Statement of the British Association of Paediatric Surgeons
Working Party on the Surgical Management of
Children Born with Ambiguous Genitalia
July 2001
Mr Laurence
Rangecroft Paediatric
Surgery/Urology Newcastle upon Tyne
Dr Caroline
Brain Paediatric
Endocrinology London
Miss Sarah
Creighton Gynaecology London
Dr Domenico Di
Ceglie Psychiatry London
Dr Amanda
Ogilvy-Stuart Neonatal Paediatrics Cambridge
Mr Patrick
Malone Paediatric
Urology Southampton
Mr Richard
Turnock Paediatric Surgery Liverpool
Written
submissions were taken from:
The
Androgen Insensitivity Syndrome Support Group (UK)
The
Congenital Adrenal Hyperplasia Network
Dr Gerard Conway Consultant Endocrinologist, London
Catherine Minto Research Fellow, UCLH, London
Introduction
The surgery of
intersex conditions in childhood is complex and demanding such that
comprehensive coverage might require a document of textbook length. It is the hope of the working party however
that this brief publication represents a fair and, above all, evidence based
summation of current thinking and suggested practice. Such is the pace of change that we may well need to review
matters in a few years time but for now I would like to thank the other members
for their considerable expertise and diligence over the last year.
(Laurence
Rangecroft, Chairman, July 2001)
1. General
Considerations
(a) The surgical management of children born
with ambiguous genitalia has always been difficult, subject to evolving
attitudes and techniques, and at times controversial. Standard protocols have stressed the need for early diagnosis,
gender assignment and appropriate surgery in infancy.1 In recent
years some authors, backed by patient support groups, have claimed that such
surgery is damaging or mutilating and, as it is essentially cosmetic, should
not be performed until the fully informed consent of the patient could be
obtained, i.e. when the child becomes ‘Gillick Competent’.2,3,4 There are, however, so many specific issues
related to the different diagnostic groups that such a policy would seem to be
too prescriptive.
(b) In view of the comparative rarity and
complex issues involved in treating these children, we would unreservedly
recommend their early referral to the nearest regional centre for both
immediate and continuing management by a multidisciplinary team. The disciplines involved should include
appropriately trained paediatric surgeons and/or paediatric urologists,
neonatologists and paediatric endocrinologists and their specialist
nurses/support workers, geneticists, biochemists, psychologists and
gynaecologists. Psychological support
for the child/adolescent and family should be well integrated with medical
input, easily accessible at the time of need and provided by, or in
consultation with, a specialised service.
These multidisciplinary teams and clinics are an obvious and important
resource for training and research and, in particular, follow up studies.
(c) While there is likely to be continuing
pressure from parents for early corrective surgery, fully informed consent for
such procedures would require them to be aware of the possibility of
non-operative management with psychological support for the child and family.
2. Congenital Adrenal Hyperplasia (CAH)
(a)
CAH
produces virilisation of the female fetus and forms the largest single
diagnostic group of children presenting at birth with ambiguous genitalia in
the United Kingdom. The degree of virilisation varies widely.
(b)
Although
some of these girls may opt to change gender in later life, published reports
to date suggest that the incidence is low and does not, of itself, constitute a
strong indication for delaying feminising genitoplasty until adolescence or
beyond.5,6 Rarely the diagnosis may be missed and a
severely virilised 46 XX individual may be raised as a boy. Assignment of gender has to be on an
individual basis, and the decision may need to include cultural considerations.
(c)
The two
essential elements of feminising genitoplasty are clitoral reduction/recession
and vaginoplasty. While the operation
of clitoral shaft resection with preservation of the glans on its neurovascular
bundles seems logical, and is probably an advance on total clitorectomy or
clitoral recession, there is no evidence that the retained glans functions well
in sexual/orgasmic terms. Indeed there
is some emerging evidence to the contrary ( see Appendix). Further revisional
procedures in adolescence are common and may do further sensory damage. Surgeons and parents need to be fully aware
that this is the case before proceeding with this irreversible procedure and
that there is a strong case for no clitoral surgery at all in lesser degrees of
clitoromegaly.
