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Estrogen delivery methods examined in girls with Turner’s syndrome
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Researchers observed little differences in the metabolic long-term effects of oral vs. transdermal 17 beta-estradiol hormone therapy in girls with Turner’s syndrome, according to new data. However, transdermal estradiol appeared to effect a more physiological estrogen milieu.
“In the postmenopausal literature a number of studies have previously suggested that estrogen given orally has deleterious effects on body composition and lipid oxidation as compared to transdermal and that it could serve as a functional [growth hormone] antagonist by suppressing [insulin-like growth factor I]. However, this has not been consistently confirmed,” the researchers wrote.
They randomly assigned 40 girls (mean age, 16.7 years) to oral or transdermal 17 beta-estradiol (Estrace, Bristol-Myers Squibb) replacement therapy (20 per group) to assess the metabolic effects of the different delivery methods.
According to data, the researchers administered titrated estradiol concentrations to normal range in both groups (mean oral dose, 2 mg; mean transdermal dose, 0.1 mg). The researchers found that fat free mass and percent fat mass, bone mineral density accrual, lipid oxidation and resting energy expenditure rates were similar between groups after 6 and 12 months of therapy.
IGF-1 concentrations appeared to be lower with oral 17 beta estradiol. However, the suppression of gonadotropins demonstrated no significant changes to lipids, glucose, osteocalcin or high-sensitivity C-reactive protein (hsCRP) between groups. Researchers wrote that estrone (E1), estrone sulfate (E1S), sex hormone-binding globulin (SHBG), and bioestrogen concentrations were significantly greater among patients who received the oral formulation.
These findings indicate girls with Turner’s syndrome displayed no differences in metabolic effects of oral vs. transdermal 17 beta-estradiol.
Disclosure: Santen reports consultancy related to estrogen for Pfizer, Novo Nordisk and TEVA Women’s Health. Mauras reports drug supply agreements and grant support from Pfizer. All other researchers report no relevant financial disclosures.
Perspective
Back to TopElizabeth Fudge, MD
The study by Torres-Santiago and colleagues compares the metabolic effects of oral vs. transdermal 17-beta cell estradiol (E2) in 40 patients with Turner’s syndrome during a 12-month period. No significant differences were seen between the oral and transdermal E2 groups in their outcome measures including fat free mass, percent fat mass, lipid oxidation or resting energy expenditure, lipids, IGF-1 levels, glucose, osteocalcin, hsCRP or bone mineral accrual assessed by DXA. Despite similar E2 levels between groups, significantly higher estrone (E1) and estrone sulfate (E1-s) concentrations were found in the oral estradiol group presumably due to hepatic metabolism of oral E2.
The clinical significance of these findings is unclear, but it is plausible that a more physiologic estrogen milieu could be of benefit. For example, a large population-based study in adults receiving estrogen-only hormone therapy with transdermal vs. oral estrogen replacement found significantly lower incidence of venous thromboembolism in the transdermal group; this finding is especially relevant in a population with an increased risk for structural cardiac defects, prosthetic cardiac valves and surgical interventions. In addition, it was found that higher GH doses were necessary to achieve target IGF-1 levels in adult GH-deficient women taking oral vs. transdermal estradiol, suggesting that oral estradiol may induce a relative GH resistance. Further, girls with Turner’s syndrome on GH therapy were shown to have significantly improved growth on parenteral estradiol replacement compared with oral estrogen, although the comparison was with conjugated estrogens.
A recent study by O’Donnell and colleagues found significantly greater uterine growth in subjects with premature ovarian failure using transdermal vs. oral estradiol, an important outcome for patients who are candidates for pregnancy.
This study provides important insights about the estrogen milieu with transdermal vs. oral estradiol, suggesting a more physiologic profile with transdermal estradiol which may have potential clinical benefit.
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