Estrogen replacement in girls with Turner syndrome: What is the optimal estrogen dose and route?

Pharmacokinetic and pharmacodynamic study of various doses oral and transdermal estrogen found that transdermal estradiol 75mcg patches most closely approximated physiologic estrogen levels in agonadal girls with Turner syndrome. (1)

     As is the case in the care of transgender women, the optimal regimen of hormone replacement for girls with Turner syndrome is not well established.  Applying knowledge from Turner syndrome to the cross-sex hormone therapy (csHT) of transwomen is to some degree intuitive; both involve long term estrogen therapy across the lifespan.  Investigators aimed to study the pharmacokinetics and pharmacodynamics of various doses and routes of 17-beta estradiol on 10 girls with Turner syndrome.  Subjects were divided into two groups; one high dose group and one low dose group.  Girls in each group were treated with both transdermal and oral preparations, with a two-week washout period between each regimen (regimens: 75mcg and 37.5mcg patch (Vivelle) changed twice/weekly, 2mg and 0.5mg micronized estradiol tablets (Estrace) once/daily.  Results were compared to integrated mean estrogen levels over one menstrual cycle in a control group of 20 healthy menstruating girls.  Levels of estradiol (e2) and estrone (e1) were measured in all subjects and controls.

     Mean serum estradiol concentrations were closest to those of the control group in the high-dose transdermal group (114 +/- 31pg/ml transdermal, 96 +/- 11pg/ml for controls) for.  Levels in the low dose transdermal and high dose groups were similar.  Levels were lowest in the low dose oral group.  Estrone (e1) concentrations were higher the oral groups, likely because of hepatic and intestinal conversion.  LH/FSH suppression was equal in both high dose groups, but more pronounced in the low dose transdermal vs. oral.  In all cases gonadotropins did not fully normalize (particularly FSH, which responds in part to inhibin, which is absent in hypogonadal states).

Comments:

     It is unclear if pharmacologic studies in Turner syndrome females are applicable in those with male physiology or genetics.  For example, transwomen’s skin and connective tissue may have different absorption characteristics with respect to transdermal delivery systems.  It is also unclear if targeting physiologic estradiol levels is an appropriate clinical target for medical transition.  While estrone is generally considered to have minimal estrogenic activity, it may serve as an estrogen reservoir and may explain why patients describe feeling “different” on oral vs. transdermal preparations with similar serum levels.  Lastly, measurement of serum estrogens is wrought with difficulties and this study was not adequately powered to draw firm conclusions.

References:

1) TaboadaM, Santen R, Lima J, Hossain J, Singh R, Klein KO, et al. Pharmacokinetics andPharmacodynamics of Oral and Transdermal 17  Estradiol in Girls withTurner Syndrome. Journal of Clinical Endocrinology & Metabolism. 2011 Aug31;96(11):3502–10.