(d)
The ease
with which vaginoplasty can be performed at any age depends on the
length of the common urogenital sinus.
The few long term follow up studies currently available suggest that the
majority of girls will require some, and often major, revisional surgery for
vaginal or introital stenosis in adolescence. 7, Appendix Since early vaginoplasty confers no obvious benefit in a young
girl, there would seem to be a strong case for delaying it until the onset of
menstruation possibly makes it mandatory.
The advent of more recent techniques for coping with the high vagina,
such as the Passerini-Glazel procedure 8, would seem unlikely to alter the outcome as regards revisional
surgery significantly. Individual
surgeons may feel that vaginoplasty is still warranted in the low, and therefore
more straightforward cases, although again it confers no obvious benefit to the
child or her parents. The occasional
patient with a urogenital sinus complicated by urinary stasis and/or infection
may require an early surgical procedure.
3. Complete Androgen Insensitivity Syndrome
(CAIS)
(a) These individuals have a 46 XY genotype,
testes which are intra-abdominal or contained in inguinal herniae, and no
internal female genitalia. The
phenotype, however is of a normal female although the vagina is invariably
short and may be severely so. Few will
be diagnosed in the neonatal period, but some will present early with hernia
and raise the issue of early gonadectomy.
All will be raised as girls and early gender assignment is not usually
an issue. Later hormonal virilisation
is not, of course, possible.
(b) Timing of gonadectomy
This remains
controversial and adequate data on which to base recommendations are scarce. 9,10,11
The foremost concern is the potential for malignant change and the age when
this may occur. It has been argued that
any such risk favours early gonadectomy but set against this is the possibility
that bone maturation and body development in puberty may be better if mediated
by the gradual and early emergence of endogenous sex steroids (aromatisation of
testosterone to oestrodial occurs normally in CAIS) compared to the somewhat
clumsy regimens of exogenous administration.
While one report has suggested an association between greater bone
mineral density and late gonadectomy there is insufficient evidence to recommend
it on that ground alone.12
In relation to
malignant change a comprehensive review in 1987 quantified the risk at 2-5% in
CAIS patients over 25 years of age, and the risk was deemed ‘small’ prior to
that age. 13 In a study of
17 post-pubertal CAIS patients from Venezuela no malignant change was found. 14
There are three
possible options:
1) Early gonadectomy, particularly if they
are contained in an inguinal hernia sac, or there are parental concerns over
malignant change, or difficulty in accepting a female phenotype whilst
testicular tissue is present.
2) Late gonadectomy performed as soon as
puberty has been completed.
3) No gonadectomy in patients who are as
well informed as possible of the potential malignancy risks. Follow up of any such individuals would need
to be assiduous and long term
It
has been suggested that cryopreservation of gonadal tissue should be undertaken
in those patients with AIS undergoing gonadectomy with a view to future
fertility treatment. Whilst the
techniques of freezing testicular tissue and reusing it are now established,
the ethical and moral issues surrounding these techniques are not clear even in
the non-intersex group. There is
currently a multidisciplinary working party convened by the British Fertility
Society looking at the issues surrounding cryopreservation and, until further
information is available, this committee does not recommend cryopreservation on
a routine basis.
(c) Vaginal lengthening
Since there is
no prospect of menstruation in these individuals, and orgasm should be possible
in all, ‘satisfactory’ intercourse in
relation to penetration is the only
physical indication for trying to increase vaginal length. Various methods of self dilation are
available and seem the preferred option with reported success rates of 85-90%.15 The Vecchietti procedure 14 is favoured by some patients but unavailable
in the UK, due to non-approval of the bougie device, and there is anecdotal
evidence that the rapid (2-3 weeks) elongation produced by this manoeuvre
leaves the vagina with insufficient support and can lead to prolapse. If total vaginal replacement is required
sigmoid colon or ileum are probably the best options but both skin or amnion
grafts have their advocates.
