The effects of the aromatase inhibitor anastrozole on bone metabolism and cardiovascular risk indices in ovariectomized, androgen-treated female-to-male transsexuals.
OBJECTIVE
Cases of men with estrogen resistance and aromatase deficiency have highlighted the effects of estrogens on bone metabolism, the cardiovascular system and biochemical variables of the metabolic syndrome. In eugonadal men, administration of an aromatase inhibitor induces a substantial elevation of LH and testosterone due to the decreased negative-feedback signal of estrogen and may thwart the interpretation of results. As there is no gonad for LH to act on, no increase of serum testosterone concentration will be seen in female-to-male transssexuals. The aim of this study was to investigate the effects of estrogen deprivation on bone metabolism and vascular parameters without the interference of counter-regulatory effects as seen in eugonadal men.


METHODS
Thirty ovariectomized female-to-male transsexuals participated in this double-blind, randomized trial. During 3 months, subjects received the aromatase inhibitor anastrozole 1 mg/day (n = 16) or a placebo (n = 14) in addition to parenteral testosterone esters (Sustanon 250 every 2 weeks).


RESULTS
Serum 17beta-estradiol (E(2)) concentration fell significantly from 134.0 +/- 78.8 to 77.7 +/- 130.6 pmol/l compared with placebo (P < 0.01). LH and FSH levels rose without the rise of testosterone levels observed in eugonadal men. Within the placebo group, E(2) remained at baseline levels. Of the endpoint variables measured (bone metabolism and vascular parameters) no significant changes were observed compared with placebo, or within the anastrozole-treated group.


CONCLUSIONS
These results may indicate that the negative effects of estrogen deprivation in men only become manifest when the concentration falls below the levels induced by our intervention with anastrozole (77 pmol/l). This assumption is supported by the observation in the anastrozole group that, although effects of the reduction of serum E(2) on vascular parameters could not be demonstrated in subjects as a group, there was a correlation between individual serum E(2) and several vascular parameters.
Department of Endocrinology, VU University Medical Center, Amsterdam, The Netherlands.
Mathijs C M
MC
Bunck
Arno W F T
AW
Toorians
Paul
P
Lips
Louis J G
LJ
Gooren
D000077384:Anastrozole; D000728:Androgens / Q000008:administration & dosage*; D047072:Aromatase Inhibitors / Q000008:administration & dosage*; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D004311:Double-Blind Method; D004958:Estradiol / Q000097:blood; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D008055:Lipids / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D009570:Nitriles / Q000008:administration & dosage*; D010052:Ovariectomy; D010919:Placebos; D012307:Risk Factors; D014189:Transsexualism / Q000188:drug therapy* / Q000601:surgery; D014230:Triazoles / Q000008:administration & dosage*
D000728:Androgens; D047072:Aromatase Inhibitors; D008055:Lipids; D009570:Nitriles; D010919:Placebos; D014230:Triazoles; D000077384:Anastrozole; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D002097:C-Reactive Protein