This study shows that women with TS treated with oral or transdermal estradiol or oral conjugated estrogen, in combination with oral medroxyprogesterone or micronized progesterone for several years, may attain a normal, mature uterine size and configuration. The age of pubertal induction was not critical. Stature and history of GH treatment did not impact the degree of uterine development. Karyotype was not a contributing factor, and 45,X women did have normal uterine development given adequate treatment (Table IV). A recent study from Germany found that only 45,X/46,XX mosaic females developed normal uterine proportions although none with 45,X did (7
). In fact, karyotype was the only significant predictor of normal uterine development in this study, with age at estrogen initiation, age at start of cyclic progestin or duration of estrogen showing no correlation to the uterine development (7
). The different findings in our study (12/21 or 57% of the subjects with mature uteri had 45,X karyotype) may be explained by the longer average duration of estrogen treatment in our subjects. The mere currency of HRT is not enough in itself to guarantee a normal uterine size if it has not been administered long enough – as illustrated in , the majority of the women with TS who had immature uterus (70%) had been taking HRT at the time of the study.
The optimal age for pubertal initiation and the safest and most effective protocol for pubertal development and maintenance HRT in girls and young women with premature ovarian failure are important issues that lack strong, evidence based support at present. According to some studies age at pubertal induction was an important factor in achieving a normal uterine size (5
). In previous years, expert opinion recommended pubertal induction with low dose estrogen treatment beginning between age 12 – 15 yrs, with gradual increases in dose until feminization is adequate, and the addition of a cyclic progestin on a regular basis after 12–24 months (10
). The average age of initiation in our group of community-treated patients was rather late at almost 16 years of age. This may be due to a trend in recent years to delay the start of estrogen treatment to promote additional statural growth under GH treatment (11
). Our study suggests that age at estrogen initiation is not critical to adequate uterine development.
Previous studies have found that the dose of estrogen is an important contributor to uterine size and maturity (8.9). Our study indicates that in addition, the type of hormone replacement therapy may play an important role. The real test of adequate uterine development is successful pregnancy, and although initial reports on assisted reproduction outcomes in TS did suggest a potential uterine problem (12
), a recent review of women with TS participating in oocyte donation programs in the U.S. found that of 146 women treated, 101 (69%) became pregnant; 94 of these pregnancies resulted in the birth of a live baby, for a miscarriage rate of only 6.4% (13
). This important observation indicates that given adequate hormonal treatment, women with TS may develop a uterus able to sustain a term pregnancy. Although the uterus may sustain a pregnancy, the cardiovascular system of the mother with TS may not (13
), so the paramount concern in considering pregnancy must be the mother’s risk factors for pregnancy complications (14
Our study has certain limitations. As with every cross sectional study, it may have unsuspected bias. Unexplained remained the fact that when compared to historic reference data, women with TS in our study had smaller uterine volumes even when they fulfilled the criteria for uterine maturity(6
). In addition, the small number of women taking transdermal estrogen therapy (n=5, ) did not allow valid conclusions regarding the effect of different modes of estrogen administration, i.e. oral versus transdermal. Future studies are needed to compare uterine size and maturity of girls with TS who have had the currently recommended “optimal” pubertal induction and hormone replacement therapy to a group of age matched girls with normal karyotypes and normal pubertal development.
Immature versus mature uterus in Turner syndrome