Reference : Pharmacodynamics of follicle stimulating hormone (FSH) in postmenopausal women during...
Scientific journals : Article
Human health sciences : General & internal medicine
Pharmacodynamics of follicle stimulating hormone (FSH) in postmenopausal women during pulsed estrogen therapy: Evidence that FSH release and synthesis are controlled by distinct pathways
Christin-Maitre, S. [> > > >]
Laveille, C. [> > > >]
Collette, Julien [Centre Hospitalier Universitaire de Liège - CHU > > Chimie médicale >]
Brion, N. [> > > >]
Reginster, Jean-Yves mailto [Université de Liège - ULiège > Département des sciences de la santé publique > Epidémiologie et santé publique >]
Journal of Clinical Endocrinology and Metabolism
Endocrine Soc
Yes (verified by ORBi)
[en] 17beta-Estradiol (E2) exerts negative feedback effects at the hypothalamo-pituitary level on serum FSH. This study investigated the effects of repeated daily administration of intranasal E2 (S21400) on the pharmacokinetics (PK) of E2 and estrone (E1) and the pharmacodynamics (PD) of FSH and assessed the PK/PD relationship between E2 and FSH using population model-dependent analysis. Postmenopausal volunteers (n = 24) received according to a balanced cross-over design, two 28-d treatments separated by a 2-month wash-out period: 300 mug E2, either alone or combined with oral dydrogesterone (20 mg/d) during the last 14 d of one of the treatments. Absorption of E2 was rapid, with maximal plasma concentrations at 10-30 min, returning to postmenopausal levels within 12 h. Over the 24-h period, FSH levels showed a U curve, with a minimum around 8 h after E2 administration. Moreover, over the treatment period, FSH basal values decreased by 17% between d 1 and 14 and an additional 5% between d 14 and 28. A PK/PD model described these short- and mid-term effects, possibly reflecting separate regulation mechanisms by E2 on FSH release and biosynthesis, respectively. The administration of progestin had no influence on E1, E2, and FSH model parameters. This study suggests that daily transient tissue exposure to E2 after pulsed estrogen therapy elicits short- and mid-term effects on the gonadotropin axis.

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