Hormone replacement therapy in Turner syndrome is important—a new meta-analysis points at many shortcomings in the available literature

Abstract

Turner syndrome (TS) can by most standards be viewed as a rare condition, although it is one of the more common rare conditions. As in all rare conditions, it is difficult to accumulate sufficient data to base treatment and care on evidence and therefore many aspects of TS is based on expert opinion. And since ovarian dysgenesis is almost inevitable early in the lives of most females with TS, estrogen replacement therapy (ERT) is cornerstone to appropriate treatment of TS, to induce puberty and uphold female sex characteristics, maintain bone mass, body composition, and possibly to avoid undue cardiovascular morbidity and positively impact neurocognitive development. However, hard endpoints are not available within the realm of TS research and much has been extrapolated from the literature concerning the effects of ERT in the postmenopausal setting. And such extrapolation may not be valid. Just considering the lengthy discussions concerning the WHI study and the possibility that the timing hypothesis for ERT exists and that the timing of start with ERT may therefore be of great importance [1]. In addition ascertainment bias is a problem in TS research, since less than two-thirds of all TS are ever diagnosed [2], decreasing the validity of clinical studies of TS.A new meta-analysis and systematic review takes a critical view at effects of ERT on bone and cardiovascular outcome in TS and includes all randomized clinical trials (RCT) on the subject [3]. Not surprisingly, only 9 RCTs could be included in quantitative assessment of effects and furthermore there were pronounced differences in the drugs used, the duration of studies spanning from 2 to 66 months, the age of the TS in the different studies and the route of administration. Therefore a pronounced inconsistency of effects across studies was identified. In addition to RCTs, the meta-analysis also includes cohort studies. Furthermore, only one study reported hard endpoints concerning bone (fractures), while no studies reported cardiovascular related hard endpoints, and thus the meta-analysis reports mainly surrogate endpoints such as change in Bone mineral density (BMD) and high density lipoproteins (HDL). Thus, this meta-analysis highlights the deplorable lack of studies within TS reporting hard endpoints and clearly emphasizes the need for such future studies. Nevertheless, the meta-analysis allows the authors to conclude that cohort studies indicate that ERT improves BMD, with physiological 17β-estradiol seemingly better than synthetic estrogens (such as ethinyl estradiol which is normally used in contraceptive pills). This finding, although data were not of high quality, is interesting, since recommendations have long focused on using physiological supplementation, with many clinicians being uneasy with the use of synthetic compounds for many years in TS [4].Results from the RCTs concerning cardiovascular surrogate markers show that oral 17β-estradiol is superior to transdermal 17β-estradiol in increasing HDL-cholesterol, while there was no difference in ...

The clinical analysis of small supernumerary marker chromosomes in 17 children with mos 45,X/46,X,+mar karyotype

“…During childhood, Turner syndrome patients may be treated with recombinant human growth hormone to promote an increase in stature. Patients would be treated with hormone to initiate puberty ~12 years old (21). In addition, mental intervention is also necessary to treat the children.…”

Turner syndrome mosaicism: Challenges in identification and management in primary care

“…Additionally, with a TS or TSM diagnosis, referral to endocrinology for assessment and evaluation of growth-promoting therapies is recommended. The endocrinologist begins a discussion regarding future reproductive capacity/issues (Gravholt, 2017; Gravholt et al, 2017). After initial genetics evaluation and diagnosis of TS or TSM, the genetics provider generally refers the patient and family back to the PCP for ongoing surveillance and management during childhood and adolescence.…”

“…For females with TSM and TS, the recommended risk surveillance is specifically for obesity, hypertension, and cardiovascular concerns including aortic root dilatation, lipid disorders, elevated liver enzymes, glucose intolerance, hearing loss, thyroid dysfunction, increased risk of melanocytic nevi, and osteopenia (Gravholt et al, 2017; Gravholt & Backeljauw, 2017; Lebenthal et al, 2018; Paolucci & Bamba, 2017; Shankar & Backeljauw, 2018). Universal among persons affected with TS or TSM are growth and fertility concerns; therefore, ongoing collaboration with endocrinology and fertility specialties is essential (Beery et al, 2018; Culen et al, 2017; Elsheikh et al, 2002; Gravholt, 2017). Finally, increased risk for mental health diagnoses has direct association with neurocognitive concerns, such as reading comprehension issues, visual–spatial issues, social cognition issues, and self-concept issues (Lin et al, 2019; Paolucci & Bamba, 2017; Sayer et al, 2009).…”