Sex Hormone Replacement Therapy in Turner Syndrome: Impact on Morbidity and Mortality

The long-term effects of female hormone replacement therapy (HRT) in Turner syndrome (TS) are unknown.

To examine morbidity, mortality and medicinal use in TS and the impact of HRT in 45,X women.

National cohort study, following all TS individuals ever diagnosed in Denmark from 1977 to 2014.

In the Danish Cytogenetic Central Registry, we identified 1156 females diagnosed with TS from 1960 to 2014, and, subsequently, Statistics Denmark randomly identified 115 577 age-matched female controls. TS women and their matched controls were linked with person-level data from the National Patient Registry and the Medication Statistics Registry, and they were compared concerning mortality, hospitalizations, and medical prescriptions. Among 329 45,X women, 44 had never been HRT treated, and 285 had been treated at some point. HRT treated women were compared with untreated concerning mortality, hospitalizations, and medical prescriptions.

Endocrine and cardiovascular mortality and morbidity were significantly increased in TS compared with the matched controls. Comparing HRT treated with nontreated 45,X women, we found a similar mortality (hazard ratio 0.83, 95% confidence interval 0.38-1.79). Among the HRT-treated 45,X women, we found a significantly lower use of antihypertensives, antidiabetics, and thyroid hormones and significantly reduced hospitalization rates for stroke and osteoporotic fractures.

Women with TS have an increased overall mortality and morbidity. HRT seems to have a beneficial effect on endocrine conditions, hypertension, and stroke in women with 45,X karyotype, with no clear impact on mortality.