(a) Conditions producing this state include
partial androgen insensitivity syndrome, 5-a reductase deficiency, testicular regression syndrome and
severe hypospadias. Historically many
of these genetically 46 XY individuals have either been raised as females or
surgially assigned as such (including castration) because of what was deemed
‘surgically possible’. Evidence for the
effects of testosterone on the foetal brain, and subsequent post-pubertal
gender identity in humans is somewhat equivocal.17 However studies from areas such as the
Dominican Republic and Papua New Guinea on ‘untreated’ 5-a reductase patients have shown a strong
tendency to virilise at puberty and almost 100% assumption of the male gender
identity/role. 18 Furthermore, follow up studies by Reilly and
Woodhouse on adult males with micropenis (defined as less than 2.5 SD below the
mean stretched length for ages or stage of sexual development) have shown
surprisingly good outcomes in terms of sexual function. 19
(b) Assignment
of such individuals to the female gender by surgery should only be undertaken
with considerable caution and following full multidisciplinary investigation
and counselling of the parents.
5. True Hermaphrodites/Mixed Gonadal
Dysgenesis
Most of the
issues in relation to these rare individuals have already been covered by the
above but there is unequivocal evidence of a greater risk of malignant change
in dysgenetic and streak gonads. 20,21 Streak gonads and any gonad inappropriate to the sex of rearing
should, therefore, be removed and any retained testis should be placed in a
palpable position for easier surveillance.
References
1. American Academy of Pediatrics. Evaluation of the Newborn with Developmental
Anomalies of the External Genitalia. Pediatrics, vol 106:1, 2000, p 138-142
2. Dreger, AD “Ambiguous Sex”…or Ambivalent
Medicine? Ethical Issues in the Medical
Treatment of Intersexuality. Hastings
Center Report, vol 28, 1998, p 24-25.
3. Kipnis, K., Diamond, M. Pediatric Ethics
and the Surgical Assignment of Sex. Journal
of Clinical Ethics, vol 9:4, 1998, p 398-410.
4. BAPS Ethical Committee. Gender Assignment
Surgery in Children. Ethical Position for Clinicians, 2000, www.baps.org.uk
5. Ehrhardt, AA, Meyer-Bahlburg, HFL.
Effects of prenatal sex hormones on
gender related behavior. Science, vol 211, 1981, p 1312-18.
6. Mosley,
M, Bidder, R, Hughes, I. Sex
role behaviour and self-image in young patients with congenital adrenal
hyperplasia. Br J Sexual Med vol 16, 1989,
p
72-75
7. Alizai, NK, Thomas, DFM, et al. Feminising genitoplasty for congenital
adrenal hyperplasia: What happens at puberty. J. Urol. Vol 161:5, 1999, p 1588-91.
8. Passerini-Glazel, G. A
new 1-stage procedure for clitovaginoplasty in severely masculinised female
pseudohermaphrodites. J. Urol., vol
142, 1989, p 565.
9. Viner, RM, Teoh, Y, Williams, DM,
Patterson, MN, Hughes, IA. Androgen insensitivity syndrome: a survey of
diagnostic procedures and management in the UK. Arch Dis Child, vol 77, 1997, p 305-309.
10. Verp,
MS, Simpson, JL. Abnormal sexual
differentiation and neoplasia. Canc Genet
Cytogenet, vol 25, 1987, p 191-218.
11. Alvarez-Nava, F, Gonzalez, S, Soto, M,
Martinez, C. Prieto, M. Complete androgen insensitivity syndrome: clinical and
anatomopathological findings in 23 patients. Genet Counselling, vol 8,
1997, p 7-12.
