The first is transdermal vs oral estradiol. The study population was Turner Syndrome patients.
(Presumably) Relevant results are bolded. The results require some interpretation. One possible conclusion is that oral estradiol is more effective but metabolizes more readily. Another is that in females, transdermal may have the most stable, long-term effects. But the most interesting bit for transsexuals is that SHBG levels are significantly higher with oral administration. SHBG is sex hormone binding globulin. Estrogen (and testosterone) binds to it. The higher the level of SHBG, the less is available for cellular take up. So more would be bad, the interesting thing being that its affinity for binding is a function of DHT. More DHT, more binding, less estradiol is bioavailable. And what inhibits DHT production? Finasteride - my conclusion being that oral estradiol administration in transsexuals may be the most effective delivery route, but only if the regimen includes finasteride.
Apologies, but the next one is a bit denser. The NKB system involves neuromuscular control, and regulation of reproductive development and processes. Also, since GnRH regulation of follicle stimulating and luteinizing hormones further downstream are involved, there is also an aspect of estrogen receptor sensitivity involved.Context: The long-term effects of pure 17β-estradiol (E2) depending on route of administration have not been well characterized.
Objective: To assess metabolic effects of oral vs. transdermal (TD) 17βE2 replacement using estrogen concentration-based dosing in girls with Turner Syndrome (TS).
Patients: Forty girls with TS, mean age: 16.7±1.7 yrs were recruited.
Design: Subjects were randomized to 17βE2 orally or TD. Doses were titrated using mean E2 concentrations of normally menstruating girls as therapeutic target. E2, estrone (E1) and estrone sulfate (E1S) (LCMSMS), a recombinant cell bioassay, and metabolites were measured, DXA scan and indirect calorimetry performed.
Main Outcome: Changes in body composition and lipid oxidation.
Results: E2 concentrations were titrated to normal range in both groups, mean oral dose: 2mg, TD: 0.1mg. After 6 and 12 months fat free mass (FFM) and %FM, bone mineral density accrual, lipid oxidation and resting energy expenditure rates were similar between groups. IGF-1 concentrations were lower on oral 17βE2 but suppression of gonadotropins was comparable with no significant changes in lipids, glucose, osteocalcin or hsCRP between groups. However, E1, E1S, SHBG and bioestrogen concentrations were significantly higher in the oral group.
Conclusions: When E2 concentrations are titrated to the normal range the route of delivery of 17βE2 does not affect differentially body composition, lipid oxidation and lipid concentrations in hypogonadal girls with TS. However, total estrogen exposure (E1, E1S, total bioestrogen) is significantly higher after oral 17βE2. TD 17βE2 results in a more physiologic estrogen milieu than oral 17βE2 administration in girls with TS.
Part of this study was transsexual-specific. One interesting aspect here is pubertal development.
Context: The recent report that loss-of-function mutations in either the gene encoding neurokinin B (NKB) or its receptor (NK3R) produce gonadotropin deficiencies in humans strongly points to NKB as a key regulator of GnRH release.
Objectives: We used NKB immunohistochemistry on postmortem human brain tissue to determine: 1) whether the human NKB system in the infundibular nucleus (INF) is sexually dimorphic; 2) at what stage in development the infundibular NKB system would diverge between men and women; 3) whether this putative structural difference is reversed in male-to-female (MtF) transsexual people; and 4) whether menopause is accompanied by changes in infundibular NKB immunoreactivity.
Methods: NKB immunohistochemical staining was performed on postmortem hypothalamus material of both sexes from the infant/pubertal period into the elderly period and from MtF transsexuals.
Results: Quantitative analysis demonstrated that the human NKB system exhibits a robust female-dominant sexual dimorphism in the INF. During the first years after birth, both sexes displayed a moderate and equivalent level of NKB immunoreactivity in the INF. The adult features emerged progressively around puberty until adulthood, where the female-dominant sex difference appeared and continued into old age. In MtF transsexuals, a female-typical NKB immunoreactivity was observed. Finally, in postmenopausal women, there was a significant increase in NKB immunoreactivity compared to premenopausal women.
Conclusion: Our results indicate that certain sex differences do not emerge until adulthood when activated by sex steroid hormones and the likely involvement of the human infundibular NKB system in the negative and positive feedback of estrogen on GnRH secretion.
