“Medical and gynecological comorbidities in adult women with Turner syndrome: our multidisciplinary clinic experience” by Farquahar M et al.
Turner syndrome (TS), associated with complete or partial loss of the second X chromosome, is the most frequent genetic disorder affecting females and occurs in 1/2500 live female births . TS is characterised by short stature and gonadal dysgenesis but affects multiple organ systems  and is associated with increased morbidity and mortality [2,3]. Using retrospective chart review, the study by Farquhar and colleagues  examined the prevalence of a range of chronic health conditions in a cohort of women with TS aged ≥18 years who attended a Canadian academic hospital multidisciplinary clinic for routine screening  at least once between February 2015 and July 2018. Demographic data, karyotype, medical history, and results of screening investigations were collected. Defined comorbidities included hypothyroidism, dysglycemia, decreased bone density, gynaecological/ cardiac and renal abnormalities, hypertension, cerebrovascular event, hearing loss, cancer history, and coeliac disease. The cohort was divided into women < 40 and ≥ 40 years, and statistical analysis of the prevalence of comorbidities was performed for the whole group and subgroups. The cohort comprised 122 women with TS, having a mean age of 37.7 (range 19-68) years (40% aged ≥ 40 years), and having XO as the commonest karyotype (39%). The average age of diagnosis was 11.4±9.1 years, with women aged < 40 years diagnosed at an earlier age and more likely to receive growth hormone. Current hormone therapy was reported by 84.4% of women with the combined oral contraceptive pill (COC) preferred (47.6% overall), although COC use was lower in women ≥ 40 years (27.2%). Overall, co-morbidity prevalence varied from hearing loss (41%), cardiac abnormality (36.1%) gynaecological disorder (35%), low bone density (29.5%), hypothyroidism (~25%), renal abnormalities (18.8%), dysglycemia (16%), hypertension (14%) to coeliac disease (9%). Women aged ≥ 40 years had a greater number of comorbidities compared with women < 40 years (2.9±2.0 versus 1.6±1.5; p=0.004). A significantly higher comorbidity prevalence in the older sub-group was observed for hypothyroidism, dysglycemia, gynaecological conditions, hypertension, and hearing loss.
Previous Danish and United Kingdom (UK) registry studies [2,3] of women with Turner syndrome (TS) have reported a threefold increase in overall mortality and increased mortality related to specific health conditions including endocrine, cardiovascular and congenital abnormalities compared with the general population. The reported prevalence of many of the comorbidities in this study by Farquhar and colleagues  is consistent with that reported in the literature , including other international TS cohorts [6-8] and our Australian cohort . It is not surprising that increasing age is associated with a higher prevalence of comorbidities and reflects the changing pattern of causes of death seen with different age groups . These findings highlight the need for ongoing monitoring of TS women throughout life. Evaluation of psychological health issues was not included in this study. However, Turner syndrome is associated with neurocognitive and psychosocial issues with increased risk of social isolation, anxiety, decreased self-esteem, and obsessive behaviour negatively impacting the quality of life. Hearing loss was the most common health condition and is of particular importance regarding the observed association with decreased quality of life and increased fracture risk in women with TS . Although not investigated in this study, previous data have shown that the prevalence of health conditions  and the risk of mortality  due to different causes vary with karyotype. Karyotype XO, as reported in this study , is the most frequent TS karyotype and is associated with the highest all-cause mortality . The COC was the most frequent type of hormone therapy used overall, although the authors commented that menopausal hormone therapy was preferentially used in women ≥ 40 years. The optimal dose and hormone therapy regimen for women with TS remains unclear; however, ethinyloestradiol COC may be associated with lower accrual of bone density and hypertension. As TS is associated with primary amenorrhoea or premature ovarian insufficiency, the recent international TS guideline  recommends that oestrogen replacement, preferably transdermal oestradiol, be commenced and continued until the usual age of menopause, with a progestogen added for endometrial protection. The COC may be necessary for contraception for the 6% of girls/ women with TS who have spontaneous menstrual cycles . Girls/ women with TS may also prefer the COC as it is perceived as “peer friendly” . As with all hormone therapy, the type, dose, and duration needs to be individualised to each woman and risk/benefits re-evaluated as circumstances change . The increased risk of mortality and the prevalence of multiple comorbidities provides a rationale for the TS clinical guideline’s recommendations  that adult women with TS require lifelong comprehensive standardized health surveillance and are best managed in a multidisciplinary clinic . This is further emphasized by the evidence of (i) suboptimal comorbidity screening of adult women with TS at the initial visit to multidisciplinary clinics in Australia  and The Netherlands  and (ii) inadequate transition from paediatric to adult care .
Adjunct Clin Assoc Prof, MBBS, B Med Sci (Hons), Ph.D., FRACP
Endocrinologist, Turner Syndrome Longterm Care Clinic, Monash Health, Clayton, Victoria, Australia Research
Fellow and Head, Early Menopause Studies Monash Centre for Health Research and Implementation-MCHRI, School of Public Health and Preventive Medicine, Monash University, 43-51 Kanooka Grove, Clayton, 3168, Victoria, Australia
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