Intranasal estradiol administration to oophorectomized women.
An open, dose-finding study into the effects of a new intranasal 17 beta-estradiol formulation using dimethyl-beta-cyclodextrin as a solubilizer was conducted in nine hysterectomized and oophorectomized patients with symptoms of estrogen deficiency. After nasal delivery of 0.34 mg estradiol in three patients, concentration-time curves of estradiol in serum and its metabolite estrone in plasma were established. High initial estradiol serum levels were found in the order of 5 nmol/l. Estrone/estradiol ratios were below unity, whereas, in contrast, estrone/estradiol ratios after oral administration of estradiol are known to exceed unity. Biological activity, as reflected by suppression of FSH and LH, was manifest. In nine patients symptoms of estrogen deficiency were assessed by a questionnaire. After 3 and 6 months of treatment, a clinically and statistically significant decrease (P less than 0.01) of the total score according to this questionnaire was found compared to the beginning of the study. Thus nasal delivery of estradiol using this cyclodextrin formulation has potential for further clinical evaluation.
Hermens
W A
WA
Department of Clinical Pharmacy and Toxicology, Maasland Hospital, Sittard, The Netherlands.
Belder
C W
CW
Merkus
J M
JM
Hooymans
P M
PM
Verhoef
J
J
Merkus
F W
FW
D000281:Administration, Intranasal; D000328:Adult; D004338:Drug Combinations; D004958:Estradiol / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy; D004970:Estrone / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007044:Hysterectomy; D007986:Luteinizing Hormone / Q000097:blood; D008875:Middle Aged; D010052:Ovariectomy
D004338:Drug Combinations; D004970:Estrone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone