonads Table 4. Gonadal distribution and Y-chromosome in 195 true hermaph-
in True Hermaphroditism rodites

Gonadal distribution Without With Total

In a previous review the c h r o m o s o m a l c o m p l e m e n t of 24 of o u r
own cases a n d of 172 true h e r m a p h r o d i t e s reported in the
literature with c h r o m o s o m a l analysis were analyzed (Van
Niekerk 1981). Since then a n additional 23 true h e r m a p h r o d i t e s
were reported with c h r o m o s o m a l analysis (Tuncbilek et al. 1978;
R a d h a r k r i s h n a n et al. 1978; C o o k a n d G a s h t i 1979; G h a n d c h i et
al. 1979; J o h n s o n et al. 1979; T e g e n k a m p et al. 1979; Valdez et al.
1979; Braren et al. 1980; Dewald et al. 1980; Schwartz et al.
1980). In Table 3 the gonadal distribution of patients for w h o m
c h r o m o s o m a l analysis was p e r f o r m e d is related to the c h r o m o -
somal complement. A n analysis of these 195 true h e r m a p h r o -
dites shows that the 46,XX c h r o m o s o m a l c o m p l e m e n t occurred
in 59.5% of cases. In 12.8% of cases 4 6 , X X / 4 6 , X Y mosaicism
was found; 46,XY was f o u n d in 12.3% a n d other mosaics in
15.3% of cases.
A m o n g s t the 116 cases with a 46,XX c h r o m o s o m a l comple-
m e n t the most c o m m o n gonadal distribution pattern was a n
ovary on the one side with a n ovotestis on the other side. This
occurred in 37% of cases. The next most c o m m o n distribution
was a n ovotestis f o u n d bilaterally in 28.4% of cases. A n ovary on
the one side a n d a testis on the other side was f o u n d in 19.8% of
cases whilst a n ovotestis on the one side a n d a testis on the other
side was f o u n d in 10.4% of cases. A r e m a i n i n g 4.4% was m a d e up
of those patients with a n ovotestis on the one side a n d a n
u n k n o w n g o n a d on the other side. Considering the total g r o u p of
true h e r m a p h r o d i t e s the prevalence of a n ovary on the one side
and ovotestes on the other side is equal to the prevalence of a n
ovary on one side a n d testes on the other. It is however of
statistical significance t h a t in the group of 46,XX true h e r m a p h -
rodites, t h a t a n ovary on one side a n d ovotestis on the o t h e r side
occur most commonly.
In Table 4 the g o n a d a l distribution is c o m p a r e d for true
h e r m a p h r o d i t e s with a Y - c h r o m o s o m e in their c h r o m o s o m a l
c o m p l e m e n t a n d those without a Y-chromosome. In the 60 true
h e r m a p h r o d i t e s with an ovary on the one side a n d a testis on the
other side a Y - c h r o m o s o m e was f o u n d in 38 (63.3%) of cases.
A m o n g s t the 79 true h e r m a p h r o d i t e s with a Y - c h r o m o s o m e a
testis was present in 48 (61%). This should be c o m p a r e d with the
overall prevalence of a testis in the large group of 406 true
h e r m a p h r o d i t e s which occurred in only 22.3%. It seems,
therefore, that the presence of a Y - c h r o m o s o m e increases the
possibility t h a t a testis is one of the gonads present.
In those true h e r m a p h r o d i t e s with an ovary on the one side
and an ovotestis on the other side, the odds that no Y-chromo-
some will be detected a n d that the patient will have a 46,XX
c h r o m o s o m e c o m p l e m e n t are 72.8%.
Y-chromosome Y-chromosome
Ovary--testis 22 38 60
Ovotestis--ovary 43 16 59
Ovotestis--ovotestis 34 11 45
Ovotestis--testis 12 10 22
Ovotestis--unknown 5 4 9
116 79 195
It seems, therefore, t h a t the testis-inducing function of a Y-
c h r o m o s o m e is strong in this regard, a n d that the presence of
two X - c h r o m o s o m e s more c o m m o n l y results in a f o r m a t i o n of
an ovotestis. The genetic control of gonadal differentiation is
t h o u g h t to be mediated by the expression of the H-Ygenes which
are considered to be associated with the Y - c h r o m o s o m e
(Wachtel 1977). F e r g u s o n - S m i t h (1966) has postulated t h a t the
condition of true h e r m a p h r o d i t i s m is the result of a cytological-
ly undetectable interchange of a part of the Y - c h r o m o s o m e onto
the X - c h r o m o s o m e . This was based on evidence t h a t the Y-
c h r o m o s o m e is associated with testicular tissue.
There is n o w a b o d y of evidence to indicate that it is n o t the
presence of the Y - c h r o m o s o m e per se t h a t determines differ-
entiation of the testes, b u t the presence of H-Y antigen (Wachtel
and K o o 1981). It is perhaps significant therefore that reduced
expression of H-Y was f o u n d in somatic tissue such as the blood,
skin a n d fascia of 4 6 , X X true h e r m a p h r o d i t e s as c o m p a r e d to
that in n o r m a l 46,XY males, a n d t h a t cells cultured from the
ovarian p o r t i o n of the h u m a n X X ovotestis, a b s o r b e d less H-Y
antibody t h a n was a b s o r b e d by cells f r o m the testicular p o r t i o n
(Winters et al. 1979). It is possible t h a t a n ovotestis m a y arise
from this H-Y+/H-Y mosaicism.
It is of great interest why the distribution of ovarian a n d
testicular tissue in an ovotestis should not be more r a n d o m .
Eicher et al. (1980) also f o u n d t h a t the distribution of ovarian
and testicular tissue within a n ovotestis of B A L B / c W t h e r m a p h -
roditic mice was not r a n d o m . They f o u n d that ovarian tissue was
situated at b o t h ends or only at the cranial end. They suggested
that such n o n - r a n d o m distribution of ovarian a n d testicular
tissue argues against the hypothesis that the organization of
testicular tissue is d e p e n d a n t only on the presence of H-Y
antigen.
Some authors assume t h a t multiple H-Y structural genes
are to be f o u n d on the Y - c h r o m o s o m e (Selden et al. 1978). W h e n
these genes are split by translocation of the Y to a n o t h e r c h r o m o -