12. Soule, SG, Conway, G, et al. Osteopaenia
as a feature of the androgen insensitivity syndrome. Clin Endocrin (Oxf), vol 43, 1995, p 671-5.
13. Verp, MS, Simpson, JL. Op.cit.
14. Alvarez-Nava, et al. Op.cit.
15. Costa, EM, Mendonca, BB, et al. Management of ambiguous genitalia in
pseudohermaphrodites: new perspectives on vaginal dilation. Fertil Steril, vol 67(2), 1997, p 229-232.
16. Barruto, F, et al. The Veccheitti
procedure for surgical treatment of vaginal agenesis: comparison of laparoscopy
and laparotomy. Int.J. of Gynecol. And
Obst. vol 64:2, 1999, p 153-8.
17. Meyer-Bahlburg, HFL. Commentary: Gender
assignment and reassignment in 46,XY pseudohermaphroditism and related
conditions. J.Clin.Endocrin. and Met, vol 84:10, 1999, p 3455-58.
18. Imperato-McGinley, J, et al. A cluster of male pseudohermaphrodites
with
5-a reductase deficiency in Papua New
Guinea. Clin. Endocrinol, vol 34: 4,
1991, p 293-8.
19. Reilly,
JM, Woodhouse, CRJ. Small penis
and male sexual role. J. Urol.,
vol
142, 1989, p 569-71.
20. Manuel,
M, Katayama, KP, Jones, HW. The
age of occurrence of gonadal tumors in intersex patients with a Y chromosome. Am. J. Obst. Gynecol, vol 124, 1976, p
293-300.
21. Savage, MO, Lowe, DG. Gonadal neoplasia and abnormal sexual
differentiation. Clin. Endocrinol.
vol 32, 1990, p 519-33.
Sarah Creighton Consultant Gynaecologist,
Catherine Minto Research Fellow
Department of Gynaecology, University College
London Hospitals.
There are three
main groups of plastic clitoral procedures:
This operation
simply removes all that can be seen of the clitoris (ie all of the glans
clitoris), and usually involves dissection and partial removal of the corpora.
Often the prepuce and clitoral hood will also be removed or used for
reconstruction elsewhere. It is believed this procedure is now rarely done in
the UK although no data are available.
2. Clitoral Recession
In this procedure, none of the clitoral
structures are removed, instead the clitoral structures are dissected out and
then folded up and moved in their entirety, backwards under the symphysis
pubis. As in the clitoral reduction procedure, the bilateral dorsal clitoral
nerves maintain their connection to the clitoral glans. This procedure was
found to cause pain on clitoral engorgement and again it is presumed this
procedure is no longer performed.
In this procedure the glans clitoris is
preserved, and the corpora are dissected and partially or totally removed. Most
procedures today will identify the two dorsal clitoral nerves and maintain
their connection to the clitoral glans. Sometimes the clitoral glans will be
reduced in size by wedge excisions, either laterally, ventrally or dorsally.
AIMS
AND BENEFITS OF SURGERY
Once a female sex of rearing has been
determined, current practice is to perform appropriate surgery to ensure the
genitalia are “normal”. The immediate aim is cosmetic. It is believed that
normal looking female genitalia encourage a stable gender identity whilst
reducing stigma and psychological distress thought to occur in children growing
up with ambiguous genitalia. This practice is based on the work of John Money
in the 1950’s and 1960’s. His premise was that infants are psychosexually
neutral until the age of 2 years and that what is required for a stable normal
gender identity is unambiguous genitalia and unequivocal assurance from parents
at to the chosen gender.
There are no long term data to support this
although there is a widely held belief that feminising genital surgery is
“successful” both cosmetically and functionally. It is however impossible to
predict the true gender identity or sexual preferences of any baby without an
Intersex condition and even more difficult with Intersex children. It is most
likely that gender identity has a multifactorial basis including anatomical,
genetic and endocrine factors. The contribution of genital appearance to gender
identity is unknown but men diagnosed
with micropenis in infancy can remain happy with a male gender identity
and have a male sexual role (Reilly and Woodhouse 1989).
