Starting Age of Oestrogen-Progestin Therapy Is Negatively Associated With Bone Mineral Density in Young Adults With Turner Syndrome Independent of Age and Body Mass Index

Satsuki Nishigaki; Tomoyo Itonaga; Yukihiro Hasegawa; Masanobu Kawai

Disclosures

Clin Endocrinol. 2021;95(1):84-91. 

In This Article

Abstract and Introduction

Abstract

Objective: Osteoporosis is an important health issue in patients with Turner syndrome (TS), and oestrogen sufficiency has been implicated in increased bone mineral density (BMD); however, the impact of the starting age of hormone replacement therapy (HRT) on bone mineral density remains unclear, particularly during young adulthood.

Design: A retrospective study from three tertiary care hospitals in Japan.

Patients: One hundred and three patients with TS aged between 18 and 30 years of age who underwent dual-energy X-ray absorptiometry.

Measurements: Anthropometric parameters, lumbar bone mineral density (L-BMD), including areal BMD (aBMD) and volumetric BMD (vBMD), karyotypes, the presence of spontaneous menarche, the starting ages of oestrogen replacement therapy (ERT) and oestrogen-progestin therapy (EPT), and the duration between starting ages of oestrogen replacement therapy and oestrogen-progestin therapy were investigated. vBMD was calculated based on the Kröger method.

Results: aBMD was lower in young adults with TS than in an age-matched reference population. L-BMD positively correlated with weight and body mass index (BMI). L-BMD was higher in subjects with spontaneous menarche (N = 22) than in those without. A dose escalation regimen of oestrogen replacement therapy was used in 84% of subjects without spontaneous menarche (N = 81). The starting age of oestrogen replacement therapy and the duration between the starting ages of oestrogen replacement therapy and oestrogen-progestin therapy negatively and independently correlated with aBMD, but not with vBMD, after adjustment with age and BMI. The starting age of oestrogen-progestin therapy negatively correlated with L-BMD independent of age and BMI.

Conclusions: Early introduction of hormone replacement therapy, particularly oestrogen-progestin therapy, is important to accrue better L-BMD in young adults with TS.

Introduction

Turner syndrome (TS) occurs in approximately one out of 2,000 live-born females and is caused by the complete or partial loss of one X chromosome.[1] Although the phenotypic features of TS are highly variable, a short stature and gonadal dysgenesis are the two main clinical features,[1] the latter of which has been associated with decreased bone mineral density and an increased risk of osteoporotic fractures during adulthood, particularly when inappropriately treated.[2] Bone accrual during the pubertal period is pivotal to acquire better bone mineral density during adulthood and decrease the risk of osteoporotic fractures later in life;[3] therefore, the appropriate initiation of hormone replacement therapy, including oestrogen replacement therapy and oestrogen-progestin therapy, during adolescence is important for skeletal health in TS.

Clinical practice guidelines for the care of girls and women with TS recommend hormone replacement therapy for the induction and maintenance of female secondary sex characteristics; however, an optimal strategy for hormone replacement therapy to attain better bone mineral density during adulthood has not yet been established.[1] Cameron-Pimblett et al reported that the starting age of oestrogen replacement therapy negatively correlated with adult bone mineral density in British women with TS ranging in ages of between 18.1 and 70.3 years old.[4] Similar findings were also independently reported.[5,6] These findings clearly indicate the importance of the early introduction of oestrogen replacement therapy in TS where appropriate; however, the inclusion of aged subjects in the study design may create a bias when interpreting the effects of hormone replacement therapy on bone mineral density because multiple variables, including age-dependent decreases in bone mass, may affect bone mineral density in aged populations. Furthermore, there is concrete evidence to show that bone mineral density during young adulthood is important determinant for the risk of osteoporotic fractures later in life.[7,8] We have recently analysed bone mineral density in TS aged between 15 and 49 years of age and found that the duration of oestrogen-progestin therapy was positively associated with bone mineral density;[9] however, the effects of the starting age of hormone replacement therapy, particularly oestrogen-progestin therapy, on bone mineral density in young adults with TS were not performed.

Based on these backgrounds, we herein investigated bone mineral density in young adults aged between 18 and 30 years old who had never been treated with anti-osteoporotic drugs, including the active form of vitamin D and bisphosphonates. We also examined the relationship between bone mineral density and the starting age of hormone replacement therapy, including oestrogen replacement therapy and oestrogen-progestin therapy, in young adults with TS.

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