some the n u m b e r of H-Y gene copies translocated may vary with
the result that a gene dosage relationship could determine the
type of gonadal differentiation. The multiple H-Y structural
genes could then be translocated either as a complex, or split by
the translocation. A n o t h e r hypothesis is t h a t a Y-linked
regulatory gene controls the H-Y structural gene ( K r o n e a n d
W o l f 1978). O t h e r authors believe t h a t sex reversal in X X
individuals can be explained by a u t o s o m a l m u t a t i o n affecting
the regulation of the H-Y gene. In the case of recessive inherit-
ance of the trait, a leaky m u t a t i o n can be considered, allowing
for residual activity of the H-Y gene ( F r a c c a r o et al. 1979). In the
heterozygous state this m u t a t i o n gives rise to a reduced H-Y
antigen titre which is n o t sufficient to induce the indifferent
gonad to become a testis. In the h o m o z y g o u s state, however, an
ovotestis or even a testis m a y become differentiated.
Recently, W o l f et al. (1980) gave evidence that the m o r p h o -
genetic effect of H-Y antigen depends on a threshold. Differ-
entiation of the indifferent g o n a d would accordingly d e p e n d on
the titre of H-Y antigen expressed by structural genes on
autosomes u n d e r control of regulatory genes on the X a n d Y
chromosomes.
W h a t e v e r hypotheses for testicular induction in the true
h e r m a p h r o d i t e are considered, they should allow for the con-
t i n u u m o f testicular to ovarian tissue ratios, referred to earlier
regarding the ovotestis, as well as the n o n - r a n d o m a r r a n g e m e n t
previously described (Van Niekerk 1974).
The Phenotype of the True Hermaphrodite
Compared with the Presence or Absence of a Y Chromosome
D a t a o n the h a b i t u s or p h e n o t y p e of the h u m a n true h e r m a p h r o -
dite is available in 106 cases which includes our own material.
A m o n g s t these 64 (60%) were considered to have a male p h e n o -
type a n d 42 (40%) a female phenotype. The latter group included
31 with a 4 6 , X X c h r o m o s o m e c o m p l e m e n t a n d 11 with a 46,XY
c h r o m o s o m a l complement. The patient with a female p h e n o t y p e
therefore has a greater tendency not to have a Y c h r o m o s o m e in
the c h r o m o s o m a l complement. It is interesting, however, t h a t
those with a male p h e n o t y p e include 36 with a 46,XX c h r o m o -
somal c o m p l e m e n t a n d 28 with a 46,XY c h r o m o s o m a l comple-
ment.
A m o n g s t the 39 cases in the group with a 46,XY cell line, 28
h a d a male p h e n o t y p e a n d only 11 a female phenotype. T h e 67
true h e r m a p h r o d i t e s with a 46,XX c h r o m o s o m a l c o m p l e m e n t
were considered to have a male p h e n o t y p e in 36 cases a n d a
female p h e n o t y p e in 31 cases.
F r o m the a b o v e - m e n t i o n e d data it is evident that the
presence of a Y c h r o m o s o m e is more c o m m o n l y associated with a
male p h e n o t y p e whilst the absence of a Y c h r o m o s o m e is not
necessarily associated with a female phenotype, a n d indeed
occurs in 54% of 4 6 , X X cases with a male phenotype. This male
p h e n o t y p e g r o u p of 46,XX true h e r m a p h r o d i t e s suggests a
greater testicular induction ability in the genome of this g r o u p as
c o m p a r e d to the 46% with a female phenotype.
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