There are no comparative data as yet published
comparing women who have undergone surgery to women who have not had surgery.
In the USA almost all babies with ambiguous genitalia have undergone genital
surgery since the 1950’s. However in the UK surgeons were initially reluctant
to perform feminising surgery and there is existing a cohort of older patients
who have not had genital surgery.
WHAT
IS A LARGE CLITORIS?
There are standard measurements available for
the average clitoris for a baby. However most clinical assessment of the genitalia
is very subjective. The genital appearance changes dramatically at puberty with
the deposition of labial and pubic fat and the arrival of pubic hair. What may
appear as a large clitoris in a baby may look much less prominent in a teenage
or adult. The majority of paediatric surgeons spend little time examining adult
female genitalia and may misjudge potential clitoral size. There is a huge
variation in size and anatomy of normal female genitalia. The patient herself
may be entirely happy with a larger clitoris than average.
FOLLOW-UP
DATA
While reports of
operative techniques to reduce clitoral size have been numerous, there have
been correspondingly few studies looking at outcomes of these surgical
techniques. Reasons often put forward for this situation are that much of this
surgery is performed on young infants by paediatric urologists and paediatric
surgeons. These clinicians will not follow up these children regularly and will
therefore not see the adult results of their surgery, either cosmetic or
functional. The genitalia and sexual functioning are extremely delicate
subjects that may be inappropriate or difficult for a paediatrician or
paediatric surgeon to discuss with patients.
A literature
review to look for functional outcomes of clitoral surgery has shown three
groups of studies;
1. Small
retrospective cohort studies or case reports performed by the original surgeon,
with vague outcome parameters. These usually concentrate on surgical technique
and most do not assess sexual function in any detail if at all. None of these
studies is well reported, and all are subject to many biases.
2. Objective
neurological assessment
Only one study
has attempted to evaluate objective clitoral sensory innervation after surgery.
Gearhart et al in 1995 performed pudendal evoked potentials in children before
and after clitoral reduction. They used stimulation of the dorsal neurovascular
bundle with unipolar electromyegraphic electrodes at the base of the clitoris
and EMG response recorded at the tip of the clitoris. He demonstrated
preservation of nerve conduction and claimed this may permit normal sexual
function in adulthood. This is an inaccurate method to study sensation as it
measures large myelinated fibres. Clitoral sensory information is carried in
non-myelinated (C fibres) and small
myelinated nerve fibres (Ad) which can
only be assessed by temperature, vibration and light touch. These studies have
not been done. In addition Chase (1996) stated that adult women who had
undergone genitoplasty as children retained normal pudendal evoked potentials
but had impaired sensation and orgasmic response.
3. Psychosexual
function
Two studies have
looked at psychosexual function in detail. Both have been published in
psychology journals and have received little surgical exposure.
a. May et al
(1996) looked at 19 women with congenital adrenal hyperplasia and compared this
with a control group of 17 women with diabetes. Structured interviews were
taped and analysed. The CAH group reported higher levels of penetration
difficulties and a pattern of persistent pain during intercourse. They were
less likely to masturbate and less likely to attain orgasm compared with the
diabetic group (58.3% compared to 88%). The CAH group were doubtful about the
success of surgery and worried about their genital appearance not being normal.
b. Dittman et al
(1992) looked at 34 women with CAH compared to a control group of 14 sisters.
The CAH women were less likely to experience orgasm with masturbation or
intercourse. They were also less likely to be sexually active.
Repeat clitoral
reductions are common especially during adolescence. It is likely that if one
procedure interferes with sexual function, then more procedures will do more
harm. Repeat procedures are common in children with CAH with poor control or
compliance.
The difficulty
with feminising surgery on babies is that the decision cannot be made by the
patient. All parents want the best for their children and want them to be happy
and “normal”. Most clinicians at present believe normal looking genitalia are
essential and are happy to recommend and advise surgery. Whilst parents want to feel able to make
their own decisions, they look to the medical profession for guidance. We
should be clear for whom we are doing the surgery i.e. clinicians and parents
rather than the baby.
However adult
patients are increasingly expressing dissatisfaction with the outcome of
surgery. There is a growing campaign – especially in the USA – for a moratorium
on feminising genital surgery. This has led to the establishment of NATFI
(North American Taskforce on Intersex) and our current working party. Some clinicians are also questioning the
need for cosmetic genital surgery (Schober 1998, 1999).
At UCLH we are
looking at long term follow up in adult Intersex womenincluding those who have
undergone surgery and those who have not. Our study is a retrospective study comprising
a standardised sexual function questionnaire (modified Golombok Rust Inventory
of Sexual Satisfaction (GRISS)), full genital examination and full review of
medical records including operative notes. So far 131 women have completed the
questionnaire and 40 have been examined. Initial results comparing women with
ambiguous genitalia during childhood who underwent surgery to those who didn’t
suggest a high level of sexual dysfunction in both groups. However the group
who had had clitoral surgery were significantly worse off with 26% unable to
achieve orgasm by any means (Minto et al 2001). We have also reviewed anatomical and cosmetic finding in
adolescents following childhood surgery and have shown that 77% of children
will require further major genital surgery during adolescence and adulthood
(Creighton et al 2001).
RECOMMENDATIONS.
1. Consultation with Intersex support groups. Seek opinions from adult
patients who have undergone surgery and parents of children who have undergone surgery
2. All data on effects of sexual function
should be discussed with the parents. The option to decline surgery must be
discussed.
3. Clitoral Surgery should be avoided on
mild and moderately virilised children.
4. Clitoral surgery on severely virilised
children must be carefully discussed with all involved in the full
understanding of effects on future. The possibility of deferring surgery should
be discussed with the parents. The possible requirement for further revision
surgery must be recognised.
Chase C 1996
Letter of response J Urol 156:1139
Creighton S,
Minto C, Steele S 2001 Cosmetic and
anatomical outcomes following feminizing childhood surgery for ambiguous
genitalia. Presented to N. American Society for Pediatric and Adolescent
Gynaecology 2001. Accepted for publication in the Lancet – publication date
July 2001
Dittman RW,
Kappes ME, Kappes MH, 1992 Sexual behaviour in adolescent and adult females
with congenital adrenal hyperplasia. Psychoneuroendocrinology Vol17 No2/3
pp153-70
Gearhart JP.,Burnett A.,Owens JH., 1995
Measurement of pudendal evoked potentials during feminising
genitoplasty:technique and applications J Urol 153:486-7
May B.,Boyle
M.,Grant D., 1996 A comparative study of sexual experiences. Journal of Health
Psychology vol 1(4) 479-492
Minto C,
Creighton S, Woodhouse C 2001 Long term sexual function in intersex conditions with
ambiguous genitalia. Presented at British Assosciation of Urological Surgeons
2001 (submitted for publication).
Money J.,Hampson
JG.,Hampson JL 1955 Hermaphroditism:recommendations concerning assignment of
sex, change of sex and psychologic management. Bull John Hopkins Hosp 97:284-300
Money J.,Hampson
JG.,Hampson JL., 1957 Imprinting and the establishment of gender role.
Arch.Neurol.Psychiatry 77:333-336
Reilly
J.,Woodhouse C., 1989 Small penis and the male sexual role. J.Urol 142:569-572
Schober JM 1998
Early feminizing genitoplasty or watchful waiting. J. Paedaitr.
Adolesce.Gynecol. 11(3):154-6
Schober J. 1999
Longterm outcomes and changing attitudes to intersexuality. BJU International
83 Supppl3, 39-50