title: Intranasal administration of estradiol in combination with progesterone to oophorectomized women: a pilot study.
abstract: A pilot study was done to investigate the pharmacokinetics and acceptability of an intranasal 17 beta-estradiol/progesterone formulation. This formulation contained dimethyl-beta-cyclodextrin as a solubilizer and absorption enhancer of the steroid hormones. The study was performed in four oophorectomized and hysterectomized patients. After nasal delivery of 0.34 mg estradiol and 0.85 mg progesterone, concentration-time curves of progesterone, estradiol and its metabolite estrone were established. Rapid absorption of progesterone and estradiol was demonstrated. Progesterone peak-levels (3.9-6.7 nmol/l) exceeded the levels which are found in the follicular phase of the menstrual cycle, but did not reach the levels of the luteal phase. Comparison with an earlier reported study in which only estradiol was administered shows that the addition of progesterone does not alter the absorption and pharmacokinetics of estradiol. The nasal formulation was well accepted by the four patients and no adverse effects were noted.
authors.affiliation: Department Clinical Pharmacy and Toxicology, Maasland Hospital, Sittard, The Netherlands.
authors.forename: W A
authors.initials: WA
authors.lastname: Hermens
authors.forename: C W
authors.initials: CW
authors.lastname: Belder
authors.forename: J M
authors.initials: JM
authors.lastname: Merkus
authors.forename: P M
authors.initials: PM
authors.lastname: Hooymans
authors.forename: J
authors.initials: J
authors.lastname: Verhoef
authors.forename: F W
authors.initials: FW
authors.lastname: Merkus
mesh_terms: D000281:Administration, Intranasal; D004958:Estradiol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015914:Estrogen Replacement Therapy / Q000379:methods*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007044:Hysterectomy; D007986:Luteinizing Hormone / Q000097:blood; D008875:Middle Aged; D010052:Ovariectomy; D010865:Pilot Projects; D011374:Progesterone / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone