Estradiol-intranasal is a
nasal spray formulation containing an aqueous
solution of 17beta-estradiol that has a unique pulse-like pharmacokinetic profile. In a well designed, placebo-controlled trial
estradiol-intranasal 200 to 400 microg/day significantly reduced the incidence and severity of climacteric symptoms in women with moderate to severe menopausal symptoms after 4 and 12 weeks' treatment. The efficacy of
estradiol-intranasal 300 microg/day was similar to that of oral
estradiol 2 mg/day in this and another double-blind placebo-controlled trial. This equivalent efficacy was maintained in a subgroup of women with initially severe symptoms, and in smokers. Reductions in the incidence of atrophic vaginal mucosa and genitourinary symptoms and increases in the karyopyknotic index achieved with
estradiol-intranasal 300 microg/day were also similar to those observed with oral
estradiol 2 mg/day. Assessments of the effects of
estradiol-intranasal on the complications of menopause (increased risk of
cardiovascular disease and
osteoporosis) are ongoing; however,
estradiol-intranasal (sequentially combined with a
progestogen) produced significant beneficial effects on some
lipid parameters and on markers of
bone resorption and formation, and bone mineral density in postmenopausal women.
Estradiol-intranasal had no significant effects on serum levels of most of the assessed haemostatic factors, or on
angiotensinogen or
insulin levels.
Estradiol-intranasal 100 to 600 microg/day was generally well tolerated in clinical trials and most adverse events were mild to moderate. The most commonly reported events were nasal symptoms and
mastalgia. There was no evidence of
endometrial hyperplasia with up to 1 year's treatment with
estradiol-intranasal 300 microg/day combined with a
progestogen. The incidence of
mastalgia and withdrawal or
breakthrough bleeding was lower with
estradiol-intranasal 300 microg/day than with oral
estradiol 2 mg/day (both administered with a
progestogen) in one trial. In another trial, the incidence of
mastalgia was lower with
estradiol-intranasal 300 microg/day than with
estradiol transdermal 50 microg (both administered with a
progestogen). However, the overall incidence of adverse events was similar between the two treatments in this trial.
CONCLUSIONS: