Estrogen Replacement in Turner Syndrome: Literature Review and Practical Considerations

Abstract

Evidence supports the effectiveness of starting pubertal estrogen replacement with low-dose transdermal E2. When transdermal E2 is unavailable or the patient prefers, evidence supports use of oral micronized E2 or an intramuscular preparation. Only when these are unavailable should ethinyl E2 be prescribed. We recommend against the use of conjugated estrogens. Once progestin is added, many women prefer the ease of use of a pill containing both an estrogen and a progestin. The risks and benefits of different types of preparations, with examples, are discussed.

Reversal learning performance in the XY* mouse model of Klinefelter and Turner Syndromes

“…We expected that if genotypes differed on behavioral measures, that some of the differences might disappear if they depended on group differences in levels of gonadal hormones in any life stage. However, sex- hormone replacement therapies in adulthood do not appear to remediate the cognitive deficits observed in people with KS (Fales et al, 2003; Kompus et al, 2011; Liberato et al, 2017; Skakkebæk et al, 2017) or TS (Klein et al, 2018; Ross et al, 2002, 2004), and the cognitive consequences of reducing/blocking sex hormones in people with either KS or TS, or in this animal model, are unknown.…”

“…Some effects of KS and TS are potentially attributed to altered levels of gonadal hormones. KS men have lower levels of testosterone than XY men (Gravholt et al, 2018; Klein et al, 2018), and TS women have altered ovarian function (Klein et al, 2018; Romans et al, 1998; Ross et al, 1995, 2004; Rovet, 2004). Accordingly, we analyzed the role of gonadal hormones on task performance by comparing gonadectomized mice to gonad-intact controls.…”

Recognition and management of adults with Turner syndrome: From the transition of adolescence through the senior years

“…Low doses of estradiol are initiated and titrated to promote secondary sexual characteristics and uterine growth without early closure of the growth plates, ensure a normal tempo of bone mineralization (Cleemann et al, ), normalize cognitive maturation (Ross, Roeltgen, Feuillan, Kushner, & Cutler Jr., ; Ross, Roeltgen, Feuillan, Kushner, & Cutler Jr., ), body composition (Cleemann et al, ), reduce lipids (Gravholt, Naeraa, et al, ) and liver enzymes (Koulouri, Ostberg, & Conway, ) and reduce cardiovascular risk in the long term (Gravholt, Naeraa, et al, ; Ostberg et al, ). Transdermal estradiol is the preferred method for estrogen administration (Gravholt, Andersen, et al, , section 6.1; Klein et al, ), but oral estradiol can also be used. Estrogen replacement strategies for pubertal induction in girls with Turner syndrome (Gravholt, Andersen, et al, , table 5) recommend increasing the dose by 25 to 100% every 6 months to attain adult dosing over the span of 2–3 years.…”

Impact of route of administration on genotoxic oestrogens concentrations using oral vs transdermal oestradiol in girls with Turner syndrome

“…These patterns have been previously associated with increased breast cancer risk 30. Oestrogen given as physiologic replacement in hypogonadal girls and women is critically important for a plethora of beneficial metabolic effects, not only for mammary and female organs normal growth, but also beneficial for plasma lipids, cardiovascular health and bone, among others 7,32. In contrast, because of the rapidly changing oestrogen milieu, the levels in pubertal girls are far more variable than in prepubertal girls, making it difficult to pick up the differences in endogenous concentrations depending on adiposity as compared to girls prior to any gonadal activation.Ever being overweight in childhood increases the risk of all cause and breast cancer death later in life,31 suggesting that there are critical developmental periods when exposure to environmental factors, including genotoxic oestrogen metabolites, could significantly affect the impact of mammary cancers later in life 31.…”

“…Ever being overweight in childhood increases the risk of all cause and breast cancer death later in life,31 suggesting that there are critical developmental periods when exposure to environmental factors, including genotoxic oestrogen metabolites, could significantly affect the impact of mammary cancers later in life 31. Oestrogen given as physiologic replacement in hypogonadal girls and women is critically important for a plethora of beneficial metabolic effects, not only for mammary and female organs normal growth, but also beneficial for plasma lipids, cardiovascular health and bone, among others 7,32. Hence, the route of administration becomes an important variable in the selection of oestrogen used as replacement.…”