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Submitted on February 28, 2006
Accepted on June 8, 2006
Department of Endocrinology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands, Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium
* To whom correspondence should be addressed. E-mail: p.deronde{at}vumc.nl.
Context Estradiol inhibits gonadotropin release in men by an action at the hypothalamus and pituitary. Due to the tissue specific regulation of aromatase, peripheral estradiol levels may not reflect brain estradiol concentrations.
Objective We evaluated whether local aromatisation of testosterone in the hypothalamus or pituitary is important for gonadotropin release and to what extent circulating estrogens affect gonadotropin levels and peripheral testosterone levels.
Design, subjects and interventions We suppressed aromatase activity in 10 young healthy men with letrozole 2,5 mg once daily, restored plasma estradiol levels with estradiol patches (first week 100 µg/day, second week 50 µg/day, third week 25 µg/day, fourth week no estradiol patch) and measured plasma testosterone, estradiol, LH, FSH and SHBG levels.
Results The mean estradiol and testosterone levels during the study ranged between 68.6 ± 38.3 and 12.6 ± 7.21 pg/ml for estradiol and 179 ± 91 and 955 ± 292 ng/dl (mean±SD) for testosterone. Levels of testosterone, LH and FSH were inversely related to peripheral estradiol levels. During letrozole use the mean plasma estradiol level needed to restore testosterone, LH and FSH levels to baseline levels was not significantly different from the baseline mean estradiol level.
Conclusions Local aromatisation of testosterone in the hypothalamo-pituitary compartment is not a prerequisite for expression of the inhibitory action of estrogens on gonadotropin secretion in men. Peripheral estradiol levels directly reflect the inhibitory tone exerted by estrogens on gonadotropin release and are a major determinant of peripheral testosterone, LH and FSH levels.
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