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Figure 2: A comparison of three key studies of the interaction between
oestrogen and growth hormone when used as treatment for girls with
Turners syndrome
(A) Oestrogen dose in each study, expressed as an estimated percentage of an
adult dose of oestrogen. (B) Average age of starting oestrogen in each study.
(C) The eect on nal height attributed to the addition of oestrogen ranging
from a height decit of 3 cm in Chernausek and colleagues,
36
zero eect in Sas
and coworkers,
11
and a height gain of 2 cm in Ross and colleagues.
22
In summary,
low-dose oestrogen allows an early start of induction of puberty with potential
gain in nal height.
336 www.thelancet.com/diabetes-endocrinology Vol 2 April 2014
Review
of Turners syndrome (and perhaps by the age of 10 years
for those with younger presentation) simul taneously with
the start of treatment with growth hormones. The starting
dose and timing of escalation of oestrogen with late
presentation should be individualised according to the
priorities of each individual, be they breast size, menarche,
or nal height. However, from our experience, an example
would be to start with a transdermal oestradiol patch
125 g twice per week, increasing to 25 g after
36 months, and then 50 g after another 6 months,
introducing progestogen after the rst breakthrough
bleed. This quite fast pace could be slowed if growth
proceeds well in the rst two visits, with monitoring of
height and uterine length at 3 month intervals.
Psychosocial aspects of late diagnosis
Specic psychological traits have been consistently
described in girls and women with Turners syndrome
with an emphasis on an increased risk for social isolation,
immaturity, and anxiety.
43,44
Identity development, social
relationships, interpersonal skills, independence and
interdependence, and psychological and emotional
challenges are major developmental issues that confront
adolescents with Turners syndrome.
45
Despite these
ndings, studies using quantitative measures of quality
of life have generally failed to capture these concerns.
4648
Specically, nal height and previous use of growth
hormone does not have a signicant negative eect on
quality of life.
4851
By contrast, ndings of several studies have shown that
late diagnosis and late induction of puberty are associated
with adverse outcomes in Turners syndrome.
49,52
These
ndings raise the question of whether early induced
puberty could contribute to better wellbeing later in life
even at the expense of a decit on nal height. Success in
nding a life partner is a particular problem for women
with Turners syndrome and a major determinant of
quality of life.
45
An important nding that might be
relevant in this area is that earlier induction of puberty is
associated with less delay in sexual debut in women with
Turners syndrome.
50
In a population-based cohort study
of 566 women with Turners syndrome aged 22626
years, by the age of 25 years, roughly 57% of women with
Turners syndrome had not had a sexual debut if
oestrogen was started after the age of 14 years compared
with 42% of those who had earlier exposure to oestrogen
in a reference group without Turners syndrome, the
gure was less than 18%.
50
Another consequence of delayed diagnosis of Turners
syndrome is that behavioural traits can interfere with
education and might be compensated for by simple
measures. For instance, a decit in mathematical
processing is common, but can be overcome if extra time
is allowed for preparation.
53,54
Similarly, social skills,
which can be slow to develop in individuals with Turners
syndrome, leading to the common nding of social
isolation in adulthood, can be the focus of psychological
intervention.
55
Lastly, some of the educational problems
relating to Turners syndrome might be the result of
unrecognised deafness, and early detection would enable
simple measures to be taken, such as placement in class.
These issues underline the need for a screening method
to allow for earlier diagnosis of Turners syndrome. Still,
the overall educational attainment of women with
Turners syndrome is equal to or better than the general
population of women.
46,5658
In conclusion, previous recommendations to delay
oestrogen treatment until the age of 15 years to optimise
height potential
36
is no longer acceptable because the
psychosocial importance of age-appropriate pubertal
maturation and other aspects of health and wellbeing
might outweigh the eect of short stature.
33
Access to
clinical psychology or experienced counsellors should be
available for women with Turners syndrome to address
the issues relating to delayed diagnosis.
Future prospects for ameliorating the eects of
late presentation of Turners syndrome
Achieving an earlier diagnosis
For girls known to have Turners syndrome before
puberty, management strategies have already been
adjusted to allow for earlier induction of puberty. The
most pressing problem is to prevent the delay in
diagnosis of Turners syndrome whereby girls miss out
on the benets of timely intervention and support.
There is no one solution for this problem and strategies
might vary between countries. Where systematic height
records are taken in school, then the possibility of
karyotype screening for all girls with short stature would
be possible.
59,60
Unfortunately, such a height-screening
programme is not in place in the UK, and mass
molecular screening at birth would not be cost eective.
Another possible method of ascertaining a risk group
would be to choose an alternative common feature of
Turners syndrome such as otitis media. Once again,
there are di culties because otitis media is very
common in the general population. As health data
resources develop, cross correlating height data at birth
and the presence of otitis media might identify a group
for whom genetic screening would be a reasonable
proposition, and further research in this area is
welcome.
Controlled trial of transdermal oestrogen in puberty
An important change in the management of puberty in
girls is the move from oral to transdermal oestrogen, but
no trial data conrm the benets that have largely been
extrapolated from observation and experience. The
emphasis of most trials in Turners syndrome have been
on nal height, which is a much easier endpoint on
which to base an outcome compared with sexual
development, socialisation, and wellbeing much later in
life. Nevertheless, an achievable goal is to achieve pubertal
milestones that match reference data more accurately.
www.thelancet.com/diabetes-endocrinology Vol 2 April 2014 337
Review
Conclusions
The late age of diagnosis of many women with Turners
syndrome is a continuing problem, and new strategies
for earlier detection would result in many benets. For
now, the management of women with Turners syndrome
in whom puberty is delayed needs specialist input,
preferably with a multidisciplinary team who have
experience in balancing the requirements for optimum
outcome in an individualised holistic way.
Conicts of interest
We declare that we have no conicts of interest.
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